http://repub.eur.nl/res/aut/10694/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/23698/ 2011-03-02T00:00:00Z Abstract BACKGROUND: Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. METHODOLOGY/PRINICIPAL FINDINGS: Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. CONCLUSIONS: SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects. http://repub.eur.nl/res/pub/24033/ 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. http://repub.eur.nl/res/pub/32826/ 2010-09-01T00:00:00Z Background-We imaged the protease activity of matrix metalloproteinases (MMPs) upregulated during aneurysm formation, using protease-activatable near-infrared fluorescence probes. We tested whether these protease-activatable sensors can directly report the in vivo activity of the key biomarkers in aneurysm, using our genetically modified fibulin-4 mouse models for aneurysm formation. Mice homozygous for the fibulin-4 reduced-expression allele (fibulin-4R/R) show dilatation of the ascending aorta and a tortuous, stiffened aorta resulting from disorganized elastic fiber networks. Strikingly, even a moderate reduction in expression of fibulin-4 in the heterozygous fibulin-4+/Rmice occasionally results in modest aneurysm formation. Methods and Results-Aorta transcriptome and protein expression analysis of fibulin-4+/Rand fibulin-4R/Ranimals identified excessive transforming growth factor-β signaling as the critical event in the pathogenesis of aneurysm formation. To determine whether a perturbed elastin lamellar structure arose from induction of transforming growth factor-β-regulated MMPs, we performed gelatin zymography and used a protease-activatable near-infrared fluorescence probe to monitor and quantify MMP upregulation in animals, using various in vivo optical imaging modules and coregistration of the fluorescence signal with CT images of the same animals. Gelatin zymography demonstrated a significant increase in the presence of the active form of MMP-9 in the aortic arch of fibulin-4R/Rmice. In vivo analysis of MMP upregulation using the near-infrared fluorescence probe and subsequent isosurface concentration mapping from reconstructed tomographic images from fibulin-4+/Rand fibulin-4R/Rmice revealed a graded increase in activation of MMPs within the aneurysmal lesions. Conclusions-We aimed to develop molecular imaging procedures for faster, earlier, and easier recognition of aortic aneurysms. We show that in vivo coregistration of MMP activity by noninvasive tomographic imaging methods allows the detection of increased MMP activity, even before the aneurysm has actually formed. http://repub.eur.nl/res/pub/21842/ 2010-09-01T00:00:00Z Various studies have shown that various cell types can be labeled with iron oxide particles and visualized by magnetic resonance imaging (MRI). However, reported protocols for cell labeling show a large variation in terms of labeling dose and incubation time. It is therefore not clear how different labeling protocols may influence labeling efficiency. Systematic assessment of the effects of various labeling protocols on labeling efficiency of human umbilical vein endothelial cells (HUVEC) using two different types of iron oxide nanoparticles, i.e. super paramagnetic iron oxide particles (SPIOs) and microparticles of iron oxide (MPIOs), demonstrated that probe concentration, incubation time and particle characteristics all influence the efficiency of label incorporation, label distribution, label retention and cell behavior. For SPIO the optimal labeling protocol consisted of a dose of 12.5μg iron/2ml/9.5cm2 and an incubation time of 24h, resulting in an average iron load of 12.0pg iron/per cell (uptake efficiency of 9.6%). At 4h many SPIOs are seen sticking to the outside of the cell instead of being taken up by the cell. For MPIO optimal labeling was obtained with a dose of 50μg iron/2ml/9.5cm2. Incubation time was of less importance since most of the particles were already incorporated within 4h with a 100% labeling efficiency, resulting in an intracellular iron load of 626pg/cell. MPIO were taken up more efficiently than SPIO and were also better tolerated. HUVEC could be exposed to and contain higher amounts of iron without causing significant cell death, even though MPIO had a much more pronounced effect on cell appearance. Using optimal labeling conditions as found for HUVEC on other cell lines, we observed that different cell types react differently to identical labeling conditions. Consequently, for each cell type separately an optimal protocol has to be established. http://repub.eur.nl/res/pub/27303/ 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. http://repub.eur.nl/res/pub/15302/ 2009-07-01T00:00:00Z