Lugt, A. van der

Automatic carotid artery distensibility measurements from CTA using nonrigid registration (Article)

2013-07-01T00:00:00Z

The distensibility of a blood vessel is a marker of atherosclerotic disease. In this paper we investigate the feasibility of measuring carotid artery distensibility on 4D CTA, both manually and using a new automatic method. On 4D CTA datasets manual (n= 38) and automatic (n= 76) measurements of the carotid distensibility were performed. A subset (n= 10) of the manual annotations were repeated by a second observer. The interobserver variability was assessed using a Bland-Altman analysis and appeared to be too large to reliably measure the distensibility using manual annotation. We compared two versions of the automatic method: one using 3D registration and one using a 4D registration method. The latter resulted in a more smooth deformation over time. The automatic method was evaluated using a synthetic deformation and by investigating whether known relations with cardiovascular risk factors could be reproduced. The relation between distensibility and cardiovascular risk factors was tested with a Mann-Whitney U test. Automatic measurements revealed an association with hypertension whereas the manual measurements did not. This relation has been found by other studies too. We conclude that carotid artery distensibility measurements should be performed automatically and that the method described in this paper is suitable for that.

The Relation of Uric Acid to Brain Atrophy and Cognition: The Rotterdam Scan Study. (Article)

2013-03-19T00:00:00Z

Background: Uric acid has been associated with focal vascular brain disease. However, it is unknown whether uric acid also relates to global brain changes such as brain atrophy. We therefore studied the relation of uric acid to brain atrophy and whether this is accompanied by worse cognitive function. Methods: In 814 persons of the population-based Rotterdam Study (mean age 62.0 years), we studied the relation of uric acid levels to brain tissue atrophy and cognition using linear regression models adjusted for age, sex and putative confounders. Brain atrophy was assessed using automated processing of magnetic resonance imaging. Cognition was assessed using a validated neuropsychological test battery and we computed compound scores of cognitive domains. Results: Higher uric acid levels were associated with white matter atrophy [difference in Z-score of white matter volume per standard deviation increase in uric acid: -0.07 (95% CI: -0.12; -0.01)], but not with gray matter atrophy. This was particularly marked when comparing hyperuricemic to normouricemic persons [Z-score difference: -0.27 (-0.43; -0.11)]. Worse cognition was primarily found in persons with hyperuricemia [-0.28 (-0.48; -0.08)]. Conclusions: Hyperuricemia is related to white matter atrophy and worse cognition. Copyright

Pediatric population-based neuroimaging and the Generation R Study: The intersection of developmental neuroscience and epidemiology (Article)

2013-01-01T00:00:00Z

Neuroimaging studies of typically developing children and adolescents have provided valuable information on global and regional developmental trajectories of brain development. As these studies become larger and population-based, they are generating an intersection between the fields of developmental neuroscience and epidemiology. However, few of these studies have adequately probed the contribution of multiple environmental and genetic factors on brain development. Studies designed to optimally evaluate the role of multiple environmental and genetic factors on brain development require both large sample sizes and the prospective collection of multiple environmental factors. The Generation R Study is a large, prospective, prenatal-cohort study of nearly 10,000 children that began in 2002 in Rotterdam, the Netherlands. In September of 2009, 6-8 year old children from the Generation R Study were invited to participate in a magnetic resonance imaging component of the study. We provide an overview of the study design and experience for the first 801 children recruited for the neuroimaging component of the study. The protocol includes a 1-h neuropsychological assessment using the NEPSY-II, a mock scanning session, and a neuroimaging session that includes high-resolution structural, diffusion tensor, and resting-state functional MRI sequences. Image quality has been good to excellent in over 80 % of the children to date. The infusion of imaging into the Generation R Study will set the stage for evaluating the role of multiple environmental and genetic factors in both typical and atypical neurodevelopment.

Vascular risk factors, apolipoprotein E, and hippocampal decline on magnetic resonance imaging over a 10-year follow-up (Article)

2012-01-12T00:00:00Z

Background: Decline of hippocampal volume on magnetic resonance imaging (MRI) may be considered as a surrogate biomarker of accumulating Alzheimer disease (AD) pathology. Previously, we showed in the prospective population-based Rotterdam Scan Study that a higher rate of decline of hippocampal volume on MRI precedes clinical AD or memory decline. We studied potential risk factors for decline of hippocampal volume. Methods: At baseline (1995-1996), 518 nondemented elderly subjects were included, and the cohort was re-examined in 1999 and in 2006. At each examination, hippocampal volume was determined using an automated segmentation procedure. In all, 301 persons had at least two three-dimensional MRI scans to assess decline in hippocampal volume. Results: Persons carrying the apolipoprotein E (APOE) e{open}4 allele had lower hippocampal volumes than persons with the e{open}3/e{open}3 genotype, but the rate of decline was not influenced by APOE genotype. In persons who did not use antihypertensive treatment, both a high (>90 mm Hg) and a low (<70 mm Hg) diastolic blood pressure were associated with a faster decline in hippocampal volume. Also, white matter lesions on baseline MRI were associated with a higher rate of decline in hippocampal volume. Conclusions: In a nondemented elderly population, persons with the APOE e{open}4 allele have a smaller hippocampal volume but not a higher rate of decline. Rate of decline of hippocampal volume was influenced by white matter lesions and diastolic blood pressure, supporting their hypothesized role in the pathogenesis of AD.

Determinants of magnetic resonance imaging detected carotid plaque components: The Rotterdam Study (Article)

2012-01-01T00:00:00Z

Aims Components of carotid atherosclerotic plaque such as intraplaque haemorrhage and lipid core are important determinants of plaque progression and destabilization. The association between plaque components and risk factors for cardiovascular disease is not well studied. Methods and Results Participants from the population-based Rotterdam Study with carotid wall thickening on ultrasound (n= 1006) underwent high-resolution magnetic resonance imaging for carotid plaque characterization. Maximum wall thickening, the degree of stenosis, and the presence of intraplaque haemorrhage, lipid core, and calcification were assessed in both carotid arteries and their associations with cardiovascular risk factors were investigated. Intraplaque haemorrhage and lipid core were present in almost 25 of plaques, respectively, and occurred simultaneously in 9 of plaques. In men, intraplaque haemorrhage and lipid core were more prevalent compared with women (28.8 vs. 18.3 and 28.9 vs. 21.7, respectively). Intraplaque haemorrhage occurred more frequently at older age [odds ratio (OR) per 10 years 1.8, 95 confidence interval 1.62.1], in men (OR 2.2, 1.72.9), in persons with hypertension (multivariate adjusted OR 1.4, 1.11.8), and in current smokers (multivariate adjusted OR 1.6, 1.22.3). Men (OR 1.5, 1.21.9) and subjects with hypercholesterolaemia (multivariate adjusted OR 1.4, 1.11.7) more often exhibited a lipid core. Conclusion In subjects from the general population with carotid wall thickening, intraplaque haemorrhage and lipid coreboth considered indicators of unstable plaqueare highly frequent and more prevalent in men compared with women. Furthermore, different risk factors are associated with these plaque components: hypertension and current smoking were risk factors for the presence of intraplaque haemorrhage, and hypercholesterolaemia was the only risk factor for lipid core presence.

Advanced magnetic resonance neuroimaging of language function recovery after aphasic stroke: A technical review (Article)

2012-01-01T00:00:00Z

Advanced magnetic resonance neuroimaging of language function recovery after aphasic stroke: a technical review. Arch Phys Med Rehabil 2012;93(1 Suppl 1):S4-14. Two advanced magnetic resonance neuroimaging techniques, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI), have recently made their way into clinically oriented research and hold great promise to study the brain's adaptive changes of function and structure after aphasic stroke, respectively. Such functional and structural neuroplasticity is thought to underlie the recovery of language function, occurring spontaneously and/or in the context of therapeutic intervention. With fMRI, brain activity can be visualized. Spontaneous brain activity, present in multiple brain networks, is measured with resting-state fMRI and language-related brain activity by having the subject perform a language task during scanning (task-based fMRI). With DTI the major white matter tracts, such as the dorsal and ventral language pathways and the commissural fibers, can be visualized and quantified. Both techniques are entirely noninvasive and thus offer the unique opportunity to perform multiple assessments within the same subject. To gain more insight in functional and structural neuroplasticity after aphasic stroke, advanced magnetic resonance neuroimaging studies in specific patient populations, at several stages after stroke and in the course of language recovery, are needed. Such studies will help to clarify the influence of the many factors that play a role in the recovery of language function and are thus vital to further the development of aphasia therapy. Application of these techniques in aphasic stroke patients, however, is not without challenge. The purpose of this article is to discuss the methodologic challenges of fMRI and DTI in the assessment of language recovery after aphasic stroke.

Global and focal brain volume in long-term breast cancer survivors exposed to adjuvant chemotherapy (Article)

2011-12-28T00:00:00Z

A limited number of studies have associated adjuvant chemotherapy with structural brain changes. These studies had small sample sizes and were conducted shortly after cessation of chemotherapy. Results of these studies indicate local gray matter volume decrease and an increase in white matter lesions. Up till now, it is unclear if non-CNS chemotherapy is associated with long-term structural brain changes. We compared focal and total brain volume (TBV) of a large set of non-CNS directed chemotherapy-exposed breast cancer survivors, on average 21 years post-treatment, to that of a population-based sample of women without a history of cancer. Structural MRI (1.5T) was performed in 184 chemotherapy-exposed breast cancer patients, mean age 64.0 (SD = 6.5) years, who had been diagnosed with cancer on average 21.1 (SD = 4.4) years before, and 368 age-matched cancer-free reference subjects from a population-based cohort study. Outcome measures were: TBV and total gray and white matter volume, and hippocampal volume. In addition, voxel based morphometry was performed to analyze differences in focal gray matter. The chemotherapy-exposed breast cancer survivors had significantly smaller TBV (-3.5 ml, P = 0.019) and gray matter volume (-2.9 ml, P = 0.003) than the reference subjects. No significant differences were observed in white matter volume, hippocampal volume, or local gray matter volume. This study shows that adjuvant chemotherapy for breast cancer is associated with long-term reductions in TBV and overall gray matter volume in the absence of focal reductions. The observed smaller gray matter volume in chemotherapy-exposed survivors was comparable to the effect of almost 4 years of age on gray matter volume reduction. These volume differences might be associated with the slightly worse cognitive performance that we observed previously in this group of breast cancer survivors.

Replication study of Chr17q25 with cerebral white matter lesion volume (Article)

2011-11-01T00:00:00Z

BACKGROUND AND PURPOSE-: Recently, the first genomewide association study on cerebral white matter lesion burden identified chr17q25 to be significantly associated with white matter lesions. We report on the first independent replication study of this genetic association. METHODS-: In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral white matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028. RESULTS-: The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with white matter lesion volume with P=1.1*10 for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only had minor influence on these associations. A meta-analysis with all published data for rs3744028 resulted in a probability value of 5.3*10. CONCLUSIONS-: This study further establishes chr17q25 as a novel genetic locus for WML volume.

Genetic determination of human facial morphology: Links between cleft-lips and normal variation (Article)

2011-11-01T00:00:00Z

Recent genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with non-syndromic cleft lip with or without cleft palate (NSCL/P), and other previous studies showed distinctly differing facial distance measurements when comparing unaffected relatives of NSCL/P patients with normal controls. Here, we test the hypothesis that genetic loci involved in NSCL/P also influence normal variation in facial morphology. We tested 11 SNPs from 10 genomic regions previously showing replicated evidence of association with NSCL/P for association with normal variation of nose width and bizygomatic distance in two cohorts from Germany (N=529) and the Netherlands (N=2497). The two most significant associations found were between nose width and SNP rs1258763 near the GREM1 gene in the German cohort (P=6 × 10 4), and between bizygomatic distance and SNP rs987525 at 8q24.21 near the CCDC26 gene (P=0.017) in the Dutch sample. A genetic prediction model explained 2% of phenotype variation in nose width in the German and 0.5% of bizygomatic distance variation in the Dutch cohort. Although preliminary, our data provide a first link between genetic loci involved in a pathological facial trait such as NSCL/P and variation of normal facial morphology. Moreover, we present a first approach for understanding the genetic basis of human facial appearance, a highly intriguing trait with implications on clinical practice, clinical genetics, forensic intelligence, social interactions and personal identity.

The Rotterdam Scan Study: Design and update up to 2012 (Article)

2011-10-01T00:00:00Z

Neuroimaging plays an important role in etiologic research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to unravel causes of neurological disease by performing neuroimaging in a population-based longitudinal setting. In 1995 and 1999 random subsets of the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. We also describe the imaging protocol and post-processing techniques, and highlight the main findings to date. Finally, we make recommendations for future research, which will also be the main focus of investigation in the Rotterdam Scan Study.

Calcification in major vessel beds relates to vascular brain disease (Article)

2011-10-01T00:00:00Z

OBJECTIVE-: Calcification in atherosclerotic plaques is a novel marker of atherosclerosis and is related to cardiovascular disease. However, its relationship with cerebrovascular disease has not been investigated extensively. We investigated the relationship between calcification in various vessel beds outside the brain and imaging markers of vascular brain disease. METHODS AND RESULTS-: A total of 885 community-dwelling people (mean age, 66.7 years) underwent computed tomography of the coronary arteries, aortic arch, and extracranial and intracranial carotid arteries to assess arterial calcification. Brain magnetic resonance imaging scans were performed to assess cerebral infarcts, microbleeds, and white matter lesions (WMLs). Calcification in each vessel bed was associated with presence of cerebral infarcts and with larger WML volume. The most prominent associations were found between intracranial carotid calcification and WML volume and between extracranial carotid calcification and infarcts. Adjustment for cardiovascular risk factors or ultrasound carotid plaque scores did not change these results. No associations were found between calcification and cerebral microbleeds. CONCLUSION-: Arterial calcification in major vessel beds is associated with vascular brain disease on magnetic resonance imaging. Most notably, larger intracranial carotid calcification load relates to larger WML volumes, and larger extracranial carotid calcification load relates to the presence of cerebral infarcts, independently of ultrasound carotid plaque score. This suggests that calcification of atherosclerotic plaque yields other information in addition to merely the presence of plaques, providing novel insights into the etiology of vascular brain disease.

Burden of atherosclerosis improves the prediction of coronary heart disease but not cerebrovascular events: The Rotterdam Study (Article)

2011-08-01T00:00:00Z

AimsSince atherosclerosis is a systemic process, risk prediction would benefit from targeting multiple components of cardiovascular disease simultaneously. To this end, it is useful to examine the predictive value of non-invasive measures of atherosclerosis in various vascular beds for both coronary heart disease (CHD) and cerebrovascular disease.Methods and resultsBetween September 2003 and February 2006, 2153 asymptomatic participants (69.6 ± 6.6 years) from the Rotterdam Study underwent a multi-detector computed tomography scan. During a median follow-up of 3.5 years, 58 CHD events (myocardial infarction and CHD death) and 52 cerebrovascular events (TIA and stroke) occurred. Participants were classified into low (<5), intermediate (510), and high (>10) 5-year risk categories based on a refitted Framingham risk model. The model was extended by coronary, aortic arch, or carotid calcium and reclassification percentages were calculated. For the outcome CHD, the C-statistic improved from 0.693 for the Framingham refitted model to 0.743, 0.740, and 0.749 by addition of coronary, aortic arch, and carotid calcium, respectively. Reclassification was most substantial in the intermediate risk group where addition of coronary calcium reclassified 56 of persons [net reclassification improvement (NRI): 15; P < 0.01)]. Adding aortic arch calcium led to a reclassification of 32 of persons (NRI: 8; P 0.01) and adding carotid calcium reclassified 51 (NRI: 9; P 0.02). In contrast, calcification in any of the three vascular beds did not improve cerebrovascular risk prediction.ConclusionCoronary, aortic arch, and carotid artery calcification significantly improved risk prediction of CHD but not of cerebrovascular events.

Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading (Article)

2011-08-01T00:00:00Z

This paper describes an evaluation framework that allows a standardized and objective quantitative comparison of carotid artery lumen segmentation and stenosis grading algorithms. We describe the data repository comprising 56 multi-center, multi-vendor CTA datasets, their acquisition, the creation of the reference standard and the evaluation measures. This framework has been introduced at the MICCAI 2009 workshop 3D Segmentation in the Clinic: A Grand Challenge III, and we compare the results of eight teams that participated. These results show that automated segmentation of the vessel lumen is possible with a precision that is comparable to manual annotation. The framework is open for new submissions through the website http://cls2009.bigr.nl.

Incidence, treatment, and case-fatality of non-traumatic subarachnoid haemorrhage in the Netherlands (Article)

2011-07-01T00:00:00Z

Background: Non-traumatic subarachnoid haemorrhage (SAH) is a devastating disorder and in the majority of cases it is caused by rupture of an intracranial aneurysm. No actual data are available on the incidence of non-traumatic SAH and aneursymal SAH (aSAH) in the Netherlands and little is known about treatment patterns of aSAH. Our purpose was therefore to assess the incidence, treatment patterns, and case-fatality of non-traumatic (a)SAH within the Dutch general population. Methods: Two population based data sources were used for this retrospective cohort study. One was the nationwide hospital discharge registry (National Medical Registration, LMR). Cases were patients hospitalized for SAH (ICD-9-code 430) in 2001-2005. The second source was the Integrated Primary Care Information (IPCI) database, a medical record database allowing for case validation. Cases were patients with validated non-traumatic (a)SAH in 1996-2006. Incidence, treatment, and case-fatality were assessed. Results: The incidence rate (IR) of non-traumatic SAH was 7.12 per 100,000 PY (95%CI: 6.94-7.31) and increased with age. The IR of aSAH was 3.78 (95%CI: 2.98-4.72). Women had a twofold increased risk of non-traumatic SAH; this difference appeared after the fourth decade. Non-traumatic SAH fatality was 30% (95%CI: 29-31%). Of aSAH patients 64% (95%CI: 53-74%) were treated with a clipping procedure, and 26% (95%CI: 17-37%) with coiling. Conclusion: Non-traumatic SAH is a rare disease with substantial case-fatality; rates in the Netherlands are similar to other countries. Case-fatality is also similar as well as age and sex patterns in incidence.

