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Objective: Recently, CT arthrography (CTa) was introduced as a non-destructive technique to quantitatively measure cartilage quality in human knees. This study investigated whether this is also possible using lower radiation dose CT protocols. Furthermore, we studied the ability of (lower radiation) CTa to distinguish between local sulphated glycosaminoglycan (sGAG) content differences., Design: Of ten human cadaveric knee joints, six CT scans using different radiation doses (81.33-8.13 mGy) were acquired after intra-articular ioxaglate injection. The capability of CTa to measure overall cartilage quality was determined in seven anatomical regions of interest (ROIs), using equilibrium partitioning of an ionic contrast agent using (EPIC)-microCT (μCT) as reference standard for sGAG content. To test the capability of CTa to spatially distinguish between local differences in sGAG content, we calculated the percentage of pixels incorrectly predicted as having high or low sGAG content by the different CTa protocols., Results: Low radiation dose CTa correlated well with EPIC-μCT in large ROIs (R = 0.78; R(2) = 0.61; P < 0.0001). CTa can also distinguish between high and low sGAG content within a single slice. However, the percentage of incorrectly predicted quality pixels increases (from 35% to 41%) when less radiation is used. This makes is hard or even impossible to differentiate between spatial differences in sGAG content in the lowest radiation scans., Conclusions: CTa acquired using low radiation exposure, comparable to a regular knee CT, is able to measure overall cartilage quality. Spatial sGAG distribution can also be determined using CTa, however for this purpose a higher radiation dose is necessary. Nevertheless, radiation dose reduction makes CTa suitable for quantitative analysis of cartilage in clinical research., (Copyright © 2012 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Background and Purpose: Intracranial atherosclerosis is worldwide one of the leading causes of stroke. However, surprisingly little is known about its prevalence and risk factors in a community-dwelling population of white descent. In this study, we determined the prevalence and investigated risk factors of intracranial internal carotid artery calcification (ICAC) as a marker of intracranial atherosclerosis., Methods: To quantify the volume of ICAC, 2495 participants (mean age, 69.6 years) from the population-based Rotterdam Study underwent a nonenhanced computed tomography of the intracranial internal carotid arteries. We calculated the prevalence of ICAC. Next, we defined sex-specific quartiles and defined the upper quartile as severe ICAC. Risk factors of ICAC were investigated by linear and logistic multivariate modeling and were stratified by sex., Results: The overall prevalence of ICAC was 82.2%. The median volume of ICAC was 44 mm3 and was larger in men. Age was independently associated with ICAC in both men and women. In men, excessive alcohol intake and smoking (OR, 1.74 [95% CI, 1.28-2.37] and 1.72 [95% CI, 1.10-2.70]) were strong risk factors of ICAC, whereas diabetes and hypertension were in women (OR, 2.02 [95% CI, 1.29-3.17] and 1.79 [95% CI, 1.20-2.68]). A low high-density-lipoprotein concentration was not associated with ICAC., Conclusions: ICAC is highly prevalent and occurs in over 80% of older, white persons. Conventional cardiovascular risk factors are associated with ICAC, but risk factor profiles differ between men and women.

Objectives: To develop prediction models that better estimate the pretest probability of coronary artery disease in low prevalence populations., Design: Retrospective pooled analysis of individual patient data., Setting: 18 hospitals in Europe and the United States., Participants: Patients with stable chest pain without evidence for previous coronary artery disease, if they were referred for computed tomography (CT) based coronary angiography or catheter based coronary angiography (indicated as low and high prevalence settings, respectively)., Main Outcome Measures: Obstructive coronary artery disease (≥ 50% diameter stenosis in at least one vessel found on catheter based coronary angiography). Multiple imputation accounted for missing predictors and outcomes, exploiting strong correlation between the two angiography procedures. Predictive models included a basic model (age, sex, symptoms, and setting), clinical model (basic model factors and diabetes, hypertension, dyslipidaemia, and smoking), and extended model (clinical model factors and use of the CT based coronary calcium score). We assessed discrimination (c statistic), calibration, and continuous net reclassification improvement by cross validation for the four largest low prevalence datasets separately and the smaller remaining low prevalence datasets combined., Results: We included 5677 patients (3283 men, 2394 women), of whom 1634 had obstructive coronary artery disease found on catheter based coronary angiography. All potential predictors were significantly associated with the presence of disease in univariable and multivariable analyses. The clinical model improved the prediction, compared with the basic model (cross validated c statistic improvement from 0.77 to 0.79, net reclassification improvement 35%); the coronary calcium score in the extended model was a major predictor (0.79 to 0.88, 102%). Calibration for low prevalence datasets was satisfactory., Conclusions: Updated prediction models including age, sex, symptoms, and cardiovascular risk factors allow for accurate estimation of the pretest probability of coronary artery disease in low prevalence populations. Addition of coronary calcium scores to the prediction models improves the estimates.

Background: Whether newer risk markers for coronary heart disease (CHD) improve CHD risk prediction remains unclear., Objective: To assess whether newer risk markers for CHD risk prediction and stratification improve Framingham risk score (FRS) predictions., Design: Prospective population-based study., Setting: The Rotterdam Study, Rotterdam, the Netherlands., Participants: 5933 asymptomatic, community-dwelling participants (mean age, 69.1 years [SD, 8.5])., Measurements: Traditional CHD risk factors used in the FRS (age, sex, systolic blood pressure, treatment of hypertension, total and high-density lipoprotein cholesterol levels, smoking, and diabetes) and newer CHD risk factors (N-terminal fragment of prohormone B-type natriuretic peptide levels, von Willebrand factor antigen levels, fibrinogen levels, chronic kidney disease, leukocyte count, C-reactive protein levels, homocysteine levels, uric acid levels, coronary artery calcium [CAC] scores, carotid intima-media thickness, peripheral arterial disease, and pulse wave velocity)., Results: Adding CAC scores to the FRS improved the accuracy of risk predictions (c-statistic increase, 0.05 [95% CI, 0.02 to 0.06]; net reclassification index, 19.3% overall [39.3% in those at intermediate risk, by FRS]). Levels of N-terminal fragment of prohormone B-type natriuretic peptide also improved risk predictions but to a lesser extent (c-statistic increase, 0.02 [CI, 0.01 to 0.04]; net reclassification index, 7.6% overall [33.0% in those at intermediate risk, by FRS]). Improvements in predictions with other newer markers were marginal., Limitation: The findings may not be generalizable to younger or nonwhite populations., Conclusion: Among 12 CHD risk markers, improvements in FRS predictions were most statistically and clinically significant with the addition of CAC scores. Further investigation is needed to assess whether risk refinements using CAC scores lead to a meaningful change in clinical outcome. Whether to use CAC score screening as a more routine test for risk prediction requires full consideration of the financial and clinical costs of performing versus not performing the test for both persons and health systems., Primary Funding Source: Netherlands Organization for Health Research and Development (ZonMw).

