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Background: Altered perfusion might play an important role in the pathophysiology of patellofemoral pain (PFP), a common knee complaint with unclear pathophysiology., Purpose: To investigate differences in dynamic contrast-enhanced (DCE)-MRI perfusion parameters between patients with PFP and healthy control subjects., Population/subjects/phantom/specimen/animal Model: Thirty-five adult patients with PFP and 44 healthy adult control subjects., Field Strength/sequence: 3T DCE-MRI consisting of a sagittal, anterior-posterior, frequency-encoded, fat-suppressed 3D spoiled gradient-echo sequence with intravenous contrast administration., Assessment: Patellar bone volumes of interest (VOIs) were delineated by a blinded observer. Quantitative perfusion parameters (k ep and k trans ) were calculated from motion-compensated DCE-MRI data by fitting Tofts' model. Weighted mean and unweighted median values of k ep and k trans were computed within the patellar bone VOIs., Statistical Tests: Differences in patellar bone perfusion parameters were compared between groups by linear regression analyses, adjusted for confounders., Results: Mean differences of weighted mean and unweighted median were 0.0039 (95% confidence interval [CI] -0.0013; 0.0091) and 0.0052 (95% CI -0.0078; 0.018) for k trans , and 0.046 (95% CI -0.021; 0.11) and 0.069 (95% CI -0.017; 0.15) for k ep , respectively. All perfusion parameters were not significantly different between groups (P-values: 0.32; 0.47 for k trans , and 0.24; 0.15) for k ep . However, a significant difference in variance between populations was observed for k trans (P-value 0.007)., Data Conclusion: Higher patellar bone perfusion parameters were found in patients with PFP when compared to healthy control subjects, but these differences were not statistically significant. This result, and the observed significant difference in k trans variance, warrant further research., Level of Evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1344-1350., (© 2018 The Authors Journal of Magnetic Resonance Imaging published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

The timely diagnosis of prosthetic heart valve endocarditis remains challenging yet of utmost importance. 18F-fluorodeoxyglucose (18 F-FDG) positron emission/computed tomography (PET/CT) and cardiac computed tomography angiography (CTA) were recently introduced as additional diagnostic tools in the most recent ESC guidelines on infective endocarditis. However, how to interpret PET/CT findings with regard to what is to be considered abnormal, what the potential confounders may be, as well as which patients benefit most from these additional imaging techniques and how to best perform them in these often-complex patients, remains unclear. This review focusses on factors regarding patient selection and image acquisition that need to be taken into account when employing 18F-FDG PET/CT and CTA in daily clinical practice, and the importance of a multidisciplinary Endocarditis Team herein. Furthermore, it emphasizes the need for standardized acquisition protocols and image interpretation, especially now that these techniques are starting to be widely embraced by the cardiovascular society.

Background: 18 F-Fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) was recently introduced as a new tool for the diagnosis of prosthetic heart valve endocarditis (PVE). Previous studies reporting a modest diagnostic accuracy may have been hampered by unstandardized image acquisition and assessment, and several confounders, as well. The aim of this study was to improve the diagnostic performance of FDG PET/CT in patients in whom PVE was suspected by identifying and excluding possible confounders, using both visual and standardized quantitative assessments., Methods: In this multicenter study, 160 patients with a prosthetic heart valve (median age, 62 years [43-73]; 68% male; 82 mechanical valves; 62 biological; 9 transcatheter aortic valve replacements; 7 other) who underwent FDG PET/CT for suspicion of PVE, and 77 patients with a PV (median age, 73 years [65-77]; 71% male; 26 mechanical valves; 45 biological; 6 transcatheter aortic valve replacements) who underwent FDG PET/CT for other indications (negative control group), were retrospectively included. Their scans were reassessed by 2 independent observers blinded to all clinical data, both visually and quantitatively on available European Association of Nuclear Medicine Research Ltd-standardized reconstructions. Confounders were identified by use of a logistic regression model and subsequently excluded., Results: Visual assessment of FDG PET/CT had a sensitivity/specificity/positive predictive value/negative predictive value for PVE of 74%/91%/89%/78%, respectively. Low inflammatory activity (C-reactive protein <40 mg/L) at the time of imaging and use of surgical adhesives during prosthetic heart valve implantation were significant confounders, whereas recent valve implantation was not. After the exclusion of patients with significant confounders, diagnostic performance values of the visual assessment increased to 91%/95%/95%/91%. As a semiquantitative measure of FDG uptake, a European Association of Nuclear Medicine Research Ltd-standardized uptake value ratio of ≥2.0 was a 100% sensitive and 91% specific predictor of PVE., Conclusions: Both visual and quantitative assessments of FDG PET/CT have a high diagnostic accuracy in patients in whom PVE is suspected. FDG PET/CT should be implemented early in the diagnostic workup to prevent the negative confounding effects of low inflammatory activity (eg, attributable to prolonged antibiotic therapy). Recent valve implantation was not a significant predictor of false-positive interpretations, but surgical adhesives used during implantation were.