Genome-wide association studies of cerebral white matter lesion burden (Article)

2011-07-01T00:00:00Z

Objective: White matter hyperintensities (WMHs) detectable by magnetic resonance imaging are part of the spectrum of vascular injury associated with aging of the brain and are thought to reflect ischemic damage to the small deep cerebral vessels. WMHs are associated with an increased risk of cognitive and motor dysfunction, dementia, depression, and stroke. Despite a significant heritability, few genetic loci influencing WMH burden have been identified. Methods: We performed a meta-analysis of genome-wide association studies (GWASs) for WMH burden in 9,361 stroke-free individuals of European descent from 7 community-based cohorts. Significant findings were tested for replication in 3,024 individuals from 2 additional cohorts. Results: We identified 6 novel risk-associated single nucleotide polymorphisms (SNPs) in 1 locus on chromosome 17q25 encompassing 6 known genes including WBP2, TRIM65, TRIM47, MRPL38, FBF1, and ACOX1. The most significant association was for rs3744028 (pdiscovery= 4.0 × 10-9; preplication= 1.3 × 10-7; pcombined= 4.0 × 10-15). Other SNPs in this region also reaching genome-wide significance were rs9894383 (p = 5.3 × 10-9), rs11869977 (p = 5.7 × 10-9), rs936393 (p = 6.8 × 10-9), rs3744017 (p = 7.3 × 10-9), and rs1055129 (p = 4.1 × 10-8). Variant alleles at these loci conferred a small increase in WMH burden (4-8% of the overall mean WMH burden in the sample). Interpretation: This large GWAS of WMH burden in community-based cohorts of individuals of European descent identifies a novel locus on chromosome 17. Further characterization of this locus may provide novel insights into the pathogenesis of cerebral WMH. Copyright

Estimating 3D lumen centerlines of carotid arteries in free-hand acquisition ultrasound (Article)

2011-06-29T00:00:00Z

Purpose: The purpose of this paper is to present a methodology to estimate the carotid artery lumen centerlines in ultrasound (US) images obtained in a free-hand examination. Challenging aspects here are speckle noise in US images, artifacts, and the lack of contrast in the direction orthogonal to the US beam direction. Method: An algorithm based on a rough lumen segmentation obtained by robust ellipse fitting was developed to deal with these conditions and estimate the lumen center in 2D B-mode scans. In a free-hand sweep examination, continuous image acquisitions are performed through time when the radiologist moves the probe on the patient's neck. The result is a series of images that show 2D cross-sections of the carotid's morphology. A tracking sensor (Flock of Birds) was attached to the probe and both were connected to a PC executing the Stradwin software, which relates spatial information to the acquisition data of the US probe. The spatial information was combined with the 2D lumen center estimates to provide a centerline in 3D. For validation, 19 carotid scans from 15 different patients were scanned, their centerlines calculated by the algorithm and compared with results acquired by manual annotations. Results: The average Euclidean distance between both among all the examinations was 0.82 mm. For each examination, the percentage of these Euclidean distances below 2 mm was calculated; the average over all examinations was 92%. Conclusion: Automated 3D estimation of carotid artery lumen centerlines in free-hand real-time ultrasound is feasible and can be performed with high accuracy. The algorithm is robust enough to keep the centerlines inside the vessel, even in the absence of contrast in parts of the vessel wall.

Multispectral MRI centerline tracking in carotid arteries (Article)

2011-06-09T00:00:00Z

We propose a minimum cost path approach to track the centerlines of the internal and external carotid arteries in multispectral MR data. User interaction is limited to the annotation of three seed points. The cost image is based on both a measure of vessel medialness and lumen intensity similarity in two MRA image sequences: Black Blood MRA and Phase Contrast MRA. After intensity inhomogeneity correction and noise reduction, the two images are aligned using affine registration. The two parameters that control the contrast of the cost image were determined in an optimization experiment on 40 training datasets. Experiments on the training datasets also showed that a cost image composed of a combination of gradient-based medialness and lumen intensity similarity increases the tracking accuracy compared to using only one of the constituents. Furthermore, centerline tracking using both MRA sequences outperformed tracking using only one of these MRA images. An independent test set of 152 images from 38 patients served to validate the technique. The centerlines of 148 images were successfully extracted using the parameters optimized on the training sets. The average mean distance to the reference standard, manually annotated centerlines, was 0.98 mm, which is comparable to the in-plane resolution. This indicates that the proposed method has a high potential to replace the manual centerline annotation.

Region based level set segmentation of the outer wall of the carotid bifurcation in CTA (Article)

2011-06-09T00:00:00Z

This paper presents a level set based method for segmenting the outer vessel wall and plaque components of the carotid artery in CTA. The method employs a GentleBoost classification framework that classifies pixels as calcified region or not, and inside or outside the vessel wall. The combined result of both classifications is used to construct a speed function for level set based segmentation of the outer vessel wall; the segmented lumen is used to initialize the level set. The method has been optimized on 20 datasets and evaluated on 80 datasets for which manually annotated data was available as reference. The average Dice similarity of the outer vessel wall segmentation was 92%, which compares favorably to previous methods.

Automated versus manual segmentation of atherosclerotic carotid plaque volume and components in CTA: associations with cardiovascular risk factors (Article)

2011-05-26T00:00:00Z

The purpose of this study was to validate automated atherosclerotic plaque measurements in carotid arteries from CT angiography (CTA). We present an automated method (three initialization points are required) to measure plaque components within the carotid vessel wall in CTA. Plaque components (calcifications, fibrous tissue, lipids) are determined by different ranges of Hounsfield Unit values within the vessel wall. On CTA scans of 40 symptomatic patients with atherosclerotic plaque in the carotid artery automatically segmented plaque volume, calcified, fibrous and lipid percentages were 0.97 ± 0.51 cm3, 10 ± 11%, 63 ± 10% and 25 ± 5%; while manual measurements by first observer were 0.95 ± 0.60 cm3, 14 ± 16%, 63 ± 13% and 21 ± 9%, respectively and manual measurement by second observer were 1.05 ± 0.75 cm3, 11 ± 12%, 61 ± 11% and 27 ± 10%. In 90 datasets, significant associations were found between age, gender, hypercholesterolemia, diabetes, smoking and previous cerebrovascular disease and plaque features. For both automated and manual measurements, significant associations were found between: age and calcium and fibrous tissue percentage; gender and plaque volume and lipid percentage; diabetes and calcium, smoking and plaque volume; previous cerebrovascular disease and plaque volume. Significant associations found only by the automated method were between age and plaque volume, hypercholesterolemia and plaque volume and diabetes and fibrous tissue percentage. Significant association found only by the manual method was between previous cerebrovascular disease and percentage of fibrous tissue. Automated analysis of plaque composition in the carotid arteries is comparable with the manual analysis and has the potential to replace it.

Prevalence and calcification of intracranial arterial stenotic lesions as assessed with multidetector computed tomography angiography (Article)

2011-05-01T00:00:00Z

BACKGROUND AND PURPOSE-Intracranial arterial stenosis (ICAS) in patients with recent ischemic stroke is associated with a high risk of recurrent stroke. More insight into the pathophysiology of ICAS could help identify patients at high risk requiring more aggressive secondary prevention. We evaluated the prevalence, distribution, calcification, and the risk factors predisposing ICAS in a European stroke population. METHODS-Consecutive patients with a transient ischemic attack or ischemic stroke (n=786) were evaluated for the presence and distribution of ICAS (≥30% luminal narrowing) by CT angiography. ICAS were categorized as symptomatic or asymptomatic, and the presence of calcification was assessed. The association of traditional cerebrovascular risk factors and the erythrocyte sedimentation rate with ICAS was analyzed. RESULTS-In 178 of 786 patients (23%), 288 ICAS were observed. Most stenoses (n=194/288; 67%) were located in the posterior circulation arteries. In 59 of 786 patients (8%), ICAS were considered symptomatic. ICAS in the basilar artery and arteries beyond the circle of Willis were mainly noncalcified. In addition to age, gender, and several traditional cerebrovascular risk factors, erythrocyte sedimentation rate was independently associated with the presence of ICAS (OR, 1.20; 95% CI, 1.06-1.36) and with the presence of noncalcified ICAS in particular (OR, 1.20; 95% CI, 1.05-1.37). CONCLUSIONS-ICAS was observed in a noteworthy number of European stroke patients. Particularly, the majority of ICAS was observed in the posterior circulation, possibly conferring worse prognosis. ICAS in distal arteries were mainly noncalcified. Association of noncalcified ICAS and erythrocyte sedimentation rate may indicate a prominent role for inflammatory factors in intracranial atherosclerotic disease.

Lobar distribution of cerebral microbleeds: The Rotterdam Scan Study (Article)

2011-05-01T00:00:00Z

Objective: To investigate the distribution of lobar microbleeds over the different lobes, taking into account lobar volume and clustering effects of multiple microbleeds. Design: Population-based, cross-sectional analysis. Setting: The Rotterdam Scan Study. Participants: A total of 198 persons (age range, 61-95 years) with lobar microbleeds. Main Outcome Measures: Distribution of microbleeds over different lobes. Results:Wefoundthat lobar cerebralmicrobleedsoccurred significantlymoreoften inthetemporallobe, aregionknown to be more affected in cerebral amyloid angiopathy. Conclusion: This study corroborates the presumed association of lobar microbleeds with cerebral amyloid angiopathy.

Effects of intima stiffness and plaque morphology on peak cap stress (Article)

2011-04-11T00:00:00Z

Background: Rupture of the cap of a vulnerable plaque present in a coronary vessel may cause myocardial infarction and death. Cap rupture occurs when the peak cap stress exceeds the cap strength. The mechanical stress within a cap depends on the plaque morphology and the material characteristics of the plaque components. A parametric study was conducted to assess the effect of intima stiffness and plaque morphology on peak cap stress.Methods: Models with idealized geometries based on histology images of human coronary arteries were generated by varying geometric plaque features. The constructed multi-layer models contained adventitia, media, intima, and necrotic core sections. For adventitia and media layers, anisotropic hyperelastic material models were used. For necrotic core and intima sections, isotropic hyperelastic material models were employed. Three different intima stiffness values were used to cover the wide range reported in literature. According to the intima stiffness, the models were classified as stiff, intermediate and soft intima models. Finite element method was used to compute peak cap stress.Results: The intima stiffness was an essential determinant of cap stresses. The computed peak cap stresses for the soft intima models were much lower than for stiff and intermediate intima models. Intima stiffness also affected the influence of morphological parameters on cap stresses. For the stiff and intermediate intima models, the cap thickness and necrotic core thickness were the most important determinants of cap stresses. The peak cap stress increased three-fold when the cap thickness was reduced from 0.25 mm to 0.05 mm for both stiff and intermediate intima models. Doubling the thickness of the necrotic core elevated the peak cap stress by 60% for the stiff intima models and by 90% for the intermediate intima models. Two-fold increase in the intima thickness behind the necrotic core reduced the peak cap stress by approximately 25% for both intima models. For the soft intima models, cap thickness was less critical and changed the peak cap stress by 55%. However, the necrotic core thickness was more influential and changed the peak cap stress by 100%. The necrotic core angle emerged as a critical determinant of cap stresses where a larger angle lowered the cap stresses. Contrary to the stiff and intermediate intima models, a thicker intima behind the necrotic core increased the peak cap stress by approximately 25% for the soft intima models. Adventitia thickness and local media regression had limited effects for all three intima models.Conclusions: For the stiff and intermediate intima models, the cap thickness was the most important morphological risk factor. However for soft intima models, the necrotic core thickness and necrotic core angle had a bigger impact on the peak cap stress. We therefore need to enhance our knowledge of intima material properties if we want to derive critical morphological plaque features for risk evaluation.

Statistical analysis of minimum cost path based structural brain connectivity (Article)

2011-03-15T00:00:00Z

Diffusion MRI can be used to study the structural connectivity within the brain. Brain connectivity is often represented by a binary network whose topology can be studied using graph theory. We present a framework for the construction of weighted structural brain networks, containing information about connectivity, which can be effectively analyzed using statistical methods. Network nodes are defined by segmentation of subcortical structures and by cortical parcellation. Connectivity is established using a minimum cost path (mcp) method with an anisotropic local cost function based directly on diffusion weighted images. We refer to this framework as Statistical Analysis of Minimum cost path based Structural Connectivity (SAMSCo) and the weighted structural connectivity networks as mcp-networks. In a proof of principle study we investigated the information contained in mcp-networks by predicting subject age based on the mcp-networks of a group of 974 middle-aged and elderly subjects. Using SAMSCo, age was predicted with an average error of 3.7. years. This was significantly better than predictions based on fractional anisotropy or mean diffusivity averaged over the whole white matter or over the corpus callosum, which showed average prediction errors of at least 4.8. years. Additionally, we classified subjects, based on the mcp-networks, into groups with low and high white matter lesion load, while correcting for age, sex and white matter atrophy. The SAMSCo classification outperformed the classification based on the diffusion measures with a classification accuracy of 76.0% versus 63.2%. We also performed a classification in groups with mild and severe atrophy, correcting for age, sex and white matter lesion load. In this case, mcp-networks and diffusion measures yielded similar classification accuracies of 68.3% and 67.8% respectively. The SAMSCo prediction and classification experiments indicate that the mcp-networks contain information regarding age, white matter lesion load and white matter atrophy, and that in case of age and white matter lesion load the mcp-network based models outperformed the predictions based on diffusion measures.

Incidence of cerebral microbleeds in the general population: The Rotterdam Scan Study (Article)

2011-03-01T00:00:00Z

BACKGROUND AND PURPOSE - Cerebral microbleeds are frequently seen in the general elderly population, but it is unknown at what rate they occur with aging and whether once present can disappear over time. METHODS - As part of the Rotterdam Scan Study, 831 persons (mean age, 68.5 years) underwent repeated brain MRI with a mean interval of 3.4 years. We assessed determinants of incident microbleeds in relation to their location with multiple logistic regressions. RESULTS - Overall prevalence of microbleeds increased from 24.4% at baseline to 28.0% at follow-up. Eighty-five persons (10.2%) developed new microbleeds. Microbleeds at baseline predicted development of new microbleeds (OR, 5.38; 95% CI, 3.34 to 8.67). In only 6 persons with microbleeds at baseline, fewer microbleeds were present at the follow-up examination. Cardiovascular risk factors, presence of lacunar infarcts, and larger white matter lesion volume at baseline were all associated with incident deep or infratentorial microbleeds, whereas people with the apolipoprotein E ε4/ε4 genotype or larger white matter lesion volume had a higher risk of incident strictly lobar microbleeds. CONCLUSIONS - Incidence of microbleeds in the general population over a 3-year interval was substantial and microbleeds rarely disappeared. Risk factors for incident microbleeds were similar to those for prevalent microbleeds and differed according to microbleed location. These results support the assessment of microbleeds on T2*-weighted MRI as a possible marker of both cerebral amyloid angiopathy and hypertensive vasculopathy progression.

Platelet aggregation inhibitors, vitamin K antagonists and risk of subarachnoid hemorrhage (Article)

2011-03-01T00:00:00Z

Background: Use of platelet aggregation inhibitors and vitamin K antagonists has been associated with an increased risk of intracranial hemorrhage (ICH). Whether the use of these antithrombotic drugs is associated with an increased risk of subarachnoid hemorrhage (SAH) remains unclear, especially as confounding by indication might play a role. Objective: The aim of the present study was to investigate whether use of platelet aggregation inhibitors or vitamin K antagonists increase the risk of SAH. Methods: We applied population-based case-control, case-crossover and case-time-control designs to estimate the risk of SAH while addressing issues both of confounding by indication and time varying exposure within the PHARMO Record Linkage System database. This system includes drug dispensing records from community pharmacies and hospital discharge records of more than 3million community-dwelling inhabitants in the Netherlands. Patients were considered a case if they were hospitalized for a first SAH (ICD-9-CM code 430) in the period between 1st January 1998 and 31st December 2006. Controls were selected from the source population, matched on age, gender and date of hospitalization. Conditional logistic regression was used to estimate multivariable adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of SAH during use of platelet aggregation inhibitors or vitamin K antagonists. In the case-crossover and case-time-control designs we selected 11 control periods preceding the index date in successive steps of 1month in the past. Results: In all, 1004 cases of SAH were identified. In the case-control analysis the adjusted OR for the risk of SAH in current use of platelet aggregation inhibitors was 1.32 (95% CI: 1.02-1.70) and in current use of vitamin K antagonists 1.29 (95% CI: 0.89-1.87) compared with no use. In the case-crossover analysis the ORs for the risk of SAH in current use of platelet aggregation inhibitors and vitamin K antagonists were 1.04 (95% CI: 0.56-1.94) and 2.46 (95% CI: 1.04-5.82), respectively. In the case-time-control analysis the OR for platelet aggregation inhibitors was 0.50 (95% CI: 0.26-0.98) and for vitamin K antagonists 1.98 (95% CI: 0.82-4.76). Conclusion: The use of platelet aggregation inhibitors was not associated with an increased SAH risk; the modest increase observed in the case-control analysis could be as a result of confounding. The use of vitamin K antagonists seemed to be associated with an increased risk of SAH. The increase was most pronounced in the case-crossover analysis and therefore cannot be explained by unmeasured confounding.