To conduct a comparison of the diagnostic performance of exercise bicycle testing and single-photon emission computed tomography (SPECT) with computed tomography coronary angiography (CTCA) for the detection of obstructive coronary artery disease (CAD) in patients with stable angina. 376 symptomatic patients (254 men, 122 women, mean age 60.4 ± 10.0 years) referred for noninvasive stress testing (exercise bicycle test and/or SPECT) and invasive coronary angiography were included. All patients underwent additional 64-slice CTCA. The diagnostic performance of exercise bicycle testing (ST segment depression), SPECT (reversible perfusion defect) and CTCA (≥50% lumen diameter reduction) was presented as sensitivity, specificity, positive and negative predictive value (PPV and NPV) to detect or rule out obstructive CAD with quantitative coronary angiography as reference standard. Comparisons of exercise bicycle testing versus CTCA (n = 334), and SPECT versus CTCA (n = 61) were performed. The diagnostic performance of exercise bicycle testing was significantly (P value < 0.001) lower compared to CTCA: sensitivity of 76% (95% CI, 71-82) vs. 100% (95% CI, 97-100); specificity of 47% (95% CI, 36-58) vs. 74% (95% CI, 63-82). We observed a PPV of 70% (95% CI, 65-75) vs. 91% (95% CI, 87-94); and NPV of 30% (95%, 25-35) vs. 99% (95%, 90-100). There was a statistically significant difference in sensitivity (P value < 0.05) between SPECT and CTCA: 89% (95% CI, 75-96) vs. 98% (95% CI, 87-100); but not in specificity (P value > 0.05): 77% (95% CI, 50-92) vs. 82% (95% CI, 56-95). We observed a PPV of 91% (95% CI, 77-97) vs. 93% (95% CI, 81-98); and NPV of 72% (95%, 46-89) vs. 93% (95%, 66-100). SPECT and CTCA yielded higher diagnostic performance compared to traditional exercise bicycle testing for the detection and rule out of obstructive CAD in patients with stable angina.

Objectives: This study sought to analyze the natural history of coronary atherosclerosis by multislice computed tomography (MSCT) and assess the serial changes in coronary plaque burden, lumen dimensions, and arterial remodeling., Background: MSCT can comprehensively assess coronary atherosclerosis by combining lumen and plaque size parameters., Methods: Thirty-two patients with acute coronary syndromes underwent 64-slice computed tomography angiography after percutaneous coronary intervention at baseline and after a median of 39 months. All patients received contemporary medical treatment. All available coronary segments in every subject were analyzed. The progression of atherosclerosis per segment and per patient was assessed by means of change in percent atheroma volume (PAV), change in normalized total atheroma volume (TAVnorm), and percent change in TAV (% change in TAV). Serial coronary remodeling was also assessed. Measures of lumen stenosis included percent diameter stenosis (%DS), minimum lumen diameter (MLD), percent area stenosis (%AS), and minimum lumen area (MLA). For each patient, the mean of all matched segments was calculated at the 2 time points. Clinical events at follow-up were documented., Results: The PAV did not change significantly (-0.15 ± 3.64%, p = 0.72). The mean change in TAVnorm was 47.36 ± 143.24 mm(3) (p = 0.071), and the % change in TAV was 6.7% (p = 0.029). The MLD and MLA increased by 0.15 mm (-0.09 to 0.24, p = 0.039) and 0.52 mm(2) (-0.38 to 1.04, p = 0.034) respectively, which was accompanied by vessel enlargement, with 53% of the patients showing expansive positive remodeling. Patients with clinical events had a larger TAVnorm at baseline (969.72 mm(3) vs. 810.77 mm(3), p = 0.010)., Conclusions: MSCT can assess the progression of coronary atherosclerosis and may be used for noninvasive monitoring of pharmacological interventions in coronary artery disease. (, Prospect: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466)., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

The purpose of the study was to show the feasibility of quantification in the case of cell death, cell migration and cell division by parametric MRI. We identify limitations for quantitative cell tracking owing to mixed parallel processes. Various intravoxel SPIO-labeled cell, super paramagnetic iron oxide particles (SPIO) and micron-sized paramagnetic iron oxide (MPIO) particle distributions were prepared by methods mimicking biologically relevant processes (compartmentalization, migration, division and cell death). R(2)* and R(2) relaxometry measurements were performed at 3.0 T; iron concentration was measured by optical emission spectrometry. The effects of spatial distribution and compartmentalization of paramagnetic iron-oxide particles on relaxivity were analyzed. Assessment of R(2)' (R(2)*-R(2)) allowed differentiation between intracellular and extracellular SPIO only if no high-iron-content extracellular particles were present. Relaxivity was sensitive to variations in cell labeling. Samples of the same cell types embedded in the same suspension media at the same cell density produced different relaxivity values, depending on the preparation of the labeled cells. In the case of cell division, a unique relationship between relaxation rate and iron concentration was found, where the relaxivity proved to be independent of initial cell labeling. In case of cell mixing, the cell density could be derived from relaxation values, even if iron concentration was undetermined. We demonstrated that relaxometry does not allow labeled cell quantification when multiple physiological processes such as cell division and cell migration coexist. The measured transversal relaxation rates were sensitive to the labeling technique. However, under special circumstances, despite the numerous limiting factors, quantification of the number of labeled cells by relaxometry was feasible., (Copyright © 2012 John Wiley & Sons, Ltd.)

Objective: Cerebral microbleeds are frequently found in the general elderly population and may reflect underlying vascular disease, but their role in cognitive function is unknown., Methods: We investigated the association between cerebral microbleeds and performance in multiple cognitive domains in 3,979 persons without dementia (mean age, 60.3 years). Mini-Mental State Examination (MMSE) score and neuropsychological tests were used to assess global cognition and the following cognitive domains: memory, information processing speed, executive function, and motor speed. We used number of microbleeds as continuous variable, and additionally distinguished between persons with no microbleeds, 1 microbleed, 2-4 microbleeds, and ≥5 microbleeds. The association of microbleeds with different cognitive domains was estimated using linear regression models. Additional adjustments were made for vascular risk factors, brain atrophy, and other imaging markers of cerebral small vessel disease. We stratified analyses by location of microbleeds., Results: A higher number of microbleeds was associated with lower MMSE score and worse performance on tests of information processing speed and motor speed. When analyzed per category, presence of 5 or more microbleeds was associated with worse performance in all cognitive domains, except memory. These associations were most robust in participants with strictly lobar microbleeds, whereas after additional adjustments associations disappeared for deep or infratentorial microbleeds., Conclusions: Presence of numerous microbleeds, especially in a strictly lobar location, is associated with worse performance on tests measuring cognitive function, even after adjustments for vascular risk factors and other imaging markers of small vessel disease. These results suggest an independent role for microbleed-associated vasculopathy in cognitive impairment.

