http://repub.eur.nl/res/aut/4569/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/39467/ 2013-03-19T00:00:00Z Objective: To retrospectively investigate whether optimisation of volume-doubling time (VDT) cutoff for fast-growing nodules in lung cancer screening can reduce false-positive referrals. Methods: Screening participants of the NELSON study underwent low-dose CT. For indeterminate nodules (volume 50-500 mm3), follow-up CT was performed 3 months after baseline. A negative baseline screen resulted in a regular second-round examination 1 year later. Subjects referred to a pulmonologist because of a fast-growing (VDT <400 days) solid nodule in the baseline or regular second round were included in this study. Histology was the reference for diagnosis, or stability on subsequent CTs, confirming benignity. Mean follow-up of non-resected nodules was 4.4 years. Optimisation of the false-positive rate was evaluated at maintained sensitivity for lung cancer diagnosis with VDT <400 days as reference. Results: Sixty-eight fast-growing nodules were included; 40 % were malignant. The optimal VDT cutoff for the 3-month follow-up CT after baseline was 232 days. This cutoff reduced false-positive referrals by 33 % (20 versus 30). For the regular second round, VDTs varied more among malignant nodules, precluding lowering of the VDT cutoff of 400 days. Conclusion: All malignant fast-growing lung nodules referred after the 3-month follow-up CT in the baseline lung cancer screening round had VDT ≤232 days. Lowering the VDT cutoff may reduce false-positive referrals. Key Points: • Lung nodules are common in CT lung cancer screening, most being benign • Short-term follow-up CT can identify fast-growing intermediate-size lung nodules • Most fast-growing nodules on short-term follow-up CT still prove to be benign • A new volume-doubling time (VDT) cut-off is proposed for lung screening • The optimised VDT cutoff may decrease false-positive case referrals for lung cancer http://repub.eur.nl/res/pub/33254/ 2011-10-26T00:00:00Z Context: Smoking is a major risk factor for both cancer and chronic obstructive pulmonary disease (COPD). Computed tomography (CT)-based lung cancer screening may provide an opportunity to detect additional individuals with COPD at an early stage. Objective: To determine whether low-dose lung cancer screening CT scans can be used to identify participants with COPD. Design, Setting, and Patients: Single-center prospective cross-sectional study within an ongoing lung cancer screening trial. Prebronchodilator pulmonary function testing with inspiratory and expiratory CT on the same day was obtained from 1140 male participants between July 2007 and September 2008. Computed tomographic emphysema was defined as percentage of voxels less than -950 Hounsfield units (HU), and CT air trapping was defined as the expiratory:inspiratory ratio of mean lung density. Chronic obstructive pulmonary disease was defined as the ratio of forced expiratory volume in the first second to forced vital capacity (FEV1/FVC) of less than 70%. Logistic regression was used to develop a diagnostic prediction model for airflow limitation. Main Outcome Measures: Diagnostic accuracy of COPD diagnosis using pulmonary function tests as the reference standard. Results: Four hundred thirty-seven participants (38%) had COPD according to lung function testing. A diagnostic model with CT emphysema, CT air trapping, body mass index, pack-years, and smoking status corrected for overoptimism (internal validation) yielded an area under the receiver operating characteristic curve of 0.83 (95% CI, 0.81-0.86). Using the point of optimal accuracy, the model identified 274 participants with COPD with 85 false-positives, a sensitivity of 63% (95% CI, 58%-67%), specificity of 88% (95% CI, 85%-90%), positive predictive value of 76% (95% CI, 72%-81%); and negative predictive value of 79% (95% CI, 76%-82%). The diagnostic model showed an area under the receiver operating characteristic curve of 0.87 (95% CI, 0.86-0.88) for participants with symptoms and 0.78 (95% CI, 0.76-0.80) for those without symptoms. Conclusion: Among men who are current and former heavy smokers, low-dose inspiratory and expiratory CT scans obtained for lung cancer screening can identify participants with COPD, with a sensitivity of 63% and a specificity of 88%. http://repub.eur.nl/res/pub/34451/ 2011-10-01T00:00:00Z Background: In computed tomography lung cancer screening programs, up to 30% of all resections are futile. OBJECTIVE: To investigate whether a preoperative positron emission tomography (PET) after a conclusive or inconclusive nonsurgical workup will reduce the resection rate for benign disease in test-positive participants of a lung cancer screening program. Methods: (18)F-Fluorodeoxyglucose-PET scans were made in 220 test positives. Nodules were classified as positive, indeterminate, or negative based on visual comparison with background activity. Gold standard for a positive PET was the presence of cancer in the resection specimen or the detection of cancer during more than 2 years follow-up. Sensitivity, specificity, positive predictive value, and negative predictive value (NPV) were calculated at participant level and 95% confidence intervals (CIs) constructed. Results: The sensitivity of PET to detect cancer was 84.2% (95% CI: 77.6-90.7%), the specificity 75.2% (95% CI: 67.1-83.3), the positive predictive value 78.9% (95% CI: 71.8-86.0), and the NPV 81.2% (95% CI: 73.6-88.8). The resection rate for benign disease was 23%, but 26% of them had a diagnosis with clinical consequences. A preoperative PET after an inconclusive nonsurgical workup reduced the resection rate for benign lesions by 11 to 15%, at the expense of missing 12 to 18% lung cancer cases. A preoperative PET after a conclusive nonsurgical workup reduced the resection rate by 78% at the expense of missing 3% lung cancer cases. Conclusion: A preoperative PET scan in participants with an inconclusive nonsurgical workup is not recommended because of the very low NPV, but after a conclusive nonsurgical workup, the resection rate for benign disease can be decreased by 72%. http://repub.eur.nl/res/pub/34042/ 2011-08-01T00:00:00Z Fluid increases resulting in higher MRI signal intensities in T2-weighted and short tau inversion recovery (STIR) sequences can be used to diagnose nerve injury. By comparing the signal intensities over time, MRI may become a new method for monitoring the healing process. Muscle edema is assessed by comparing the signal intensity of affected muscle with that of nonaffected muscle. However, in severe forearm trauma, the signal of nondenervated muscle may also be increased by wound edema, thus masking the effect of denervation. Hence, the purpose of this study was to investigate the influence of wound edema on muscle signal intensity in 29 consecutive patients examined on a 1.5-T MRI scanner at 1, 3, 6, 9 and 12 months after severe forearm trauma. The long-term course of wound edema and the influence of wound distance were thus investigated using a standardized imaging, calibration and post-processing protocol. The signal intensities of nondenervated intrinsic hand muscles were measured in the affected and contralateral sides. Muscle signal intensities were increased on the trauma side at 1 and 3 months (18% and 7.4%, respectively; p<0.001) and normalized thereafter. In the contralateral hand, no significant signal changes were seen. No relationship was found between wound distance and the severity of wound edema. This study shows that wound edema influences muscle signal intensity comparisons in patients with forearm trauma. When comparing denervated muscle with nondenervated muscle, an additional scan of the contralateral side is indicated during the first 6 months after trauma to assess the extent of wound edema. After 6 months, the ipsilateral side can be used for muscle signal intensity comparisons. http://repub.eur.nl/res/pub/33424/ 2011-06-01T00:00:00Z Background: Anastomotic leakage (AL) is the most feared complication of colorectal surgery. Atherosclerosis is suggested to have a detrimental effect on anastomotic healing. This study aimed to analyze the calcium score, a measure for atherosclerosis, as a risk factor for AL. Study design: The calcium scores of colorectal patients operated on in 2 Dutch university medical centers were determined using a computed tomography scan and calcium scoring software. The aorta, common iliac arteries, internal and external iliac arteries were studied. Additionally, patient- and operation-related factors were scored. Results: A total of 122 patients were included. In patients with AL, calcium scores were significantly higher in the left common iliac artery (561.4 vs 156.0, P =.028), right common iliac artery (542.0 vs 144.4, P =.041), both common iliac arteries together (1,103.3 vs 301.9, P =.046), and the left internal iliac artery (716.3 vs 35.3, P =.044). Conclusions: Patients with higher calcium scores in the iliacal arteries have an increased leakage risk. http://repub.eur.nl/res/pub/31539/ 2011-02-09T00:00:00Z Background: Coronary artery calcification (CAC) has been proposed to be the underlying mechanism of the increased risk of coronary heart disease with reductions in glomerular filtration rate (GFR). Since renal function diminishes with aging we