BACKGROUND: Tissue engineering and regenerative medicine are two rapidly advancing fields of research offering potential for effective treatment of cartilage lesions. Today, chondrocytes are the cell type of choice for use in cartilage repair approaches such as autologous chondrocyte implantation. To verify the safety and efficacy of such approaches it is necessary to determine the fate of these transplanted cells. One way of doing this is prelabelling cells before implantation and tracking them using imaging techniques. The use of superparamagnetic iron oxide (SPIO) for tracking of cells with magnetic resonance imaging (MRI) is ideal for this purpose. It is non-radioactive, does not require viral transfection and is already approved for clinical use as a contrast agent. OBJECTIVE: The purpose of this study was to assess the effect of SPIO labelling on adult human chondrocyte behaviour. METHODS: Cells were culture expanded and dedifferentiated for two passages and then labelled with SPIO. Effect on cell proliferation was tested. Furthermore, cells were cultured for 21 days in alginate beads in redifferentiation medium. Following this period, cells were analysed for expression of cartilage-related genes, proteoglycan production and collagen protein expression. RESULTS: SPIO labelling did not significantly affect any of these parameters relative to unlabelled controls. We also demonstrated SPIO retention within the cells for the full duration of the experiment. CONCLUSIONS: This paper demonstrates for the first time the effects of SPIO labelling on chondrocyte behaviour, illustrating its potential for in vivo tracking of implanted chondrocytes. http://repub.eur.nl/res/pub/16391/ 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. http://repub.eur.nl/res/pub/24381/ 2009-04-17T00:00:00Z Purpose: To assess biventricular functional reserve (FR), NT-proBNP levels and exercise performance, in relation to right ventricular volume in patients with pulmonary regurgitation (PR) after repair of tetralogy of Fallot (TOF) at young age. Methods: In 53 TOF patients (maximum age at repair 2.0 years, interval since repair 15 (5) years) without residual lesions except PR, biventricular FR (derived from magnetic resonance imaging with dobutamine stress), NT-proBNP levels, maximal workload, and peak oxygen uptake were assessed. Results: Mean right ventricular end-diastolic volume was 140(38) ml/m2. Median pulmonary regurgitant fraction was 37% (range 0-57%). Biventricular systolic stress response was normal: mean (SD) ESV decreased (ΔRVESV - 17(8) ml/m2, ΔLVESV - 11(5)), SV increased (ΔRVSV + 12(9) ml/m2, ΔLVSV + 9(6)), FR was positive in all (RV-FR + 11(5)%, LV-FR + 13(6)). No serious adverse effects to dobutamine were encountered. NT-proBNP was increased in 2 patients. Median level was 10 pmol/L (range 2-42). NT-proBNP correlated with PR-percentage but not with right ventricular size. High-risk levels of NT-proBNP indicated a smaller RV-FR and a smaller decrease of biventricular ESV. Mean (SEM) VO2maxwas 96(3)%, mean Workloadmax89(2)% of predicted. Conclusion: At mid to long term follow-up overall NT-proBNP levels are normal and biventricular functional reserve and exercise tolerance are well preserved in TOF repaired at young age, irrespective of RV volume. This questions the validity of isolated PR or RV volume criteria for pulmonary valve replacement in this group. Low-dose dobutamine stress testing is well tolerated and may be a useful additional tool for clinical decision making. http://repub.eur.nl/res/pub/26927/ 2009-02-01T00:00:00Z To evaluate feasibility and diagnostic quality of ultra-short TR/TE two-dimensional (2D) steady state free precession (SSFP) MRI for cystic fibrosis (CF) patients. We performed lung MRI at 1.5 Tesla in 20 CF-patients (6-17 years, 12 males). Axial, coronal, and sagittal sections were acquired in inspiration and expiration with maximum breath-hold time 10 s. MR and CT images were scored using a modified Brody scoring system to assess bronchiectasis, mucous plugging, atelectasis/consoli-dations, and air trapping. All images were scored by two experienced observers. A complete MR investigation took maximally 15 min. Maximal breath-holds were only 10 s and well tolerated. MRI identified major bronchiectasis, mucous plugging and at-electasis. End-expiratory scans showed patches of parenchyma with reduced signal intensity that may corresponded to areas of trapped air on expiratory CT scans. This MRI protocol based on ultra-short TR/TE 2D SSFP is quick and well tolerated and provides highly relevant imaging features as seen on CT in CF patients. Most importantly, the SNR of the expiratory scans enables to visualize air trapping. The