In the current study cell labeling was performed with water-soluble gadolinium (Gd)-DTPA containing liposomes, to allow for cell tracking by MRI. Liposomes were used to assure a highly concentrated intracellular build up of Gd, aiming to overcome the relatively low MRI sensitivity of Gd (compared to T2 contrast agents). Liposomes were positively charged (cationic) to facilitate uptake by binding to anionic charges in the cell membrane of bone marrow-derived mesenchymal stem cells (MSCs). We determined the cellular Gd load by variations in labeling time (1, 4, and 24 h) and liposome concentration (125, 250, 500, 1000 μM lipid), closely monitoring effects on cell viability, proliferation rate, and differentiation ability. Labeling was both time and dose dependent. Labeling for 4 h was most efficient regarding the combination of processing time and final cellular Gd uptake. Labeling for 4 h with low-dose concentration (125 μM lipid, corresponding to 52 ± 3 μM Gd) yielded an intracellular load of 30 ± 2.5 pg Gd cell(-1), without any effects on cell viability, proliferation, and cell differentiation. Gd liposomes, colabeled with fluorescent dyes, exhibited a prolonged cellular retention, with an endosomal distribution pattern. In vitro assay over 20 days demonstrated a drop in the average Gd load per cell, as a result of mitosis. However, there was no significant change in the sum of the Gd load in all daughter cells at endpoint (20 days), indicating an excellent cellular retention of Gd. MSCs labeled with Gd liposomes were imaged with MRI at both 1.5T and 3.0T, resulting in excellent visualization both in vitro and in vivo. Prolonged in vivo imaging of 500,000 Gd-labeled cells was possible for at least 2 weeks (3.0T). In conclusion, Gd-loaded cationic liposomes (125 μM lipid) are an excellent candidate to label cells, without detrimental effects on cell viability, proliferation, and differentiation, and can be visualized by MRI.

Background: Assessment of tumor size changes is crucial in clinical trials and patient care. We compared imatinib-induced volume changes of liver metastases (LM) from gastro-intestinal stromal tumors (GIST) to RECIST and Choi criteria and their association with overall survival (OS)., Methods: LM from 84 GIST patients (training and validation set) were evaluated using manual and semi-automated Computed Tomography measurements at baseline, after 3, 6 and 12 months of imatinib. The ability of uni-dimensional (1D) and three-dimensional (3D) measurements to detect size changes (increase/decrease) ≥20% was evaluated. Volumetric response cut-offs were derived from minimally relevant changes (+20/-30%) by RECIST, considering lesions as spherical or ellipsoidal., Results: 3D measurements detected size changes ≥20% more frequently than 1D at every time-point (P≤0.008). 3D and Choi criteria registered more responses than RECIST at 3 and 6 months for 3D-spheres (P≤0.03) and at all time-points for 3D-ellipsoids and Choi criteria (P<0.001). Progressive disease by 3D criteria seems to better correlate to OS at late time-points than other criteria., Conclusion: Volume criteria (especially ellipsoids) classify a higher number of patients as imatinib-responders than RECIST. Volume discriminates size changes better than diameter in GIST and constitutes a feasible and robust method to evaluate response and predict patient benefit.

Stem cell therapies hold the great promise and interest for cardiac regeneration among scientists, clinicians and patients. However, advancement and distillation of a standard treatment regimen are not yet finalised. Into this breach step recent developments in the imaging biosciences. Thus far, these technical and protocol refinements have played a critical role not only in the evaluation of the recovery of cardiac function but also in providing important insights into the mechanism of action of stem cells. Molecular imaging, in its many forms, has rapidly become a necessary tool for the validation and optimisation of stem cell engrafting strategies in preclinical studies. These include a suite of radionuclide, magnetic resonance and optical imaging strategies to evaluate non-invasively the fate of transplanted cells. In this review, we highlight the state-of-the-art of the various imaging techniques for cardiac stem cell presenting the strengths and limitations of each approach, with a particular focus on clinical applicability.

Aims: Components of carotid atherosclerotic plaque such as intraplaque haemorrhage and lipid core are important determinants of plaque progression and destabilization. The association between plaque components and risk factors for cardiovascular disease is not well studied., Methods and Results: Participants from the population-based Rotterdam Study with carotid wall thickening on ultrasound (n = 1006) underwent high-resolution magnetic resonance imaging for carotid plaque characterization. Maximum wall thickening, the degree of stenosis, and the presence of intraplaque haemorrhage, lipid core, and calcification were assessed in both carotid arteries and their associations with cardiovascular risk factors were investigated. Intraplaque haemorrhage and lipid core were present in almost 25% of plaques, respectively, and occurred simultaneously in 9% of plaques. In men, intraplaque haemorrhage and lipid core were more prevalent compared with women (28.8 vs. 18.3 and 28.9 vs. 21.7%, respectively). Intraplaque haemorrhage occurred more frequently at older age [odds ratio (OR) per 10 years 1.8, 95% confidence interval 1.6-2.1], in men (OR 2.2, 1.7-2.9), in persons with hypertension (multivariate adjusted OR 1.4, 1.1-1.8), and in current smokers (multivariate adjusted OR 1.6, 1.2-2.3). Men (OR 1.5, 1.2-1.9) and subjects with hypercholesterolaemia (multivariate adjusted OR 1.4, 1.1-1.7) more often exhibited a lipid core., Conclusion: In subjects from the general population with carotid wall thickening, intraplaque haemorrhage and lipid core-both considered indicators of unstable plaque-are highly frequent and more prevalent in men compared with women. Furthermore, different risk factors are associated with these plaque components: hypertension and current smoking were risk factors for the presence of intraplaque haemorrhage, and hypercholesterolaemia was the only risk factor for lipid core presence.

Purpose: To investigate the predictive value of 64-slice computed tomography coronary angiography (CTCA) for major adverse cardiac events (MACEs) in patients with suspected or known coronary artery disease (CAD)., Materials and Methods: Seven hundred and sixty-seven consecutive patients (496 men, age 62±11 y) with suspected or known heart disease referred to an outpatient clinic underwent 64-slice CTCA. The patients were followed for the occurrence of MACE (ie, cardiac death, nonfatal myocardial infarction, unstable angina)., Results: Eleven thousand five hundred and sixty-four coronary segments were assessed. Of these, 178 (1.5%) were not assessable because of insufficient image quality. Overall, CTCA revealed the absence of CAD in 219 (28.5%) patients, nonobstructive CAD (coronary plaque ≤50%) in 282 (36.8%) patients, and obstructive CAD in 266 (34.7%) patients. A total of 21 major cardiac events (4 cardiac deaths, 12 myocardial infarctions, and 5 unstable angina) occurred during a mean follow-up of 20 months. One noncardiac death occurred. Seventeen events occurred in the group of patients with obstructive CAD, and 4 events occurred in the group with nonobstructive CAD. The event rate was 0% among patients with normal coronary arteries at CTCA. In multivariate analysis, the presence of obstructive CAD and diabetes were the only independent predictors of MACE., Conclusions: Coronary plaque evaluation by CTCA provides an independent prognostic value for the prediction of MACE. Patients with normal CTCA findings have an excellent prognosis at follow-up.

Background: Coronary artery calcification (CAC) detected by computed tomography is a noninvasive measure of coronary atherosclerosis, which underlies most cases of myocardial infarction (MI). We sought to identify common genetic variants associated with CAC and further investigate their associations with MI., Methods and Results: Computed tomography was used to assess quantity of CAC. A meta-analysis of genome-wide association studies for CAC was performed in 9961 men and women from 5 independent community-based cohorts, with replication in 3 additional independent cohorts (n=6032). We examined the top single-nucleotide polymorphisms (SNPs) associated with CAC quantity for association with MI in multiple large genome-wide association studies of MI. Genome-wide significant associations with CAC for SNPs on chromosome 9p21 near CDKN2A and CDKN2B (top SNP: rs1333049; P=7.58×10(-19)) and 6p24 (top SNP: rs9349379, within the PHACTR1 gene; P=2.65×10(-11)) replicated for CAC and for MI. Additionally, there is evidence for concordance of SNP associations with both CAC and MI at a number of other loci, including 3q22 (MRAS gene), 13q34 (COL4A1/COL4A2 genes), and 1p13 (SORT1 gene)., Conclusions: SNPs in the 9p21 and PHACTR1 gene loci were strongly associated with CAC and MI, and there are suggestive associations with both CAC and MI of SNPs in additional loci. Multiple genetic loci are associated with development of both underlying coronary atherosclerosis and clinical events.