Background: Stents are commonly used to treat aortic coarctation. The objective of this study was to evaluate the post-implantation computed tomography (CT) image quality of different stent types used to treat aortic coarctation., Methods: Adult and paediatric patients with stent-treated aortic coarctation who underwent contrast-enhanced CT were retrospectively included from three tertiary care centres. CT scans were subjectively scored for image quality using a 4-point scale (1 = unacceptable; 2 = poor; 3 = good; 4 = excellent). Furthermore, the amount of stent-induced blooming artefacts was measured as the percentage of the difference between outer and inner stent diameters over the outer stent diameter., Results: A total of 35 children and 34 adults implanted with 71 stents of six different types were included. The most commonly used stent type was the Cheatham Platinum stent (52 stents, 73%). The subjective image quality of the Cheatham Platinum stents was moderate with a score of 2.0±0.8 (mean ± standard deviation) in children and 2.3±0.6 in adults. The image quality in patients with Formula stents was 2.3±1.2. The Cheatham Platinum stents induced 34-48% blooming, the Formula stents 44-55%. The image quality in patients with the less commonly used Atrium Advanta V12, IntraStent, AndraStent and Palmaz stents was scored 3 (good) to 4 (excellent) with less blooming. The electrocardiographic gating and tube voltage (kVp) did not affect image quality., Conclusions: There is a substantial variation in CT image quality and blooming artefacts for different stent types used to treat aortic coarctation.

Aims: The autopsy rate worldwide is alarmingly low (0-15%). Mortality statistics are important, and it is, therefore, essential to perform autopsies in a sufficient proportion of deaths. The imaging autopsy, non-invasive, or minimally invasive autopsy (MIA) can be used as an alternative to the conventional autopsy in an attempt to improve postmortem diagnostics by increasing the number of postmortem procedures. The aim of this study was to determine the diagnostic accuracy of postmortem magnetic resonance imaging (MRI), computed tomography (CT), and CT-guided biopsy for the detection of acute and chronic myocardial ischaemia., Methods and Results: We included 100 consecutive adult patients who died in hospital, and for whom next-of-kin gave permission to perform both conventional autopsy and MIA. The MIA consists of unenhanced total-body MRI and CT followed by CT-guided biopsies. Conventional autopsy was used as reference standard. We calculated sensitivity and specificity and receiver operating characteristics curves for CT and MRI as the stand-alone test or combined with biopsy for detection of acute and chronic myocardial infarction (MI). Sensitivity and specificity of MRI with biopsies for acute MI was 0.97 and 0.95, respectively and 0.90 and 0.75, respectively for chronic MI. MRI without biopsies showed a high specificity (acute: 0.92; chronic: 1.00), but low sensitivity (acute: 0.50; chronic: 0.35). CT (total Agatston calcium score) had a good diagnostic value for chronic MI [area under curve (AUC) 0.74, 95% confidence interval (CI) 0.64-0.84], but not for acute MI (AUC 0.60, 95% CI 0.48-0.72)., Conclusion: We found that the combination of MRI with biopsies had high sensitivity and specificity for the detection of acute and chronic myocardial ischaemia.

Aims: More than 50% of patients with heart failure have preserved ejection fraction characterized by diastolic dysfunction. The prevalance of diastolic dysfunction is higher in females and associates with multiple comorbidities such as hypertension (HT), obesity, hypercholesterolemia (HC), and diabetes mellitus (DM). Although its pathophysiology remains incompletely understood, it has been proposed that these comorbidities induce systemic inflammation, coronary microvascular dysfunction, and oxidative stress, leading to myocardial fibrosis, myocyte stiffening and, ultimately, diastolic dysfunction. Here, we tested this hypothesis in a swine model chronically exposed to three common comorbidities., Methods and Results: DM (induced by streptozotocin), HC (produced by high fat diet), and HT (resulting from renal artery embolization), were produced in 10 female swine, which were followed for 6 months. Eight female healthy swine on normal pig-chow served as controls. The DM + HC + HT group showed hyperglycemia, HC, hypertriglyceridemia, renal dysfunction and HT, which were associated with systemic inflammation. Myocardial superoxide production was markedly increased, due to increased NOX activity and eNOS uncoupling, and associated with reduced NO production, and impaired coronary small artery endothelium-dependent vasodilation. These abnormalities were accompanied by increased myocardial collagen content, reduced capillary/fiber ratio, and elevated passive cardiomyocyte stiffness, resulting in an increased left ventricular end-diastolic stiffness (measured by pressure-volume catheter) and a trend towards a reduced E/A ratio (measured by cardiac MRI), while ejection fraction was maintained., Conclusions: The combination of three common comorbidities leads to systemic inflammation, myocardial oxidative stress, and coronary microvascular dysfunction, which associate with myocardial stiffening and LV diastolic dysfunction with preserved ejection fraction.

