Genicular artery embolization as a novel treatment for mild to moderate knee osteoarthritis: protocol design of a randomized sham-controlled clinical trial.

INTRODUCTION: Knee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis. METHODS AND ANALYSIS: Fifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions. ETHICS AND DISSEMINATION: This trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT03884049. Registered on 21 March 2019.

Compressed Sensing 3D-GRASE for faster High-Resolution MRI.

PURPOSE: High-resolution three-dimensional (3D) structural MRI is useful for delineating complex or small structures of the body. However, it requires long acquisition times and high SAR, limiting its clinical use. The purpose of this work is to accelerate the acquisition of high-resolution images by combining compressed sensing and parallel imaging (CSPI) on a 3D-GRASE sequence and to compare it with a (CS)PI 3D-FSE sequence. Several sampling patterns were investigated to assess their influence on image quality. METHODS: The proposed k-space sampling patterns are based on two undersampled k-space grids, variable density (VD) Poisson-disc, and VD pseudo-random Gaussian, and five different trajectories described in the literature. Bloch simulations are performed to obtain the transform point spread function and evaluate the coherence of each sampling pattern. Image resolution was assessed by the full-width at half-maximum (FWHM). Prospective CSPI 3D-GRASE phantom and in vivo experiments in knee and brain are carried out to assess image quality, SNR, SAR, and acquisition time compared to PI 3D-GRASE, PI 3D-FSE, and CSPI 3D-FSE acquisitions. RESULTS: Sampling patterns with VD Poisson-disc obtain the lowest coherence for both PD-weighted and T2 -weighted acquisitions. VD pseudo-random Gaussian obtains lower FWHM, but higher sidelobes than VD Poisson-disc. CSPI 3D-GRASE reduces acquisition time (43% for PD-weighted and 40% for T2 -weighted) and SAR (∼45% for PD-weighted and T2 -weighted) compared to CSPI 3D-FSE. CONCLUSIONS: CSPI 3D-GRASE reduces acquisition time compared to a CSPI 3DFSE acquisition, preserving image quality. The design of the sampling pattern is crucial for image quality in CSPI 3D-GRASE image acquisitions.

Carotid Plaque Morphology and Ischemic Vascular Brain Disease on MRI.

BACKGROUND AND PURPOSE: Vulnerable carotid plaque components are reported to increase the risk of cerebrovascular events. Yet, the relation between plaque composition and subclinical ischemic brain disease is not known. We studied, in the general population, the association between carotid atherosclerotic plaque characteristics and ischemic brain disease on MR imaging. MATERIALS AND METHODS: From the population-based Rotterdam Study, 951 participants underwent both carotid MR imaging and brain MR imaging. The presence of intraplaque hemorrhage, lipid core, and calcification and measures of plaque size was assessed in both carotid arteries. The presence of plaque characteristics in relation to lacunar and cortical infarcts and white matter lesion volume was investigated and adjusted for cardiovascular risk factors. Stratified analyses were conducted to explore effect modification by sex. Additional analyses were conducted per carotid artery in relation to vascular brain disease in the ipsilateral hemisphere. RESULTS: Carotid intraplaque hemorrhage was significantly associated with the presence of cortical infarcts (OR, 1.9; 95% confidence interval, 1.1-3.3). None of the plaque characteristics were related to the presence of lacunar infarcts. Calcification was the only characteristic that was associated with higher white matter lesion volume. There was no significant interaction by sex. CONCLUSIONS: The presence of carotid intraplaque hemorrhage on MR imaging is independently associated with MR imaging-defined cortical infarcts, but not with lacunar infarcts. Plaque calcification, but not vulnerable plaque components, is related to white matter lesion volume.

Influence of delayed gadolinium enhanced MRI of cartilage (dGEMRIC) protocol on T2-mapping: is it possible to comprehensively assess knee cartilage composition in one post-contrast MR examination at 3 Tesla?

OBJECTIVE: To evaluate the possibility of assessing knee cartilage with T2-mapping and delayed gadolinium enhanced magnetic resonance imaging (MRI) of cartilage (dGEMRIC) in one post-contrast MR examination at 3 Tesla (T). DESIGN: T2 mapping was performed in 10 healthy volunteers at baseline; directly after baseline; after 10 min of cycling; and after 90 min delay, and in 16 osteoarthritis patients before and after intravenous administration of a double dose gadolinium dimeglumine contrast agent, reflecting key dGEMRIC protocol elements. Differences in T2 relaxation times between each timepoint and baseline were calculated for 6 cartilage regions using paired t tests or Wilcoxon signed-rank tests and the smallest detectable change (SDC). RESULTS: After cycling, a significant change in T2 relaxation times was found in the lateral weight-bearing tibial plateau (+1.0 ms, P = 0.04). After 90 min delay, significant changes were found in the lateral weight-bearing femoral condyle (+1.2 ms, P = 0.03) and the lateral weight-bearing tibial plateau (+1.3 ms, P = 0.01). In these regions of interests (ROIs), absolute differences were small and lower than the corresponding SDCs. T2-mapping after contrast administration only showed statistically significantly lower T2 relaxation times in the medial posterior femoral condyle (-2.4 ms, P < 0.001) with a change exceeding the SDC. CONCLUSION: Because dGEMRIC protocol elements resulted in only small differences in T2 relaxation times that were not consistent and lower than the SDC in the majority of regions, our results suggest that T2-mapping and dGEMRIC can be performed reliably in a single imaging session to assess cartilage biochemical composition in knee osteoarthritis (OA) at 3 T.