examined the association between GFR and CAC in the Rotterdam Study, a population-based study of elderly individuals. Methods: The study was performed in 1703 subjects without a history of coronary heart disease. GFR was estimated using the modification of diet in renal disease equation. We used analysis of covariance to test for mean differences in CAC between GFR tertiles. Results: The mean CAC scores in the middle and lowest GFR tertile did not significantly differ from the mean CAC score in the highest GFR tertile (geometric mean CAC score 4.1 and 4.3 vs 4.2). In a multivariable model the mean CAC score did also not differ between the GFR tertiles. As the interaction term between age and GFR was significant (P = 0.037), we divided the population in two age categories based on median age of 70 years. Below 70 years, the mean CAC scores did not differ between the GFR tertiles. Above median age, mean CAC score in the lowest GFR tertile was significantly higher than the mean CAC score in the highest tertile in a multivariable model (CAC 4.9 vs 4.5, p = 0.010). Conclusion: In this population-based study we observed that the association between CAC and GFR is modified by age. In participants at least 70 years of age, a decrease in GFR was associated with increased CAC. http://repub.eur.nl/res/pub/28019/ 2010-10-19T00:00:00Z Objectives The purpose of this study was to examine the effect of coronary artery calcium (CAC) on the classification of 10-year hard coronary heart disease (CHD) risk and to empirically derive cut-off values of the calcium score for a general population of elderly patients. Background Although CAC scoring has been found to improve CHD risk prediction, there are limited data on its impact in clinical practice. Methods The study comprised 2,028 asymptomatic participants (age 69.6 ± 6.2 years) from the Rotterdam Study. During a median follow-up of 9.2 years, 135 hard coronary events occurred. Persons were classified into low (<10%), intermediate (10% to 20%), and high (>20%) 10-year coronary risk categories based on a Framingham refitted risk model. In a second step, the model was extended by CAC, and reclassification percentages were calculated. Cutoff values of CAC for persons in the intermediate-risk category were empirically derived based on 10-year hard CHD risk. Results Reclassification by means of CAC scoring was most substantial in persons initially classified as intermediate risk. In this group, 52% of men and women were reclassified, all into more accurate risk categories. CAC values above 615 or below 50 Agatston units were found appropriate to reclassify persons into high or low risk, respectively. Conclusions In a general population of elderly patients at intermediate CHD risk, CAC scoring is a powerful method to reclassify persons into more appropriate risk categories. Empirically derived CAC cutoff values at which persons at intermediate risk reclassified to either high or low risk were 615 and 50 Agatston units, respectively. http://repub.eur.nl/res/pub/27320/ 2010-05-01T00:00:00Z Background: Epidemiologic and experimental data suggest a cardioprotective effect of n23 (omega-3) fatty acids from fish [eicosapentaenoic acid (EPA) plus docosahexaenoic acid (DHA)]. Objective: The objective was to examine the association of fish and EPA plus DHA intakes with coronary calcification in a general older population. Design: Diet was assessed between 1990 and 1993 by using a semiquantitative 170-item food-frequency questionnaire. Coronary calcification was assessed ≈7 y later by electron-beam computed tomography in 1570 asymptomatic cardiac subjects with complete dietary data (44% men, mean age of 64 y). Calcium scores according to Agatston's method were divided into ≤10 (no/minimal coronary calcification), 11-400 (mild/moderate calcification), and >400 (severe calcification). Prevalence ratios (PRs) for mild/moderate and severe calcification were obtained in categories of fish and EPA plus DHA intake. PRs were adjusted for age, sex, body mass index, diabetes mellitus, socioeconomic status, smoking, alcohol intake, physical activity, and dietary factors. Results: Subjects with a fish intake >19 g/d had a significantly lower prevalence of mild/moderate calcification (PR: 0.87; 95% CI: 0.78, 0.98; full model) than did subjects who consumed no fish. Subjects with a high fish intake also had a lower prevalence of severe calcifi-cation (PR: 0.88; 95% CI: 0.74, 1.04), which was borderline statistically significant. EPA plus DHA intake showed no significant associations (PR: 0.93 and 0.97, respectively; P > 0.05). Conclusions: We found a weak inverse association between fish intake and coronary calcification. If confirmed in other population-based studies, more research is warranted to determine which components in fish can inhibit vascular calcification. http://repub.eur.nl/res/pub/27399/ 2010-04-01T00:00:00Z Background: Coronary artery calcium (CAC) and thoracic aorta calcium (TAC) can be detected simultaneously on low-dose, non-gated computed tomography (CT) scans. CAC has been shown to predict cardiovascular (CVD) and coronary (CHD) events. A comparable association between TAC and CVD events has yet to be established, but TAC could be a more reproducible alternative to CAC in low-dose, non-gated CT. This study compared CAC and TAC as independent predictors of all-cause mortality and cardiovascular events in a population of heavy smokers using low-dose, non-gated CT. Methods: Within the NELSON study, a population-based lung cancer screening trial, the CT screen group consisted of 7557 heavy smokers aged 50-75 years. Using a case-cohort study design, CAC and TAC scores were calculated in a total of 958 asymptomatic subjects who were followed up for all-cause death, and CVD, CHD and non-cardiac events (stroke, aortic aneurysm, peripheral arterial occlusive disease). We used Cox proportional-hazard regression to compute hazard ratios (HRs) with adjustment for traditional cardiovascular risk factors. Results: A close association between the prevalence of TAC and increasing levels of CAC was established (p<0.001). Increasing CAC and TAC risk categories were associated with all-cause mortality (p for trend=0.01 and 0.001, respectively) and CVD events (p for trend <0.001 and 0.03, respectively). Compared with the lowest quartile (reference category), multivariate-adjusted HRs across categories of CAC were higher (all-cause mortality, HR: 9.13 for highest quartile; CVD events, HR: 4.46 for highest quartile) than of TAC scores (HR: 5.45 and HR: 2.25, respectively). However, TAC is associated with non-coronary events (HR: 4.69 for highest quartile, p for trend=0.01) and CAC was not (HR: 3.06 for highest quartile, p for trend=0.40). Conclusions: CAC was found to be a stronger predictor than TAC of all-cause mortality and CVD events in a high-risk population of heavy smokers scored on low-dose, non-gated CT. TAC, however, is stronger associated with non-cardiac events than CAC and could prove to be a preferred marker for these events. http://repub.eur.nl/res/pub/19248/ 2010-01-01T00:00:00Z http://repub.eur.nl/res/pub/28104/ 2010-01-01T00:00:00Z Objective: To assess volumetric measurement variability in pulmonary nodules detected at low-dose chest CT with three reconstruction settings. Methods: The volume of 200 solid pulmonary nodules was measured three times using commercially available semi-automated software of low-dose chest CT data-sets reconstructed with 1 mm section thickness and a soft kernel (A), 2 mm and a soft kernel (B), and 2 mm and a sharp kernel (C), respectively. Repeatability coefficients of the three measurements within each setting were calculated by the Bland and Altman method. A three-level model was applied to test the impact of reconstruction setting on the measured volume. Results: The repeatability coefficients were 8.9, 22.5 and 37.5% for settings A, B and C. Three-level analysis showed that settings A and C yielded a 1.29 times higher estimate of nodule volume compared with setting B (P=0.03). The significant interaction among setting, nodule location and morphology demonstrated that the effect of the reconstruction setting was different for different types of nodules. Low-dose CT reconstructed with 1 mm section thickness and a soft kernel provided the most repeatable volume measurement. Conclusion: A wide, nodule-type-dependent range of agreement between volume measurements with different reconstruction settings suggests strict consistency is required for serial CT studies. http://repub.eur.nl/res/pub/32674/ 2009-12-03T00:00:00Z BACKGROUND: The use of multidetector computed tomography (CT) in lung-cancer screening trials involving subjects with an increased risk of lung cancer has highlighted the problem for the clinician of deciding on the best course of action when noncalcified pulmonary nodules are detected by CT. METHODS: A total of 7557 participants underwent CT screening in years 1, 2, and 4 of a randomized trial of lung-cancer screening. We used software to evaluate a noncalcified nodule according to its volume or volume-doubling time. Growth was defined as an increase in volume of at least 25% between two scans. The first-round screening test was considered to be negative if the volume of a nodule was less than 50 mm3, if it was 50 to 500 mm3 but had not grown by the time of the 