Objectives: Multidetector CT (MDCT) is a valuable tool for functional prosthetic heart valve (PHV) assessment. However, radiation exposure remains a concern. We assessed a novel CT-acquisition protocol for comprehensive PHV evaluation at limited dose., Methods: Patients with a PHV were scanned using a third-generation dual-source CT scanner (DSCT) and iterative reconstruction technique (IR). Three acquisitions were obtained: a non-enhanced scan; a contrast-enhanced, ECG-triggered, arterial CT angiography (CTA) scan with reconstructions at each 5 % of the R-R interval; and a delayed high-pitch CTA of the entire chest. Image quality was scored on a five-point scale. Radiation dose was obtained from the reported CT dose index (CTDI) and dose length product (DLP)., Results: We analysed 43 CT examinations. Mean image quality score was 4.1±1.4, 4.7±0.5 and 4.2±0.6 for the non-contrast-enhanced, arterial and delayed acquisitions, respectively, with a total mean image quality of 4.3±0.7. Mean image quality for leaflet motion was 3.9±1.4. Mean DLP was 28.2±17.1, 457.3±168.6 and 68.5±47.2 mGy.cm for the non-contrast-enhanced (n=40), arterial (n=43) and delayed acquisition (n=43), respectively. The mean total DLP was 569±208 mGy.cm and mean total radiation dose was 8.3±3.0 mSv (n=43)., Conclusion: Comprehensive assessment of PHVs is possible using DSCT and IR at moderate radiation dose., Key Points: • Prosthetic heart valve dysfunction is a potentially life-threatening condition. • Dual-source CT can adequately assess valve leaflet motion and anatomy. • We assessed a comprehensive protocol with three acquisitions for PHV evaluation. • This protocol is associated with good image quality and limited dose.

Purpose: To propose and evaluate new k-space trajectories for 3D-GRASE to improve scan time over 3D-FSE/TSE for high resolution structural imaging., Methods: Five different Cartesian k-space trajectories were developed and evaluated. They combine ideas of existing k-space trajectories for 3D-GRASE and 3D-FSE/TSE. T2 and T2* are linearly or radially modulated in k-space to achieve the desired contrast while including the autocalibration region needed for the parallel imaging reconstruction technique. Phase modulation among echoes was corrected in reconstruction to remove remaining artefacts. Simulation and in-vivo experiments on a 3T scanner were conducted to evaluate the performance of the different k-space trajectories., Results: Two of the proposed k-space trajectories for high resolution structural imaging with 3D-GRASE obtained images comparable to 3D-FSE with lower specific absorption rate (PD/T2: 41%/75%) and shorter acquisition time (PD/T2: 27%/20%)., Conclusions: 3D-GRASE image quality strongly depends on the k-space trajectory. With an optimal trajectory, 3D-GRASE may be preferable over 3D-FSE/TSE for structural high-resolution MRI., (Copyright © 2017 Elsevier Inc. All rights reserved.)

T2-mapping is a widely used quantitative MRI technique in osteoarthritis research. An important challenge for its application in the context of high tibial osteotomy (HTO) is the presence of metallic fixation devices. In this study, we evaluated the possibility of performing T2-mapping after a HTO, by assessing the extent of magnetic susceptibility artifacts and the influence on T2 relaxation times caused by two commonly used fixation devices. T2-mapping with a 3D fast spin-echo sequence at three Tesla was performed on 11 human cadaveric knee joints before and after implantation of a titanium plate and screws (n = 5) or cobalt chrome staples (n = 6). Mean T2 relaxation times were calculated in six cartilage regions, located in the distal and posterior cartilage of femoral condyles and the cartilage of tibial plateaus, both medially and laterally. T2 relaxation times before and after the implantation were compared with paired t-tests and Wilcoxon rank tests. Due to the extent of the magnetic susceptibility artifact, it was not possible to segment the knee cartilage and thus calculate T2 relaxation times in the lateral weight-bearing femoral and tibial cartilage regions only in the cobalt chrome group. In all cartilage regions of the titanium implanted knees and those unaffected by artifacts due to cobalt chrome implants, T2 relaxation times did not significantly differ between the two scans. Our results suggest that accurate T2-mapping after a HTO procedure is possible in all areas after implantation of a titanium fixation device and in most areas after implantation of a cobalt chrome fixation device. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1206-1212, 2018., (© 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.)