Objectives: We determined the extent, severity, distribution and type of coronary plaques in cardiac asymptomatic patients with familial hypercholesterolemia (FH) using computed tomography (CT)., Background: FH patients have accelerated progression of coronary artery disease (CAD) with earlier major adverse cardiac events. Non-invasive CT coronary angiography (CTCA) allows assessing the coronary plaque burden in asymptomatic patients with FH., Materials and Methods: A total of 140 asymptomatic statin treated FH patients (90 men; mean age 52 ± 8 years) underwent CT calcium scoring (Agatston) and CTCA using a Dual Source CT scanner with a clinical follow-up of 29 ± 8 months. The extent, severity (obstructive or non-obstructive plaque based on >50% or <50% lumen diameter reduction), distribution and type (calcified, non-calcified, or mixed) of coronary plaque were evaluated., Results: The calcium score was 0 in 28 (21%) of the patients. In 16% of the patients there was no CT-evidence of any CAD while 24% had obstructive disease. In total 775 plaques were detected with CT coronary angiography, of which 11% were obstructive. Fifty four percent of all plaques were calcified, 25% non-calcified and 21% mixed. The CAD extent was related to gender, treated HDL-cholesterol and treated LDL-cholesterol levels. There was a low incidence of cardiac events and no cardiac death occurred during follow-up., Conclusion: Development of CAD is accelerated in intensively treated male and female FH patients. The extent of CAD is related to gender and cholesterol levels and ranges from absence of plaque in one out of 6 patients to extensive CAD with plaque causing >50% lumen obstruction in almost a quarter of patients with FH., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: To compare image quality, radiation dose, and their relationship with heart rate of computed tomographic (CT) coronary angiographic scan protocols by using a 128-section dual-source CT scanner., Materials and Methods: Institutional review board approved the study; all patients gave informed consent. Two hundred seventy-two patients (175 men, 97 women; mean ages, 58 and 59 years, respectively) referred for CT coronary angiography were categorized according to heart rate: less than 65 beats per minute (group A) and 65 beats per minute or greater (group B). Patients were randomized to undergo prospective high-pitch spiral scanning and narrow-window prospective sequential scanning in group A (n = 160) or wide-window prospective sequential scanning and retrospective spiral scanning in group B (n = 112). Image quality was graded (1 = nondiagnostic; 2 = artifacts present, diagnostic; 3 = no artifacts) and compared (Mann-Whitney and Student t tests)., Results: In group A, mean image quality grade was significantly lower with high-pitch spiral versus sequential scanning (2.67 ± 0.38 [standard deviation] vs 2.86 ± 0.21; P < .001). In a subpopulation (heart rate, <55 beats per minute), mean image quality grade was similar (2.81 ± 0.30 vs 2.94 ± 0.08; P = .35). In group B, image quality grade was comparable between sequential and retrospective spiral scanning (2.81 ± 0.28 vs 2.80 ± 0.38; P = .54). Mean estimated radiation dose was significantly lower (high-pitch spiral vs sequential scanning) in group A (for 100 kV, 0.81 mSv ± 0.30 vs 2.74 mSv ± 1.14 [P < .001]; for 120 kV, 1.65 mSv ± 0.69 vs 4.21 mSv ± 1.20 [P < .001]) and in group B (sequential vs retrospective spiral scanning) (for 100 kV, 4.07 mSv ± 1.07 vs 5.54 mSv ± 1.76 [P = .02]; for 120 kV, 7.50 mSv ± 1.79 vs 9.83 mSv ± 3.49 [P = .1])., Conclusion: A high-pitch spiral CT coronary angiographic protocol should be applied in patients with regular and low (<55 beats per minute) heart rates; a sequential protocol is preferred in all others., (© RSNA, 2011.)

Rationale and Objectives: To compare two semiautomated methods for measurement of infarcted myocardium area on delayed contrast enhanced magnetic resonance imaging, with histopathology findings as standard of reference., Materials and Methods: Percentage area of myocardial infarction was measured in 10 Yorkshire landrace pigs manually and using two semiautomated methods. The first (standard deviation method) used two operator-selected regions of interest (ROIs) and nine different cutoff values (one to nine times the standard deviation of signal intensity in normal myocardium) to identify infarction. The second (threshold method) used threshold values based on percentages of maximum signal intensity to identify infarction. Results were compared with histopathology findings., Results: Difference between percentage area of infarction obtained with standard deviation method and autopsy specimens was in the range: -13.5% to +13.2%. With threshold method (thresholds from 30% to 90% of signal intensity), difference was -15% to +23%. Manual contouring underestimated infarcted area by 2% comparing to autopsy results. The best agreement between histopathology and semi-automated software was achieved for 4 standard deviations with standard deviation method: difference -0.45%, and for a percentage threshold of 70% (difference +0.67%) with threshold method. However, with standard deviation method, there was statistically significant difference between ROIs based on their location in viable myocardium: mean difference 1.7 ± 4%, P < .0001., Conclusion: Semiautomated measurement of myocardial infarcted area on delayed enhanced magnetic resonance images performs well compared to autopsy. The threshold method, based on percentages of maximum signal intensity is preferable over standard deviation method, which is more susceptible to variability from location of ROIs within viable myocardium., (Copyright © 2011. Published by Elsevier Inc.)

Background and Purpose: Recently, the first genomewide association study on cerebral white matter lesion burden identified chr17q25 to be significantly associated with white matter lesions. We report on the first independent replication study of this genetic association., Methods: In a population-based cohort study, we investigated the association between the 6 genomewide significant single nucleotide polymorphisms at that locus and cerebral white matter lesion volume on MRI, measured quantitatively, adjusted for age, sex, and intracranial volume. Adjustments for ApoE4 carriership and cardiovascular risk factors were evaluated separately. Finally, we performed a meta-analysis of all published data for the single most significant single nucleotide polymorphism, rs3744028., Results: The risk alleles of all the 6 single nucleotide polymorphisms were significantly associated with white matter lesion volume with P=1.1*10(-3) for rs3744028, adjusted for age, sex, and intracranial volume. Additional adjustments only had minor influence on these associations. A meta-analysis with all published data for rs3744028 resulted in a probability value of 5.3*10(-17)., Conclusions: This study further establishes chr17q25 as a novel genetic locus for WML volume.