3-month follow-up CT, or if, in the case of those that had grown, the volume-doubling time was 400 days or more. RESULTS: In the first and second rounds of screening, 2.6% and 1.8% of the participants, respectively, had a positive test result. In round one, the sensitivity of the screen was 94.6% (95% confidence interval [CI], 86.5 to 98.0) and the negative predictive value 99.9% (95% CI, 99.9 to 100.0). In the 7361 subjects with a negative screening result in round one, 20 lung cancers were detected after 2 years of follow-up. CONCLUSIONS: Among subjects at high risk for lung cancer who were screened in three rounds of CT scanning and in whom noncalcified pulmonary nodules were evaluated according to volume and volume-doubling time, the chances of finding lung cancer 1 and 2 years after a negative first-round test were 1 in 1000 and 3 in 1000, respectively. (Current Controlled Trials number, ISRCTN63545820.). Copyright http://repub.eur.nl/res/pub/24201/ 2009-08-01T00:00:00Z Object: Nerve regeneration could be monitored by comparing MRI image intensities in time, as denervated muscles display increased signal intensity in STIR sequences. In this study long-term reproducibility of STIR image intensity was assessed under clinical conditions and the required image intensity nonuniformity correction was improved by using phantom scans obtained at multiple positions. Methods: Three-dimensional image intensity nonuniformity was investigated in phantom scans. Next, over a three-year period, 190 clinical STIR hand scans were obtained using a standardized acquisition protocol, and corrected for intensity nonuniformity by using the results of phantom scanning. The results of correction with 1, 3, and 11 phantom scans were compared. The image intensities in calibration tubes close to the hands were measured every time to determine the reproducibility of our method. Results: With calibration, the reproducibility of STIR image intensity improved from 7.8 to 6.4%. Image intensity nonuniformity correction with 11 phantom scans gave significantly better results than correction with 1 or 3 scans. Conclusions: The image intensities in clinical STIR images acquired at different times can be compared directly, provided that the acquisition protocol is standardized and that nonuniformity correction is applied. Nonuniformity correction is preferably based on multiple phantom scans. http://repub.eur.nl/res/pub/24355/ 2009-06-01T00:00:00Z Purpose: To retrospectively evaluate whether baseline nodule density or changes in density or nodule features could be used to discriminate between benign and malignant solid indeterminate nodules. Materials and methods: Solid indeterminate nodules between 50 and 500 mm3(4.6-9.8 mm) were assessed at 3 and 12 months after baseline lung cancer screening (NELSON study). Nodules were classified based on morphology (spherical or non-spherical), shape (round, polygonal or irregular) and margin (smooth, lobulated, spiculated or irregular). The mean CT density of the nodule was automatically generated in Hounsfield units (HU) by the Lungcare©software. Results: From April 2004 to July 2006, 7310 participants underwent baseline screening. In 312 participants 372 solid purely intra-parenchymal nodules were found. Of them, 16 (4%) were malignant. Benign nodules were 82.8 mm3(5.4 mm) and malignant nodules 274.5 mm3(8.1 mm) (p = 0.000). Baseline CT density for benign nodules was 42.7 HU and for malignant nodules -2.2 HU (p = ns). The median change in density for benign nodules was -0.1 HU and for malignant nodules 12.8 HU (p < 0.05). Compared to benign nodules, malignant nodules were more often non-spherical, irregular, lobulated or spiculated at baseline, 3-month and 1-year follow-up (p < 0.0001). In the majority of the benign and malignant nodules there was no change in morphology, shape and margin during 1 year of follow-up (p = ns). Conclusion: Baseline nodule density and changes in nodule features cannot be used to discriminate between benign and malignant solid indeterminate pulmonary nodules, but an increase in density is suggestive for malignancy and requires a shorter follow-up or a biopsy. http://repub.eur.nl/res/pub/25463/ 2009-01-01T00:00:00Z Purpose: To retrospectively determine whether baseline nodule characteristics at 3-month and 1-year volume doubling time (VDT) are predictive for lung cancer in solid indeterminate noncalcified nodules (NCNs) detected at baseline computed tomographic (CT) screening. Materials and Methods: The study, conducted between April 2004 and May 2006, was institutional review board approved. Patient consent was waived for this retrospective evaluation. NCNs between 5 and 10 mm in diameter (n = 891) were evaluated at 3 months and 1 year to assess growth (VDT < 400 days). Baseline assessments were related to growth at 3 months and 1 year by using x2and Mann-Whitney U tests. Baseline assessments and growth were related to the presence of malignancy by using univariate and multivariate logistic regression analyses. Results: At 3 months and at 1 year, 8% and 1% of NCNs had grown, of which 15% and 50% were malignant, respectively. One-year growth was related to morphology (P < .01), margin (P < .0001), location (P < .001), and size (P < .01). All cancers were nonspherical and purely intra-parenchymal, without attachment to vessels, the pleura, or fissures. In nonsmooth unattached nodules, a volume of 130 mm3or larger was the only predictor for malignancy (odds ratio, 6.3; 95% confidence interval [CI]: 1.7, 23.0). After the addition of information on the 3-month VDT, large volume (odds ratio, 4.9; 95% CI: 1.2, 20.1) and 3-month VDT (odds ratio, 15.6; 95% CI: 4.5, 53.5) helped predict malignancy. At 1 year, only the 1-year growth remained (odds ratio, 213.3; 95% CI: 18.7, 2430.9) as predictor for malignancy. Conclusion: In smooth or attached solid indeterminate NCNs, no malignancies were found at 1-year follow-up. In nonsmooth purely intraparenchymal NCNs, size is the main baseline predictor for malignancy. When follow-up data are available, growth is a strong predictor for malignancy, especially at 1-year follow-up. http://repub.eur.nl/res/pub/29797/ 2008-11-01T00:00:00Z Purpose: To evaluate prospectively the value of size, shape, margin and density in discriminating between benign and malignant CT screen detected solid non-calcified pulmonary nodules. Material and methods: This study was institutional review board approved. For this study 405 participants of the NELSON lung cancer screening trial with 469 indeterminate or potentially malignant solid pulmonary nodules (>50 mm3) were selected. The nodules were classified based on size, shape (round, polygonal, irregular) and margin (smooth, lobulated, spiculated). Mean nodule density and nodule volume were automatically generated by software. Analyses were performed by univariate and multivariate logistic regression. Results were presented as likelihood ratios (LR) with 95% confidence intervals (CI). Receiver operating characteristic analysis was performed for mean density as predictor for lung cancer. Results: Of the 469 nodules, 387 (83%) were between 50 and 500 mm3, 82 (17%) >500 mm3, 59 (13%) malignant, 410 (87%) benign. The median size of the nodules was 103 mm3(range 50-5486 mm3). In multivariate analysis lobulated nodules had LR of 11 compared to smooth; spiculated nodules a LR of 7 compared to smooth; irregular nodules a LR of 6 compared to round and polygonal; volume a LR of 3. The mean nodule CT density did not predict the presence of lung cancer (AUC 0.37, 95% CI 0.32-0.43). Conclusion: In solid non-calcified nodules larger than 50 mm3, size and to a lesser extent a lobulated or spiculated margin and irregular shape increased the likelihood that a nodule was malignant. Nodule density had no discriminative power. http://repub.eur.nl/res/pub/28836/ 2008-08-01T00:00:00Z Purpose: To retrospectively assess volume measurement variability in solid pulmonary nodules (volume, 15-500 mm3) detected at lung cancer screening and to quantify the independent effects of nodule morphology, size, and location. Materials and Methods: This retrospective study was a substudy of the screening program that was approved by the Dutch Ministry of Health, and all participants provided written informed consent. Two independent readers used semiautomated software to measure the volume of pulmonary nodules detected in 6774 participants aged 50-75 years (5917 men). Nodules were classified according to their location (purely intraparenchymal, pleural based, juxtavascular, or fissure attached), morphology (smooth, polylobulated, spiculated, or irregular), and size (<50 mm3or >50 mm3). The level of agreement was expressed by using the absolute values of the relative volume differences (RVDs). Multivariate logistic regression analysis was performed, and odds ratios (ORs) were computed to quantify the independent effects of morphology, location, and size on RVD categories. Results: Altogether, 4225 nodules in 2239 participants were included. Complete agreement in volume was obtained for 3646 (86%) of the nodules. Disagreement was small (absolute value of RVD < 5%) for 173 (4%) nodules, moderate (absolute value of RVD ≥ 5% but < 15%) for 232 (6%), and large (absolute value of RVD ≥ 15%) for 174 (4%). Multivariate analysis showed that the ORs of volume disagreement