Accurate diagnosis of vertebral osteoporotic fractures is crucial for the identification of individuals at high risk of future fractures. Different methods for radiological assessment of vertebral fractures exist, but a gold standard is lacking. The aim of our study was to estimate statistical measures of agreement and prevalence of osteoporotic vertebral fractures in the population-based Rotterdam Study, across two assessment methods. The quantitative morphometry assisted by SpineAnalyzer® (QM SA) method evaluates vertebral height loss that affects vertebral shape whereas the algorithm-based qualitative (ABQ) method judges endplate integrity and includes guidelines for the differentiation of vertebral fracture and nonfracture deformities. Cross-sectional radiographs were assessed for 7582 participants aged 45 to 95 years. With QM SA, the prevalence was 14.2% (95% CI, 13.4% to 15.0%), compared to 4.0% (95% CI, 3.6% to 4.5%) with ABQ. Inter-method agreement according to kappa (κ) was 0.24. The highest agreement between methods was among females (κ = 0.31), participants age >80 years (κ = 0.40), and at the L 1 level (κ = 0.40). With ABQ, most fractures were found at the thoracolumbar junction (T 12 -L 1 ) followed by the T 7 -T 8 level, whereas with QM SA, most deformities were in the mid thoracic (T 7 -T 8 ) and lower thoracic spine (T 11 -T 12 ), with similar number of fractures in both peaks. Excluding mild QM SA deformities (grade 1 with QM) from the analysis increased, the agreement between the methods from κ = 0.24 to 0.40, whereas reexamining mild deformities based on endplate depression increased agreement from κ = 0.24 to 0.50 (p <0.001). Vertebral fracture prevalence differs significantly between QM SA and ABQ; reexamining QM mild deformities based on endplate depression would increase the agreement between methods. More widespread and consistent application of an optimal method may improve clinical care. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Background: The harm of screening (unnecessary biopsies and overdiagnosis) generally outweighs the benefit of reducing prostate cancer (PCa) mortality in men aged ≥70 yr. Patient selection for biopsy using risk stratification and magnetic resonance imaging (MRI) may improve this benefit-to-harm ratio., Objective: To assess the potential of a risk-based strategy including MRI to selectively identify men aged ≥70 yr with high-grade PCa., Design, Setting, and Participants: Three hundred and thirty-seven men with prostate-specific antigen ≥3.0 ng/ml at a fifth screening (71-75 yr) in the European Randomized study of Screening for Prostate Cancer Rotterdam were biopsied. One hundred and seventy-nine men received six-core transrectal ultrasound biopsy (TRUS-Bx), while 158 men received MRI, 12-core TRUS-Bx, and fusion TBx in case of Prostate Imaging Reporting and Data System ≥3 lesions., Outcome Measurements and Statistical Analysis: The primary outcome was the overall, low-grade (Gleason Score 3+3) and high-grade (Gleason Score ≥ 3+4) PCa rate. Secondary outcome was the low- and high-grade PCa rate detected by six-core TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx. Tertiary outcome was the reduction of biopsies and low-grade PCa detection by upfront risk stratification with the Rotterdam Prostate Cancer Risk Calculator 4., Results and Limitations: Fifty-five percent of men were previously biopsied. The overall, low-grade, and high-grade PCa rates in biopsy naïve men were 48%, 27%, and 22%, respectively. In previously biopsied men these PCa rates were 25%, 20%, and 5%. Sextant TRUS-Bx, 12-core TRUS-Bx, and MRI ± TBx had a similar high-grade PCa rate (11%, 12%, and 11%) but a significantly different low-grade PCa rate (17%, 28%, and 7%). Rotterdam Prostate Cancer Risk Calculator 4-based stratification combined with 12-core TRUS-Bx ± MRI-TBx would have avoided 65% of biopsies and 68% of low-grade PCa while detecting an equal percentage of high-grade PCa (83%) compared with a TRUS-Bx all men approach (79%)., Conclusions: After four repeated screens and ≥1 previous biopsies in half of men, a significant proportion of men aged ≥70 yr still harbor high-grade PCa. Upfront risk stratification and the combination of MRI and TRUS-Bx would have avoided two-thirds of biopsies and low-grade PCa diagnoses in our cohort, while maintaining the high-grade PCa detection of a TRUS-Bx all men approach. Further studies are needed to verify these results., Patient Summary: Prostate cancer screening reduces mortality but is accompanied by unnecessary biopsies and overdiagnosis of nonaggressive tumors, especially in repeatedly screened elderly men. To tackle these drawbacks screening should consist of an upfront risk-assessment followed by magnetic resonance imaging and transrectal ultrasound-guided biopsy., (Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Stent placement is commonly used to treat aortic coarctation. Although invasive angiography remains the gold standard, follow-up is often performed using computed tomography, which allows rapid, noninvasive assessment of the aorta and surrounding tissues. The goal of this pictorial essay is to provide a guide to the interpretation of these examinations. Normal and abnormal computed tomographic appearance of different stent types is shown along with reconstructions that can help assess stent integrity and the stent position in relation to the aortic wall and branches. Furthermore, imaging findings of complications including aortic wall injuries, restenosis, and intimal hyperplasia are depicted.

Objective: The purpose of this study was to assess the a priori chance that primary cystic lesions of the retrorectal space are malignant and to investigate MRI characteristics that indicate malignancy., Materials and Methods: Patients referred to a center for colorectal surgery were recruited from 2000 to 2014. Lesions were proven by clinical assessment and histopathology. MRI was performed at 1.5 T with examinations evaluated by two radiologists. Interobserver agreement was assessed (Cohen kappa) and differences between malignant and benign lesions calculated (Fisher exact test)., Results: Twenty-eight patients (22 women, six men; age range, 18-70 years) with 31 lesions were included. Lesions were categorized as tailgut cysts (n = 16, 52%), teratomas (n = 9, 29%), lesions of colorectal origin (n = 4, 13%), or neurogenic lesions (n = 2, 6%). Five patients (18%) had malignant lesions. Colorectal lesions had the highest percentage of malignancy (3/4, 75%). A solid tissue component was found in all five (100%) malignant lesions and two (8%) of the benign lesions, which were both teratomas (p < 0.05). Sensitivity and specificity for malignancy according to the presence of a solid tissue component was 100% (5/5) and 92% (24/26). For unilocularity, multilocularity, debris, septa, and wall thickening, differences were not significant. Interobserver agreement was excellent (κ = 1) for all characteristics except debris (κ = 0.795)., Conclusion: The majority of retrorectal cystic lesions are benign. The presence of a solid tissue component should raise suspicion for malignancy.