Sorafenib induced thyroiditis in two patients with hepatocellular carcinoma (Article)

2011-02-01T00:00:00Z

Background: Sorafenib is a multi-targeted tyrosine kinase inhibitor licensed for the treatment of hepatocellular carcinoma and renal cell carcinoma. Thyroid function test abnormalities have been reported for different tyrosine kinase inhibitors, but only limited data on thyroid function test abnormalities related to sorafenib are available, demonstrating the occurrence of hypothyroidism in patients treated with sorafenib. Summary: We describe two patients who developed temporary hyperthyroidism during the course of sorafenib treatment, which was followed by overt and subclinical hypothyroidism, respectively. Thyroid ultrasonography showed an atrophic thyroid gland in patient 1, and signs of thyroiditis in patient 2. Detailed reassessment of thyroid volumes on routinely performed computerized tomography scans showed a gradual decrease in thyroid volume during sorafenib treatment in one patient, suggesting progressive thyroid destruction. Conclusion: This case report describes in detail and for the first time two cases of sorafenib-induced thyroiditis. We assume that this sorafenib-induced destructive thyroiditis is an important cause of sorafenib-induced hypothyroidism.

Association between carotid artery plaque ulceration and plaque composition evaluated with multidetector CT angiography (Article)

2011-02-01T00:00:00Z

Background and Purpose- Symptomatic carotid artery plaque ulceration is associated with distinct plaque components such as a large lipid-rich necrotic core (LR-NC) in ischemic stroke patients with a 50% carotid stenosis. We evaluated the associations between carotid artery plaque ulceration and plaque characteristics in ischemic stroke patients with 50% stenosis, as well as in those with a low degree of stenosis (0% to 49%). Methods- Consecutive patients (n=346) with symptoms in the anterior circulation were evaluated with multidetector CT angiography (MDCTA) for the presence of atherosclerotic plaque, degree of stenosis, and plaque ulceration in the symptomatic carotid artery. Plaque volume and plaque component proportions of LR-NC, fibrous tissue, and calcification were measured. The associations between plaque ulceration and plaque characteristics were analyzed using logistic regression. Results- Atherosclerotic plaque was present in 185 patients. Plaque ulcerations were present in 38 (21%) patients, of which half had a low degree stenosis (0% to 49%). Plaque volume was significantly larger in ulcerated plaques. After adjustment for age, sex, and degree of stenosis, LR-NC proportion was strongly associated with plaque ulceration (odds ratio, 2.21; 95% CI, 1.49 to 3.27), whereas calcification proportion was inversely associated with plaque ulceration (odds ratio, 0.60; 95% CI, 0.40 to 0.89). These associations remained significant in patients with a low degree stenosis (0% to 49%). CONCLUSION-: Plaque volume, degree of stenosis, and LR-NC proportion evaluated noninvasively with MDCTA are associated with carotid artery plaque ulceration, even in patients with a low degree stenosis (0% to 49%). Plaque volume and composition analysis with MDCTA may identify rupture prone plaques and improve risk stratification in ischemic stroke patients.

Evolution of atherosclerotic carotid plaque morphology: Do ulcerated plaques heal? A serial multidetector ct angiography study (Article)

2011-02-01T00:00:00Z

Background: Atherosclerotic carotid plaque rupture may lead to thromboembolization, causing transient ischemic attack or ischemic stroke. Carotid plaque ulceration on angiography is associated with plaque rupture. Although healing of ruptured plaques has been described in coronary arteries, little is known about the natural development of plaque ulcerations in carotid arteries. We therefore explored the evolution of carotid plaque surface morphology with serial multidetector CT angiography (MDCTA). Methods: From a registry of patients with transient ischemic attack or minor ischemic stroke, we selected 83 patients who had undergone serial MDCTA of the carotid arteries. Arteries subjected to revascularization procedures between the two scans were excluded (n = 11). Plaque surface morphology was classified as smooth, irregular or ulcerated on both baseline and follow-up MDCTA. Progression (i.e. development of irregularities or ulceration) and regression (i.e. disappearance of irregularities or ulceration) in morphology were evaluated. Results: The mean time interval between the MDCTA scans was 21 ± 13 months. At baseline, 28 (18%) arteries were normal, 124 (80%) contained atherosclerotic plaque and 3 (2%) were occluded. Plaque surface morphology was smooth in 86 arteries (55%), irregular in 23 (15%) and ulcerated in 15 (10%). At follow-up, surface morphology was unchanged in 88% of arteries, had progressed in 8% and regressed in 4%. Most importantly, plaque morphology remained unchanged in most ulcerated plaques (10/15; 67%). One ulcerated plaque had progressed, whereas 4 had regressed. New ulcerations had developed in 2 nonulcerated plaques. Conclusion: MDCTA allows evaluation of temporal changes in atherosclerotic carotid plaque morphology. Plaque surface morphology remained unchanged in most arteries. Carotid ulcerations persist for a long time, and may remain a potential source of thromboembolism. Copyright

Genetic risk factors for cerebral small-vessel disease in hypertensive patients from a genetically isolated population (Article)

2011-01-01T00:00:00Z

Background: Asymptomatic cerebral lesions on MRI such as white matter lesions (WML), lacunes and microbleeds are commonly seen in older people. We examined the role of a series of candidate genes involved in blood pressure regulation and amyloid metabolism. Materials and Methods: The study was embedded in a family-based cohort sampled from a Dutch genetically isolated population. We selected individuals between 55 and 75 years of age with hypertension (N=129). Volumes of WML and presence of lacunes and microbleeds were assessed with MRI. We studied three genes involved in blood pressure regulation (angiotensin, angiotensin II type 1 receptor, α-adducin) and two genes involved in the amyloid pathway (apolipoprotein E (APOE) and sortilin-related receptor gene (SORL1)). Results: All participants had WML (median volume, 3.1 ml; interquartile range, 1.5e6.5 ml); lacunar infarcts were present in 15.5% and microbleeds in 23.3%. Homozygosity for the APOE ε4 allele was associated with lacunes (OR, 4.8; 95% CI, 1.2 to 19.3). Individuals carrying two copies of the variant allele of four single nucleotide polymorphism (SNPs) located at the 3'-end of SORL1 (rs1699102, rs3824968, rs2282649, rs1010159) had significantly more often microbleeds (highest OR, 6.87; 95% CI, 1.78 to 26.44). Conclusion: The association of SORL1 with microbleeds suggests that the amyloid cascade is involved in the aetiology of microbleeds in populations with hypertension.

Remedial action and feedback processing in a time-estimation task: Evidence for a role of the rostral cingulate zone in behavioral adjustments without learning (Article)

2011-01-01T00:00:00Z

The present study examined the role of the rostral cingulate zone (RCZ) in feedback processing, and especially focused on effects of modality of the feedback stimulus and remedial action. Participants performed a time-estimation task in which they had to estimate a 1-second interval. After the estimation participants received verbal (correct/false) or facial (fearful face/happy face) feedback. Percentage of positive and negative feedback was kept at 50% by dynamically adjusting the interval in which estimations were labeled correct. Contrary to predictions of the reinforcement learning theory, which predicts more RCZ activation when the outcome of behavior is worse than expected, we found that the RCZ was more active after positive feedback than after negative feedback, independent of the modality of the feedback stimulus. More in line with the suggested role of the RCZ in reinforcement learning was the finding that the RCZ was more active after negative feedback that was followed by a correct adjustment as compared to negative feedback followed by an incorrect adjustment. Both findings can be explained in terms of the RCZ being involved in facilitating remedial action as opposed to the suggested signaling function (outcome is worse than expected) proposed by the reinforcement learning theory.

Robust CTA lumen segmentation of the atherosclerotic carotid artery bifurcation in a large patient population (Article)

2010-12-01T00:00:00Z

We propose and validate a semi-automatic method for lumen segmentation of the carotid bifurcation in computed tomography angiography (CTA). First, the central vessel axis is obtained using path tracking between three user-defined points. Second, starting from this path, the segmentation is automatically obtained using a level set. The cost and speed functions for path tracking and segmentation make use of intensity and homogeneity slice-based image features. The method is validated on a large data set of 234 carotid bifurcations of 129 ischemic stroke patients with atherosclerotic disease. The results are compared to manually obtained lumen segmentations. Parameter optimization is carried out on a subset of 30 representative carotid bifurcations. With the optimized parameter settings the method successfully tracked the central vessel paths in 201 of the remaining 204 bifurcations (99%) which were not part of the training set. Comparison with manually drawn segmentations shows that the average overlap between the method and observers is similar (for the inter-observer set the results were 92% vs. 87% and for the intra-observer set 94% vs. 94%). Therefore the method has potential to replace the manual procedure of lumen segmentation of the atherosclerotic bifurcation in CTA. © 2010 Elsevier B.V.

A case study of melodic intonation therapy (MIT) in the subacute stage of aphasia: Early re-reactivation of left hemisphere structures (Article)

2010-12-01T00:00:00Z

Intracranial aneurysm segmentation in 3D CT angiography: Method and quantitative validation (Article)

2010-12-01T00:00:00Z

Accurately quantifying aneurysm shape parameters is of clinical importance, as it is an important factor in choosing the right treatment modality (i.e. coiling or clipping), in predicting rupture risk and operative risk and for pre-surgical planning. The first step in aneurysm quantification is to segment it from other structures that are present in the image. As manual segmentation is a tedious procedure and prone to inter- and intra-observer variability, there is a need for an automated method which is accurate and reproducible. In this paper a novel semi-automated method for segmenting aneurysms in Computed Tomography Angiography (CTA) data based on Geodesic Active Contours is presented and quantitatively evaluated. Three different image features are used to steer the level set to the boundary of the aneurysm, namely intensity, gradient magnitude and variance in intensity. The method requires minimum user interaction, i.e. clicking a single seed point inside the aneurysm which is used to estimate the vessel intensity distribution and to initialize the level set. The results show that the developed method is reproducible, and performs in the range of interobserver variability in terms of accuracy.

A semi-automatic method for segmentation of the carotid bifurcation and bifurcation angle quantification on black blood MRA (Article)

2010-11-22T00:00:00Z

Quantitative information about the geometry of the carotid artery bifurcation may help in predicting the development of atherosclerosis. A geodesic active contours based segmentation method combining both gradient and intensity information was developed for semi-automatic, accurate and robust quantification of the carotid bifurcation angle in Black Blood MRA data. The segmentation method was evaluated by comparing its accuracy to inter and intra observer variability on a large dataset that has been acquired as part of a longitudinal population study which investigates the natural progression of carotid atherosclerosis. Furthermore, the method is shown to be robust to initialization differences. The bifurcation angle obtained from the segmented lumen corresponds well with the angle derived from the manual lumen segmentation, which demonstrates that the method has large potential to replace manual segmentations for extracting the carotid bifurcation angle from Black Blood MRA data.

Statistical analysis of structural brain connectivity (Article)

2010-11-22T00:00:00Z

We present a framework for statistical analysis in large cohorts of structural brain connectivity, derived from diffusion weighted MRI. A brain network is defined between subcortical gray matter structures and a cortical parcellation obtained with FreeSurfer. Connectivity is established through minimum cost paths with an anisotropic local cost function and is quantified per connection. The connectivity network potentially encodes important information about brain structure, and can be analyzed using multivariate regression methods. The proposed framework can be used to study the relation between connectivity and e.g. brain function or neurodegenerative disease. As a proof of principle, we perform principal component regression in order to predict age and gender, based on the connectivity networks of 979 middle-aged and elderly subjects, in a 10-fold cross-validation. The results are compared to predictions based on fractional anisotropy and mean diffusivity averaged over the white matter and over the corpus callosum. Additionally, the predictions are performed based on the best predicting connection in the network. Principal component regression outperformed all other prediction models, demonstrating the age and gender information encoded in the connectivity network.

Imaging tests in determination of brain death (Article)

2010-11-01T00:00:00Z

Long-term changes in cerebellar activation during functional recovery from transient peripheral motor paralysis (Article)

2010-11-01T00:00:00Z

Localized altered cerebellar cortical activity can be associated with short-term changes in motor learning that take place in the course of hours, but it is unknown whether it can be correlated to long-term recovery from transient peripheral motor diseases, and if so, whether it occurs concomitantly in related brain regions. Here we show in a longitudinal fMRI study of patients with unilateral Bell's palsy that increases in ipsilateral cerebellar activity follow the recovery course of facial motor functions over at least one and a half years. These findings hold true for changes in brain activity related to both oral and peri-orbital activation, even though these processes are differentially mediated by unilateral and bilateral brain connectivities, respectively. Activation of non-facial musculature, which was studied for control, does not show any change in cerebellar activity over time. The localized changes in cerebellar activities following activation of facial functions occur concomitantly with increases in activity of the facial region in the contralateral primary motor cortex suggesting that the cerebellum acts together with the cerebral cortex in long-term adaptation to transient pathological sensorimotor processing.

Prediction of dementia by hippocampal shape analysis (Article)

2010-10-25T00:00:00Z

This work investigates the possibility of predicting future onset of dementia in subjects who are cognitively normal, using hippocampal shape and volume information extracted from MRI scans. A group of 47 subjects who were non-demented normal at the time of the MRI acquisition, but were diagnosed with dementia during a 9 year follow-up period, was selected from a large population based cohort study. 47 Age and gender matched subjects who stayed cognitively intact were selected from the same cohort study as a control group. The hippocampi were automatically segmented and all segmentations were inspected and, if necessary, manually corrected by a trained observer. From this data a statistical model of hippocampal shape was constructed, using an entropy-based particle system. This shape model provided the input for a Support Vector Machine classifier to predict dementia. Cross validation experiments showed that shape information can predict future onset of dementia in this dataset with an accuracy of 70%. By incorporating both shape and volume information into the classifier, the accuracy increased to 74%.

Microstructural brain injury in post-concussion syndrome after minor head injury (Article)

2010-10-06T00:00:00Z

Introduction: After minor head injury (MHI), post-concussive symptoms commonly occur. The purpose of this study was to correlate the severity of post-concussive symptoms in MHI patients with MRI measures of microstructural brain injury, namely mean diffusivity (MD) and fractional anisotropy (FA), as well as the presence of microhaemorrhages. Methods: Twenty MHI patients and 12 healthy controls were scanned at 3 T using diffusion tensor imaging (DTI) and high-resolution gradient recalled echo (HRGRE) T2*-weighted sequences. One patient was excluded from the analysis because of bilateral subdural haematomas. DTI data were preprocessed using Tract Based Spatial Statistics. The resulting MD and FA images were correlated with the severity of post-concussive symptoms evaluated with the Rivermead Postconcussion Symptoms Questionnaire. The number and location of microhaemorrhages were assessed on the HRGRE T2*-weighted images. Results: Comparing patients with controls, there were no differences in MD. FA was decreased in the right temporal subcortical white matter. MD was increased in association with the severity of post-concussive symptoms in the inferior fronto-occipital fasciculus (IFO), the inferior longitudinal fasciculus and the superior longitudinal fasciculus. FA was reduced in association with the severity of post-concussive symptoms in the uncinate fasciculus, the IFO, the internal capsule and the corpus callosum, as well as in the parietal and frontal subcortical white matter. Microhaemorrhages were observed in one patient only. Conclusions: The severity of post-concussive symptoms after MHI was significantly correlated with a reduction of white matter integrity, providing evidence of microstructural brain injury as a neuropathological substrate of the post-concussion syndrome.

Carotid, aortic arch and coronary calcification are related to history of stroke: The Rotterdam Study (Article)

2010-10-01T00:00:00Z

Objective: Multidetector computed tomography (MDCT), which has been mainly used to study coronary atherosclerosis, also enables non-invasive measurement of carotid and aortic atherosclerosis and might be suitable for screening in the general population. The aim of this study was to investigate the associations of carotid artery, aortic arch and coronary artery calcification as assessed by MDCT, with presence of stroke. Methods: The study was embedded in the population-based Rotterdam Study and comprises 2521 persons (mean age 69.7 ± 6.8 years, 48% males) that underwent an MDCT scan. History of stroke was reported by 96 persons. We used multivariable logistic regression to investigate the associations of calcification in the carotid arteries, aortic arch, and coronary arteries with presence of stroke. Results: We found strong and graded associations of prevalent stroke with carotid artery (OR quartile 4 versus 1 (95% CI): 5.0 (2.2-11.0)), aortic arch (3.3 (1.5-7.4)) and coronary artery calcification (3.1 (1.3-7.3)), independent of cardiovascular risk factors. Only the association of carotid artery calcification with presence of stroke was independent of calcification in the other two vessel beds. Conclusion: In this population-based study, we found a strong and graded association of prevalent stroke with carotid artery, aortic arch and coronary artery calcification, independent of cardiovascular risk factors. After additional adjustment for calcification in the other vessel beds, prevalent stroke was still significantly related to carotid calcification, but no longer to aortic arch or coronary calcification.