were 15.7, 3.1, and 1.9 for irregular, spiculated, and polylobulated nodules, respectively; 3.5, 2.6, and 2.1 for juxtavascular, pleural-based, and fissure-attached nodules, respectively; and 1.3 for large nodules compared with smooth, purely intraparenchymal, and small reference nodules. Conclusion: Nodule morphology, location, and size influence volume measurement variability, particularly for juxtavascular and irregular nodules. http://repub.eur.nl/res/pub/30097/ 2008-05-01T00:00:00Z BACKGROUND - The role of coffee in the cardiovascular system is not yet clear. We examined the relation of coffee intake with coronary calcification in a population-based cohort. METHODS AND RESULTS - The study involved 1570 older men and women without coronary heart disease who participated in the Rotterdam Study. Coffee intake was assessed with a semiquantitative food frequency questionnaire. Coronary calcification was detected with electron beam computed tomography. Severe calcification was defined as an Agatson calcium score >400. Sex-specific odds ratios (ORs) with 95% confidence intervals (95% CI) were obtained by logistic regression with adjustment for age, smoking, body mass index, education, and intake of energy and alcohol. In multivariable analysis, coronary calcification in women was significantly reduced for moderate (>3 to 4 cups) and high (>4 cups) coffee intake, compared with a daily intake of 3 cups or less (OR of 0.41 [95% CI: 0.25 to 0.65] and 0.54 [0.33 to 0.87], respectively). The association persisted after additional adjustment for tea and other dietary confounders, and was not modified by smoking. A nonsignificant inverse relationship was also found in men who smoked, whereas in nonsmoking men a direct association was observed. CONCLUSION - The present study suggests a beneficial effect of coffee drinking against coronary calcification, particularly in women. More research is needed to confirm these findings and to clarify possible effect modification by gender and smoking. http://repub.eur.nl/res/pub/35074/ 2007-12-01T00:00:00Z Aims: Although prospective studies have unequivocally shown that C-reactive protein (CRP) is an independent predictor of future cardiovascular events, studies on the association between CRP and atherosclerosis have provided inconsistent results. We investigated the association of CRP with extent and progression of atherosclerosis in multiple vessel beds in a large, population-based cohort study. Methods: In the Rotterdam Study, standardized measurements of coronary and extra-coronary atherosclerosis were performed in 1962 persons and 6582 persons, respectively. Progression of extra-coronary atherosclerosis during a mean follow-up period of 6.4 years was assessed in 3757 persons. Results: Independent and graded associations were found of CRP with the number of carotid plaques and carotid plaque progression ((OR 1.72; 95% CI 1.14-2.59) for severe progression in participants with CRP > 3 mg/dl versus participants with CRP < 1 mg/dl). Similarly, CRP was independently and graded related to ankle-brachial-index (ABI) and worsening ABI over the years ((OR 1.99; 95% CI 1.37-2.88) for severe progression in participants with CRP > 3 mg/dl versus participants with CRP < 1 mg/dl). Although CRP was independently related to the highest level of carotid intima-media thickness (IMT), the association with change in IMT was not significant. Furthermore, there was an independent, graded relation between CRP and aortic calcification, but no independent association was observed with progression of aortic calcification, nor with the amount of coronary calcification. Conclusion: In this population-based study, independent and graded associations were present of CRP with extent and progression of carotid plaques and ABI, while associations with carotid IMT and aortic and coronary calcification were less pronounced. http://repub.eur.nl/res/pub/36419/ 2007-08-01T00:00:00Z http://repub.eur.nl/res/pub/36988/ 2007-08-01T00:00:00Z http://repub.eur.nl/res/pub/36890/ 2007-07-13T00:00:00Z Background: Asymptomatic subjects at intermediate coronary risk may need diagnostic testing for risk stratification. Both measurement of coronary calcium scores and exercise testing are well established tests for this purpose. However, it is not clear which test should be preferred as initial diagnostic test. We evaluated the prevalence of documented coronary artery disease (CAD) according to calcium scores and exercise test results. Methods: Asymptomatic subjects with ST-T changes on a rest ECG were selected from the population based PREVEND cohort study and underwent measurement of calcium scores by electron beam tomography and exercise testing. With calcium scores ≥10 or a positive exercise test, myocardial perfusion imaging (MPS) or coronary angiography (CAG) was recommended. The primary endpoint was documented obstructive CAD (≥50% stenosis). Results: Of 153 subjects included, 149 subjects completed the study protocol. Calcium scores ≥400, 100-399, 10-99 and <10 were found in 16, 29, 18 and 86 subjects and the primary endpoint was present in 11 (69%), 12 (41%), 0 (0%) and 1 (1%) subjects, respectively. A positive, nondiagnostic and negative exercise test was present in 33, 27 and 89 subjects and the primary endpoint was present in 13 (39%), 5 (19%) and 6 (7%) subjects, respectively. Receiver operator characteristics analysis showed that the area under the curve, as measure of diagnostic yield, of 0.91 (95% CI 0.84-0.97) for calcium scores was superior to 0.74 (95% CI 0.64-0.83) for exercise testing (p = 0.004). Conclusion: Measurement of coronary calcium scores is an appropriate initial non-invasive test in asymptomatic subjects at increased coronary risk. http://repub.eur.nl/res/pub/35347/ 2007-07-01T00:00:00Z The female advantage in coronary heart disease occurrence is not completely understood. To characterize gender differences in cardiovascular disease by vascular site, the authors compared degrees of coronary, carotid, peripheral, and aortic atherosclerosis in men and women aged ≥55 years from the population-based Rotterdam Study (Rotterdam, the Netherlands). Data were collected between 1997 and 2000. A subset of 2,013 participants had data on both coronary calcification and one or more measures of extracoronary atherosclerosis, including intima-media thickness (IMT), carotid plaques, ankle-arm index (AAI), and aortic calcification. The multivariable-adjusted male:female odds ratios for calcium score > 1,000 were 7.8 (95% confidence interval (CI): 3.2, 19.3), 5.4 (95% CI: 2.8, 10.2), and 3.0 (95% CI: 1.7, 5.2) in the lowest, middle, and highest age tertiles, respectively. For IMT > 1.0 mm, severe carotid plaques, AAI < 0.90, and severe aortic calcification, ratios did not decline with age. Overall multivariable-adjusted male:female odds ratios for these measures were 2.9 (95% CI: 2.0, 4.1), 2.0 (95% CI: 1.4, 2.8), 0.9 (95% CI: 0.7, 1.3), and 1.0 (95% CI: 0.8, 1.5), respectively. The authors conclude that the gender difference in atherosclerosis is larger in the coronary vessels than in other vascular beds. Remarkably, it is absent in the aorta and the lower-extremity vessels. Factors causing this site-specific gender difference require further investigation. http://repub.eur.nl/res/pub/36454/ 2007-06-01T00:00:00Z The purpose of this study was to prospectively determine the frequency and spectrum of incidental findings (IFs) and their clinical implications in a high risk population for lung cancer undergoing low-dose multidetector computed tomography (MDCT) screening for lung cancer. Scans of 1,929 participants were evaluated for lung lesions and IFs by two radiologists. IFs were categorised as not clinically relevant or possibly clinically relevant. Findings were considered possibly clinically relevant if they could require further evaluation or could have substantial clinical implications. All possibly clinically relevant IFs were reviewed by a third radiologist, who determined its clinical relevance. Of all 1,929 participants, 1,410 (73%) had not clinically relevant IFs and 163 (8%) had possibly clinically relevant IFs of which 129 (79%) were indeed considered clinically relevant. Additional imaging was performed mainly by ultrasound (112 of 118, 96%). All but one lesion were concluded to be benign, mostly cysts (n = 115, 80%). Only 21 (1%) participants had findings with clinical implications. In one participant a malignancy was found, yet without any clinical benefit since no curative treatment was possible. Based on our results, we advise against systematically searching for and reporting of IFs in lung cancer screening studies using low-dose MDCT. http://repub.eur.nl/res/pub/35506/ 2007-04-01T00:00:00Z Objectives: Although several studies have recently suggested that lipoprotein-associated phospholipase A2 (Lp-PLA2) is an independent predictor of coronary events, only one study has examined the association between Lp-PLA2 and coronary calcification, using young adults. We investigated the association between Lp-PLA2 activity and coronary calcification assessed by electron-beam computed tomography (EBT) in a population of older participants. Methods and results: The Rotterdam Coronary Calcification Study is a population-based study in men and women aged ≥55 years. Coronary calcification assessed by EBT was quantified