Objective: The Bentall procedure is associated with several complications often accompanied by accumulation of fluid around the aortic graft. CT is the imaging modality of choice to detect these complications. Since these early complications are, however, not easily distinguished from physiological postoperative changes, our aim was to compare the appearance and amount of peri-aortic fluid on early CT scans following Bentall procedures with either an uncomplicated or a complicated course and follow-up., Methods: Ninety-four scans performed within 3 months of a Bentall procedure were retrospectively included. Patients were divided into either the uncomplicated or the complicated group based on occurrence of Bentall-related complications or death up until 1-year after surgery. Diffuse fluid ("stranding") was distinguished from organized, more clearly delineated fluid collections such as haematomas, and was graded both subjectively and quantitatively., Results: Forty-seven patients were assigned to each group. Stranding was found on most of the scans, both in the uncomplicated (7.7±3.9mm, range 0-17mm) and complicated (6.9±5.5mm, range 0-19mm) groups (p=0.32). There were, however, significantly more fluid collections (6 vs. 28; p <0.001), particularly haematomas (1 vs. 17; p<0.001), in the complicated group. When looking at isolated stranding, there was still no significant difference between the two groups (7.8±3.6mm vs. 9.2±3.7mm; p=0.22)., Conclusion: Isolated stranding of up to 17mm is a common finding on postoperative CT within three months of a Bentall procedure, regardless of the occurrence of complications during the procedure or within a 1-year follow-up. Fluid collections are more worrisome indicators of complications that may require closer monitoring., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the frequency of total-body CT and MR features of postmortem change in in-hospital deaths., Materials and Methods: In this prospective blinded cross-sectional study, in-hospital deceased adult patients underwent total-body postmortem CT and MR followed by image-guided biopsies. The presence of PMCT and PMMR features related to postmortem change was scored retrospectively and correlated with postmortem time interval, post-resuscitation status and intensive care unit (ICU) admittance., Results: Intravascular air, pleural effusion, periportal edema, and distended intestines occurred more frequently in patients who were resuscitated compared to those who were not. Postmortem clotting was seen less often in resuscitated patients (p = 0.002). Distended intestines and loss of grey-white matter differentiation in the brain showed a significant correlation with postmortem time interval (p = 0.001, p<0.001). Hyperdense cerebral vessels, intravenous clotting, subcutaneous edema, fluid in the abdomen and internal livores of the liver were seen more in ICU patients. Longer postmortem time interval led to a significant increase in decomposition related changes (p = 0.026)., Conclusions: There is a wide variety of imaging features of postmortem change in in-hospital deaths. These imaging features vary among clinical conditions, increase with longer postmortem time interval and must be distinguished from pathologic changes.

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., (Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

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., (© 2017 by American Journal of Neuroradiology.)

The aim was to investigate whether diffusion-weighted magnetic resonance imaging (DWI) detects and monitors inflammatory and lung function changes during respiratory tract exacerbations (RTE) treatment in patients with cystic fibrosis (CF).29 patients with RTE underwent DWI pre- and post-antibiotic treatment. A control group of 27 stable patients, matched for age and sex, underwent DWI with the same time gap as those undergoing RTE treatment. Clinical status and lung function were assessed at each DWI time point. The CF-MRI scoring system was used to assess structural lung changes in both CF groups.Significant reduction in the DWI score over the course of antibiotic treatment (p<0.0001) was observed in patients with RTE, but not in the control group. DWI score had a strong inverse correlation with clinical status (r=-0.504, p<0.0001) and lung function (r=-0.635, p<0.0001) in patients with RTE. Interestingly, there were persistent significant differences in the CF-MRI score between the RTE and control group at both baseline and follow-up (p<0.001), while the differences in DWI score were only observed at baseline (p<0.001).DWI is a promising imaging method for noninvasive detection of pulmonary inflammation during RTE, and may be used to monitor treatment efficacy of anti-inflammatory treatment., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Objectives: The aim of this study is to assess the effect of blood pressure (BP) on coronary computed tomography angiography (CTA) derived computational fractional flow reserve (CTA-FFR)., Materials and Methods: Twenty-one patients who underwent coronary CTA and invasive FFR were retrospectively identified. Ischemia was defined as invasive FFR ≤0.80. Using a work-in-progress computational fluid dynamics algorithm, CTA-FFR was computed with BP measured before CTA, and simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg respectively. Correlation between CTA-FFR and invasive FFR was assessed using Pearson test. The repeated measuring test was used for multiple comparisons of CTA-FFR values by simulated BP inputs., Results: Twenty-nine vessels (14 with invasive FFR ≤0.80) were assessed. The average CTA-FFR for measured BP (134 ± 20/73 ± 12 mmHg) was 0.77 ± 0.12. Correlation between CTA-FFR by measured BP and invasive FFR was good (r = 0.735, P < 0.001). For simulated BPs of 60/50, 90/60, 110/70, 130/80, 150/90, and 180/100 mmHg, the CTA-FFR increased: 0.69 ± 0.13, 0.73 ± 0.12, 0.75 ± 0.12, 0.77 ± 0.11, 0.79 ± 0.11, and 0.81 ± 0.10 respectively (P < 0.05)., Conclusion: Measurement of the BP just before CTA is preferred for accurate CTA-FFR simulation. BP variations in the common range slightly affect CTA-FFR. However, inaccurate BP assumptions differing from the patient-specific BP could cause misinterpretation of borderline significant lesions., Key Points: • The blood pressure (BP) affects the CTA-FFR computation. • Measured BP before CT examination is preferable for accurate CTA-FFR simulation. • Inaccurate BP assumptions can cause misinterpretation of borderline significant lesions.