Quantitative in vivo CT arthrography of the human osteoarthritic knee to estimate cartilage sulphated glycosaminoglycan content: correlation with ex-vivo reference standards.

OBJECTIVE: Recently, computed tomography arthrography (CTa) was introduced as quantitative imaging biomarker to estimate cartilage sulphated glycosaminoglycan (sGAG) content in human cadaveric knees. Our aim was to assess the correlation between in vivo CTa in human osteoarthritis (OA) knees and ex vivo reference standards for sGAG and collagen content. DESIGN: In this prospective observational study 11 knee OA patients underwent CTa before total knee replacement (TKR). Cartilage X-ray attenuation was determined in six cartilage regions. Femoral and tibial cartilage specimens harvested during TKR were re-scanned using equilibrium partitioning of an ionic contrast agent with micro-CT (EPIC-µCT), which served as reference standard for sGAG. Next, cartilage sGAG and collagen content were determined using dimethylmethylene blue (DMMB) and hydroxyproline assays. The correlation between CTa X-ray attenuation, EPIC-µCT X-ray attenuation, sGAG content and collagen content was assessed. RESULTS: CTa X-ray attenuation correlated well with EPIC-µCT (r = 0.76, 95% credibility interval (95%CI) 0.64 to 0.85). CTa correlated moderately with the DMMB assay (sGAG content) (r = -0.66, 95%CI -0.87 to -0.49) and to lesser extent with the hydroxyproline assay (collagen content) (r = -0.56, 95%CI -0.70 to -0.36). CONCLUSIONS: Outcomes of in vivo CTa in human OA knees correlate well with sGAG content. Outcomes of CTa also slightly correlate with cartilage collagen content. Since outcomes of CTa are mainly sGAG dependent and despite the fact that further validation using hyaline cartilage of other joints with different biochemical composition should be conducted, CTa may be suitable as quantitative imaging biomarker to estimate cartilage sGAG content in future clinical OA research.

Choice of diffusion tensor estimation approach affects fiber tractography of the fornix in preterm brain.

BACKGROUND AND PURPOSE: Neonatal DTI enables quantitative assessment of microstructural brain properties. Although its use is increasing, it is not widely known that vast differences in tractography results can occur, depending on the diffusion tensor estimation methodology used. Current clinical work appears to be insufficiently focused on data quality and processing of neonatal DTI. To raise awareness about this important processing step, we investigated tractography reconstructions of the fornix with the use of several estimation techniques. We hypothesized that the method of tensor estimation significantly affects DTI tractography results. MATERIALS AND METHODS: Twenty-eight DTI scans of infants born <29 weeks of gestation, acquired at 30-week postmenstrual age and without intracranial injury observed, were prospectively collected. Four diffusion tensor estimation methods were applied: 1) linear least squares; 2) weighted linear least squares; 3) nonlinear least squares, and 4) robust estimation of tensors by outlier rejection. Quality of DTI data and tractography results were evaluated for each method. RESULTS: With nonlinear least squares and robust estimation of tensors by outlier rejection, significantly lower mean fractional anisotropy values were obtained than with linear least squares and weighted linear least squares. Visualized quality of tract reconstruction was significantly higher by use of robust estimation of tensors by outlier rejection and correlated with quality of DTI data. CONCLUSIONS: Quality assessment and choice of processing methodology have considerable impact on neonatal DTI analysis. Dedicated acquisition, quality assessment, and advanced processing of neonatal DTI data must be ensured before performing clinical analyses, such as associating microstructural brain properties with patient outcome.

In vivo MRI mapping of iron oxide-labeled stem cells transplanted in the heart.