in a calcium score according to Agatston's method. Lp-PLA2 activity measured in samples collected 7 years before scanning (n = 520) was associated with coronary calcification in men after adjustment for age. The odds ratio per standard deviation of Lp-PLA2 activity of having a total calcium score >1000 was 1.6 (95% confidence interval: 1.1-2.4), as compared to a total calcium score ≤100. After adjustment for non-HDL and HDL-cholesterol, this association disappeared. In women, the association was less consistent. For Lp-PLA2 measured concurrently to scanning (n = 703), no association was found with coronary calcification. Conclusions: Lp-PLA2 activity is moderately associated with coronary calcification after adjustment for age. The effect of Lp-PLA2 on coronary calcification may be exerted through its effect on LDL-cholesterol. http://repub.eur.nl/res/pub/35575/ 2007-02-15T00:00:00Z A method to obtain the optimal selection criteria, taking into account available resources and capacity and the impact on power, is presented for the Dutch-Belgian randomised lung cancer screening trial (NELSON). NELSON investigates whether 16-detector multi-slice computed tomography screening will decrease lung cancer mortality compared to no screening. A questionnaire was sent to 335,441 (mainly) men, aged 50-75. Smoking exposure (years smoked, cigarettes/day, years quit) was determined, and expected lung cancer mortality was estimated for different selection scenarios for the 106,931 respondents, using lung cancer mortality data by level of smoking exposure (US Cancer Prevention Study I and II). Selection criteria were chosen so that the required response among eligible subjects to reach sufficient sample size was minimised and the required sample size was within our capacity. Inviting current and former smokers (quit ≤ 10 years ago) who smoked >15 cigarettes/day during >25 years or >10 cigarettes/day during >30 years was most optimal. With a power of 80%, 17,300-27,900 participants are needed to show a 20-25% lung cancer mortality reduction 10 years after randomisation. Until October 18, 2005 11,103 (first recruitment round) and 4,325 (second recruitment round) (total = 15,428) participants have been randomised. Selecting participants for lung cancer screening trials based on risk estimates is feasible and helpful to minimize sample size and costs. When pooling with Danish trial data (n = ±4,000) NELSON is the only trial without screening in controls that is expected to have 80% power to show a lung cancer mortality reduction of at least 25% 10 years after randomisation. http://repub.eur.nl/res/pub/15686/ 2006-07-01T00:00:00Z BACKGROUND: In metastatic bone disease, prophylactic fixation of impending long bone fracture is preferred over surgical treatment of a manifest fracture. There are no reliable guidelines for prediction of pathological fracture risk, however. We aimed to determine whether finite element (FE) models constructed from quantitative CT scans could be used for predicting pathological fracture load and location in a cadaver model of metastatic bone disease. MATERIAL AND METHODS: Subject-specific FE models were constructed from quantitative CT scans of 11 pairs of human femora. To simulate a metastatic defect, a transcortical hole was made in the subtrochanteric region in one femur of each pair. All femora were experimentally loaded in torsion until fracture. FE simulations of the experimental set-up were performed and torsional stiffness and strain energy density (SED) distribution were determined. RESULTS: In 15 of the 22 cases, locations of maximal SED fitted with the actual fracture locations. The calculated torsional stiffness of the entire femur combined with a criterion based on the local SED distribution in the FE model predicted 82% of the variance of the experimental torsional failure load. INTERPRETATION: In the future, CT scan-based FE analysis may provide a useful tool for identification of impending pathological fractures requiring prophylactic stabilization. http://repub.eur.nl/res/pub/13867/ 2005-07-26T00:00:00Z BACKGROUND: Coronary calcification detected by electron beam tomography may improve cardiovascular risk prediction. The technique is particularly promising in the elderly because the predictive power of cardiovascular risk factors weakens with age. We investigated the prognostic value of coronary calcification for cardiovascular events and mortality in a general, asymptomatic population of elderly subjects. METHODS AND RESULTS: From 1997 to 2000, electron beam tomography scanning to assess coronary calcification was performed in subjects of the population-based Rotterdam Study. Risk factors were measured by standardized procedures. Coronary calcium scores were available for 1795 asymptomatic participants (mean age, 71 years; range, 62 to 85 years). During a mean follow-up of 3.3 years, 88 cardiovascular events, including 50 coronary events, occurred. The risk of coronary heart disease increased with increasing calcium score. The multivariate-adjusted relative risk of coronary events was 3.1 (95% CI, 1.2 to 7.9) for calcium scores of 101 to 400, 4.6 (95% CI, 1.8 to 11.8) for calcium scores of 401 to 1000, and 8.3 (95% CI, 3.3 to 21.1) for calcium scores >1000 compared with calcium scores of 0 to 100. The predictive value in subjects >70 years of age was similar. Risk prediction based on the cardiovascular risk factors improved when coronary calcification was added. CONCLUSIONS: Coronary calcification is a strong and independent predictor of coronary heart disease, also in the elderly. Coronary calcification improves prediction of coronary events based on cardiovascular risk factors. Risk stratification by assessment of coronary calcification may have an important role in the primary prevention of coronary heart disease events in the elderly. http://repub.eur.nl/res/pub/13510/ 2004-11-01T00:00:00Z Cerebral white matter lesions are frequently observed on magnetic resonance imaging (MRI) scans in elderly people and are associated with stroke and dementia. Elevated blood pressure is presumed one of the main risk factors, although data are almost exclusively derived from cross-sectional studies. We assessed in 10 European cohorts the relation between concurrently and previously measured blood pressure levels, hypertension, its treatment, and severe cerebral white matter lesions. In total, 1805 nondemented subjects aged 65 to 75 years were sampled from ongoing community-based studies that were initiated 5 to 20 years before the MRI. White matter lesions in the periventricular and subcortical region were rated separately using semiquantitative measures. We performed logistic regression analyses adjusted for potential confounders in 1625 people with complete data. Concurrently and formerly assessed diastolic and systolic blood pressure levels were positively associated with severe white matter lesions. Both increases and decreases in diastolic blood pressure were associated with more severe periventricular white matter lesions. Increase in systolic blood pressure levels was associated with more severe periventricular and subcortical white matter lesions. People with poorly controlled hypertension had a higher risk of severe white matter lesions than those without hypertension, or those with controlled or untreated hypertension. Higher blood pressure was associated with an increased risk of severe white matter lesions. Successful treatment of hypertension may reduce this risk; however, a potential negative effect of decreasing diastolic blood pressure level on the occurrence of severe periventricular white matter lesions should be taken into account. http://repub.eur.nl/res/pub/13516/ 2004-10-01T00:00:00Z OBJECTIVE: To study the association between white matter lesions (WML) in specific locations and the risk of dementia. DESIGN: The Rotterdam Scan Study, a prospective population-based cohort study. We scored periventricular and subcortical WML on magnetic resonance imaging and observed participants until January 2002 for incident dementia. SETTING: General population. PARTICIPANTS: We included 1077 people aged 60 to 90 years who did not have dementia at baseline. MAIN OUTCOME MEASURE: Incident dementia by Diagnostic and Statistical Manual of Mental Disorders, Third Edition (DSM III-R) criteria. RESULTS: During a mean follow-up of 5.2 years, 45 participants developed dementia. Higher severity of periventricular WML increased the risk of dementia, whereas the association between subcortical WML and dementia was less prominent. The adjusted hazard ratio of dementia for each standard deviation increase in periventricular WML severity was 1.67 (95% confidence interval, 1.25-2.24). This increased risk was independent of other risk factors for dementia and partly independent of other structural brain changes on magnetic resonance imaging. CONCLUSION: White matter lesions, especially in the periventricular region, increase the risk of dementia in elderly people. http://repub.eur.nl/res/pub/22488/ 2004-05-01T00:00:00Z OBJECTIVE: To study whether lower arterial oxygen saturation (SaO(2)) and chronic obstructive pulmonary disease (COPD) are associated with cerebral white matter lesions and lacunar infarcts. METHODS: We measured SaO(2) twice with a pulse oximeter, assessed the presence of COPD, and performed MRI in 