Purpose To investigate the association between N-terminal pro-B-type natriuretic peptide (NT-proBNP), which is a marker of heart disease, and markers of subclinical brain damage on magnetic resonance (MR) images in community-dwelling middle-aged and elderly subjects without dementia and without a clinical diagnosis of heart disease. Materials and Methods This prospective population-based cohort study was approved by a medical ethics committee overseen by the national government, and all participants gave written informed consent. Serum levels of NT-proBNP were measured in 2397 participants without dementia or stroke (mean age, 56.6 years; age range, 45.7-87.3 years) and without clinical diagnosis of heart disease who were drawn from the population-based Rotterdam Study. All participants were examined with a 1.5-T MR imager. Multivariable linear and logistic regression analyses were used to investigate the association between NT-proBNP level and MR imaging markers of subclinical brain damage, including volumetric, focal, and microstructural markers. Results A higher NT-proBNP level was associated with smaller total brain volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.021; 95% confidence interval [CI]: -0.034, -0.007; P = .003) and was predominantly driven by gray matter volume (mean difference in z score per standard deviation increase in NT-proBNP level, -0.037; 95% CI: -0.057, -0.017; P < .001). Higher NT-proBNP level was associated with larger white matter lesion volume (mean difference in z score per standard deviation increase in NT-proBNP level, 0.090; 95% CI: 0.051, 0.129; P < .001), with lower fractional anisotropy (mean difference in z score per standard deviation increase in NT-proBNP level, -0.048; 95% CI: -0.088, -0.008; P = .019) and higher mean diffusivity (mean difference in z score per standard deviation increase in NT-proBNP level, 0.054; 95% CI: 0.018, 0.091; P = .004) of normal-appearing white matter. Conclusion In community-dwelling persons, higher serum NT-proBNP levels are associated with volumetric and microstructural MR imaging markers of subclinical brain damage. © RSNA, 2016 Online supplemental material is available for this article.

Aims: Increasing evidence suggests involvement of the amount of liver fat in the development of cardiovascular disease. We investigated the relation of liver fat with cardiovascular risk factors and subclinical vascular disease in the general population., Methods and Results: Between 2003 and 2006, 2351 persons from the population-based Rotterdam Study (mean age 69.6 ± 6.7 years, 47.2% males) underwent non-enhanced computed tomography. We measured the mean liver attenuation value in Hounsfield units and quantified the following markers of subclinical vascular disease: epicardial fat volume and volumes of coronary (CAC), aortic (AAC), extracranial (ECAC), and intracranial carotid calcification (ICAC). Using linear regression, we investigated associations between traditional cardiovascular risk factors and mean liver attenuation. We also investigated relations of mean liver attenuation with markers of subclinical vascular disease, adjusting for cardiovascular risk factors. We found strong associations of waist circumference, diastolic blood pressure, and diabetes with lower mean liver attenuation [multivariable-adjusted beta per unit increase in waist circumference: -2.54 (95% CI: -3.10; -1.99); diastolic blood pressure: -0.52 (95% CI: -0.88; -0.17); and the presence of diabetes: -21.91 (95% CI: -31.76; -12.06)]. Moreover, we found that larger mean liver attenuation values were associated with smaller volumes of epicardial fat and CAC, independent of cardiovascular risk factors [beta per 1-SD increase in mean liver attenuation value: -0.05 (95% CI: -0.08; -0.02) and -0.05 (95% CI: -0.10; -0.01), respectively]., Conclusion: Larger amounts of liver fat are related to larger volumes of epicardial fat and CAC, independent of traditional cardiovascular risk factors, providing important novel insights into the role of liver fat as a marker of vascular disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Background and Purpose: The presence of subclinical vascular brain disease, including white matter lesions and lacunar infarcts, substantially increases the risk of clinical stroke. White matter microstructural integrity is considered an earlier, potentially better, marker of the total burden of vascular brain disease. Its association with risk of stroke, a focal event, remains unknown., Methods: From the population-based Rotterdam Study, 4259 stroke-free participants (mean age: 63.6 years, 55.6% women) underwent brain magnetic resonance imaging, including diffusion magnetic resonance imaging, between 2006 and 2011. All participants were followed up for incident stroke until 2013. Cox proportional hazards models were used to associate markers of the microstructure of normal-appearing white matter with risk of stroke, adjusting for age, sex, white matter lesion volume, lacunar infarcts, and additionally for cardiovascular risk factors. Finally, we assessed the predictive value of white matter microstructural integrity for stroke beyond the Framingham Stroke Risk Profile., Results: During 18 476 person-years of follow-up, 58 people experienced a stroke. Both lower fractional anisotropy and higher MD increased risk of stroke, independent of age, sex, cardiovascular risk factors, white matter lesion volume, and lacunar infarcts (hazard ratio per SD increase in: fractional anisotropy: 0.75 [95% confidence interval, 0.57-0.98] and MD: 1.50 [95% confidence interval, 1.08-2.09]). MD improved stroke prediction beyond the Framingham Stroke Risk Profile (continuous net reclassification improvement: 0.52 [95% confidence interval, 0.24-0.81])., Conclusions: Future stroke is predicted not only by prevalent vascular lesions but also by subtle alterations in the microstructure of normal-appearing white matter. Inclusion of this effect in risk prediction models produces a significant advantage in stroke prediction compared with the existing Framingham Stroke Risk Profile., (© 2016 American Heart Association, Inc.)