In various stem cell therapy approaches poor cell survival has been recognized as an important factor limiting therapeutic efficacy. Therefore noninvasive monitoring of cell fate is warranted for developing clinically effective stem cell therapy. In this study we investigated the use of voxel-based R2 mapping as a tool to monitor the fate of iron oxide-labeled cells in the myocardium. Mesenchymal stem cells were transduced with the luciferase gene, labeled with ferumoxide particles and injected in the myocardium of healthy rats. Cell fate was monitored over a period of 8 weeks by bioluminescence and quantitative magnetic resonance imaging. Bioluminescence signal increased during the first week followed by a steep decrease to undetectable levels during the second week. MR imaging showed a sharp increase in R2 values shortly after injection at the injection site, followed by a very gradual decrease of R2 over a period of 8 weeks. No difference in the appearances on R2-weighted images was observed between living and dead cells over the entire time period studied. No significant correlation between the bioluminescence optical data and R2 values was observed and quantitative R2 mapping appeared not suitable for the in vivo assessment of stem cell. These results do not follow previous in vitro reports where it was proposed that living cells may be distinguished from dead cells on the basis of the R2 relaxivities (intracellular and extracellular iron oxides). Cell proliferation, cell migration, cell death, extracellular superparamagnetic iron oxide dispersion and aggregation exhibit different relaxivities. In vivo these processes happen simultaneously, making quantification very complex, if not impossible.

Standardized evaluation framework for evaluating coronary artery stenosis detection, stenosis quantification and lumen segmentation algorithms in computed tomography angiography.

Though conventional coronary angiography (CCA) has been the standard of reference for diagnosing coronary artery disease in the past decades, computed tomography angiography (CTA) has rapidly emerged, and is nowadays widely used in clinical practice. Here, we introduce a standardized evaluation framework to reliably evaluate and compare the performance of the algorithms devised to detect and quantify the coronary artery stenoses, and to segment the coronary artery lumen in CTA data. The objective of this evaluation framework is to demonstrate the feasibility of dedicated algorithms to: (1) (semi-)automatically detect and quantify stenosis on CTA, in comparison with quantitative coronary angiography (QCA) and CTA consensus reading, and (2) (semi-)automatically segment the coronary lumen on CTA, in comparison with expert's manual annotation. A database consisting of 48 multicenter multivendor cardiac CTA datasets with corresponding reference standards are described and made available. The algorithms from 11 research groups were quantitatively evaluated and compared. The results show that (1) some of the current stenosis detection/quantification algorithms may be used for triage or as a second-reader in clinical practice, and that (2) automatic lumen segmentation is possible with a precision similar to that obtained by experts. The framework is open for new submissions through the website, at http://coronary.bigr.nl/stenoses/.

Reproducibility of 3D delayed gadolinium enhanced MRI of cartilage (dGEMRIC) of the knee at 3.0 T in patients with early stage osteoarthritis.

OBJECTIVES: To assess the reproducibility of 3D delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) at 3 T in early stage knee osteoarthritis (OA) patients. METHODS: In 20 patients, 3D dGEMRIC at 3 T was acquired twice within 7 days. To correct for patient motion during acquisition, all images were rigidly registered in 3D. Eight anatomical cartilage ROIs were analysed on both images of each patient. Capability of dGEMRIC to yield T1 maps that reproducibly distinguish spatial differences in cartilage quality was assessed in two ROIs within a single slice in each patient. Reproducibility was assessed using ICCs and Bland-Altman plots. RESULTS: ICCs ranged from 0.87 to 0.95, indicating good reproducibility. T1 maps revealed reproducible spatial differences in cartilage quality (ICC 0.79). Based on the Bland-Altman plots, we defined a threshold of 95 ms to determine if a change in dGEMRIC outcome in longitudinal research was statistically significant. CONCLUSIONS: 3D knee dGEMRIC at 3 T combined with 3D image registration is a highly reproducible measure of cartilage quality in early stage OA. Therefore, dGEMRIC may be a valuable tool in the non-invasive evaluation of cartilage quality changes in longitudinal research in patients with early stage OA and focal cartilage defects.

Structural and diffusion MRI measures of the hippocampus and memory performance.

Hippocampal atrophy on MRI and changes in diffusion tensor imaging (DTI) measures of the hippocampus have been reported in patients with Alzheimer's disease. We examined the association between hippocampal volumes, DTI measures of the hippocampus and memory performance in 892 non-demented persons (age ≥ 55 years) across different age groups. Hippocampal volume was segmented on 3D volumetric MRI scans. The segmentations were co-registered to mean diffusivity (MD) and fractional anisotropy (FA) maps to yield mean hippocampal MD and FA measurements. Higher MD of the hippocampus was associated with impaired verbal memory performance. In all persons ≥ 55 years, a higher MD of the hippocampus was associated with a worse memory performance. Hippocampal volumes were very weakly positively associated with delayed recall and only in persons > 65 years. FA of the hippocampus was not associated with memory performance. Follow-up studies will be needed to determine whether higher MD of hippocampus at younger ages could be an earlier marker of incident Alzheimer's disease than hippocampal volume.