Purpose: To evaluate dual energy based methods for bone removal in computed tomography angiography (CTA) images and compare these with single energy based methods that use an additional, nonenhanced, CT scan., Methods: Four different bone removal methods were applied to CT scans of an anthropomorphic thorax phantom, acquired with a second generation dual source CT scanner. The methods differed by the way information on the presence of bone was obtained (either by using an additional, nonenhanced scan or by scanning with two tube voltages at the same time) and by the way the bone was removed from the CTA images (either by masking or subtracting the bone). The phantom contained parts which mimic vessels of various diameters in direct contact with bone. Both a quantitative and qualitative analysis of image quality after bone removal was performed. Image quality was quantified by the contrast-to-noise ratio (CNR) normalized to the square root of the dose (CNRD). At locations where vessels touch bone, the quality of the bone removal and the vessel preservation were visually assessed. The dual energy based methods were assessed with and without the addition of a 0.4 mm tin filter to the high voltage x-ray tube filtration. For each bone removal method, the dose required to obtain a certain CNR after bone removal was compared with the dose of a reference scan with the same CNR but without automated bone removal. The CNRD value of the reference scan was maximized by choosing the lowest tube voltage available., Results: All methods removed the bone completely. CNRD values were higher for the masking based methods than for the subtraction based methods. Single energy based methods had a higher CNRD value than the corresponding dual energy based methods. For the subtraction based dual energy method, tin filtration improved the CNRD value with approximately 50%. For the masking based dual energy method, it was easier to differentiate between iodine and bone when tin filtration was applied. The CNRD value decreased only with 4% in that case. Compared to the dual scan based methods, the dual energy based methods had the advantage that only a single scan was made without the need of image registration. This might be easier to implement in clinical practice. Vessel preservation was better with bone subtraction than with bone masking. Smaller vessels were completely occluded by the bone mask. None of the bone removal methods was dose neutral., Conclusions: In general, dual scan based methods that use the lowest tube voltage available, have a higher CNR than the dual energy based approaches at the same dose level. Tin filtration improves the ability to differentiate between iodine and bone for the dual energy based masking method. In clinical practice, the advantages of the dual energy masking method might outweigh its disadvantage of a slightly higher dose penalty compared to the conventional dual scan masking method.

Objectives: The aim of this study was to assess the (cost-) effectiveness of screening asymptomatic individuals at intermediate risk of coronary heart disease (CHD) for coronary artery calcium with computed tomography (CT)., Background: Coronary artery calcium on CT improves prediction of CHD., Methods: A Markov model was developed on the basis of the Rotterdam Study. Four strategies were evaluated: 1) current practice; 2) current prevention guidelines for cardiovascular disease; 3) CT screening for coronary calcium; and 4) statin therapy for all individuals. Asymptomatic individuals at intermediate risk of CHD were simulated over their remaining lifetime. Quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios were calculated., Results: In men, CT screening was more effective and more costly than the other 3 strategies (CT vs. current practice: +0.13 QALY [95% confidence interval (CI): 0.01 to 0.26], +$4,676 [95% CI: $3,126 to $6,339]; CT vs. statin therapy: +0.04 QALY [95% CI: -0.02 to 0.13], +$1,951 [95% CI: $1,170 to $2,754]; and CT vs. current guidelines: +0.02 QALY [95% CI: -0.04 to 0.09], +$44 [95% CI: -$441 to $486]). The incremental cost-effectiveness ratio of CT calcium screening was $48,800/QALY gained. In women, CT screening was more effective and more costly than current practice (+0.13 QALY [95% CI: 0.02 to 0.28], +$4,663 [95% CI: $3,120 to $6,277]) and statin therapy (+0.03 QALY [95% CI: -0.03 to 0.12], +$2,273 [95% CI: $1,475 to $3,109]). However, implementing current guidelines was more effective compared with CT screening (+0.02 QALY [95% CI: -0.03 to 0.07]), only a little more expensive (+$297 [95% CI: -$8 to $633]), and had a lower cost per additional QALY ($33,072/QALY vs. $35,869/QALY). Sensitivity analysis demonstrated robustness of results in women but considerable uncertainty in men., Conclusions: Screening for coronary artery calcium with CT in individuals at intermediate risk of CHD is probably cost-effective in men but is unlikely to be cost-effective in women., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

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

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

Objective: Similar to delayed gadolinium enhanced MRI of cartilage, it might be possible to image cartilage quality using CT arthrography (CTa). This study assessed the potential of CTa as a clinically applicable tool to evaluate cartilage quality in terms of sulphated glycosaminoglycan content (sGAG) and structural composition of the extra-cellular matrix (ECM)., Methods: Eleven human cadaveric knee joints were scanned on a clinical CT scanner. Of each knee joint, a regular non-contrast CT (ncCT) and an ioxaglate injected CTa scan were performed. Mean X-ray attenuation of both scans was compared to identify contrast influx in seven anatomical regions of interest (ROIs). All ROIs were rescanned with contrast-enhanced μCT, which served as the reference standard for sGAG content. Mean X-ray attenuation from both ncCT and CTa were correlated with μCT results and analyzed with linear regression. Additionally, residual values from the linear fit between ncCT and μCT were used as a covariate measure to identify the influence of structural composition of cartilage ECM on contrast diffusion into cartilage in CTa scans., Results: CTa resulted in higher X-ray attenuation in cartilage compared to ncCT scans for all anatomical regions. Furthermore, CTa correlated excellent with reference μCT values (sGAG) (R=0.86; R(2)=0.73; P<0.0001). When corrected for structural composition of cartilage ECM, this correlation improved substantially (R=0.95; R(2)=0.90; P<0.0001)., Conclusions: Contrast diffusion into articular cartilage detected with CTa correlates with sGAG content and to a lesser extent with structural composition of cartilage ECM. CTa may be clinically applicable to quantitatively measure the quality of articular cartilage., (Copyright © 2011 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study was to evaluate the role of MRI in the diagnosis and differential diagnosis of urethral diverticula in symptomatic women., Materials and Methods: Women referred for MRI at a single institution because of suspicion of urethral diverticula were included. All MRI examinations were independently evaluated by two radiologists and compared with patients' follow-up data. Sensitivity and specificity of MRI for urethral diverticula were calculated using surgery and clinical confirmation as the reference standards. Image quality of the urethra and periurethral region performed with the endoluminal coil was compared with the pelvic phased-array coil., Results: From a study group of 60 patients (mean age, 44 years), 20 patients (33%) had urethral diverticula and 28 (47%) had an alternative diagnosis, of which 13 (46%) were visualized with MRI. In the remaining 12 patients (20%) no abnormalities were found. For urethral diverticula, MRI had both sensitivity and specificity of 100%. Twenty patients had a total of 27 diverticula; these were mostly locally round (n = 12) with sharp margins (n = 25) and high (n = 19) homogeneous (n = 16) signal intensity on T2-weighted sequences. The ostium of urethral diverticula was identified in 23 diverticula (85%) by both readers. Agreement was 93% with κ = 0.72. Endoluminal coil placement in the vagina showed the best image quality of the urethra and periurethral region., Conclusion: Dedicated MRI is an excellent imaging modality for urethral diverticula; furthermore, MRI will show the alternative diagnosis in almost one half of the remaining patients.