1077 non-demented people from a general population (aged 60-90 years). We rated periventricular white matter lesions (on a scale of 0-9) and approximated a total subcortical white matter lesion volume (range 0-29.5 ml). All analyses were adjusted for age and sex and additionally for hypertension, diabetes, body mass index, pack years smoked, cholesterol, haemoglobin, myocardial infarction, and left ventricular hypertrophy. RESULTS: Lower SaO(2) was independent of potential confounders associated with more severe periventricular white matter lesions (score increased by 0.12 per 1% decrease in SaO(2) (95% confidence interval 0.01 to 0.23)). Participants with COPD had more severe periventricular white matter lesions than those without (adjusted mean difference in score 0.70 (95% confidence interval 0.23 to 1.16)). Lower SaO(2) and COPD were not associated with subcortical white matter lesions or lacunar infarcts. CONCLUSION: Lower SaO(2) and COPD are associated with more severe periventricular white matter lesions. http://repub.eur.nl/res/pub/10277/ 2004-01-01T00:00:00Z AIMS: We examined associations between cardiovascular risk factors and coronary calcification assessed by electron-beam tomography (EBT) in an unselected population of older subjects. METHODS AND RESULTS: The Rotterdam Coronary Calcification Study is a population-based study in subjects > =55 years. Participants underwent EBT scanning. Coronary calcification was quantified according to the Agatston score. Cardiovascular risk factors were assessed 7 years before and concurrently to scanning. We used the first 2013 participants for the present analyses. Risk factors assessed 7 years before scanning were strongly associated with calcium score. Associations with blood pressure and cholesterol attenuated when measured concurrently to scanning. Although the number of risk factors was strongly associated with a high calcium score in asymptomatic subjects, 29% of the men and 15% of the women without risk factors had a high calcium score. CONCLUSIONS: This population-based study in older subjects shows that cardiovascular risk factors are associated with coronary calcification. Associations were stronger for risk factors measured at earlier age. Almost 30% of the men and 15% of the women without risk factors had extensive coronary calcification. http://repub.eur.nl/res/pub/10034/ 2003-01-01T00:00:00Z Patients with Alzheimer's disease have higher plasma homocysteine levels than controls, but it is uncertain whether higher plasma homocysteine levels are involved in the early pathogenesis of the disease. Hippocampal, amygdalar and global brain atrophy on brain MRI have been proposed as early markers of Alzheimer's disease. In the Rotterdam Scan Study, a population-based study of age-related brain changes in 1077 non-demented people aged 60-90 years, we investigated the association between plasma homocysteine levels and severity of hippocampal, amygdalar and global brain atrophy on MRI. We used axial T(1)-weighted MRIs to visualize global cortical brain atrophy (measured semi-quantitatively; range 0-15) and a 3D HASTE (half-Fourier acquisition single-shot turbo spin echo) sequence in 511 participants to measure hippocampal and amygdalar volumes. We had non-fasting plasma homocysteine levels in 1031 of the participants and in 505 of the participants with hippocampal and amygdalar volumes. Individuals with higher plasma homocysteine levels had, on average, more cortical atrophy [0.23 units (95% CI 0.07-0.38 units) per standard deviation increase in plasma homocysteine levels] and more hippocampal atrophy [difference in left hippocampal volume -0.05 ml (95% CI -0.09 to -0.01) and in right hippocampal volume -0.03 ml (95% CI -0.07 to 0.01) per standard deviation increase in plasma homocysteine levels]. No association was observed between plasma homocysteine levels and amygdalar atrophy. These results support the hypothesis that higher plasma homocysteine levels are associated with more atrophy of the hippocampus and cortical regions in elderly at risk of Alzheimer's disease. http://repub.eur.nl/res/pub/10099/ 2003-01-01T00:00:00Z BACKGROUND AND PURPOSE: The prevalence of silent brain infarcts in healthy elderly people is high, and these lesions are associated with an increased risk of stroke. The incidence of silent brain infarcts is unknown. We investigated the incidence and cardiovascular risk factors for silent brain infarcts. METHODS: The Rotterdam Scan Study is a prospective, population-based cohort study of 1077 participants 60 to 90 years of age. All participants underwent cranial MRI in 1995 to 1996, and 668 participants had a second MRI in 1999 to 2000 (response rate, 70%) with a mean interval of 3.4 years. We assessed cardiovascular risk factors by interview and physical examination at baseline. Associations between risk factors and incident silent infarcts were analyzed by multiple logistic regression. RESULTS: Ninety-three participants (14%) had > or =1 new infarcts on the second MRI; of these, 81 had only silent and 12 had symptomatic infarcts. The incidence of silent brain infarcts strongly increased with age and was 5 times higher than that of symptomatic stroke. A prevalent silent brain infarct strongly predicted a new silent infarct on the second MRI (age- and sex-adjusted odds ratio, 2.9; 95% confidence interval, 1.7 to 5.0). Age, blood pressure, diabetes mellitus, cholesterol and homocysteine levels, intima-media thickness, carotid plaques, and smoking were associated with new silent brain infarcts in participants without prevalent infarcts. CONCLUSIONS: The incidence of silent brain infarcts on MRI in the general elderly population strongly increases with age. The cardiovascular risk factors for silent brain infarcts are similar to those for stroke. http://repub.eur.nl/res/pub/9820/ 2002-01-21T00:00:00Z BACKGROUND AND PURPOSE: Silent brain infarcts are commonly seen on magnetic resonance imaging (MRI) both in patients with a first stroke and in healthy elderly persons. These infarcts seem associated with an increased risk of stroke. It is unclear whether risk factors for silent infarcts differ from those for symptomatic stroke. We investigated the prevalence of, and cardiovascular risk factors for, silent brain infarcts. METHODS: The Rotterdam Scan Study is a population-based cohort study among 1077 participants 60 to 90 years of age. Participants underwent cerebral MRI. We assessed cardiovascular risk factors by interview and physical examination. Associations between risk factors and presence of infarcts were analyzed by logistic regression and adjusted for age, sex, and relevant confounders. RESULTS: For 259 participants (24%) 1 or more infarcts on MRI were seen; 217 persons had only silent and 42 had symptomatic infarcts. The prevalence odds ratio (OR) of both silent and symptomatic infarcts increased with age by 8% per year (95% CI, 1.06 to 1.10 and 1.04 to 1.13, respectively). Silent infarcts were more frequent in women (age-adjusted OR, 1.4; 95% CI, 1.0 to 1.8). Hypertension was associated with silent infarcts (age- and sex-adjusted OR, 2.4; 95% CI, 1.7 to 3.3), but diabetes mellitus and smoking were not. CONCLUSIONS: Silent brain infarcts are 5 times as prevalent as symptomatic brain infarcts in the general population. Their prevalence increases with age and seems higher in women. Hypertension is associated with silent infarcts, but other cardiovascular risk factors are not. http://repub.eur.nl/res/pub/4776/ 2002-01-01T00:00:00Z http://repub.eur.nl/res/pub/9831/ 2002-01-01T00:00:00Z BACKGROUND AND PURPOSE: Coronary calcification as detected by electron-beam CT measures the atherosclerotic plaque burden and has been reported to predict coronary events. Because atherosclerosis is a generalized process, coronary calcification may also be associated with manifest atherosclerotic disease at other sites of the vascular tree. We examined whether coronary calcification as detected by electron-beam CT is related to the presence of stroke. METHODS: From 1997 onward, subjects were invited to participate in the prospective Rotterdam Coronary Calcification Study and undergo electron-beam CT to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2013 subjects (mean age [SD], 71 [5.7] years). Fifty subjects had experienced stroke before scanning. RESULTS: Subjects were 2 times more likely to have experienced stroke when their calcium score was between 101 and 500 (odds ratio [OR], 2.1; 95% CI, 0.9 to 4.7) and 3 times more likely when their calcium score was above 500 (OR, 3.3; 95% CI, 1.5 to 7.2), compared with subjects in the lowest calcium score category (0 to 100). Additional adjustment for cardiovascular risk factors did not materially alter the risk estimates. CONCLUSIONS: In this population-based study, a markedly graded association was found between coronary calcification and stroke. The results suggest that coronary calcification as detected by electron-beam CT may be useful to identify subjects at high risk of stroke. http://repub.eur.nl/res/pub/9876/ 2002-01-01T00:00:00Z White matter lesions are frequently found on cerebral MRI scans of elderly people and are thought to be important in the pathogenesis of dementia. Hyper tension has been associated with the presence of white matter lesions but this has been investigated almost exclusively in cross-sectional