preliminary results of this study suggest MRI as a noteworthy additional imaging tool for routine monitoring of CF patients. http://repub.eur.nl/res/pub/16797/ 2009-01-01T00:00:00Z Through labelling of cells with magnetic contrast agents it is possible to follow the fate of transplanted cells in vivo with magnetic resonance imaging (MRI) as has been demonstrated in animal studies as well as in a clinical setting. A large variety of labelling strategies are available that allow for prolonged and sensitive detection of the labelled cells with MRI. The various protocols each harbour specific advantages and disadvantages. In choosing a particular labelling strategy it is also important to ascertain that the labelling procedure does not negatively influence cell functionality, for which a large variety of assays are available. In order to overcome the challenges still faced in fully exploiting the benefits of in vivo cell tracking by MRI a good understanding and standardisation of the procedures and assays used will be crucial. http://repub.eur.nl/res/pub/28945/ 2008-07-01T00:00:00Z Context: In Turner syndrome (TS), GH treatment is well established. Data on cardiac status after discontinuation of treatment are scarce. This study aimed to assess biventricular size and function in TS at least 6 months after discontinuation of GH treatment. Methods: TS patients and healthy women prospectively underwent cardiac magnetic resonance imaging. Ventricular two-dimensional tomographic cine data were acquired to obtain biventricular volume, mass, and ejection fraction. Atrioventricular valve flow measurements were performed using a two-dimensional flow-sensitized sequence. Flow velocity curves were calculated and indices of biventricular diastolic filling were derived. Results: Thirty-one patients [mean (SD) age 20 (2) yr, body surface area 1.75 (0.15)m2, 5 (2) yr after GH discontinuation] and 23 normal control women [age 21 (2) yr, body surface area 1.80 (0.13)m2] were included. Compared with controls, patients had smaller mean end-diastolic volumes [right ventricle (RV), 84 (11) ml/m2vs. 79 (10), P = 0.02; left ventricle (LV), 81 (10) vs. 72 (9), P < 0.001], end-systolic volumes [RV 38 (7) ml/m2vs. 36 (6), P = 0.04; LV 34 (5) vs. 29 (4), P < 0.001], and stroke volumes [RV 46 (6) ml/m2vs. 43 (6), P = 0.03; LV, 47 (7) vs. 44 (4), P = 0.02]. Patients had a higher meanheart rate [79 (13) beats/min vs. 71 (10), P < 0.05]. Biventricular ejection fraction, mass, cardiac output, and diastolic filling pattern were comparable. Conclusion: After discontinuation of GH treatment TS patients showed no myocardial hypertrophy and well-preserved biventricular function. Ventricular volumes were smaller in Turner patients, compared with controls, whereas mean heart rate was higher. These last observations may be part of the natural development in TS and not linked to GH treatment, which at this point we consider safe. Copyright http://repub.eur.nl/res/pub/29074/ 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. http://repub.eur.nl/res/pub/29173/ 2008-07-01T00:00:00Z Institutional Review Board approval and signed informed consent were obtained by all participants for an ongoing sequence optimization project at 3.0 T. The purpose of this study was to evaluate breath-hold diffusion-induced blackblood echo-planar imaging (BBEPI) as a potential alternative for specific absorption rate (SAR)-intensive spin-echo sequences, in particular, the fast spin-echo (FSE) sequences, at 3.0 T. Fourteen healthy volunteers (seven men, seven women; mean age ± standard deviation, 32.7 years ± 6.8) were imaged for this purpose. Liver coverage (20 cm, z-axis) was always performed in one 25-second breath hold. Imaging parameters were varied interactively with regard to echo time, diffusion b value, and voxel size. Images were evaluated and compared with fat-suppressed T2-weighted FSE images for image quality, liver delineation, geometric distortions, fat suppression, suppression of the blood signal, contrast-to-noise ratio (CNR), and signal-to-noise ratio (SNR). An optimized short- (25 msec) and long-echo (80 msec) BBEPI provided full anatomic, single breath-hold liver coverage (100 and 50 sections, respectively), with resulting voxel sizes of 3.3 x 2.7 x 2.0 mm and 3.3 x 2.7 x 4.0 mm, respectively. Repetition time was 6300 msec, matrix size was 160 x 192, and an acceleration factor of 2.00 was used. b Values of more than 20 sec/mm2showed better suppression of the blood signal but b values of 10 sec/mm2provided improved volume coverage and signal consistency. Compared with fat-suppressed T2-weighted FSE, the optimized BBEPI sequence provided (a) comparable image quality and liver