Background: To investigate the causes of paravalvular aortic regurgitation (PAR) after the implantation of the Medtronic CoreValve prosthesis (MCRS)., Methods and Results: Fifty-six patients underwent MSCT before TAVI with a MCRS and PAR was assessed with transthoracic echocardiography (TTE) between 5 and 10 days after TAVI. The aortic annulus smallest and largest orthogonal diameters and the mean diameter from the area were determined on MSCT on an axial image at the nadir of all three native leaflets. PAR was related to relevant anatomical structures on MSCT according to a clockface in the orientation of the parasternal short axis view on TTE. PAR ≥ 1 was present in 25% of the patients and was associated with a larger annulus, a lower degree of over sizing and with more aortic root calcification. On MSCT post TAVI malapposition was seen predominantly at the aorto-mitral fibrous continuity and the aspect of the largest diameter of the aortic annulus on the inside curve of the ascending aorta. PAR was predominantly seen at these two anatomic locations and less frequent in the area that contains the ventricular membranous septum and the area between the non- and right coronary sinus., Conclusions: Mild to moderate PAR is common after TAVI with the MCRS. The availability of additional (larger) prosthesis sizes in combination with improved sizing based on mean annulus diameter (e.g., D(CSA)) may help to reduce PAR., (Copyright © 2011 Wiley-Liss, Inc.)

This paper describes an evaluation framework that allows a standardized and objective quantitative comparison of carotid artery lumen segmentation and stenosis grading algorithms. We describe the data repository comprising 56 multi-center, multi-vendor CTA datasets, their acquisition, the creation of the reference standard and the evaluation measures. This framework has been introduced at the MICCAI 2009 workshop 3D Segmentation in the Clinic: A Grand Challenge III, and we compare the results of eight teams that participated. These results show that automated segmentation of the vessel lumen is possible with a precision that is comparable to manual annotation. The framework is open for new submissions through the website http://cls2009.bigr.nl., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We investigated the development of pulmonary lesions in ferrets by means of computed tomography (CT) following infection with the 2009 pandemic A/H1N1 influenza virus and compared the scans with gross pathology, histopathology and immunohistochemistry. Ground-glass opacities observed by CT scanning in all infected lungs corresponded to areas of alveolar oedema at necropsy. These areas were most pronounced on day 3 and gradually decreased from days 4 to 7 post-infection. This pilot study shows that the non-invasive imaging procedure allows quantification and characterization of influenza-induced pulmonary lesions in living animals under biosafety level 3 conditions and can thus be used in pre-clinical pharmaceutical efficacy studies.

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

Objective: To determine the calcium score and coronary plaque burden in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH) compared with a control group of patients with low probability of coronary artery disease, having non-anginal chest pain, using CT., Design, Setting and Patients: 101 asymptomatic patients with FH (mean age 53 ± 7 years; 62 men) and 126 patients with non-anginal chest pain (mean age 56 ± 7 years; 80 men) underwent CT calcium scoring and CT coronary angiography. All patients with FH were treated with statins during a period of 10 ± 8 years before CT. The coronary calcium score and plaque burden were determined and compared between the two patient groups., Results: The median total calcium score was significantly higher in patients with FH (Agatston score = 87, IQR 5-367) than in patients with non-anginal chest pain (Agatston score = 7, IQR 0-125; p < 0.001). The overall coronary plaque burden was significantly higher in patients with FH (p < 0.01). Male patients with FH, whose low-density lipoprotein cholesterol levels were reduced by statins below 3.0 mmol/l, had significantly less coronary calcium (p < 0.01) and plaque burden (p = 0.02)., Conclusion: The coronary plaque burden is high in asymptomatic middle-aged patients with FH despite intense statin treatment.

Background: There are physiological reasons for the effects of positioning on hemodynamic variables and cardiac dimensions related to altered intra-abdominal and intra-thoracic pressures. This problem is especially evident in pregnant women due to the additional aorto-caval compression by the enlarged uterus. The purpose of this study was to investigate the effect of postural changes on cardiac dimensions and function during mid and late pregnancy using cardiovascular magnetic resonance (CMR)., Methods: Healthy non-pregnant women, pregnant women at 20th week of gestation and at 32nd week of gestation without history of cardiac disease were recruited to the study and underwent CMR in supine and left lateral positions. Cardiac hemodynamic parameters and dimensions were measured and compared between both positions., Results: Five non-pregnant women, 6 healthy pregnant women at mid pregnancy and 8 healthy pregnant women at late pregnancy were enrolled in the study. In the group of non-pregnant women left ventricular (LV) cardiac output (CO) significantly decreased by 9% (p=0.043) and right ventricular (RV) end-diastolic volume (EDV) significantly increased by 5% (p=0.043) from the supine to the left lateral position. During mid pregnancy LV ejection fraction (EF), stroke volume (SV), left atrium lateral diameter and left atrial supero-inferior diameter increased significantly from the supine position to the left lateral position: 8%, 27%, 5% and 11%, respectively (p<0.05). RV EDV, SV and right atrium supero-inferior diameter significantly increased from the supine to the left lateral position: 25%, 31% and 13% (p<0.05), respectively. During late pregnancy a significant increment of LV EF, EDV, SV and CO was observed in the left lateral position: 11%, 21%, 35% and 24% (p<0.05), respectively. Left atrial diameters were significantly larger in the left lateral position compared to the supine position (p<0.05). RV CO was significantly increased in the left lateral position compared to the supine position (p<0.05)., Conclusions: During pregnancy positional changes affect significantly cardiac hemodynamic parameters and dimensions. Pregnant women who need serial studies by CMR should be imaged in a consistent position. From as early as 20 weeks the left lateral position should be preferred on the supine position because it positively affects venous return, SV and CO.

Aims: The aim was to validate, update, and extend the Diamond-Forrester model for estimating the probability of obstructive coronary artery disease (CAD) in a contemporary cohort., Methods and Results: Prospectively collected data from 14 hospitals on patients with chest pain without a history of CAD and referred for conventional coronary angiography (CCA) were used. Primary outcome was obstructive CAD, defined as ≥ 50% stenosis in one or more vessels on CCA. The validity of the Diamond-Forrester model was assessed using calibration plots, calibration-in-the-large, and recalibration in logistic regression. The model was subsequently updated and extended by revising the predictive value of age, sex, and type of chest pain. Diagnostic performance was assessed by calculating the area under the receiver operating characteristic curve (c-statistic) and reclassification was determined. We included 2260 patients, of whom 1319 had obstructive CAD on CCA. Validation demonstrated an overestimation of the CAD probability, especially in women. The updated and extended models demonstrated a c-statistic of 0.79 (95% CI 0.77-0.81) and 0.82 (95% CI 0.80-0.84), respectively. Sixteen per cent of men and 64% of women were correctly reclassified. The predicted probability of obstructive CAD ranged from 10% for 50-year-old females with non-specific chest pain to 91% for 80-year-old males with typical chest pain. Predictions varied across hospitals due to differences in disease prevalence., Conclusion: Our results suggest that the Diamond-Forrester model overestimates the probability of CAD especially in women. We updated the predictive effects of age, sex, type of chest pain, and hospital setting which improved model performance and we extended it to include patients of 70 years and older.

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

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.