Prevalence and risk factors of cerebral microbleeds: An update of the rotterdam scan study (Article)

2010-10-01T00:00:00Z

BACKGROUND AND PURPOSE-: We previously reported on the high prevalence of cerebral microbleeds (CMBs) in community-dwelling people aged 60 years and older. Moreover, we found that their spatial distribution likely reflects differences in underlying etiology. We have since almost quadrupled the number of participants in our study and expanded it to include persons of 45 years and older. We examined the prevalence and determinants of microbleeds in this larger and younger cohort from the general population. METHODS-: In 3979 persons (mean age, 60.3 years), we performed brain MRI at 1.5T, including a sequence optimized for visualization of CMBs. Associations between APOE genotype, cardiovascular risk factors, and markers of cerebrovascular disease with the presence and location of CMBs were assessed by multiple logistic regression adjusted for age, sex, and relevant confounders. RESULTS-: Microbleed prevalence gradually increased with age, from 6.5% in persons aged 45 to 50 years to 35.7% in participants of 80 years and older. Overall, 15.3% of all subjects had at least 1 CMB. Cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial region, whereas APOE ϵ4 and diastolic blood pressure were related to microbleeds in a strictly lobar location. CONCLUSIONS-: Findings in this larger population are in line with our previous results and, more importantly, extend these to a younger age group. CMBs are already present at middle age, and prevalence rises strongly with increasing age. We confirmed that determinants of the presence of cerebral microbleeds differ according to their location in the brain.

An ontological modeling approach to cerebrovascular disease studies: The NEUROWEB case (Article)

2010-08-01T00:00:00Z

The NEUROWEB project supports cerebrovascular researchers' association studies, intended as the search for statistical correlations between a feature (e.g., a genotype) and a phenotype. In this project the phenotype refers to the patients' pathological state, and thus it is formulated on the basis of the clinical data collected during the diagnostic activity. In order to enhance the statistical robustness of the association inquiries, the project involves four European Union clinical institutions. Each institution provides its proprietary repository, storing patients' data. Although all sites comply with common diagnostic guidelines, they also adopt specific protocols, resulting in partially discrepant repository contents. Therefore, in order to effectively exploit NEUROWEB data for association studies, it is necessary to provide a framework for the phenotype formulation, grounded on the clinical repository content which explicitly addresses the inherent integration problem. To that end, we developed an ontological model for cerebrovascular phenotypes, the NEUROWEB Reference Ontology, composed of three layers. The top-layer (Top Phenotypes) is an expert-based cerebrovascular disease taxonomy. The middle-layer deconstructs the Top Phenotypes into more elementary phenotypes (Low Phenotypes) and general-use medical concepts such as anatomical parts and topological concepts. The bottom-layer (Core Data Set, or CDS) comprises the clinical indicators required for cerebrovascular disorder diagnosis. Low Phenotypes are connected to the bottom-layer (CDS) by specifying what combination of CDS values is required for their existence. Finally, CDS elements are mapped to the local repositories of clinical data. The NEUROWEB system exploits the Reference Ontology to query the different repositories and to retrieve patients characterized by a common phenotype.

MRI-based quantification of outflow boundary conditions for computational fluid dynamics of stenosed human carotid arteries (Article)

2010-08-01T00:00:00Z

Accurate assessment of wall shear stress (WSS) is vital for studies on the pathogenesis of atherosclerosis. WSS distributions can be obtained by computational fluid dynamics (CFD) using patient-specific geometries and flow measurements. If patient-specific flow measurements are unavailable, in- and outflow have to be estimated, for instance by using Murray's Law. It is currently unknown to what extent this law holds for carotid bifurcations, especially in cases where stenoses are involved. We performed flow measurements in the carotid bifurcation using phase-contrast MRI in patients with varying degrees of stenosis. An empirical relation between outflow and degree of area stenosis was determined and the outflow measurements were compared to estimations based on Murray's Law. Furthermore, the influence of outflow conditions on the WSS distribution was studied. For bifurcations with an area stenosis smaller than 65%, the outflow ratio of the internal carotid artery (ICA) to the common carotid artery (CCA) was 0.62±0.12 while the outflow ratio of the external carotid artery (ECA) was 0.35±0.13. If the area stenosis was larger than 65%, the flow to the ICA decreased linearly to zero at 100% area stenosis. The empirical relation fitted the flow data well (R2=0.69), whereas Murray's Law overestimated the flow to the ICA substantially for larger stenosis, resulting in an overestimation of the WSS. If patient-specific flow measurements of the carotid bifurcation are unavailable, estimation of the outflow ratio by the presented empirical relation will result in a good approximation of calculated WSS using CFD.

Three-dimensional registration of histology of human atherosclerotic carotid plaques to in-vivo imaging (Article)

2010-08-01T00:00:00Z

An accurate spatial relationship between 3D in-vivo carotid plaque and lumen imaging and histological cross sections is required to study the relationship between biomechanical parameters and atherosclerotic plaque components. We present and evaluate a fully three-dimensional approach for this registration problem, which accounts for deformations that occur during the processing of the specimens. By using additional imaging steps during tissue processing and semi-automated non-linear registration techniques, a 3D-reconstruction of the histology is obtained.The methodology was evaluated on five specimens obtained from patients, operated for severe atherosclerosis in the carotid bifurcation. In more than 80% of the histology slices, the quality of the semi-automated registration with computed tomography angiography (CTA) was equal to or better than the manual registration. The inter-observer variability was between one and two in-vivo CT voxels and was equal to the manual inter-observer variability. Our technique showed that the angles between the normals of the registered histology slices and the in-vivo CTA scan direction ranged 6-56°, indicating that proper 3D-registration is crucial for establishing a correct spatial relation with in-vivo imaging modalities. This new 3D-reconstruction technique of atherosclerotic plaque tissue opens new avenues in the field of biomechanics as well as in the field of image processing, where it can be used for validation purposes of segmentation algorithms.

Suspected carotid artery stenosis: Cost-effectiveness of CT angiography in work-up of patients with recent TIA or minor ischemic stroke (Article)

2010-08-01T00:00:00Z

Purpose: To assess the effectiveness and cost-effectiveness of state-of-the-art noninvasive diagnostic imaging strategies in patients with a transient ischemic attack (TIA) or minor stroke who are suspected of having carotid artery stenosis (CAS). Materials and Methods: All prospectively evaluated patients provided informed consent, and the local ethics committee approved this study. Diagnostic performance, treatment, long-term events, quality of life, and costs resulting from strategies employing duplex ultrasonography (US), computed tomographic (CT) angiography, contrast material-enhanced magnetic resonance (MR) angiography, and combinations of these modalities were modeled in a decision tree and Markov model. Data sources included a prospective diagnostic cohort study, a meta-analysis, and a review of the literature. Outcomes were costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios, and net health benefits (QALY-equivalents), with a willingness-to-pay threshold of €50 000 per QALY and a societal perspective. The strategy with the highest net health benefit was considered the most cost effective. Extensive one-way, two-way, and probabilistic sensitivity analyses to explore the effect of varying parameter values were performed. The reference case analysis assumed that patients underwent surgery 2-4 weeks after the first symptoms, and the effect of earlier intervention was explored. Results: The reference case analysis showed that duplex US combined with CT angiography and surgery for 70%-99% stenoses was the most cost-effective strategy, with a net health benefit of 13.587 and 15.542 QALY-equivalents in men and women, respectively. In men, the CT angiography strategy with a 70%-99% cutoff yielded slightly more QALYs, at an incremental cost of €71 419 per QALY, compared with duplex US combined with CT angiography. In patients with a high-risk profile, in patients with a high prior probability of disease, and when patients could be treated within 2 weeks after the first symptoms, the CT angiography strategy with surgery for 50%-99% stenoses was the most cost-effective strategy. Conclusion: In diagnosing CAS, duplex US should be the initial test, and, if its results are positive, CT angiography should be performed; patients with 70%-99% stenoses should then undergo carotid endarterectomy. In patients with a high-risk profile, a high probability of CAS, or who can undergo surgery without delay, immediate CT angiography and surgery for 50%-99% stenoses is indicated.

Imaging of the fibrous cap in atherosclerotic carotid plaque (Article)

2010-08-01T00:00:00Z

In the last two decades, a substantial number of articles have been published to provide diagnostic solutions for patients with carotid atherosclerotic disease. These articles have resulted in a shift of opinion regarding the identification of stroke risk in patients with carotid atherosclerotic disease. In the recent past, the degree of carotid artery stenosis was the sole determinant for performing carotid intervention (carotid endarterectomy or carotid stenting) in these patients. We now know that the degree of stenosis is only one marker for future cerebrovascular events. If one wants to determine the risk of these events more accurately, other parameters must be taken into account; among these parameters are plaque composition, presence and state of the fibrous cap (FC), intraplaque haemorrhage, plaque ulceration, and plaque location. In particular, the FC is an important structure for the stability of the plaque, and its rupture is highly associated with a recent history of transient ischaemic attack or stroke. The subject of this review is imaging of the FC.

Accuracy and reproducibility study of automatic MRI brain tissue segmentation methods (Article)

2010-07-01T00:00:00Z

The ability to study changes in brain morphometry in longitudinal studies majorly depends on the accuracy and reproducibility of the brain tissue quantification. We evaluate the accuracy and reproducibility of four previously proposed automatic brain tissue segmentation methods: FAST, SPM5, an automatically trained k-nearest neighbor (kNN) classifier, and a conventional kNN classifier based on a prior training set. The intensity nonuniformity correction and skull-stripping mask were the same for all methods. Evaluations were performed on MRI scans of elderly subjects derived from the general population. Accuracy was evaluated by comparison to two manual segmentations of MRI scans of six subjects (mean age 65.9 ± 4.4. years). Reproducibility was assessed by comparing the automatic segmentations of 30 subjects (mean age 57.0 ± 3.7. years) who were scanned twice within a short time interval. All methods showed good accuracy and reproducibility, with only small differences between methods. The conventional kNN classifier was the most accurate method with similarity indices of 0.82/0.90/0.94 for cerebrospinal fluid/gray matter/white matter, but it showed the lowest reproducibility. FAST yielded the most reproducible segmentation volumes with volume difference standard deviations of 0.55/0.49/0.38 (percentage of intracranial volume) respectively. The results of the reproducibility experiment can be used to calculate the required number of subjects in the design of a longitudinal study with sufficient power to detect changes over time in brain (tissue) volume. Example sample size calculations demonstrate a rather large effect of the choice of segmentation method on the required number of subjects.

Atherosclerotic plaque ulceration in the symptomatic internal carotid artery is associated with nonlacunar ischemic stroke (Article)

2010-06-01T00:00:00Z

Background and Purpose: Atherosclerotic carotid plaque ulceration is considered a marker of previous plaque rupture and subsequent thromboembolism. It can be accurately detected with multidetector CTA. We hypothesized that atherosclerotic plaque ulceration is associated with nonlacunar ischemic stroke rather than lacunar stroke. Methods: Prospectively, 750 consecutive patients with transient ischemic attack or ischemic stroke symptoms in the anterior cerebral circulation were evaluated for the presence of atherosclerotic plaque ulceration in the symptomatic carotid artery with multidetector CTA. Patients with stroke attributable to cardiac embolism or other specific etiologies and patients with amaurosis fugax were excluded. Ischemic strokes in the remaining 534 patients were classified as nonlacunar (n≤236) or lacunar (n≤298) based on clinical symptoms and multidetector CT of the brain. Ulceration was defined as extension of contrast material beyond the vascular lumen into the surrounding plaque. RESULTS: Plaque ulceration in the symptomatic carotid artery was more common in nonlacunar strokes (n≤47; 20%) as compared to lacunar strokes (n≤20; 7%; P<0.001). After adjustment for age, gender, cardiovascular risk factors, and degree of stenosis, ulcerations were independently associated with nonlacunar stroke compared to lacunar stroke (odds ratio, 2.70; 95% confidence interval, 1.43-5.09). Conclusions: Atherosclerotic carotid plaque ulceration is associated with nonlacunar ischemic stroke, independent of the degree of carotid stenosis. These results suggest that nonlacunar stroke and lacunar stroke are caused by different pathophysiological mechanisms.

Frequency of ubiquitin and FUS-positive, TDP-43-negative frontotemporal lobar degeneration (Article)

2010-05-01T00:00:00Z

Frontotemporal lobar degeneration (FTLD) is a clinically, genetically and pathologically heterogeneous disorder. Within FTLD with ubiquitin-positive inclusions (FTLD-U), a new pathological subtype named FTLD-FUS was recently found with fused in sarcoma (FUS) positive, TDP-43-negative inclusions, and striking atrophy of the caudate nucleus. The aim of this study was to determine the frequency of FTLD-FUS in our pathological FTLD series, and to describe the clinical, neuroimaging and neuropathological features of FTLD-FUS, especially caudate atrophy. Demographic and clinical data collected prospectively from 387 patients with frontotemporal dementia (FTD) yielded 74 brain specimens. Immunostaining was carried out using a panel of antibodies, including AT-8, ubiquitin, p62, FUS, and TDP-43. Cortical and caudate atrophy on MRI (n = 136) was rated as normal, mildmoderate or severe. Of the 37 FTLD-U cases, 33 were reclassified as FTLD-TDP and four (0.11, 95%: 0.00-0.21) as FTLD-FUS, with ubiquitin and FUS-positive, p62 and TDP-43-negative neuronal intranuclear inclusions (NII). All four FTLD-FUS cases had a negative family history, behavioural variant FTD (bvFTD), and three had an age at onset ≤40 years. MRI revealed mild-moderate or severe caudate atrophy in all, with a mean duration from onset till MRI of 63 months (range 16-119 months). In our total clinical FTD cohort, we found 11 patients (0.03; 95% CI: 0.01-0.05) with bvFTD, negative family history, and age at onset ≤40 years. Caudate atrophy was present in 10 out of 136 MRIs, and included all four FUS-cases. The newly identified FTLD-FUS has a frequency of 11% in FTLD-U, and an estimated frequency of three percent in our clinical FTD cohort. The existence of this pathological subtype can be predicted with reasonable certainty by age at onset ≤40 years, negative family history, bvFTD and caudate atrophy on MRI.

New ischaemic brain lesions on MRI after stenting or endarterectomy for symptomatic carotid stenosis: a substudy of the International Carotid Stenting Study (ICSS) (Article)

2010-04-01T00:00:00Z

Background: The International Carotid Stenting Study (ICSS) of stenting and endarterectomy for symptomatic carotid stenosis found a higher incidence of stroke within 30 days of stenting compared with endarterectomy. We aimed to compare the rate of ischaemic brain injury detectable on MRI between the two groups. Methods: Patients with recently symptomatic carotid artery stenosis enrolled in ICSS were randomly assigned in a 1:1 ratio to receive carotid artery stenting or endarterectomy. Of 50 centres in ICSS, seven took part in the MRI substudy. The protocol specified that MRI was done 1-7 days before treatment, 1-3 days after treatment (post-treatment scan), and 27-33 days after treatment. Scans were analysed by two or three investigators who were masked to treatment. The primary endpoint was the presence of at least one new ischaemic brain lesion on diffusion-weighted imaging (DWI) on the post-treatment scan. Analysis was per protocol. This is a substudy of a registered trial, ISRCTN 25337470. Findings: 231 patients (124 in the stenting group and 107 in the endarterectomy group) had MRI before and after treatment. 62 (50%) of 124 patients in the stenting group and 18 (17%) of 107 patients in the endarterectomy group had at least one new DWI lesion detected on post-treatment scans done a median of 1 day after treatment (adjusted odds ratio [OR] 5·21, 95% CI 2·78-9·79; p<0·0001). At 1 month, there were changes on fluid-attenuated inversion recovery sequences in 28 (33%) of 86 patients in the stenting group and six (8%) of 75 in the endarterectomy group (adjusted OR 5·93, 95% CI 2·25-15·62; p=0·0003). In patients treated at a centre with a policy of using cerebral protection devices, 37 (73%) of 51 in the stenting group and eight (17%) of 46 in the endarterectomy group had at least one new DWI lesion on post-treatment scans (adjusted OR 12·20, 95% CI 4·53-32·84), whereas in those treated at a centre with a policy of unprotected stenting, 25 (34%) of 73 patients in the stenting group and ten (16%) of 61 in the endarterectomy group had new lesions on DWI (adjusted OR 2·70, 1·16-6·24; interaction p=0·019). Interpretation: About three times more patients in the stenting group than in the endarterectomy group had new ischaemic lesions on DWI on post-treatment scans. The difference in clinical stroke risk in ICSS is therefore unlikely to have been caused by ascertainment bias. Protection devices did not seem to be effective in preventing cerebral ischaemia during stenting. DWI might serve as a surrogate outcome measure in future trials of carotid interventions. Funding: UK Medical Research Council, the Stroke Association, Sanofi-Synthélabo, European Union, Netherlands Heart Foundation, and Mach-Gaensslen Foundation.