studies. We studied prospectively the association of these lesions with the duration and treatment of hypertension. We randomly sampled 1077 subjects aged between 60 and 90 years from two prospective population-based studies. One-half of the study subjects had their blood pressure measured between 1975 and 1978 and the other half between 1990 and 1993. All subjects underwent 1.5 T MRI scanning; white matter lesions in the subcortical and periventricular regions were rated separately. Subjects with hypertension had increased rates of both types of white matter lesion. Duration of hypertension was associated with both periventricular and subcortical white matter lesions. This relationship was influenced strongly by age. For participants with >20 years of hypertension and aged between 60 and 70 years at the time of follow-up, the relative risks for subcortical and periventricular white matter lesions were 24.3 [95% confidence interval (CI) 5.1-114.8] and 15.8 (95% CI 3.4-73.5), respectively, compared with normotensive subjects. Subjects with successfully treated hypertension had only moderately increased rates of subcortical white matter lesions and periventricular white matter lesions (relative risk 3.3, 95% CI 1.3-8.4 and 2.6, 95% CI 1.0-6.8, respectively) compared with normotensive subjects. For poorly controlled hypertensives, these relative risks were 8.4 (95% CI 3.1-22.6) and 5.8 (95% CI 2.1-16.0), respectively. In conclusion, we found a relationship between long-standing hypertension and the presence of white matter lesions. Our findings are consistent with the view that effective treatment may reduce the rates of both types of white matter lesion. Adequate treatment of hypertension may therefore prevent white matter lesions and the associated cognitive decline. http://repub.eur.nl/res/pub/9895/ 2002-01-01T00:00:00Z PURPOSE: To evaluate whether mangafodipir trisodium (Mn-DPDP)-enhanced magnetic resonance (MR) imaging surpasses dual-phase spiral computed tomography (CT) in differentiating focal liver lesions. MATERIALS AND METHODS: One hundred forty-five patients who had or were suspected of having focal liver lesions were included in a multicenter study and underwent dual-phase spiral CT and enhanced MR imaging. Image interpretations performed by independent experienced radiologists were compared with the final diagnosis that was based on all available clinical information (including histopathologic findings in 77 patients) and that was determined with consensus. Differences in classifications by using either enhanced MR imaging or dual-phase spiral CT were analyzed with the McNemar test, and receiver operating characteristic (ROC) curves were used to compare the diagnostic performance of enhanced MR imaging and dual-phase spiral CT. RESULTS: Lesion classification was correct in 108 (74%) patients with enhanced MR imaging and in 83 (57%) with dual-phase spiral CT (P =.001). Lesions were correctly classified as either malignant or benign in 123 (85%) patients with enhanced MR imaging and in 98 (68%) with dual-phase spiral CT (P =.001). Classification of lesions as either hepatocellular or nonhepatocellular was correct in 130 (90%) patients with enhanced MR imaging and in 93 (64%) with dual-phase spiral CT (P =.001). These differences remained when analyses were restricted to histopathologically confirmed diagnoses. Comparison of the ROC curves illustrated that enhanced MR imaging performance surpassed that of dual-phase spiral CT. CONCLUSION: Mn-DPDP-enhanced MR imaging is superior to dual-phase spiral CT in classification of focal liver lesions. http://repub.eur.nl/res/pub/9980/ 2002-01-01T00:00:00Z AIMS: Available data are insufficient to determine the relation between coronary calcification and coronary events in the general population. We cross-sectionally examined the association between coronary calcification and myocardial infarction in the prospective Rotterdam Coronary Calcification Study. METHODS AND RESULTS: From 1997 onwards, subjects were invited for electron-beam computed tomography scanning to detect coronary calcification. The study was embedded in the population-based Rotterdam Study. Calcifications were quantified in a calcium score according to Agatston's method. Calcium scores were available for 2,013 participants with a mean age of 71 years (standard deviation, 5.7 years). A history of myocardial infarction prior to scanning was present in 229 subjects. Compared to subjects in the lowest calcium score category (0-100), the age-adjusted odds ratio for myocardial infarction in subjects in the highest calcium score category (above 2,000) was 7.7 (95% confidence interval, 4.1-14.5) for men, and 6.7 (95% confidence interval, 2.4-19.1) for women. Additional adjustment for cardiovascular risk factors only slightly altered the estimates. The association was observed across all age subgroups, i.e. also in subjects of 70 years and older. CONCLUSION: A strong and graded association was found between coronary calcification and myocardial infarction. The association remained at high ages. http://repub.eur.nl/res/pub/9555/ 2001-01-01T00:00:00Z OBJECTIVE: White matter lesions are often seen on MR scans of elderly non-demented and demented people. They are attributed to degenerative changes of small vessels and are implicated in the pathogenesis of cognitive decline and dementia. There is evidence that especially periventricular white matter lesions are related to cognitive decline, whereas subcortical white matter lesions may be related to late onset depression. The frequency distribution of subcortical and periventricular white matter lesions according to age and sex reported. METHODS: A total of 1077 subjects aged between 60-90 years were randomly sampled from the general population. All subjects underwent 1.5T MR scanning; white matter lesions were rated separately for the subcortical region and the periventricular region. RESULTS: Of all subjects 8% were completely free of subcortical white matter lesions, 20% had no periventricular white matter lesions, and 5% had no white matter lesions in either of these locations. The proportion with white matter lesions increased with age, similarly for men and women. Women tended to have more subcortical white matter lesions than men (total volume 1.45 ml v 1. 29 ml; p=0.33), mainly caused by marked differences in the frontal white matter lesion volume (0.89 ml v 0.70 ml; p=0.08). Periventricular white matter lesions were also more frequent among women than men (mean grade 2.5 v 2.3; p=0.07). Also severe degrees of subcortical white matter lesions were more common in women than in men (OR 1.1; 95% confidence interval (95% CI) 0.8-1.5) and periventricular white matter lesions (OR 1.2; 95% CI 0.9-1.7), albeit that none of these findings were statistically significant. CONCLUSIONS: The prevalence and the degree of cerebral white matter lesions increased with age. Women tended to have a higher degree of white matter lesions than men. This may underlie the finding of a higher incidence of dementia in women than in men, particularly at later age. http://repub.eur.nl/res/pub/9621/ 2001-01-01T00:00:00Z http://repub.eur.nl/res/pub/9246/ 2000-01-01T00:00:00Z BACKGROUND AND PURPOSE: MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. METHODS: We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531 subjects in late life. RESULTS: The presence of aortic atherosclerosis during midlife was significantly associated with the presence of periventricular white matter lesions approximately 20 years later (adjusted relative risk, 2.4; 95% CI, 1.2 to 5.0); the relative risks increased linearly with the severity of aortic atherosclerosis. No association was found between midlife aortic atherosclerosis and subcortical white matter lesions (adjusted relative risk, 1.1; 95% CI, 0.5 to 2.3) or between late-life aortic atherosclerosis and white matter lesions. CONCLUSIONS: The pathogenetic process that leads to cerebral periventricular white matter lesions starts already in or before midlife. The critical period for intervention directed at prevention of white matter lesions and its cognitive consequences may be long before these lesions become clinically detectable. http://repub.eur.nl/res/pub/9254/ 2000-01-01T00:00:00Z Profound alterations in host metabolism in lung cancer patients with weight loss have been reported, including elevated phosphomonoesters (PMEs) as detected by 31P magnetic resonance spectroscopy (MRS). In healthy subjects, infusion of L-alanine induced significant increases in hepatic PMEs and phosphodiesters (PDEs) due to rising concentrations of 3-phosphoglycerate and phosphoenolpyruvate, respectively. The aim of the present study was to monitor these changes in the tumor-free liver of lung cancer patients during L-alanine infusion by means of simultaneous 31P MRS and turnover measurements. Twenty-one lung cancer patients without liver metastases with (CaWL) or without weight loss (CaWS), and 12 healthy control subjects were studied during an i.v. L-alanine challenge of 1.4-2.8 mmol/kg followed by 2.8 mmol/kg/h for 90 min. Plasma L-alanine concentrations increased during alanine infusion, from 0.35-0.37 mM at baseline to 5.37 +/- 0.14 mM in the CaWL patients, 6.67 +/- 0.51 mM in the CaWS patients, and 8.47 +/- 0.88 mM in the controls (difference from baseline