Radiological interpretation and reporting have become a commodity that may be farmed out elsewhere on the planet: teleradiology. The impact of this development fully depends on our understanding of the role of radiology as a specialty. If radiology is solely defined as the provision of medical image interpretation then commoditization of radiology through teleradiology services will lead to a deterioration in the status of radiologists. They may even become redundant as hospital specialists. However, if radiology is seen in a broader context with much more emphasis on its added value through specialized consultancy, then teleradiology may be an important instrument for improvement and optimalisation of imaging services.

Objective: To assess the influence of sex on the diagnostic performance of computed tomography coronary angiography (CTCA)., Methods: A total of 916 symptomatic patients (30.5% women) without earlier history of coronary artery intervention underwent both CTCA and invasive coronary angiography. Descriptive diagnostic parameters, to detect obstructive coronary artery disease (CAD; ≥ 50% lumen diameter narrowing) on CTCA, were compared between women and men on a per-patient, per-vessel, and per-segment level. Adjusted values were calculated for clustered segments and differences in sex variables using logistic multivariate regression models in general estimated equations., Results: Women were older, had less typical chest complaints, and had a lower prevalence, extent, and severity of CAD compared with men. Multivariate analysis on a per-patient level revealed no difference in sensitivity (98 vs. 99%, P=0.15), specificity (78 vs. 82%, P=0.65), positive predictive value (PPV; 87 vs. 95%, P=0.10), negative predictive value (NPV; 97 vs. 98%, P=0.63), and diagnostic odds ratio (DOR; 198 vs. 721, P=0.07). No difference was found on per-vessel level analysis (sensitivity 95 vs. 97%, P=0.14; specificity 89 vs. 87%, P=0.93; PPV 73 vs. 79%, P=0.06; NPV 98 vs. 98%, P=0.72; and DOR 143 vs. 240, P=0.08). Per-segment analysis revealed a lower sensitivity (88 vs. 94%, P<0.001) and DOR (163 vs. 302, P=0.002) in women compared with men, without a difference in specificity (96 vs. 95%, P=0.19), PPV (64 vs. 69%, P=0.07), and NPV (99 vs. 99%, P=0.08)., Conclusion: CTCA can accurately rule out obstructive CAD in both women and men. CTCA is less accurate in women to detect individual obstructive disease.

Objective: Multidetector computed tomography (MDCT), which has been mainly used to study coronary atherosclerosis, also enables non-invasive measurement of carotid and aortic atherosclerosis and might be suitable for screening in the general population. The aim of this study was to investigate the associations of carotid artery, aortic arch and coronary artery calcification as assessed by MDCT, with presence of stroke., Methods: The study was embedded in the population-based Rotterdam Study and comprises 2521 persons (mean age 69.7±6.8 years, 48% males) that underwent an MDCT scan. History of stroke was reported by 96 persons. We used multivariable logistic regression to investigate the associations of calcification in the carotid arteries, aortic arch, and coronary arteries with presence of stroke., Results: We found strong and graded associations of prevalent stroke with carotid artery (OR quartile 4 versus 1 (95% CI): 5.0 (2.2-11.0)), aortic arch (3.3 (1.5-7.4)) and coronary artery calcification (3.1 (1.3-7.3)), independent of cardiovascular risk factors. Only the association of carotid artery calcification with presence of stroke was independent of calcification in the other two vessel beds., Conclusion: In this population-based study, we found a strong and graded association of prevalent stroke with carotid artery, aortic arch and coronary artery calcification, independent of cardiovascular risk factors. After additional adjustment for calcification in the other vessel beds, prevalent stroke was still significantly related to carotid calcification, but no longer to aortic arch or coronary calcification., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

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

The treatment of coronary artery stenosis has progressively shifted over the past decades, from surgical (CABG) to percutaneous (PCI and stenting). The recent introduction of drug-eluting stents further reduced the occurrence of in-stent re-stenosis (ISR). However, a non-negligible number of patients need imaging/functional tests when symptoms recur. Multi-Slice CT Coronary Angiography (CT-CA) is a clinical reality for the evaluation of coronary artery stenosis, but still under evaluation in the follow-up of coronary stents. Several factors may impair proper depiction of in-stent lumen even with the most recent CT equipments. In highly selected populations CT-CA may play a clinical role even though the performance requirements both from the technical standpoint (i.e., CT scanner) and from the training (i.e., operators' experience) are still very demanding. In the meantime CT technology should improve towards higher contrast, spatial and temporal resolution in order to achieve the results that may be proper for clinical implementation.

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 12.5 µg iron/2 ml/9.5 cm(2) and an incubation time of 24 h, resulting in an average iron load of 12.0 pg iron/per cell (uptake efficiency of 9.6%). At 4 h 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 50 µg iron/2 ml/9.5 cm(2). Incubation time was of less importance since most of the particles were already incorporated within 4 h with a 100% labeling efficiency, resulting in an intracellular iron load of 626 pg/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., (Copyright © 2010 John Wiley & Sons, Ltd.)

Aims: Whereas transthoracic echocardiography is the modality of choice for the diagnosis of severe aortic stenosis and cine-fluoroscopy is used to guide the implantation of the TAVI prosthesis, we believe that multislice computer tomography (MSCT) is the modality of choice for evaluation of the aortic root with a view to selecting patients with suitable anatomy and to guide sizing. We aim to describe an anatomical approach for the step by step interrogation of a 3D MSCT dataset to obtain the measurements of the aortic root required for patient selection, sizing and selection of the optimal angulation of the C-arm during the implantation procedure., Methods and Results: The landmarks used to anatomically define the aortic annulus and structures of the aortic root may be used to define the same structures for measurement on a 3D MSCT dataset by setting up orthogonal cut-planes including one axial to the aortic annulus. This allows true axial diameter measurements and also enables us to define the valve plane., Conclusions: Measurement on the axial images avoids incorrect diameter measurements that do not pass through the central axis.