A 10-year follow-up of hippocampal volume on magnetic resonance imaging in early dementia and cognitive decline (Article)

2010-04-01T00:00:00Z

Hippocampal atrophy is frequently observed on magnetic resonance images from patients with Alzheimer's disease and persons with mild cognitive impairment. Even in asymptomatic elderly, a small hippocampal volume on magnetic resonance imaging is a risk factor for developing Alzheimer's disease. However, not everyone with a small hippocampus develops dementia. With the increased interest in the use of sequential magnetic resonance images as potential surrogate biomarkers of the disease process, it has also been shown that the rate of hippocampal atrophy is higher in persons with Alzheimer's disease compared to those with mild cognitive impairment and the healthy elderly. Whether a higher rate of hippocampal atrophy also predicts Alzheimer's disease or subtle cognitive decline in non-demented elderly is unknown. We examine these associations in a group of 518 elderly (age 60-90 years, 50 female), taken from the population-based Rotterdam Scan Study. A magnetic resonance imaging examination was performed at baseline in 1995-96 that was repeated in 1999-2000 (in 244 persons) and in 2006 (in 185 persons). Using automated segmentation procedures, we assessed hippocampal volumes on all magnetic resonance imaging scans. All persons were free of dementia at baseline and followed over time for cognitive decline and incident dementia. Persons had four repeated neuropsychological tests at the research centre over a 10-year period. We also continuously monitored the medical records of all 518 participants for incident dementia. During a total follow-up of 4360 person-years, (mean 8.4, range 0.1-11.3), 50 people developed incident dementia (36 had Alzheimer's disease). We found an increased risk to develop incident dementia per standard deviation faster rate of decline in hippocampal volume [left hippocampus 1.6 (95 confidence interval 1.2-2.3, right hippocampus 1.6 (95 confidence interval 1.2-2.1)]. Furthermore, decline in hippocampal volume predicted onset of clinical dementia when corrected for baseline hippocampal volume. In people who remained free of dementia during the whole follow-up period, we found that decline in hippocampal volume paralleled, and preceded, specific decline in delayed word recall. No associations were found in this sample between rate of hippocampal atrophy, Mini Mental State Examination and tests of executive function. Our results suggest that rate of hippocampal atrophy is an early marker of incipient memory decline and dementia, and could be of additional value when compared with a single hippocampal volume measurement as a surrogate biomarker of dementia.

Intracranial aneurysm segmentation in 3D CT angiography: Method and quantitative validation with and without prior noise filtering (Article)

2010-03-25T00:00:00Z

Intracranial aneurysm volume and shape are important factors for predicting rupture risk, for pre-surgical planning and for follow-up studies. To obtain these parameters, manual segmentation can be employed; however, this is a tedious procedure, which is prone to inter- and intra-observer variability. Therefore there is a need for an automated method, which is accurate, reproducible and reliable. This study aims to develop and validate an automated method for segmenting intracranial aneurysms in Computed Tomography Angiography (CTA) data. Also, it is investigated whether prior smoothing improves segmentation robustness and accuracy. The proposed segmentation method is implemented in the level set framework, more specifically Geodesic Active Surfaces, in which a surface is evolved to capture the aneurysmal wall via an energy minimization approach. The energy term is composed of three different image features, namely; intensity, gradient magnitude and intensity variance. The method requires minimal user interaction, i.e. a single seed point inside the aneurysm needs to be placed, based on which image intensity statistics of the aneurysm are derived and used in defining the energy term. The method has been evaluated on 15 aneurysms in 11 CTA data sets by comparing the results to manual segmentations performed by two expert radiologists. Evaluation measures were Similarity Index, Average Surface Distance and Volume Difference. The results show that the automated aneurysm segmentation method is reproducible, and performs in the range of inter-observer variability in terms of accuracy. Smoothing by nonlinear diffusion with appropriate parameter settings prior to segmentation, slightly improves segmentation accuracy.

Brain tissue volumes in relation to cognitive function and risk of dementia (Article)

2010-03-01T00:00:00Z

We investigated in a population-based cohort study the association of global and lobar brain tissue volumes with specific cognitive domains and risk of dementia. Participants (n = 490; 60-90 years) were non-demented at baseline (1995-1996). From baseline brain MRI-scans we obtained global and lobar volumes of CSF, GM, normal WM, white matter lesions and hippocampus. We performed neuropsychological testing at baseline to assess information processing speed, executive function, memory function and global cognitive function. Participants were followed for incident dementia until January 1, 2005. Larger volumes of CSF and WML were associated with worse performance on all neuropsychological tests, and an increased risk of dementia. Smaller WM volume was related to poorer information processing speed and executive function. In contrast, smaller GM volume was associated with worse memory function and increased risk of dementia. When investigating lobar GM volumes, we found that hippocampal volume and temporal GM volume were most strongly associated with risk of dementia, even in persons without objective and subjective cognitive deficits at baseline, followed by frontal and parietal GM volumes.

Genome-wide association studies of mri-defined brain infarcts: Meta-analysis from the charge consortium (Article)

2010-02-01T00:00:00Z

Background and Purpose-Previous studies examining genetic associations with MRI-defined brain infarct have yielded inconsistent findings. We investigated genetic variation underlying covert MRI infarct in persons without histories of transient ischemic attack or stroke. We performed meta-analysis of genome-wide association studies of white participants in 6 studies comprising the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. Methods-Using 2.2 million genotyped and imputed single nucleotide polymorphisms, each study performed crosssectional genome-wide association analysis of MRI infarct using age- and sex-adjusted logistic regression models. Study-specific findings were combined in an inverse-variance-weighted meta-analysis, including 9401 participants with mean age 69.7 (19.4% of whom had 1 MRI infarct). Results-The most significant association was found with rs2208454 (minor allele frequency, 20%), located in intron 3 of MACRO domain containing 2 gene and in the downstream region of fibronectin leucine-rich transmembrane protein 3 gene. Each copy of the minor allele was associated with lower risk of MRI infarcts (odds ratio, 0.76; 95% confidence interval, 0.68-0.84; P4.64107). Highly suggestive associations (P1.0105) were also found for 22 other single nucleotide polymorphisms in linkage disequilibrium (r20.64) with rs2208454. The association with rs2208454 did not replicate in independent samples of 1822 white and 644 black participants, although 4 single nucleotide polymorphisms within 200 kb from rs2208454 were associated with MRI infarcts in the black population sample. Conclusions-This first community-based, genome-wide association study on covert MRI infarcts uncovered novel associations. Although replication of the association with top single nucleotide polymorphisms failed, possibly because of insufficient power, results in the black population sample are encouraging, and further efforts at replication are needed.

Vascular brain disease and depression in the elderly (Article)

2010-01-01T00:00:00Z

Background: Cross-sectional studies have shown an association between vascular brain disease and depression. Longitudinal data are scarce. In a population-based study we investigated this relationship both cross-sectionally and longitudinally. Methods: Brain MRIs were administered to 479 persons aged 60-90 years at baseline (1995-1996). Brain atrophy, white matter lesions and brain infarcts are all markers of vascular brain disease. At baseline and at follow-up examinations, we also identified persons with depressive symptoms and syndromes using the Center for Epidemiological Studies Depression Scale and psychiatric interviews. Medical records were continuously monitored to identify incident depression. Follow-up was complete until October 2005. Results: At baseline, 36 persons had depressive symptoms. Brain atrophy, white matter lesions, and infarcts were associated with presence of depressive symptoms. During follow-up, 92 persons developed depressive symptoms, 35 of whom were categorized as having depressive syndrome. There was no association of any MRI marker with incident depressive symptoms or syndromes. Conclusions: Markers of vascular brain disease were associated with depression cross-sectionally. However, when these markers and risk of depression were assessed longitudinally, no relationship was found.

A Sales Force–Specific Theory-of-Mind Scale: Tests of Its Validity by Classical Methods and Functional Magnetic Resonance Imaging (Article)

2009-10-01T00:00:00Z

The goal of this article is to develop a new theory-driven scale for measuring salespeople's interpersonal-mentalizing skills—that is, a salesperson's ability to “read the minds” of customers in the sense of first recognizing customer intentionality and processing subtle interpersonal cues and then adjusting volitions accordingly. Drawing from research on autism and neuroscience, the authors develop a model of brain functioning that differentiates better-skilled from less-skilled interpersonal mentalizers. They establish the convergent, discriminant, concurrent, predictive, and nomological validities of measures of the scale using four methods in four separate studies: confirmatory factor analysis, structural equation models, multitrait–multimethod matrix procedures, and functional magnetic resonance imaging. The study is one of the first to test the validity of measures of a scale not only in traditional ways but also by adopting procedures from neuroscience.

Postconcussion syndrome after minor head injury: Brain activation of working memory and attention (Article)

2009-09-15T00:00:00Z

After minor head injury (MHI) postconcussive symptoms (PCS) such as memory and attention deficits frequently occur. It has been hypothesised that PCS are caused by microstructural damage to the brain due to shearing injury, which is not detectable with conventional imaging, and may be responsible for a functional deficit. The purpose of this study was to correlate functional magnetic resonance imaging brain activation of working memory and selective attention with PCS. 21 MHI patients and 12 healthy controls were scanned at 3T. Stimulation paradigms were the n-back and Counting Stroop tasks to engage working memory and selective attention, respectively. Functional data analysis consisted of random effects group analyses, correlating brain activation patterns with the severity of PCS as evaluated with the Rivermead postconcussion symptoms questionnaire. At minimal working memory load, activation was seen in patients with greater severity of PCS in the working memory network. With an increase of working memory load, increase of activation was more pronounced in patients with greater severity of PCS. At high and increased working memory load, activation associated with the severity of PCS was seen in the posterior parietal area, parahippocampal gyrus, and posterior cingulate gyrus. Activation related to selective attention processing was increased with greater severity of PCS. The increased activity in relation to working memory and attention, and the recruitment of brain areas outside the working memory network at high working memory load, may be considered a reflection of the brain's compensatory response to microstructural injury in patients with PCS.

Incidental findings on brain magnetic resonance imaging (Article)

2009-09-05T00:00:00Z

Cerebellar contributions to the processing of saccadic errors (Article)

2009-09-01T00:00:00Z

Saccades are fast eye movements that direct the point of regard to a target in the visual field. Repeated post-saccadic visual errors can induce modifications of the amplitude of these saccades, a process known as saccadic adaptation. Two experiments using the same paradigm were performed to study the involvement of the cerebrum and the cerebellum in the processing of saccadic errors using functional magnetic resonance imaging and in-scanner eye movement recordings. In the first active condition, saccadic adaptation was prevented using a condition in which the saccadic target was shifted to a variable position during the saccade towards it. This condition induced random saccadic errors as opposed to the second active condition in which the saccadic target was not shifted. In the baseline condition, subjects looked at a stationary dot. Both active conditions compared with baseline evoked activation in the expected saccade-related regions using a stringent statistical threshold [the frontal and parietal eye fields, primary visual area, MT/V5, and the precuneus (V6) in the cerebrum; vermis VI-VII; and lobule VI in the cerebellum, known as the oculomotor vermis). In the direct comparison between the two active conditions, significantly more cerebellar activation (vermis VIII, lobules VIII-X, left lobule VIIb) was observed with random saccadic errors (using a more relaxed statistical threshold). These results suggest a possible role for areas outside the oculomotor vermis of the cerebellum in the processing of saccadic errors. Future studies of these areas with, e.g., electrophysiological recordings, may reveal the nature of the error signals that drive the amplitude modification of saccadic eye movements.

Withdrawal of statins and risk of subarachnoid hemorrhage (Article)

2009-08-01T00:00:00Z

BACKGROUND AND PURPOSE-: Vascular endothelium, which can be affected by statins, is believed to play a substantial role in subarachnoid hemorrhage (SAH). Our objective was to estimate the association between use and withdrawal of statins and the risk of SAH. METHODS-: We conducted a population-based case-control study within the PHARMO database. A case was defined as a person hospitalized for SAH (ICD-9-CM code 430) in the period January 1, 1998 to December 31, 2006. Ten randomly chosen controls were matched to each case on age, gender, and calendar date. RESULTS-: During the study period 1004 incident cases of SAH were identified. Current use of statins did not significantly decrease the risk of SAH (OR=0.77, 95% CI 0.55 to 1.07). The odds ratio for recent withdrawal compared to nonusers was 1.62 (95% CI 0.96 to 2.73). Compared to current use, recent withdrawal was associated with an increased risk of SAH (OR=2.34, 95% CI 1.35 to 4.05). Interaction analysis showed that the effect of statin withdrawal was highest in patients who had also recently stopped antihypertensive drugs (OR=6.77, 95% CI 2.10 to 21.8). CONCLUSIONS-: Current use of statins seems to lower the risk of SAH, although the reduction was not significant in new users. Statin withdrawal increased the risk of SAH by a factor 2, even more in patients who had also recently stopped their antihypertensive treatment.

Cerebral microbleed preceding symptomatic intracerebral hemorrhage in a stroke-free person (Article)

2009-07-24T00:00:00Z

Reply to: Inadequate Acoustical Temporal Bone Window in Patients with Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density (Article)

2009-07-01T00:00:00Z

Differences between smooth pursuit and optokinetic eye movements using limited lifetime dot stimulation: A functional magnetic resonance imaging study (Article)

2009-06-18T00:00:00Z

In this study, we examined possible differences in brain activation between smooth pursuit and optokinetic reflexive (OKR) eye movements using functional magnetic resonance imaging (fMRI). Eighteen healthy subjects performed two different eye movement paradigms. In the first paradigm, smooth pursuit eye movements were evoked by a single moving dot. In the second paradigm, optokinetic eye movements without a foveal smooth pursuit component were evoked by a moving pattern of multiple dots with a limited lifetime. As expected, the two eye movement systems show overlapping pathways, but the direct comparison of the activation patterns between the two experiments showed that the frontal eye field, MT/V5 and cerebellar area VI appear to be more activated during smooth pursuit than during optokinetic eye movements. These results showed that the smooth pursuit and optokinetic eye movement systems can be differentiated with fMRI using limited lifetime dots as an effective OKR stimulus. © Journal compilation

Use of antithrombotic drugs and the presence of cerebral microbleeds: The Rotterdam Scan Study (Article)

2009-06-01T00:00:00Z

Background: Cerebral microbleeds are hemosiderin deposits in the brain that are indicative of microangiopathy. Microbleeds in strictly lobar brain locations have been related to cerebral amyloid angiopathy, a bleeding-prone disease state. Objective: To investigate the relation between antithrombotic drug use and the presence of cerebral microbleeds, especially those in strictly lobar locations. Design: A population-based, cross-sectional analysis that used magnetic resonance imaging (MRI) to assess the presence and location of microbleeds. Complete information on outpatient use of platelet aggregation inhibitors and anticoagulant drugs before MRI was obtained from automated pharmacy records. Setting: The Rotterdam Scan Study, a population-based imaging study in a general elderly community in the Netherlands. Participants: A population-based sample of 1062 persons from a longitudinal cohort, 60 years and older, free of dementia, who underwent MRI examinations between August 15, 2005, and November 22, 2006. Main Outcome Measures: Presence of cerebral microbleeds on MRI. Results: Compared with nonusers of antithrombotic drugs, cerebral microbleeds were more prevalent among users of platelet aggregation inhibitors (adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.21-2.41). We did not find a significant association for anticoagulant drugs and microbleed presence (OR, 1.49; 95% CI, 0.82-2.71). Strictly lobar microbleeds were more prevalent among aspirin users (adjusted OR compared with nonusers, 2.70; 95% CI, 1.45-5.04) than among persons using carbasalate calcium (adjusted OR, 1.16; 95% CI, 0.66-2.02). This difference was even more pronounced when comparing persons who had used similar dosages of both drugs. Conclusions: This cross-sectional study shows that use of platelet aggregation inhibitors is related to the presence of cerebral microbleeds. Furthermore, aspirin and carbasalate calcium use may differently relate to the presence of strictly lobar microbleeds.

White Matter microstructural integrity and cognitive function in a general elderly population (Article)

2009-05-01T00:00:00Z

Context: The role of macrostructural white matter changes, such as atrophy and white matter lesions, in cognitive decline is increasingly being recognized. However, in the elderly population, these macrostructural changes do not account for all variability in cognition. Measures reflecting white matter microstructural integrity may provide additional information to investigate the relation between white matter changes and cognition. Objective: To study the relation between white matter integrity and cognition in the general elderly population, using diffusion tensor imaging and taking into account macrostructural white matter changes. Design: Cross-sectional population-based study. Setting: A general community in the Netherlands. Participants: A population-based sample of 860 persons, older than 60 years, free of dementia. We performed multisequence magnetic resonance imaging, which included diffusion tensor imaging, and extensive neuropsychological testing. Fractional anisotropy, mean diffusivity, and directional diffusivities were measured globally in white matter lesions and normal-appearing white matter. Main Outcome Measures: Performance on neuro- psychological tests in the following cognitive domains: memory, executive function, information processing speed, global cognition, and motor speed. Results: Regardless of macrostructural white matter changes, a higher mean diffusivity or higher axial and radial diffusivities within white matter lesions or normal- appearing white matter were related to worse performance on tasks assessing information processing speed and global cognition. In addition, diffusivity within white matter lesions related to memory, while in normal-appearing white matter, it furthermore related to executive function. Lower mean fractional anisotropy in white matter lesions or normal-appearing white matter related to worse information processing speed and motor speed. Conclusions: Microstructural integrity of both white matter lesions and normal-appearing white matter is associated with cognitive function, regardless of white matter atrophy and white matter lesion volume. This suggests that measuring white matter integrity has added value beyond macrostructural assessment of white matter changes to study the relation between white matter and cognition.