Integrated diagnostics: proceedings from the 9th biennial symposium of the International Society for Strategic Studies in Radiology.

The International Society for Strategic Studies in Radiology held its 9th biennial meeting in August 2011. The focus of the programme was integrated diagnostics and massive computing. Participants discussed the opportunities, challenges, and consequences for the discipline of radiology that will likely arise from the integration of diagnostic technologies. Diagnostic technologies are increasing in scope, including advanced imaging techniques, new molecular imaging agents, and sophisticated point-of-use devices. Advanced information technology (IT), which is increasingly influencing the practice of medicine, will aid clinical communication and the development of "population images" that represent the phenotype of particular diseases, which will aid the development of diagnostic algorithms. Integrated diagnostics offer increased operational efficiency and benefits to patients through quicker and more accurate diagnoses. As physicians with the most expertise in IT, radiologists are well placed to take the lead in introducing IT solutions and cloud computing to promote integrated diagnostics. To achieve this, radiologists must adapt to include quantitative data on biomarkers in their reports. Radiologists must also increase their role as participating physicians, collaborating with other medical specialties, not only to avoid being sidelined by other specialties but also to better prepare as leaders in the selection and sequence of diagnostic procedures. Key Points • New diagnostic technologies are yielding unprecedented amounts of diagnostic information.• Advanced IT/cloud computing will aid integration and analysis of diagnostic data.• Better diagnostic algorithms will lead to faster diagnosis and more rapid treatment.

CT arthrography of the human knee to measure cartilage quality with low radiation dose.

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.

Cerebral microbleeds are associated with worse cognitive function: the Rotterdam Scan Study.

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.

Diagnostic performance of exercise bicycle testing and single-photon emission computed tomography: comparison with 64-slice computed tomography coronary angiography.

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.

Clinically applied CT arthrography to measure the sulphated glycosaminoglycan content of cartilage.

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.

Evaluation framework for carotid bifurcation lumen segmentation and stenosis grading.

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.

Diagnostic accuracy of 64-slice computed tomography coronary angiography in a large population of patients without revascularisation: registry data and review of multicentre trials.

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.

Risk factors for coronary, aortic arch and carotid calcification; The Rotterdam Study.

This study was performed to examine the association of cardiovascular risk factors with calcification in the coronary arteries, aortic arch and carotid arteries, assessed by multislice computed tomography (MSCT). This study was embedded in the Rotterdam Study, a population-based study in subjects aged 55 years and over. From October 2003 until December 2004, subjects were invited to undergo a MSCT scan. Coronary, aortic arch and carotid calcification were quantified according to the Agatston score. Analyses were performed in the first 1003 subjects. Age and current smoking were the strongest independent risk factors for arterial calcification. The odds ratio (OR) for age in women, irrespective of the vessel bed, was 1.1 (P<0.001) and in men it was 1.2 with aortic arch and 1.1 with carotid calcification (both P<0.001). Current smoking was associated with aortic arch calcification with an OR of 3.5 in women and of 4.7 in men (both P<0.001); and with carotid calcification with an OR of 2.1 in women (P<0.05) and of 4.1 in men (P<0.01). Hypertension, hypercholesterolemia and diabetes were also independently related to calcification, although not consistent across all vessel beds and for men and women. Obesity tended to be inversely related to arterial calcification in women, whereas low high-density lipoprotein-cholesterol showed no relation with arterial calcification. In conclusion, although associations were not completely consistent across the different vessel beds and for men and women, our results indicate that generally the same risk factors are present for atherosclerosis in the coronary, aortic arch and carotid circulation.

Ferumoxides-protamine sulfate is more effective than ferucarbotran for cell labeling: implications for clinically applicable cell tracking using MRI.

The use of superparamagnetic iron oxide (SPIO) for labeling cells holds great promise for clinically applicable cell tracking using magnetic resonance imaging. For clinical application, an effectively and specifically labeled cell preparation is highly desired (i.e. a large amount of intracellular iron and a negligible amount of extracellular iron). In this study we performed a direct comparison of two SPIO labeling strategies that have both been reported as efficient and clinically translatable approaches. These approaches are cell labeling using ferumoxides-protamine complexes or ferucarabotran particles. Cell labeling was performed on primary human bone marrow stromal cells (hBMSCs) and chondrocytes. For both cell types ferumoxides-protamine resulted in a higher percentage of labeled cells, a higher total iron load, a larger amount of intracellular iron and a lower amount of extracellular iron aggregates, compared with ferucarbotran. Consequently, hBMSC and chondrocyte labeling with ferumoxides-protamine is more effective and results in more specific cell labeling than ferucarbotran.