delineation, (b) acceptable geometric distortions, (c) improved suppression of fat and blood signals, and (d) high CNR and SNR. BBEPI is feasible for fast, low-SAR, thin-section morphologic imaging of the entire liver in a single breath hold at 3.0 T. http://repub.eur.nl/res/pub/15199/ 2008-05-01T00:00:00Z Successful cell therapy will depend on the ability to monitor transplanted cells. With cell labeling, it is important to demonstrate efficient long term labeling without deleterious effects on cell phenotype and differentiation capacity. We demonstrate long term (7 weeks) retention of superparamagnetic iron oxide particles (SPIO) by mesenchymal stem cells (MSCs) in vivo, detectable by MRI. In vitro, multilineage differentiation (osteogenic, chondrogenic and adipogenic) was demonstrated by histological evaluation and molecular analysis in SPIO labeled and unlabeled cells. Gene expression levels were comaparable to unlabeled controls in adipogenic and chondrogenic conditions however not in the osteogenic condition. MSCs seeded into a scaffold for 21 days and implanted subcutaneously into nude mice for 4 weeks, showed profoundly altered phenotypes in SPIO labeled samples compared to implanted unlabeled control scaffolds, indicating chondrogenic differentiation. This study demonstrates long term MSC traceability using SPIO and MRI, uninhibited multilineage MSC differentiation following SPIO labeling, though with subtle but significant phenotypical alterations. http://repub.eur.nl/res/pub/29097/ 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. http://repub.eur.nl/res/pub/29489/ 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. http://repub.eur.nl/res/pub/28799/ 2008-01-01T00:00:00Z OBJECTIVES: To reduce interstudy variability using long-axis information for correcting short-axis (SA) contours at basal and apical level for left-ventricular analysis by magnetic resonance imaging. MATERIALS AND METHODS: A total of 20 patients with documented heart failure and 20 volunteers underwent magnetic resonance imaging examination twice for measuring endocardial end-diastolic volume, endocardial end-systolic volume, mass, and ejection fraction. The boundary of the left ventricle, the mitral valve plane, and apex were marked manually on the 2- and 4-chamber long-axis images. Automatic epicardial and endocardial contour detection was performed on the SA images using the intersection of the outlines from the long axis as starting positions. The same observer compared the interstudy variability of this method with analysis that was based on the SA images only. RESULTS: The interstudy variability decreased when information from the long axis was included; for end-systolic volume, 9.6% versus 4.7% (P = 0.00014); for end-diastolic volume, 4.9% versus 2.5% (P = 0.0011); for mass, 7.4% versus 5.0% (P = 0.11); and for ejection fraction 12.2% versus 5.6% (P = 0.0017), respectively. CONCLUSIONS: Identification of the mitral valve plane and apex on long-axis images to limit the extent of volume at the base and the apex of the heart reduces interstudy variability for left-ventricular functional assessment. http://repub.eur.nl/res/pub/30170/ 2008-01-01T00:00:00Z Purpose: To determine the benefits of variable-rate selective-excitation (VERSE) radio frequency (RF) pulses for increased slice coverage in breathhold (BH) fat-suppressed T2-weighted fast spin-echo (FS-T2W-FSE) liver imaging at 3.0T. Materials and Methods: A total of 12 healthy volunteers were imaged on 3.0T, using FS-T2W-FSE. Slice coverage and specific absorption rate (SAR) levels were monitored for VERSE-RF and standard-RF (sRF), respectively. BH time was 25 seconds; slice thickness 3.5 mm. Maximum coverage was recorded for interactive variation of repetition time (TR), bandwidth (BW), and echo-train length (ETL). Image quality was assessed qualitatively and quantitatively. Results: Total slice coverage was always higher using VERSE-RF, but varied depending on the selected parameters. For BW ≥ 62.5 kHz, slice coverage using VERSE increased between 38% (TR = 8200 msec) and 58% (TR = 2500 msec). Maximum coverage was obtained for TR = 5000 msec, ETL = 12, and BW ≥ 62.5 kHz; with a mean of 31.8 slices for VERSE-RF and 22.5 slices for sRF, respectively (P < 0.005, 41% increased coverage). SAR was lower for VERSE-RF using BW < 41.67 kHz (P < 0.05), and equal to sRF for higher BW. Image quality was best for TR ≤ 5000 msec (P < 0.05). FS was more homogeneous for lower ETL (P < 0.05). Blood suppression was best for TR ≤ 5000 msec (P < 0.05). Conclusion: VERSE-RF pulses can be applied for thin-slice BH FS-T2W liver imaging at 3.0T, with significantly improved slice coverage. http://repub.eur.nl/res/pub/20946/ 