Purpose To present an updated prevalence estimate for incidental findings on brain magnetic resonance (MR) images and provide information on clinical relevance, including natural course, over a period of up to 9 years. Materials and Methods This study was approved by the institutional review board and all participants gave informed consent. In a prospective population-based setting, structural brain MR imaging was performed in 5800 participants (mean age, 64.9 years; 3194 women [55.1%]). Trained reviewers recorded abnormalities, which were subsequently evaluated by neuroradiologists. The prevalence with 95% confidence interval (CI) of incidental findings was determined, and clinical management of findings that required the attention of a medical specialist was followed. Follow-up imaging in the study context provided information on the natural course of findings that were not referred. Results In 549 of 5800 participants (9.5% [95% CI: 8.7%, 10.3%]), incidental findings were found, of which meningiomas (143 of 5800; 2.5% [95% CI: 2.1%, 2.9%]) and cerebral aneurysms (134 of 5800; 2.3% [95% CI: 2.0%, 2.7%]) were most common. A total of 188 participants were referred to medical specialists for incidental findings (3.2% [95% CI: 2.8%, 3.7%]). Of these, 144 (76.6% [95% CI: 70.1%, 82.1%]) either underwent a wait-and-see policy or were discharged after the initial clinical visit. The majority of meningiomas and virtually all aneurysms not referred or referred but untreated remained stable in size during follow-up. Conclusion Incidental findings at brain MR imaging that necessitate further diagnostic evaluation occur in over 3% of the general middle-aged and elderly population, but are mostly without direct clinical consequences. © RSNA, 2016.

Objectives: In this study, we evaluated a cloud-based platform for cardiac magnetic resonance (CMR) four-dimensional (4D) flow imaging, with fully integrated correction for eddy currents, Maxwell phase effects, and gradient field non-linearity, to quantify forward flow, regurgitation, and peak systolic velocity over the pulmonary artery., Methods: We prospectively recruited 52 adult patients during one-year period from July 2014. The 4D flow and planar (2D) phase-contrast (PC) were acquired during same scanning session, but 4D flow was scanned after injection of a gadolinium-based contrast agent. Eddy-currents were semi-automatically corrected using the web-based software. Flow over pulmonary valve was measured and the 4D flow values were compared against the 2D PC ones., Results: The mean forward flow was 92 (±30) ml/cycle measured with 4D flow and 86 (±29) ml/cycle measured with 2D PC, with a correlation of 0.82 and a mean difference of -6ml/cycle (-41-29). For the regurgitant fraction the correlation was 0.85 with a mean difference of -0.95% (-17-15). Mean peak systolic velocity measured with 4D flow was 92 (±49) cm/s and 108 (±56) cm/s with 2D PC, having a correlation of 0.93 and a mean difference of 16cm/s (-24-55)., Conclusion: 4D flow imaging post-processed with an integrated cloud-based application accurately quantifies pulmonary flow. However, it may underestimate the peak systolic velocity., (Copyright © 2016. Published by Elsevier Ireland Ltd.)

Background: Structural abnormalities of the patellofemoral joint might play a role in the pathogenesis of patellofemoral pain (PFP), a common knee problem among young and physically active individuals. No previous study has investigated if PFP is associated with structural abnormalities of the patellofemoral joint using high-resolution magnetic resonance imaging (MRI)., Purpose: To investigate the presence of structural abnormalities of the patellofemoral joint on high-resolution MRI in patients with PFP compared with healthy control subjects., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Patients with PFP and healthy control subjects between 14 and 40 years of age underwent high-resolution 3-T MRI. All images were scored using the Magnetic Resonance Imaging Osteoarthritis Knee Score with the addition of specific patellofemoral features. Associations between PFP and the presence of structural abnormalities were analyzed using logistic regression analyses adjusted for age, body mass index (BMI), sex, and sports participation., Results: A total of 64 patients and 70 control subjects were included in the study. Mean ± SD age was 23.2 ± 6.4 years, mean BMI ± SD was 22.9 ± 3.4 kg/m(2), and 56.7% were female. Full-thickness cartilage loss was not present. Minor patellar cartilage defects, patellar bone marrow lesions, and high signal intensity of the Hoffa fat pad were frequently seen in both patients (23%, 53%, and 58%, respectively) and control subjects (21%, 51%, and 51%, respectively). After adjustment for age, BMI, sex, and sports participation, none of the structural abnormalities were statistically significantly associated with PFP., Conclusion: Structural abnormalities of the patellofemoral joint have been hypothesized as a factor in the pathogenesis of PFP, but the study findings suggest that structural abnormalities of the patellofemoral joint on MRI are not associated with PFP., (© 2016 The Author(s).)

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., (Copyright © 2016 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.)