White matter lesion extension to automatic brain tissue segmentation on MRI (Article)

2009-05-01T00:00:00Z

A fully automated brain tissue segmentation method is optimized and extended with white matter lesion segmentation. Cerebrospinal fluid (CSF), gray matter (GM) and white matter (WM) are segmented by an atlas-based k-nearest neighbor classifier on multi-modal magnetic resonance imaging data. This classifier is trained by registering brain atlases to the subject. The resulting GM segmentation is used to automatically find a white matter lesion (WML) threshold in a fluid-attenuated inversion recovery scan. False positive lesions are removed by ensuring that the lesions are within the white matter. The method was visually validated on a set of 209 subjects. No segmentation errors were found in 98% of the brain tissue segmentations and 97% of the WML segmentations. A quantitative evaluation using manual segmentations was performed on a subset of 6 subjects for CSF, GM and WM segmentation and an additional 14 for the WML segmentations. The results indicated that the automatic segmentation accuracy is close to the interobserver variability of manual segmentations.

Atherosclerotic plaque volume and composition in symptomatic carotid arteries assessed with multidetector CT angiography; relationship with severity of stenosis and cardiovascular risk factors (Article)

2009-04-22T00:00:00Z

The purpose of this study was to examine the volume and the composition of atherosclerotic plaque in symptomatic carotid arteries and to investigate the relationship between these plaque features and the severity of stenosis and the presence of cardiovascular risk factors. One hundred patients with cerebrovascular symptoms underwent CT angiography. We measured plaque volume (PV) and the relative contribution of plaque components (calcifications, fibrous tissue, and lipid) in the symptomatic artery. The contribution of different components was measured as the number of voxels within defined ranges of HU values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Fifty-seven patients had atherosclerotic plaque in the symptomatic carotid artery. The severity of stenosis and PV were moderately correlated. Age and smoking were independently related to PV. Patients with hypercholesterolemia had significantly less lipid and more calcium in their plaques than patients without hypercholesterolemia. Other cardiovascular risk factors were not significantly related to PV or plaque composition. Luminal stenosis of the carotid artery partly reflects the amount of atherosclerotic carotid disease. Plaque volume and plaque composition are associated with cardiovascular risk factors.

Atherosclerotic plaque surface morphology in the carotid bifurcation assessed with multidetector computed tomography angiography (Article)

2009-04-01T00:00:00Z

Background and Purpose - Complicated (irregular or ulcerated) carotid plaques have proven to be independent predictors of stroke. We analyzed the frequency and location of plaque irregularities in a large cohort of patients with ischemic cerebrovascular disease and the relation with severity of stenosis, cardiovascular risk factors, and symptomatology. Methods - Multidetector CT angiography images from 406 patients were evaluated. Plaque surface morphology was classified as smooth, irregular, or ulcerated. The location of the ulceration was defined as proximal or distal to the point of maximum stenosis. Results - Atherosclerotic plaques with an open lumen were present in 448 carotid arteries; these plaques were classified as: smooth, 276 (62%); irregular, 99 (22%); and ulcerated, 73 (16%). Sixty-two (69%) of the ulcerations were located proximal to the point of maximum luminal stenosis. Complicated plaques were significantly (P<0.001) more common in carotid arteries with stenosis >30% than in those with stenosis <30%. There is an association between complicated plaques and hypercholesterolemia (OR, 3.0) and a trend toward an association with smoking (OR, 1.9). Complicated plaques are more often present in the symptomatic carotid artery than in the contralateral asymptomatic carotid artery; however, this is fully attributed to a significantly higher degree of stenosis in the symptomatic arteries. Conclusions - Multidetector CT angiography allows the classification of atherosclerotic carotid plaque surface. Complicated plaques are frequent in atherosclerotic carotid disease, especially with higher stenosis degree. Ulcerations are mostly located in the proximal part of the atherosclerotic plaque. Hypercholesterolemia and smoking are related with the presence of complicated plaques.

Mirror-Induced Visual Illusion of Hand Movements: A Functional Magnetic Resonance Imaging Study (Article)

2009-04-01T00:00:00Z

Matthys K, Smits M, Van der Geest JN, Van der Lugt A, Seurinck R, Stam HJ, Selles RW. Mirror-induced visual illusion of hand movements: a functional magnetic resonance imaging study. Objective: To identify neural networks associated with the use of a mirror to superimpose movement of 1 hand on top of a nonmoving contralateral hand (often referred to as mirror therapy or mirror-induced visual illusion). Design: A functional magnetic resonance imaging (fMRI) study of mirror-induced visual illusion of hand movements using a blocked design in a 1.5T magnetic resonance imaging scanner. Neural activation was compared in a no-mirror experiment and a mirror experiment. Both experiments consisted of blocks of finger tapping of the right hand versus rest. In the mirror experiment, movement of the left hand was simulated by mirror reflection of right hand movement. Setting: University medical center. Participants: Eighteen healthy subjects. Interventions: Not applicable. Main Outcome Measures: Differences in fMRI activation between the 2 experiments. Results: In the mirror experiment, we found supplementary activation compared with the no-mirror experiment in 2 visual areas: the right superior temporal gyrus (STG) and the right superior occipital gyrus. Conclusions: In this study, we found 2 areas uniquely associated with the mirror-induced visual illusion of hand movements: the right STG and the right superior occipital gyrus. The STG is a higher-order visual region involved in the analysis of biological stimuli and is activated by observation of biological motion. The right superior occipital gyrus is located in the secondary visual cortex within the dorsal visual stream. In the literature, the STG has been linked with the mirror neuron system. However, we did not find activation within the frontoparietal mirror neuron system to support further a link with the mirror neuron system. Future studies are needed to explore the mechanism of mirror induced visual illusions in patient populations in more detail.

Comparison of three radiolabelled peptide analogues for CCK-2 receptor scintigraphy in medullary thyroid carcinoma (Article)

2009-03-06T00:00:00Z

Purpose: Cholecystokinin 2 (CCK-2) receptor overexpression has been demonstrated in a high percentage of medullary thyroid carcinomas (MTC). Analogous to somatostatin receptors, CCK-2 receptors might be viable targets for radionuclide scintigraphy and/or radionuclide therapy. Several CCK-2 receptor-binding radiopeptides have been developed, and some have been carried through into clinical studies. However, these studies are mostly limited and difficult to compare. The aim of this study was to evaluate the diagnostic and therapeutic potential of three promising CCK-2 receptor-binding radiopeptides in patients with MTC. Methods: 111In-DOTA-(D)Asp-Tyr-Nle-Gly-Trp-Nle- Asp-Phe-NH2 (111In-DOTA-CCK), a CCK analogue, and the gastrin-based ligands 99mTc-N4-Gly-(D)Glu-(Glu) 5-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 (99mTc- demogastrin 2) and 111In-DOTA-(D)Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe- NH2 (111In-DOTA-MG11) were each administered to the same group of six patients. Planar images made at 3-5, 7 and 24 h p.i. were used for comparison of tumour visualisation and renal uptake. Results: 99mTc-demogastrin 2 scintigraphy visualised all known lesions and new lesions in four of six patients. 111In-DOTA-CCK and 111In-DOTA-MG11 on the other hand missed several lesions; tumour uptake of these two radiopharmaceuticals was quite low. Comparison of retention of renal activity showed no major differences between the three radiopeptides. Conclusion: 99mTc-demogastrin 2 scintigraphy appeared most promising as a diagnostic tool in patients with MTC. Further studies are required to evaluate its value in patient management. Direct comparisons of the compounds studied strongly suggests that 111In-DOTA-CCK and 111In-DOTA-MG11 have less potential as imaging agents than 99mTc-demogastrin 2. These DOTA-linked compounds are considered unlikely to be useful for radionuclide therapy because of low tumour uptake.

Intracranial internal carotid artery calcifications: Association with vascular risk factors and ischemic cerebrovascular disease (Article)

2009-01-01T00:00:00Z

BACKGROUND AND PURPOSE: Atherosclerotic calcifications are present not only in the extracranial carotid bifurcation but also in the intracranial part of the internal carotid artery. We assessed the association between intracranial internal carotid artery calcifications and cardiovascular risk factors in patients with ischemic cerebrovascular disease and the association between calcifications and the presence of this disease. MATERIALS AND METHODS: Patients undergoing multidetector CT (MDCT) angiography of the carotid arteries for assessment of stenosis degree were included in the study. A semiautomatic custom-made system to quantify calcifications was developed. The associations between the volume of calcifications and cardiovascular risk factors and the type of ischemic cerebrovascular symptoms were assessed with logistic regression. RESULTS: MDCT angiography was performed in 406 patients (age, 62 ± 14 years; 242 men). Men had a significantly higher calcification volume (66 mm3) than women (33 mm3). Calcification volume was positively associated with age in both men and women. Smoking, hypercholesterolemia, and a history of cardiac disease were independently related to the presence of calcifications. A history of cardiac disease and ischemic cerebrovascular disease were independently related to the volume of calcifications. No association was found between calcifications and the presence or type of ischemic cerebrovascular disease in the vascular territory of the intracranial internal carotid artery. CONCLUSIONS: Calcifications were associated with higher age and male gender. The presence and volume of calcifications were independently associated with cardiovascular risk factors. Calcifications were not related to the presence or type of ischemic cerebrovascular disease.

Cortical and cerebellar activation induced by reflexive and voluntary saccades (Article)

2009-01-01T00:00:00Z

Reflexive saccades are driven by visual stimulation whereas voluntary saccades require volitional control. Behavioral and lesional studies suggest that there are two separate mechanisms involved in the generation of these two types of saccades. This study investigated differences in cerebral and cerebellar activation between reflexive and self-paced voluntary saccadic eye movements using functional magnetic resonance imaging. In two experiments (whole brain and cerebellum) using the same paradigm, differences in brain activations induced by reflexive and self-paced voluntary saccades were assessed. Direct comparison of the activation patterns showed that the frontal eye fields, parietal eye field, the motion-sensitive area (MT/V5), the precuneus (V6), and the angular and the cingulate gyri were more activated in reflexive saccades than in voluntary saccades. No significant difference in activation was found in the cerebellum. Our results suggest that the alleged separate mechanisms for saccadic control of reflexive and self-paced voluntary are mainly observed in cerebral rather than cerebellar areas.

White matter atrophy and lesion formation explain the loss of structural integrity of white matter in aging (Article)

2008-11-15T00:00:00Z

The importance of macrostructural white matter changes, including white matter lesions and atrophy, in intact brain functioning is increasingly being recognized. Diffusion tensor imaging (DTI) enables measurement of the microstructural integrity of white matter. Loss of white matter integrity in aging has been reported, but whether this is inherent to the aging process itself or results from specific white matter pathology is unknown. In 832 persons aged 60 years and older from the population-based Rotterdam Study, we measured fractional anisotropy (FA) and directional diffusivities in normal-appearing white matter using DTI. All subjects' DTI measures were projected onto a common white matter skeleton to enable robust voxelwise comparison. With increasing age, multiple regions showed significant decreases in FA or increases in axial or radial diffusivity in normal-appearing white matter. However, nearly all of these regional changes were explained by either white matter atrophy or by white matter lesions; each of which related to changes in distinct brain regions. These results indicate that loss of white matter integrity in aging is primarily explained by atrophy and lesion formation and not by the aging process itself. Furthermore, white matter atrophy and white matter lesion formation relate to loss of integrity in distinct brain regions, indicating the two processes are pathophysiologically different.

Intravestibular lipoma: An important imaging diagnosis (Article)

2008-11-01T00:00:00Z

Assessment of feasibility of endovascular treatment of ruptured intracranial aneurysms with 16-detector row CT angiography (Article)

2008-11-01T00:00:00Z

Background: It is unclear whether 16-detector row CT angiography (CTA) can replace digital subtraction angiography (DSA) to assess the feasibility of endovascular treatment (EVT) in the acute phase after aneurysmal subarachnoid hemorrhage. Methods: We studied 80 consecutive patients with aneurysmal subarachnoid hemorrhage, who underwent both CTA and DSA. Two interventional neuroradiologists independently scored CTA and, immediately thereafter, DSA with respect to feasibility of EVT. We determined whether CTA without DSA was sufficient for a definite judgment. We also assessed interobserver agreement. Results: The 2 readers judged EVT to be feasible in 24 and 37 patients with CTA alone and not feasible in 34 and 20 patients. In these patients, DSA yielded additional information in 6 (reader 1) and 5 patients (reader 2), which did not affect treatment decision. In 19 and 7 patients, DSA was considered inferior to CTA. In the remaining patients (n = 22 and 23, respectively), feasibility of EVT could not be judged with CTA alone, and DSA results were required in addition for a treatment decision. Interobserver agreement on feasibility of EVT was just fair (κ <0.40). Conclusions: In our series of patients, 16-detector row CTA was a reliable investigation to assess feasibility of EVT of ruptured intracranial aneurysms in most patients. Further, we found that interobserver disagreement on feasibility of EVT was considerable.

Intravestibular lipoma: An important imaging diagnosis (Article)

2008-11-01T00:00:00Z

Total cerebral blood flow in relation to cognitive function: The Rotterdam Scan study (Article)

2008-10-01T00:00:00Z

Cerebral hypoperfusion has been associated with worse cognitive function. We investigated the association between cerebral blood flow and cognition and whether this association is independent of brain volume. In 892 participants, aged 60 to 91 years, of the population-based Rotterdam Scan study, we measured total cerebral blood flow (tCBF) and brain volume using magnetic resonance imaging. Lower tCBF was associated with worse information-processing speed, executive function, and global cognition. However, after correcting tCBF for brain volume, these associations disappeared. The association between tCBF and cognition may be mediated or confounded by brain atrophy. Future studies on tCBF should take into account brain atrophy.

Optimizing computed tomographic angiography image segmentation using Fitness Based Partitioning (Article)

2008-07-21T00:00:00Z

Computed Tomographic Angiography (CTA) has become a popular image modality for the evaluation of arteries and the detection of narrowings. For an objective and reproducible assessment of objects in CTA images, automated segmentation is very important. However, because of the complexity of CTA images it is not possible to find a single parameter setting that results in an optimal segmentation for each possible image of each possible patient. Therefore, we want to find optimal parameter settings for different CTA images. In this paper we investigate the use of Fitness Based Partitioning to find groups of images that require a similar parameter setting for the segmentation algorithm while at the same time evolving optimal parameter settings for these groups. The results show that Fitness Based Partitioning results in better image segmentation than the original default parameter solutions or a single parameter solution evolved for all images.

Risk of thrombolysis-related hemorrhage associated with microbleed presence (Article)

2008-07-01T00:00:00Z

Cerebral microbleeds: Accelerated 3D T2-weighted GRE MR imaging versus conventional 2D T2-weighted GRE MR imaging for detection (Article)

2008-07-01T00:00:00Z

The purpose of this study was to prospectively compare high-spatial- resolution accelerated three-dimensional (3D) T2*-weighted gradient-recalled-echo (GRE) magnetic resonance (MR) images with conventional two-dimensional (2D) T2*-weighted GRE MR images for the depiction of cerebral microbleeds. After obtaining institutional review board approval and informed consent, 200 elderly participants (age range, 69.7-96.7 years; 108 [54%] women) were imaged at 1.5 T by using both sequences. Presence, number, and location of microbleeds were recorded for both sequences, and differences were tested by using McNemar and signed rank tests. Cerebral microbleeds were detected in significantly more participants on 3D T2*-weighted GRE images (35.5%) than on 2D T2*-weighted GRE images (21.0%; P < .001). Furthermore, in persons with microbleeds visualized on both image sets, significantly more microbleeds (P < .001) were seen on 3D images than on 2D images. For both sequences, the proportion of participants with a microbleed in a lobar (cortical gray and subcortical white matter), deep, or infratentorial location was similar. In conclusion, accelerated 3D T2*-weighted GRE images depict more microbleeds than do conventional 2D T2*-weighted GRE images.

Cerebral arteries: Fully automated segmentation from ct angiography - A feasibility study (Article)

2008-06-01T00:00:00Z

The purpose of this study was to retrospectively assess the feasibility of a fully automated image postprocessing tool for the segmentation of the arterial cerebrovasculature from computed tomographic (CT) angiography in 27 patients (nine men, 18 women; mean age, 55 years; age range, 33-76 years) with subarachnoid hemorrhage. The institutional review board approved this study, and informed consent was waived. The proposed method, which does not require the acquisition of an additional CT scan for bone suppression, consists of the following: (a) automatic detection of the main arteries for initialization, (b) segmentation of these arteries through the skull base, and (c) suppression of the large veins near the skull. The parameters of this method were optimized on the training subset of nine patients, and the method was successful at segmentation of the arteries in 15 (83%) of the 18 remaining patients. The difference between automatic and manual diameter measurements was 0.0 mm ± 0.4 (standard deviation). The study results showed that fully automated segmentation of the cerebral arteries is feasible.

Brain tissue volumes in the general elderly population. The Rotterdam Scan Study (Article)

2008-06-01T00:00:00Z

We investigated how volumes of cerebrospinal fluid (CSF), grey matter (GM) and white matter (WM) varied with age, sex, small vessel disease and cardiovascular risk factors in the Rotterdam Scan Study. Participants (n = 490; 60-90 years) were non-demented and 51.0% had hypertension, 4.9% had diabetes mellitus, 17.8% were current smoker and 54.0% were former smoker. We segmented brain MR-images into GM, normal WM, white matter lesion (WML) and CSF. Brain infarcts were rated visually. Volumes were expressed as percentage of intra-cranial volume. With increasing age, volumes of total brain, normal WM and total WM decreased; that of GM remained unchanged; and that of WML increased, in both men and women. Excluding persons with infarcts did not alter these results. Persons with larger load of small vessel disease had smaller brain volume, especially normal WM volume. Diastolic blood pressure, diabetes mellitus and current smoking were also related to smaller brain volume. In the elderly, higher age, small vessel disease and cardiovascular risk factors are associated with smaller brain volume, especially WM volume.