and between groups during alanine infusion, all P < 0.001). Glucose turnover and liver PME levels at baseline were significantly elevated in the CaWL patients. Alanine infusion increased whole-body glucose turnover by 8 +/- 3% in the CaWS patients (P = 0.03), whereas no significant change occurred in the CaWL and controls. PME levels increased by 50 +/- 16% in controls (area under the curve, P < 0.01) and by 87 +/- 31% in the CaWS patients (P < 0.05) after 45-90 min. In contrast, no significant changes in PME levels were observed in the CaWL patients. Plasma insulin concentrations increased during L-alanine infusion in all groups to levels that were lower in the CaWL patients than in the CaWS patients and controls (P < 0.05). In lung cancer patients, but not in controls, changes in PME and PDE levels during alanine infusion were inversely correlated with their respective baseline levels (r = -0.82 and -0.86, respectively; P < 0.001). In addition, changes in PMEs during alanine infusion in lung cancer patients were inversely correlated with the degree of weight loss (r = -0.54; P < 0.05). This study demonstrates the presence of major alterations in the pathway of hepatic gluconeogenesis in weight-losing lung cancer patients, as shown by elevated glucose flux before and during L-alanine infusion, and by the increased PME and PDE levels, which reflect accumulation of gluconeogenic intermediates in these patients. Weight-stable lung cancer patients show accelerated increases in PME and PDE levels during L-alanine infusion, suggesting enhanced induction of the gluconeogenic pathway. Our results suggest altered gluconeogenic enzyme activities and elevated alanine uptake within the livers of weight-losing/weight-stable lung cancer patients. http://repub.eur.nl/res/pub/9364/ 2000-01-01T00:00:00Z http://repub.eur.nl/res/pub/9391/ 2000-01-01T00:00:00Z Our consensus-based strategy in the diagnostic management of patients with pulmonary embolism involves a perfusion lung scan, a ventilation lung scan, compression ultrasonography and pulmonary angiography, in sequence. We compared the diagnostic approach in patients with clinically suspected pulmonary embolism before the active implementation of this strategy (retrospective analysis of 618 patients, April 1992-March 1995) and after (prospective study of 250 patients, April 1995-March 1996), with another assessment 1 year later. The measured outcomes were: (i) final diagnosis of pulmonary embolism either directly by pulmonary angiography, indirectly by compression ultrasonography of the leg veins, or with a high probability from a ventilation/perfusion lung scan; (ii) prescription of anticoagulant therapy. Before strategy implementation, pulmonary embolism was adequately confirmed or excluded in 11% of patients with an abnormal perfusion lung scan; in 55% the diagnosis remained uncertain, but the patient received anticoagulants. After implementation, these figures were 58.5% and 13%, respectively. A modest further improvement was observed 1 year later. Active implementation of a consensus-based strategy in the diagnosis of pulmonary embolism increases definite diagnoses, and reduces the numbers treated with anticoagulants. It induces a rapid change in the diagnostic behaviour of physicians. http://repub.eur.nl/res/pub/9395/ 2000-01-01T00:00:00Z BACKGROUND: Virtual reality techniques have recently been introduced into clinical medicine. This study examines the possibility of coronary artery fly-through using a dataset obtained by noninvasive coronary angiography with contrast-enhanced electron-beam computed tomography. METHODS AND RESULTS: Ten patients were examined, and 40 to 60 transaxial tomograms (thickness, 1.5 mm; in-plane pixel dimensions, approximately 0.5x0.5 mm) were obtained after intravenous contrast injection. The datasets were processed on a graphics workstation using volume-rendering software. For fly-throughs, the contrast-enhanced lumen was made transparent and other tissue was made opaque. Then, key frames were selected in a path through the vessel, with software interpolation of frames between key frames. A typical movie contained 150 to 300 frames (10 to 15 key frames). Fly-throughs of coronary bypass grafts (n=3), left anterior descending arteries (LAD; n=6), and the intermediate branch (n=1) were reconstructed. Coronary calcifications were seen in 3 patients. The fly-through of the intermediate branch, the bypass grafts, and one of the LADs did not show any irregularities. In 2 cases, a stenosis was visible in the LAD; its presence was confirmed by conventional coronary angiography. CONCLUSIONS: Recent developments in fast-volume rendering using special-purpose hardware in combination with noninvasive coronary angiography with electron beam computed tomography have provided the possibility of performing coronary artery fly-throughs. http://repub.eur.nl/res/pub/9455/ 2000-01-01T00:00:00Z http://repub.eur.nl/res/pub/9461/ 2000-01-01T00:00:00Z 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/9532/ 2000-01-01T00:00:00Z BACKGROUND: There is evidence for a vascular cause of late-life depression. Cerebral white matter lesions are thought to represent vascular abnormalities. White matter lesions have been related to affective disorders and a history of late-onset depression in psychiatric patients. Their relation with mood disturbances in the general population is not known. We investigated the relation between white matter lesions and the presence of depressive symptoms or a history of depression in a population-based study. METHODS: In a sample of 1077 nondemented elderly adults, we assessed the presence and severity of subcortical and periventricular white matter lesions using magnetic resonance imaging, presence of depressive symptoms, and history of depression. Using multiple regression analysis, we examined the relation among white matter lesions, depressive symptoms, and history of depression. RESULTS: Most of the subjects had white matter lesions. Persons with severe white matter lesions (upper quintile) were 3 to 5 times more likely to have depressive symptoms as compared with persons with only mild or no white matter lesions (lowest quintile) (periventricular odds ratio [OR] = 3.3; 95% confidence interval [CI], 1.2-9.5; subcortical OR = 5.4; 95% CI, 1.8-16.5). In addition, persons with severe subcortical but not periventricular white matter lesions were more likely to have had a history of depression with an onset after age 60 years (OR = 3.4; 95% CI, 1.1-10.7) compared with persons with only mild or no white matter lesions. CONCLUSION: The severity of subcortical white matter lesions is related to the presence of depressive symptoms and to a history of late-onset depression. 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. http://repub.eur.nl/res/pub/9169/ 1999-01-01T00:00:00Z Intravenous coronary angiography with electron beam computed tomography (EBCT) allows for the non-invasive visualisation of coronary arteries. With dedicated computer hardware and software, three dimensional renderings of the coronary arteries can be constructed, starting from the individual transaxial tomograms. This article describes image acquisition, postprocessing techniques, and the results of clinical studies. EBCT coronary angiography is a promising coronary artery imaging technique. Currently it is a reasonably robust technique for the visualisation and assessment of the left main and left anterior descending coronary artery. The right and circumflex coronary arteries can be visualised less consistently. Improvements in image acquisition and postprocessing techniques are expected to improve visualisation and diagnostic accuracy of the technique. http://repub.eur.nl/res/pub/8943/ 1998-01-01T00:00:00Z BACKGROUND:-Noninvasive detection of coronary stenoses with electron beam CT (EBCT) after intravenous injection of contrast medium has recently emerged. We sought to determine the diagnostic accuracy of EBCT angiography in the clinical setting using conventional coronary angiography as the "gold standard." METHODS AND RESULTS: Thirty-seven patients (30 men) were investigated. After intravenous injection of 150 mL of contrast medium, 40 to 60 consecutive transaxial tomograms, covering the proximal and middle parts of the coronary arteries, were obtained with ECG triggering at end diastole during breath-holding. Three-dimensional reconstructions of the proximal and middle parts of the arteries were compared with the conventional angiograms. Of the 259 proximal and middle coronary segments, 211 (81%) were analyzable by EBCT. Of the left anterior descending coronary artery (LAD) segments, 95% were assessable. Right coronary artery (RCA) and left circumflex artery (LCx) segments were assessable in 66% and 76%, respectively. Overall sensitivity and specificity to detect a >50% diameter stenosis were 77% and 94%, respectively. This was 82% and 92% for the LAD, 60% and 97% for the RCA, and 83% and 89% for the LCx (all figures based on assessable lesions). CONCLUSIONS: Intravenous EBCT coronary angiography is a promising coronary imaging technique. The technique is not yet robust enough to be an alternative to conventional coronary angiography. It can detect and rule out significant coronary artery disease of the left main proximal and mid portions of the LAD with good accuracy.