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. http://repub.eur.nl/res/pub/36654/ 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. http://repub.eur.nl/res/pub/36667/ 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. http://repub.eur.nl/res/pub/35497/ 2007-04-01T00:00:00Z Purpose: To prospectively assess, with magnetic resonance (MR) imaging, right ventricular (RV) diastolic function after repair of tetralogy Fallot (TOF) at rest and during pharmacologic stress and to study relationship between main pulmonary artery end-diastolic forward flow (EDFF) (indicative of restrictive RV physiology) and clinical status. Materials and Methods: Institutional medical ethics committee approval and patient or parent informed consent were obtained. Patients with TOF corrected through the transatrial-transpulmonary approach underwent MR imaging at rest and during dobutamine stress and maximal exercise testing. Two-dimensional (2D) cine volumetric data were acquired. Flow measurements were performed with a standard 2D flow-sensitized sequence. MR imaging flow curves for tri-cuspid and pulmonary valves were combined into RV time-volume change curves, from which indexes of RV filling were derived. Patient results were compared with published data in control subjects. Student t tests, Mann-Whitney U tests, analysis of covariance, and paired and one-sample t tests were used. Results: Thirty-six patients (mean age at repair, 0.9 year ± 0.5 [standard deviation]; median age at study inclusion, 17 years, [range, 7-23 years]; 26 male and 10 female patients) were included. Abnormalities in RV filling included impaired relaxation (prolonged deceleration time, P = .002; smaller early filling fraction, P = .02) in the entire group compared with published data in healthy control subjects and signs of restriction to RV filling (smaller atrial filling fraction and higher early filling/atrial filling peak ratio, P < .05 for both) in patients with EDFF (n = 24) compared with patients without EDFF (n = 12). Stress response was abnormal in patients with EDFF, who developed impaired RV relaxation not appreciated at rest. Patients with EDFF had more severe pulmonary regurgitation (P < .05) and poorer exercise performance (P < .001). Conclusion: In patients with TOF corrected with currently widely accepted surgical strategies, pulmonary artery EDFF relates to worse clinical state at mid- to long-term follow-up. Dobutamine stress imaging may unmask abnormalities in RV diastolic filling not appreciated with rest imaging alone. http://repub.eur.nl/res/pub/35515/ 2007-04-01T00:00:00Z Regeneration of infarcted myocardium by injecting stem cells has been proposed to prevent heart failure. We studied the i.c. administration of human umbilical cord blood stem cells (USSC) in a porcine model of myocardial infarction (MI) and reperfusion. In 15 swine, MI was induced by balloon-occlusion of the left circumflex coronary artery (LCX) for 2 h followed by reperfusion. Five swine served as healthy controls. One week later, magnetic resonance imaging (MRI) was performed to assess left ventricular (LV) function and infarct size. Then, under immune suppression, 6 of the 12 surviving MI swine received intracoronary injection of ∼ 108human USSC in the LCX while the other MI-swine received medium. Four weeks later all swine underwent follow-up MRI, and were sacrificed for histology. One week after MI, end-diastolic volume (92 ± 3 mL) and LV mass (75 ± 2 g) were larger, while ejection fraction (42 ± 2%) was smaller than in healthy control (68 ± 3 mL, 66 ± 3 g and 55 ± 3%, all P < 0.05). Regional wall thickening (- 7 ± 2%) in the LCX area became akinetic. No difference in global and regional LV function at 5 weeks was observed between MI animals receiving USSC or medium. Infarct size after USSC treatment was significantly larger (20 ± 3 g vs. 8 ± 2 g, P < 0.05). USSC survived only in the infarct border zone at 5 weeks and did not express cardiomyocyte or endothelial markers. Histology showed that intracoronary injection of USSC caused micro infarctions by obstructing blood vessels. In swine with a 1 week old MI, injection of USSC via the intracoronary route does not improve LV function 4 weeks later. http://repub.eur.nl/res/pub/13945/ 2005-10-01T00:00:00Z Angiogenesis is a very important process for tumor growth and proliferation. Given its high temporal and spatial resolution, magnetic resonance (MR) imaging is well suited for use in the assessment of angiogenesis. MR angiography can be used clinically and experimentally for identification of tumor feeding and draining vessels, for tumor characterization, and for treatment planning. The morphologic structure of tumor vessels can be