Inadequate Acoustical Temporal Bone Window in Patients with a Transient Ischemic Attack or Minor Stroke: Role of Skull Thickness and Bone Density (Article)

2008-06-01T00:00:00Z

Transcranial Doppler (TCD) ultrasonography may provide important diagnostic and prognostic information in patients with ischemic stroke or transient ischemic attack. TCD also enhances the effect of thrombolytic treatment in patients with acute stroke. In some patients, especially elderly women, TCD cannot be performed because of temporal bone window failure (WF). We investigated whether skull thickness or bone density on computed tomography scans predicts WF. In 182 patients with a transient ischemic attack or minor ischemic stroke, skull thickness and bone density measurements were made at the level of the temporal bone window. Multiple logistic regression analysis was used to relate independent variables to WF and to adjust the estimates for possible confounding factors. TCD signals were absent on the symptomatic side in 22 female and 11 male patients (18%). Both skull thickness and radiodensity at the level of the temporal bone window were strongly related to WF as well as age and female gender. After adjustment according to age and gender, skull thickness at the temporal bone window was an independent prognostic factor of WF (odds ratio [OR]: 2.3 per mm increase in skull thickness, 95% confidence interval [CI]: 1.4 to 3.8). Radiodensity of the temporal bone decreased with age in women (-52 HU per 10 y over 50 y of age, 95% CI: -73 to -30) but in men (-10 HU per 10 y over 50 y of age, 95% CI: -33 to 13), no statistically significant association was observed. We computed probabilities of WF for each patient individually. With a probability cut point of 50%, 33% of the patients with WF and 97% of the patient without WF were correctly identified. The area under the receiver operating characteristic (ROC) curve of this simple prediction model including age, gender and skull thickness was 0.88; the area under the ROC curve of a gender-stratified model including age, skull thickness and radiodensity was 0.90. This difference was not statistically or clinically significant p = 0.13). WF is more common in women because density of the temporal bone in elderly women is low. Absence of WF can be predicted by a combination of three simple parameters: skull thickness, age and gender. This may help to select patients with ischemic stroke for diagnostic TCD screening and to facilitate targeted delivery of ultrasound-enhanced thrombolysis. (E-mail: a.wijnhoud@erasmusmc.nl).

Arteriolar Oxygen Saturation, Cerebral Blood Flow, and Retinal Vessel Diameters. The Rotterdam Study (Article)

2008-05-01T00:00:00Z

Objective: Retinal vessel diameters, in particular larger venular diameters, have been associated with cerebrovascular disease. Larger retinal venular diameters may reflect cerebral ischemia. The authors investigated whether arteriolar oxygen saturation (SaO2) and total cerebral blood flow (CBF), indicators of cerebral oxygen supply, are associated with retinal arteriolar or venular diameters. Design: Cross-sectional study performed within the population-based Rotterdam Study. Participants: Randomly selected participants aged 55 years or older (n = 696), who underwent both an eye examination and brain magnetic resonance imaging (MRI). Methods: Arteriolar oxygen saturation was determined by pulse oximetry on the right index finger. Cerebral blood flow was assessed using a phase-contrast MRI sequence that measured the flow in the basilar and both internal carotid arteries. Brain volume was measured to express CBF per 100 ml brain volume. Retinal arteriolar and venular diameters were measured on digitized fundus color transparencies on 1 eye of each participant. Regression models were used to investigate the association of SaO2and CBF with retinal vessel diameters. Main Outcome Measures: Mean retinal arteriolar and venular diameters (in micrometers). Results: Lower SaO2was associated with larger venular diameters. Persons with SaO2less than 96% (n = 113) had on average 5 μm larger venular diameters compared with those with SaO2of 96% or more (n = 583; age- and gender-adjusted mean difference, 5.6 μm; 95% confidence interval, 1.2-10.0). Cerebral blood flow was not related to venular diameters when analyzed separately. Additional analyses showed that the association between SaO2and venular widening was confined to participants within the lowest tertile of CBF. No associations were found between SaO2or CBF and arteriolar diameters. Additional adjustment for established cardiovascular risk factors did not change the results. Conclusions: An association of lower SaO2with larger retinal venular diameters was observed, in particular in the presence of lower CBF. These findings suggest that venular widening may reflect a lower oxygen supply, especially to the brain.

fMRI of optokinetic eye movements with and without a contribution of smooth pursuit (Article)

2008-04-01T00:00:00Z

BACKGROUND AND PURPOSE: Optokinetic eye movements are elicited when tracking a moving pattern. It can be argued that a moving pattern of stripes invokes both the optokinetic and the smooth pursuit eye movement system, which may confound the observed brain activation patterns using functional magnetic resonance imaging (fMRI). A moving pattern of limited-lifetime-dot stimulation does not target the smooth pursuit eye movement system. METHODS: fMRI was used to compare the cortical activity elicited by an optokinetic eye movement response evoked by a moving pattern of stripes and a moving pattern of limited lifetime dots. RESULTS: The eye movement behavior showed that both types of stimuli evoked an adequate and similar optokinetic eye movement response, but stimulation with stripes evoked more activation in the frontal and parietal eye fields, MT/V5, and in the cerebellar area VI than stimulation with limited-lifetime dots. CONCLUSIONS: These brain areas are implicated in smooth pursuit eye movements. Our results suggest that indeed both the optokinetic and the smooth pursuit eye movement system are involved in tracking a moving pattern of stripes.

Prevalence and risk factors of cerebral microbleeds: The Rotterdam Scan Study (Article)

2008-04-01T00:00:00Z

BACKGROUND: Cerebral microbleeds are focal deposits of hemosiderin that can be visualized with MRI. Little is known on their prevalence in the general population and on their etiology. It has been suggested that, in analogy to spontaneous intracranial hemorrhage, the etiology of microbleeds differs according to their location in the brain, with lobar microbleeds being caused by cerebral amyloid angiopathy and deep or infratentorial microbleeds resulting from hypertension and atherosclerosis. We investigated the prevalence of and risk factors for microbleeds in the general population aged 60 years and older. METHODS: This study is based on 1,062 persons (mean age 69.6 years) from the population-based Rotterdam Scan Study. MRI was performed at 1.5 T and included a sequence optimized to increase the conspicuity of microbleeds. We assessed the relation of APOE genotype, cardiovascular risk factors, and markers of small vessel disease to the presence and location of microbleeds with multiple logistic regression. RESULTS: Overall prevalence of cerebral microbleeds was high and increased with age from 17.8% in persons aged 60-69 years to 38.3% in those over 80 years. APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers. In contrast, cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location but not in a lobar location. CONCLUSION: The prevalence of cerebral microbleeds is high. Our data support the hypothesis that strictly lobar microbleeds are related to cerebral amyloid angiopathy, whereas microbleeds in a deep or infratentorial location result from hypertensive or atherosclerotic microangiopathy.

Assessment of atherosclerotic carotid plaque volume with multidetector computed tomography angiography (Article)

2008-03-31T00:00:00Z

Purpose: The amount of atherosclerotic plaque and its components (calcifications, fibrous tissue, and lipid core) could be better predictors of acute events than the now currently used degree of stenosis. Therefore, we evaluated a dedicated software tool for volume measurements of atherosclerotic carotid plaque and its components in multidetector computed tomography angiography (MDCTA) images. Materials and Methods: Data acquisition was approved by the Institutional Review Board and all patients gave written informed consent. MDCTA images of 56 carotid arteries were analyzed by three observers. Plaque volumes were assessed by manual drawing of the outer vessel contour. The luminal boundary was determined based on a Hounsfield-Unit (HU) threshold. The contribution of different components was measured by the number of voxels within defined ranges of HU-values (calcification >130 HU, fibrous tissue 60-130 HU, lipid core <60 HU). Interobserver variability (IOV) was assessed. Results: Plaque volume was 1,259 ± 621 mm3. The calcified, fibrous and lipid volumes were 238 ± 252 mm3, 647± 277 mm3 and 376± 283 mm3, respectively. IOV was moderate with interclass correlation coefficients (ICC) ranging from 0.76 to 0.99 and coefficients of variation (COV) ranging from 3% to 47%. Conclusion: Atherosclerotic carotid plaque volume and plaque component volumes can be assessed with MDCTA with a reasonable observer variability.

An fMRI study on smooth pursuit and fixation suppression of the optokinetic reflex using similar visual stimulation (Article)

2008-03-01T00:00:00Z

This study compares brain activation patterns evoked by smooth pursuit and by fixation suppression of the optokinetic reflex (OKR) using similar retinal stimulation. Functional magnetic resonance imaging (fMRI) was performed during smooth pursuit stimulation in which a moving target was presented on a stationary pattern of stripes, and during fixation suppression of OKR in which a stationary target was presented on a moving pattern of stripes. All subjects could effectively ignore the background pattern and were able to keep the target continuously on the fovea with few saccades, in both experiments. Smooth pursuit evoked activation in the frontal eye fields (FEF), the supplementary eye fields (SEF), the parietal eye fields (PEF), the motion-sensitive area (MT/V5), and in lobules and vermis VI of the cerebellum (oculomotor areas). Fixation suppression of OKR induced activation in the FEF, PEF, and MT/V5. The direct comparison analysis revealed more activation in the right lobule VI of the cerebellum and in the right lingual and calcarine gyri during smooth pursuit than during fixation suppression of OKR. Using similar retinal stimulation, our results show that smooth pursuit and fixation suppression of the OKR appear to activate largely overlapping pathways. The increased activity in the oculomotor areas of the cerebellum during smooth pursuit is probably due to the presence of an active eye movement component.

The association of arterial stiffness and arterial calcification: The Rotterdam Study (Article)

2008-03-01T00:00:00Z

Total cerebral blood flow and total brain perfusion in the general population: The Rotterdam Scan Study (Article)

2008-02-01T00:00:00Z

Reduced cerebral perfusion may contribute to the development of cerebrovascular and neurodegenerative diseases. Little is known on cerebral perfusion in the general population, as most measurement techniques are too invasive for application in large groups of healthy individuals. Total cerebral blood flow (tCBF) can be noninvasively measured by magnetic resonance imaging (MRI) but is highly correlated with brain volume. We calculated total brain perfusion by dividing tCBF by brain volume, and we investigated determinants of total brain perfusion in comparison with tCBF. Secondly, we studied whether persons with a low tCBF or low total brain perfusion have a larger volume of white matter lesions (WML). This study is based on 892 persons aged 60 to 91 years from the Rotterdam Study, a population-based cohort study. We performed two-dimensional (2D) phase-contrast MRI for tCBF measurement. Brain volume and WML volume were quantitatively assessed. Cardiovascular determinants were assessed by interview and physical examination. We assessed associations between cardiovascular determinants and flow measures with linear regression models, adjusted for age and sex. Associations between tCBF or total brain perfusion and WML volume were assessed using general linear models. We found that determinants of tCBF and total brain perfusion differed largely due to the large influence of brain volume on tCBF values. Persons with low total brain perfusion had a significantly larger WML volume compared with those with high total brain perfusion. Prospective studies are required to unravel whether hypoperfusion contributes to WML formation or that tissue damage, manifested by WML, leads to brain hypoperfusion.

Is a fetal origin of the posterior cerebral artery a risk factor for TIA or ischemic stroke? A study with 16-multidetector-row CT angiography (Article)

2008-02-01T00:00:00Z

Background and purpose: Fetal origin of the posterior cerebral artery (PCA) is not uncommon. Whether patients with this anomaly have a higher risk of ischemic stroke in the territory of the PCA is not known. The clinical benefit of screening for a fetal origin in patients with TIA or stroke in the territory of the PCA and an ipsilateral atherosclerotic carotid stenosis is not clear. This study assessed the frequency of a fetal origin of the PCA in patients with a TIA or infarct in the territory of the PCA with 16-multidetector-row CT angiography (CTA). Methods: 82 patients (52 male; mean age = 64; range 19 to 90 years) with isolated homonymous hemianopia and/or a PCA infarct underwent CTA of the carotid artery and circle of Willis. Results: A fetal origin of the PCA at the symptomatic side was present in 14 patients (17 %) and at the asymptomatic side in 18 patients (22%) (OR: 0.7; 95 % CI: 0.3 to 1.7). Severity of stenosis (NASCET criteria) of the ICA at the symptomatic side was < 30%, 30-49% and ≥ 50% in 72, 2 and 8 patients, respectively. Number and frequency of a fetal origin in these groups were 12 (17 %), 0 (0%) and 2 (25 %), respectively. There was no association between a severe carotid stenosis and a fetal origin of the PCA at the symptomatic side. Conclusion: This study does not provide arguments for an increased risk of ischemic stroke in the territory of the PCA in patients with a fetal origin of the PCA. A few patients with a TIA or infarct in the territory of the PCA have a fetal origin of the PCA in combination with a high-grade stenosis of the ipsilateral ICA, but not more often than one would expect from chance. Nevertheless, these patients may benefit from carotid endarterectomy.

Kidney function is related to cerebral small vessel disease (Article)

2008-01-01T00:00:00Z

BACKGROUND AND PURPOSE - Poor kidney function, as measured by glomerular filtration rate (GFR), is closely associated with presence of glomerular small vessel disease. Given the hemodynamic similarities between the vascular beds of the kidney and the brain, we hypothesized an association between kidney function and markers of cerebral small vessel disease on MRI. We investigated this association in a population-based study of elderly persons. METHODS - We measured GFR using the Cockcroft-Gault equation in 484 participants (60 to 90 years of age) from the Rotterdam Scan Study. Using automated MRI-analysis we measured global as well as lobar and deep volumes of gray matter and white matter, and volume of WML. Lacunar infarcts were rated visually. Volumes of deep white matter and WML and presence of lacunar infarcts reflected cerebral small vessel disease. We used linear and logistic regression models to investigate the association between GFR and brain imaging parameters. Analyses were adjusted for age, sex, and additionally for cardiovascular risk factors. RESULTS - Persons with lower GFR had less deep white matter volume (difference in standardized volume per SD decrease in GFR: -0.15 [95% CI -0.26 to -0.04]), more WML (difference per SD decrease in GFR: 0.14 [95% CI 0.03 to 0.25]), and more often lacunar infarcts, although the latter was not significant. GFR was not associated with gray matter volume or lobar white matter volume. Additional adjustment for cardiovascular risk factors yielded similar results. CONCLUSIONS - Impaired kidney function is associated with markers of cerebral small vessel disease as assessed on MRI.

Incidental findings on brain MRI in the general population (Article)

2007-11-01T00:00:00Z

Background: Magnetic resonance imaging (MRI) of the brain is increasingly used both in research and in clinical medicine, and scanner hardware and MRI sequences are continually being improved. These advances are likely to result in the detection of unexpected, asymptomatic brain abnormalities, such as brain tumors, aneurysms, and subclinical vascular pathologic changes. We conducted a study to determine the prevalence of such incidental brain findings in the general population. Methods: The subjects were 2000 persons (mean age, 63.3 years; range, 45.7 to 96.7) from the population-based Rotterdam Study in whom high-resolution, structural brain MRI (1.5 T) was performed according to a standardized protocol. Two trained reviewers recorded all brain abnormalities, including asymptomatic brain infarcts. The volume of white-matter lesions was quantified in milliliters with the use of automated post-processing techniques. Two experienced neuroradiologists reviewed all incidental findings. All diagnoses were based on MRI findings, and additional histologic confirmation was not obtained. Results: Asymptomatic brain infarcts were present in 145 persons (7.2%). Among findings other than infarcts, cerebral aneurysms (1.8%) and benign primary tumors (1.6%), mainly meningiomas, were the most frequent. The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence. Conclusions: Incidental brain findings on MRI, including subclinical vascular pathologic changes, are common in the general population. The most frequent are brain infarcts, followed by cerebral aneurysms and benign primary tumors. Information on the natural course of these lesions is needed to inform clinical management. Copyright

Ultrasound, computed tomography, or the combination for the detection of supraclavicular lymph nodes in patients with esophageal or gastric cardia cancer: A comparative study (Article)

2007-09-01T00:00:00Z

Background and Objectives: Both ultrasound (US) and computed tomography (CT) can be used to detect supraclavicular lymph node metastases. Aim was to compare US, US plus fine-needle aspiration (US-FNA), CT, US + CT, and US-FNA + CT for the detection of these metastases in esophageal or gastric cardia cancer patients. Methods: Between 1994 and 2004, 567 patients underwent US and CT for esophageal or gastric cardia cancer staging. Gold standard was postoperative detection of lymph nodes in the resected specimen, FNA, or a radiological result with follow-up. Results: Sensitivities of US (75%), US-FNA (72%), US + CT (80%), and US-FNA + CT (79%) were higher than sensitivity of CT alone (25%) (P < 0.001). Specificities were high for US-FNA (100%), CT (99%), and US-FNA + CT (99%), whereas those of US alone (91%) and US + CT (91%) were lower (P < 0.001). In 4/65 (6%) patients with true-positive malignant lymph nodes, CT was positive with US and/or US-FNA being negative. However, in 36/65 (55%) patients, US and/or US-FNA were positive with CT being negative. Conclusion: US-FNA seems the preferred diagnostic modality for the detection of supraclavicular lymph node metastases in patients with esophageal or gastric cardia cancer. Sensitivity of metastases detection only slightly improves if US-FNA is combined with CT. A prospective, comparative study is however needed.