Objectives: This study sought to quantify contractile reserve of chronic dysfunctional myocardium, in particular in segments with intermediate transmural extent of infarction (TEI), using low-dose dobutamine cardiac magnetic resonance (CMR) in patients with a chronic total coronary occlusion (CTO)., Background: Recovery of dysfunctional segments with intermediate TEI after percutaneous coronary intervention is variable and difficult to predict, and may be related to contractility of the unenhanced rim., Methods: Fifty-one patients (mean age 60 +/- 9 years, 76% male) with a CTO underwent CMR at baseline and 35 patients underwent CMR at follow-up to quantify segmental wall thickening (SWT) at rest during 5 and 10 microg/kg/min dobutamine, and at follow-up. Delayed-enhancement CMR was performed to quantify TEI. Dysfunctional segments were stratified according to TEI, end-diastolic wall thickness (EDWT), or unenhanced rim thickness, and SWT was quantified. Segments with an intermediate TEI (25% to 75%) were further stratified according to baseline SWT of the unenhanced rim (SWT(UR)) (<45% and >45%), and SWT was quantified. For each parameter, odds ratio (OR) and diagnostic performance for the prediction of contractile reserve were calculated., Results: Significant contractile reserve was present in dysfunctional segments with EDWT >6 mm, unenhanced rim thickness >3 mm, or TEI of <25%; only TEI had significant relation with contractile reserve (OR: 0.98; 95% confidence interval [CI]: 0.96 to 0.99; p = 0.02). In segments with intermediate TEI (n = 58), mean SWT did not improve significantly. However, segments with SWT(UR) <45% showed contractile reserve and improved at follow-up, whereas segments with SWT(UR) >45% were unchanged. SWT(UR) had a significant relation with contractile reserve (OR: 0.98; 95% CI: 0.97 to 0.99; p = 0.02)., Conclusions: CMR quantification of transmurality of infarcted myocardium allows the assessment of the potential of dysfunctional segments to improve in function during dobutamine of most segments. However, in segments with intermediate TEI, measurement of baseline contractility of the epicardial rim better identifies which segments maintain contractile reserve., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Computed tomography coronary angiography (CTCA) has become a popular noninvasive test for diagnosing coronary artery disease., Objective: To compare the accuracy and clinical utility of stress testing and CTCA for identifying patients who require invasive coronary angiography (ICA)., Design: Observational study., Setting: University medical center in Rotterdam, the Netherlands., Patients: 517 patients referred by their treating physicians for evaluation of chest symptoms by using stress testing or ICA., Intervention: Stress testing and CTCA in all patients., Measurements: Diagnostic accuracy of stress testing and CTCA compared with ICA; pretest probabilities of disease by Duke clinical score; and clinical utility of noninvasive testing, defined as a pretest or posttest probability that suggests how to proceed with testing (no further testing if < or =5%, proceed with ICA if between 5% and 90%, and refer directly for ICA if > or =90%)., Results: Stress testing was not as accurate as CTCA; CTCA sensitivity approached 100%. In patients with a low (<20%) pretest probability of disease, negative stress test or CTCA results suggested no need for ICA. In patients with an intermediate (20% to 80%) pretest probability, a positive CTCA result suggested need to proceed with ICA (posttest probability, 93% [95% CI, 92% to 93%]) and a negative result suggested no need for further testing (posttest probability, 1% [CI, 1% to 1%]). Physicians could proceed directly with ICA in patients with a high (>80%) pretest probability (91% [CI, 90% to 92%])., Limitations: Referral and verification bias might have influenced findings. Stress testing provides functional information that may add value to that from anatomical (CTCA or ICA) imaging., Conclusion: Computed tomography coronary angiography seems most valuable in patients with intermediate pretest probability of disease, because the test can distinguish which of these patients need invasive angiography. These findings need to be confirmed before CTCA can be routinely recommended for these patients.

Purpose: To retrospectively evaluate renal, vascular, and urinary tract visualization following a single postcontrast multidetector computed tomographic (CT) urographic sequence performed with three limited-volume bolus injections., Materials and Methods: The institutional review board approved this retrospective study. Patient informed consent was waived. Triple-bolus multidetector CT urography was performed in 110 patients. Triple-bolus protocol consisted of 30 mL of contrast material at 2 mL/sec at 0 seconds, 50 mL at 1.5 mL/sec at 435 seconds, 65 mL at 3 mL/sec at 488 seconds, with total abdominal scanning time of 510 seconds. Two independent readers rated urinary tract opacification and qualitatively and quantitatively assessed renal parenchymal and vascular contrast enhancement. Upper urinary tract (UUT) distention was measured by one reader. Interobserver agreement was assessed by using kappa statistics., Results: Complete opacification of the intrarenal collecting system and proximal ureter was achieved in 91% (184 of 202) (kappa = 0.62) and 82% (166 of 202) (kappa = 0.94) of segments, respectively. The distal ureter was not opacified in 21% of the cases (kappa = 0.92), and the bladder was not opacified in 20% of the cases. Mean distention was higher for proximal (3.9 mm) than for distal (3.7 mm) segments. Image quality of renal parenchymal enhancement was excellent in 76% of cases. Arteries showed better contrast enhancement than veins (excellent rating in 89% vs 59% of the cases). Radiation dose calculated for triple-bolus acquisition was 9.8 mSv., Conclusion: Triple-bolus multidetector CT urography is a dose-efficient protocol acquiring corticomedullary-nephrographic-excretory and vascular enhancement phases in a single acquisition and provides sufficient opacification and distention of the UUT. Simultaneously, adequate image quality of renal parenchyma and vascular anatomy is achieved.

Objectives: The aim of the study was to compare the coronary artery calcium score (CACS) and computed tomography coronary angiography (CTCA) for the assessment of non-obstructive/obstructive coronary artery disease (CAD) in high-risk asymptomatic subjects., Methods: Two hundred and thirteen consecutive asymptomatic subjects (113 male; mean age 53.6 +/- 12.4 years) with more than one risk factor and an inconclusive or unfeasible non-invasive stress test result underwent CACS and CTCA in an outpatient setting. All patients underwent conventional coronary angiography (CAG). Data from CACS (threshold for positive image: Agatston score 1/100/1,000) and CTCA were compared with CAG regarding the degree of CAD (non-obstructive/obstructive; or=50% lumen reduction)., Results: The mean calcium score was 151 +/- 403 and the prevalence of obstructive CAD was 17% (8% one-vessel and 10% two-vessel disease). Per-patient sensitivity, specificity, positive and negative predictive values of CACS were: 97%, 75%, 45%, and 100%, respectively (Agatston >or=1); 73%, 90%, 60%, and 94%, respectively (Agatston >or=100); 30%, 98%, 79%, and 87%, respectively (Agatston >or=1,000). Per-patient values for CTCA were 100%, 98%, 97%, and 100%, respectively (p < 0.05). CTCA detected 65% prevalence of all CAD (48% non-obstructive), while CACS detected 37% prevalence of all CAD (21% non-obstructive) (p < 0.05)., Conclusion: CACS proved inadequate for the detection of obstructive and non-obstructive CAD compared with CTCA. CTCA has a high diagnostic accuracy for the detection of non-obstructive and obstructive CAD in high-risk asymptomatic patients with inconclusive or unfeasible stress test results.

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

Purpose: This study was undertaken to evaluate the diagnostic accuracy of computed tomography coronary angiography (CT-CA) for the detection of significant coronary artery stenosis (> or =50% lumen reduction) compared with conventional coronary angiography (CCA) in a registry and to review major multicentre trials., Materials and Methods: A total of 1,372 patients (882 men, 490 women; mean age 59.3+/-11.9 years) in sinus rhythm were studied with CT-CA (64-slice technology) and CCA. The diagnostic accuracy of CT-CA was evaluated against quantitative CCA as a reference standard for coronary artery stenosis. Positive and negative likelihood ratios and inter- and intraobserver agreement were calculated., Results: The prevalence of disease was 53%. CCA demonstrated the absence of significant coronary artery disease in 46.6% (639/1372), single-vessel disease in 24.7% (337/1372) and multivessel disease in 28.9% (396/1372) of patients. In per-patient analysis sensitivity, specificity and positive and negative predictive value of CT-CA were 99% [confidence interval (CI) 97-99], 92% (CI 89-94), 94% (CI 91-95) and 99% (CI 97-99), respectively. Per-patient and per-segment likelihood ratios (LR+=12.4 and LR-=0.011; LR+=18.3 and LR-=0.064, respectively), were good. Inter- and intraobserver variability was 0.78 and 0.85, respectively., Conclusions: CT-CA is a reliable diagnostic modality both in terms of sensitivity and negative predictive value. Differences in trial results are also due to the different parameters used for patient inclusion.