investigated in relation to tumor vessel permeability with use of specific contrast agents. To gain insight into tumor angiogenesis in vivo, the authors compared images obtained with digital photography, high-resolution MR angiography, and intravital microscopy through a dorsal skin-fold window in a rodent model. The close correlation between images obtained with these various modalities, with regard to the depiction of the developing tumor vasculature, indicates that noninvasive quantification of angiogenesis may be possible with MR imaging. Future directions in tumor imaging may include so-called four-dimensional MR angiography, in which high-resolution three-dimensional MR angiography is combined with dynamic contrast-enhanced MR imaging. http://repub.eur.nl/res/pub/4776/ 2002-01-01T00:00:00Z http://repub.eur.nl/res/pub/9474/ 2000-01-01T00:00:00Z PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. RESULTS: Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. CONCLUSION: Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting. http://repub.eur.nl/res/pub/9475/ 2000-01-01T00:00:00Z PURPOSE: To assess the clinical value of a magnetic resonance (MR) coronary angiography strategy involving a small targeted volume to image one coronary segment in a single breath hold for the detection of greater than 50% stenosis. MATERIALS AND METHODS: Thirty-eight patients referred for elective coronary angiography were included. The coronary arteries were localized during single-breath-hold, three-dimensional imaging of the entire heart. MR coronary angiography was then performed along the major coronary branches with a double-oblique, three-dimensional, gradient-echo sequence. Conventional coronary angiography was the reference-standard method. RESULTS: Adequate visualization was achieved with MR coronary angiography in 85%-91% of the proximal coronary arterial branches and in 38%-76% of the middle and distal branches. Overall, 187 (69%) of 272 segments were suitable for comparison between conventional and MR coronary angiography. The diagnostic accuracy of MR coronary angiography for the detection of hemodynamically significant stenoses was 92%; sensitivity, 68%; and specificity, 97%. The sensitivity in individual segments was 50%-77%, whereas the specificity was 94%-100%. CONCLUSION: Adequate visualization of the major coronary arterial branches was possible in the majority of patients. The observed accuracy of MR coronary angiography for detection of hemodynamically significant coronary arterial stenosis is promising, but it needs to be higher before this modality can be used reliably in a clinical setting. http://repub.eur.nl/res/pub/8988/ 1999-01-01T00:00:00Z End-expiration, 21-second breath-hold, three-dimensional magnetic resonance (MR) cholangiopancreatography (MRCP) was developed with segmented echo-planar imaging. In 15 healthy subjects and 14 randomly selected patients undergoing liver studies, three-dimensional MRCP images were obtained and volume rendered. In 15 (100%) healthy subjects and 13 (93%) patients, clear depiction of biliary, hepatic, and pancreatic ducts (with lumen diameter of at least 2 mm) was possible with good signal-to-noise ratio. http://repub.eur.nl/res/pub/9168/ 1999-01-01T00:00:00Z BACKGROUND: Magnetic resonance coronary angiography is challenging because of the motion of the vessels during cardiac contraction and respiration. Additional challenges are the small calibre of the arteries and their complex three dimensional course. Respiratory gating, turboflash acquisition, and volume rendering techniques may meet the necessary requirements for appropriate visualisation. OBJECTIVE: To determine the diagnostic accuracy of respiratory gated magnetic resonance imaging (MRI) for the detection of significant coronary artery stenoses evaluated with three dimensional postprocessing software. METHODS: 32 patients referred for elective coronary angiography were studied with a retrospective respiratory gated three dimensional gradient echo MRI technique. Resolution was 1.9 x 1.25 x 2 mm. After manual segmentation three dimensional evaluation was performed with a volume rendering technique. RESULTS: Overall 74% (range 50% to 90%) of the proximal and mid coronary artery segments were visualised with an image quality suitable for further analysis. Sensitivity and specificity for the detection of significant stenoses were 50% and 91%, respectively. CONCLUSIONS: Volume rendering of respiratory gated MRI techniques allows adequate visualisation of the coronary arteries in patients with a regular breathing pattern. Significant lesions in the major coronary artery branches can be identified with a moderate sensitivity and a high specificity.