Incorporating Functional MR Imaging into Diffusion Tensor Tractography in the Preoperative Assessment of the Corticospinal Tract in Patients with Brain Tumors (Article)

2007-08-01T00:00:00Z

BACKGROUND AND PURPOSE: Our goal was to improve the preoperative assessment of the cortico- spinal tract (CST) in patients with brain tumors. We investigated whether the integration of functional MR imaging (fMRI) data and diffusion tensor (DT) tractography can be used to evaluate the spatial relationship between the hand and foot fibers of the CST and tumor borders. MATERIALS AND METHODS: We imaged 10 subjects: 1 healthy volunteer and 9 patients. Imaging consisted of a 3D T1-weighted sequence, a gradient-echo echo-planar imaging (EPI) sequence for fMRI, and a diffusion-weighted EPI sequence for DT tractography. DT tractography was initiated from a seed region of interest in the white matter area subjacent to the maximal fMRI activity in the precentral cortex. The target region of interest was placed in the cerebral peduncle. RESULTS: In the healthy volunteer, we successfully tracked hand, foot, and lip fibers bilaterally by using fMRI-based DT tractography. In all patients, we could track the hand fibers of the CST bilaterally. In 4 patients who also performed foot tapping, we could clearly distinguish hand and foot fibers. We were able to depict the displacement of hand and foot fibers by tumor and the course of fibers through areas of altered signal intensity. CONCLUSION: Incorporating fMRI into DT tractography in the preoperative assessment of patients with brain tumors may provide additional information on the course of important white matter tracts and their relationship to the tumor. Only this approach allows a distinction between the CST compo- nents, while visualization of the CST is improved when fiber tracking is hampered by tumor (infiltration) or perifocal edema.

Association between calcification in the coronary arteries, aortic arch and carotid arteries: The Rotterdam study (Article)

2007-08-01T00:00:00Z

Objective: The present study was performed to examine the prevalence of and associations between calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT), in an elderly population. Methods and results: This study was part of the population-based Rotterdam study. From October 2003 until July 2004, subjects underwent a 16-slice MSCT scan. Calcification was quantified by calculating the Agatston, volume and mass score. Current analyses were performed in 600 subjects (mean age 74 years). The prevalences of calcification in the coronary and carotid arteries were higher in men compared to women. However, aortic arch calcification was more prevalent among women. In men, correlation coefficients based on the Agatston score ranged from 0.40 (between coronary and aortic arch calcification) to 0.54 (between aortic arch and carotid calcification) (p < 0.001). Correlation coefficients for women ranged from 0.30 (between coronary and aortic arch calcification) to 0.40 (between coronary and carotid calcification) (p < 0.001). Conclusions: While the prevalences of calcification in the coronary and the carotid arteries were higher in men compared to women, aortic arch calcification was more prevalent among women. Moderate to strong correlations between calcification in different vessel beds were found.

Plaque rupture in the carotid artery is localized at the high shear stress region: A case report (Article)

2007-08-01T00:00:00Z

BACKGROUND AND PURPOSE - Cerebrovascular events are related to atherosclerotic disease in the carotid arteries and are frequently caused by rupture of a vulnerable plaque. These ruptures are often observed at the upstream region of the plaque, where the wall shear stress (WSS) is considered to be highest. High WSS is known for its influence on many processes affecting tissue regression. Until now, there have been no serial studies showing the relationship between plaque rupture and WSS. SUMMARY OF CASE - We investigated a serial MRI data set of a 67-year-old woman with a plaque in the carotid artery at baseline and an ulcer at 10-month follow up. The lumen, plaque components (lipid/necrotic core, intraplaque hemorrhage), and ulcer were segmented and the lumen contours at baseline were used for WSS calculation. Correlation of the change in plaque composition with the WSS at baseline showed that the ulcer was generated exclusively at the high WSS location. CONCLUSIONS - In this serial MRI study, we found plaque ulceration at the high WSS location of a protruding plaque in the carotid artery. Our data suggest that high WSS influences plaque vulnerability and therefore may become a potential parameter for predicting future events.

Evaluation of an improved technique for lumen path definition and lumen segmentation of atherosclerotic vessels in CT angiography (Article)

2007-07-01T00:00:00Z

Vessel image analysis is crucial when considering therapeutical options for (cardio-) vascular diseases. Our method, VAMPIRE (Vascular Analysis using Multiscale Paths Inferred from Ridges and Edges), involves two parts: a user defines a start- and endpoint upon which a lumen path is automatically defined, and which is used for initialization; the automatic segmentation of the vessel lumen on computed tomographic angiography (CTA) images. Both parts are based on the detection of vessel-like structures by analyzing intensity, edge, and ridge information. A multi-observer evaluation study was performed to compare VAMPIRE with a conventional method on the CTA data of 15 patients with carotid artery stenosis. In addition to the start- and endpoint, the two radiologists required on average 2.5 (SD: 1.9) additional points to define a lumen path when using the conventional method, and 0.1 (SD: 0.3) when using VAMPIRE. The segmentation results were quantitatively evaluated using Similarity Indices, which were slightly lower between VAMPIRE and the two radiologists (respectively 0.90 and 0.88) compared with the Similarity Index between the radiologists (0.92). The evaluation shows that the improved definition of a lumen path requires minimal user interaction, and that using this path as initialization leads to good automatic lumen segmentation results.

Visual claudicatio: Diagnosis with 64-slice computed tomography (Article)

2007-06-01T00:00:00Z

We present a case of a 78-year-old male referred presented to our institution with amaurosis fugax after walking 20 steps ("visual claudicatio"). Duplex ultrasound was not able to visualize the carotid arteries. Multislice computed tomography (Sensation 64 Cardiac, Siemens, Germany) of the cerebro-vascular circulation was performed from its origin at the level of the aortic arch to the circle of Willis. The investigation demonstrated a complete occlusion of both common carotid arteries at their origin and a severe origo stenosis of both vertebral arteries. An important collateral circulation of the vertebral arteries through the minor vessels of the neck was also displayed. Both comunicans posterior arteries were small but patent. The intra-cranial arteries were patent. Multislice CT of the cerebro-vascular circulation is an optimal tool for a comprehensive evaluation when duplex ultrasound fails.

Quadrature coil design for high-resolution carotid artery imaging scores better than a dual phased-array coil design with the same volume coverage (Article)

2007-05-01T00:00:00Z

Purpose: To evaluate the ability of a custom-built coil design to provide improved signal-to-noise ratio (SNR) and less signal drop with increasing depth at the carotid artery. Materials and Methods: Phased-array surface coils can provide a high SNR to image the carotid vessel wall. However, given the required field-of-view (FOV) and penetration depth, these coils show either a fast signal drop with increasing depth or a moderate SNR at increased coil size. A quadrature surface coil (a butterfly coil in conjunction with a linear single-loop coil) was compared with a phased-array coil in phantom and human studies. Results: The phantom studies showed that the quadrature coil has better SNR over the required FOV than a standard phased-array coil (26% at 3 cm depth). Conclusion: The quadrature coil enables better image quality to be achieved.

Fiber density asymmetry of the arcuate fasciculus in relation to functional hemispheric language lateralization in both right- and left-handed healthy subjects: A combined fMRI and DTI study (Article)

2007-04-15T00:00:00Z

Previously reported leftward asymmetry in language-related gray and white matter areas of the brain has been proposed as a structural correlate of left-sided functional hemispheric language lateralization. However, structural asymmetry in non-left-sided functional language lateralization has as yet not been studied. Furthermore, the neuroanatomical basis of the reported volumetric white matter asymmetry is not fully understood. In 20 healthy volunteers, including 13 left-handers, we performed functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). We studied the relative fiber density (RFD) of the arcuate fasciculus (AF), using DT-tractography, in relation to functional hemispheric language lateralization. Hemispheric language lateralization was right-sided in five left-handed individuals. We demonstrated an overall significant leftward asymmetry in RFD of the AF, irrespective of handedness or functional language lateralization. Furthermore, in right-handers, the degree of structural asymmetry was found to be correlated with the degree of functional lateralization. We conclude that structural asymmetry in the AF does not seem to reflect functional hemispheric language lateralization, as has been proposed previously. Our findings suggest that the previously reported white matter asymmetry may be explained by a structural asymmetry in the arcuate fasciculus. These findings have important implications for the understanding of the functional and structural lateralization of brain regions as well as for the clinical evaluation of language function.

MDCT detection of fibromuscular dysplasia of the internal carotid artery. (Article)

2007-04-01T00:00:00Z

OBJECTIVE: The purpose of this article is to describe two cases in which fibromuscular dysplasia of the internal carotid artery was diagnosed with CT angiography. CONCLUSIONS: CT angiography can depict the characteristic findings of fibromuscular dysplasia. If patients with cerebrovascular symptoms undergo screening with CT angiography of the supraaortic vessels, more cases of fibromuscular dysplasia will be recognized as a cause of neurologic symptoms.

Histogram-based selective deblurring to improve computed tomography imaging of calcifications (Article)

2007-01-01T00:00:00Z

OBJECTIVES: Computed tomography (CT) imaging of small high-density structures, eg, calcifications, is hampered by image blur. This study aims to deconvolve calcifications in the transverse and longitudinal directions while avoiding noise amplification and edge-ringing artifacts in the surrounding low-density structures. MATERIALS AND METHODS: A method referred to as histogram-based selective deblurring (HiSD) has been developed to generate a restored image by combining the low-intensity (ie, Hounsfield Units) information of the original image with the high-intensity information of the deconvolved image. HiSD is evaluated on phantom and in vitro atherosclerotic plaque CT images by comparing the original and restored images with their corresponding reference micro-CT images both qualitatively and quantitatively. RESULTS: HiSD reduces calcification blur in the transverse and longitudinal directions without introducing noise and ringing-artifacts in the surrounding tissues. Calcification area and volume measurements are significantly improved in the restored images (reducing on average overestimation by 32% and 83%, respectively). CONCLUSIONS: HiSD significantly improves CT visualization and quantification of small high-density structures imaged in vitro.

Functional MR imaging of language processing: an overview of easy-to-implement paradigms for patient care and clinical research (Article)

2006-10-01T00:00:00Z

Functional magnetic resonance (MR) imaging is one of the most commonly used functional neuroimaging techniques for studying the cerebral representation of language processing and is increasingly being used for both patient care and clinical research. In patient care, functional MR imaging is primarily used in the preoperative evaluation of (a) the relationship of a lesion to critical language areas and (b) hemispheric dominance. In clinical research, this modality is used to study language disorders due to neurologic disease and is generally aimed at language function recovery. A variety of language paradigms (verbal fluency, passive listening, comprehension) have been developed for the study of language processing and its separate components. All of the tasks are easy to implement, analyze, and perform. Silent gap acquisition is preferable for the imaging of specific language processing components because auditory stimuli are not degraded by imager noise. On the other hand, continuous acquisition allows more data to be acquired in less time, thereby increasing statistical power and decreasing the effects of motion artifacts. Although functional MR imaging cannot yet replace intraoperative electrocortical stimulation in patients undergoing neurosurgery, it may be useful for guiding surgical planning and mapping, thereby reducing the extent and duration of craniotomy.

Intravenous contrast material administration at helical 16-detector row CT coronary angiography: effect of iodine concentration on vascular attenuation. (Article)

2005-08-01T00:00:00Z

The institutional review board approved this study, and all patients gave written informed consent. One hundred twenty-five patients scheduled to undergo retrospectively electrocardiographically gated 16-detector row computed tomographic coronary angiography were prospectively randomized into the following five groups with respect to the intravenous administration of a 140-mL bolus of contrast material at 4 mL/sec: group 1 (iohexol [300 mg of iodine per milliliter]), group 2 (iodixanol [320 mg I/mL]), group 3 (iohexol [350 mg I/mL]), group 4 (iomeprol [350 mg I/mL]), and group 5 (iomeprol [400 mg I/mL]). Attenuation was measured in the descending aorta and coronary arteries. One-way analysis of variance was used to compare groups. Mean attenuation values in the descending aorta were significantly (P < .05) lower in group 1 and higher in group 5 compared with the mean values in the other three groups. The same pattern was observed in the coronary arteries. Contrast materials with higher iodine concentrations yield significantly higher attenuation in the descending aorta and coronary arteries.

Intravenous contrast material administration at 16-detector row helical CT coronary angiography: test bolus versus bolus-tracking technique. (Article)

2004-01-01T00:00:00Z

PURPOSE: To compare test bolus and bolus-tracking techniques for intravenous contrast material administration at 16-detector row computed tomographic (CT) coronary angiography. MATERIALS AND METHODS: This study had institutional review board approval, and patients gave informed consent. Thirty-eight patients (mean age, 60 years; three women) were randomized into two groups according to bolus timing technique: group 1 (20-mL test bolus with 100-mL main bolus) and group 2 (bolus tracking with 100-mL main bolus). All patients underwent electrocardiography-gated 16-detector row CT coronary angiography with 12 detectors (collimation, 0.75 mm; rotation time, 420 msec). In group 1, test bolus peak attenuation was used as a delay, while in group 2, a +100-HU threshold in ascending aorta triggered angiographic acquisition, with an additional 4-second delay for patient instruction. Attenuation was measured in the longitudinal direction throughout the examination in three main vessels: ascending aorta (region of interest [ROI] 1), descending aorta (ROI 2), and main pulmonary artery (ROI 3). Mean attenuation and slope of bolus geometry curve were calculated in each patient and ROI. Attenuation at origin of coronary arteries was measured. Student t test was used to compare results. RESULTS: Mean scan delay was 6 seconds longer in group 2 (P < .05). Average attenuation values were 306.6 HU +/- 44.0 (standard deviation) and 328.2 HU +/- 58.6 (P > .05) in ROI 1, 291.6 HU +/- 45.1 and 326.4 HU +/- 62.6 (P > .05) in ROI 2, and 354.7 HU +/- 78.0 and 305.3 HU +/- 71.4 (P < .05) in ROI 3 for groups 1 and 2, respectively. Average slope values were 5.8 and -0.8 (P < .05) in ROI 1, 7.7 and 0.7 (P < .05) in ROI 2, and -1.0 and -13.3 (P < .05) in ROI 3 for groups 1 and 2, respectively. Average attenuation values in left main, left anterior descending, and left circumflex arteries were higher in group 2 (P < .05); there were no differences (P > .05) between groups in right coronary artery. CONCLUSION: Bolus-tracking yields more homogeneous enhancement than does the test bolus technique.

Noninvasive detection of a ruptured aneurysm at a basilar artery fenestration with submillimeter multisection CT angiography (Article)

2003-01-01T00:00:00Z

The criterion standard for the detection of intracranial aneurysms is digital subtraction angiography. MR imaging and CT provide good accuracy in the evaluation of brain arteries and aneurysms. We herein report a case of a ruptured aneurysm at a basilar artery fenestration. The diagnosis was assessed with 16-row multisection CT angiography and was confirmed by using digital subtraction angiography. The patient was successfully treated with coil placement.

Intravascular ultrasound: validation and clinical application (Doctoral Thesis)

1996-12-18T00:00:00Z

Atherogenesis is a process with an insidious onset and course. Once clinical signs and symptoms have become manifest, the obstructive lesion is usually at an advanced stage. Arteriography is the standard method for evaluation of atherosclerotic disease and has been useful in identifying the location and approximate severity of the stenotic lesion. Although arteriography provides a silhouette of the vessel lumen, it does not provide accurate knowledge on cross-sectional lumen area, vessel area, shape and morphology of the stenotic lesion. Intravascular ultrasound (lVUS) may overcome these limitations by providing a tomographic image of the vessel. The aim of this work is to validate IVUS and to evaluate subsequent clinical application of this imaging technique. The subjects dealt with in this dissertation are categorised into 5 main topics. I) displacement sensing device; 2) validation of IVUS-derived parameters; 3) the spectrum of vascular morphology before and after intervention determined by IVUS; 4) IVUS as a research tool; 5) IVUS as a clinical tool

Computerized assessment of coronary lumen and atherosclerotic plaque dimensions in three-dimensional intravascular ultrasound correlated with histomorphometry. (Article)

1996-01-01T00:00:00Z

Intravascular ultrasound (IVUS), which depicts both lumen and plaque, offers the potential to improve on the limitations of angiography for the assessment of the natural history of atherosclerosis and progression or regression of the disease. To facilitate measurements and increase the reproducibility of quantitative IVUS analyses, a computerized contour detection system was developed that detects both the luminal and external vessel boundaries in 3-dimensional sets of IVUS images. To validate this system, atherosclerotic human coronary segments (n = 13) with an area obstruction ≥40% (40% to 61%) were studied in vitro by IVUS. The computerized IVUS measurements (areas and volumes) of the lumen, total vessel, plaque-media complex, and percent obstruction were compared with findings by manual tracing of the IVUS images and of the corresponding histologic cross sections obtained at 2-mm increments (n = 100). Both area and volume measurements by the contour detection system agreed well with the results obtained by manual tracing, showing low mean between-method differences (−3.7% to 0.3%) with SDs not exceeding 6% and high correlation coefficients (r = 0.97 to 0.99). Measurements of the lumen, total vessel, plaque-media complex, and percent obstruction by the contour detection system correlated well with histomorphometry of areas (r = 0.94, 0.88, 0.80, and 0.88) and volumes (r = 0.98, 0.91, 0.83, and 0.91). Systematic differences between the results by the contour detection system and histomorphometry (29%, 13%, −9%, and −22%, respectively) were found, most likely resulting from shrinkage during tissue fixation. The results of this study indicate that this computerized IVUS analysis system is reliable for the assessment of coronary atherosclerosis in vivo.