Purpose: To determine longitudinally the rate of change in diffusion-tensor imaging (DTI) parameters of white matter microstructure with aging and to investigate whether cardiovascular risk factors influence this longitudinal change., Materials and Methods: This prospective population-based cohort study was approved by a dedicated ethics committee overseen by the national government, and all participants gave written informed consent. Community-dwelling participants without dementia were examined by using a research-dedicated 1.5-T magnetic resonance (MR) imager on two separate visits that were, on average, 2.0 years apart. Among 810 persons who were eligible for imaging at baseline, longitudinal imaging data were available for 501 persons (mean age, 69.9 years; age range, 64.1-91.1 years). Changes in normal-appearing white matter DTI characteristics in the tract centers were analyzed globally to investigate diffuse patterns of change and then locally by using voxelwise multilinear regression. The influence of cardiovascular risk factors was assessed by treating them as additional determinants in both analyses., Results: Over the 2.0-year follow-up interval, global fractional anisotropy (FA) decreased by 0.0042 (P < .001), while mean diffusivity (MD) increased by 8.1 × 10(-6) mm(2)/sec (P < .001). Voxelwise analysis of the brain white matter skeleton showed an average decrease of 0.0082 (Pmean = .002) in FA in 57% of skeleton voxels. The sensorimotor pathway, however, showed an increase of 0.0078 (Pmean = .009) in FA. MD increased by 10.8 × 10(-6)mm(2)/sec (Pmean < .001) on average in 79% of white matter skeleton voxels. Additionally, white matter degeneration was more pronounced in older persons. Cardiovascular risk factors were generally not associated with longitudinal changes in white matter microstructure., Conclusion: Longitudinal diffusion analysis indicates widespread microstructural deterioration of the normal-appearing white matter in normal aging, with relative sparing of sensorimotor fibers., ((©) RSNA, 2015 Online supplemental material is available for this article.)

Purpose: To determine if T1ρ mapping can be used as an alternative to delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) in the quantification of cartilage biochemical composition in vivo in human knees with osteoarthritis., Materials and Methods: This study was approved by the institutional review board. Written informed consent was obtained from all participants. Twelve patients with knee osteoarthritis underwent dGEMRIC and T1ρ mapping at 3.0 T before undergoing total knee replacement. Outcomes of dGEMRIC and T1ρ mapping were calculated in six cartilage regions of interest. Femoral and tibial cartilages were harvested during total knee replacement. Cartilage sulphated glycosaminoglycan (sGAG) and collagen content were assessed with dimethylmethylene blue and hydroxyproline assays, respectively. A four-dimensional multivariate mixed-effects model was used to simultaneously assess the correlation between outcomes of dGEMRIC and T1ρ mapping and the sGAG and collagen content of the articular cartilage., Results: T1 relaxation times at dGEMRIC showed strong correlation with cartilage sGAG content (r = 0.73; 95% credibility interval [CI] = 0.60, 0.83) and weak correlation with cartilage collagen content (r = 0.40; 95% CI: 0.18, 0.58). T1ρ relaxation times did not correlate with cartilage sGAG content (r = 0.04; 95% CI: -0.21, 0.28) or collagen content (r = -0.05; 95% CI = -0.31, 0.20)., Conclusion: dGEMRIC can help accurately measure cartilage sGAG content in vivo in patients with knee osteoarthritis, whereas T1ρ mapping does not appear suitable for this purpose. Although the technique is not completely sGAG specific and requires a contrast agent, dGEMRIC is a validated and robust method for quantifying cartilage sGAG content in human osteoarthritis subjects in clinical research., ((©) RSNA, 2015.)

Background: Retropatellar cartilage damage has been suggested as an etiological factor for patellofemoral pain (PFP), a common knee condition among young and physically active individuals. To date, there is no conclusive evidence for an association between cartilage defects and PFP. Nowadays, advanced quantitative magnetic resonance imaging (MRI) techniques enable estimation of cartilage composition., Purpose: To investigate differences in patellofemoral cartilage composition between patients with PFP and healthy control subjects using quantitative MRI., Study Design: Cross-sectional study; Level of evidence, 3., Methods: Patients with PFP and healthy control subjects underwent 3.0-T MRI including delayed gadolinium-enhanced MRI of cartilage and T1ρ and T2 mapping. Differences in relaxation times of patellofemoral cartilage were compared between groups by linear regression analyses, adjusted for age, body mass index, sex, sports participation, and time of image acquisition., Results: This case-control study included 64 patients and 70 controls. The mean (±SD) age was 23.2 ± 6.4 years and the mean body mass index was 22.9 ± 3.4 kg/m(2); 56.7% were female. For delayed gadolinium-enhanced MRI of cartilage, the mean T1GD relaxation times of patellar (657.8 vs 669.4 ms) and femoral cartilage (661.6 vs 659.8 ms) did not significantly differ between patients and controls. In addition, no significant difference was found in mean T1ρ relaxation times of patellar (46.9 vs 46.0 ms) and femoral cartilage (50.8 vs 50.2 ms) and mean T2 relaxation times of patellar (33.2 vs 32.9 ms) and femoral cartilage (36.7 vs 36.6 ms) between patients and controls. Analysis of prespecified medial and lateral subregions within the patellofemoral cartilage also revealed no significant differences., Conclusion: There was no difference in composition of the patellofemoral cartilage, estimated with multiple quantitative MRI techniques, between patients with PFP and healthy control subjects. However, clinically relevant differences could not be ruled out for T1ρ in the adolescent population. Retropatellar cartilage damage has long been hypothesized as an important factor in the pathogenesis of PFP, but study findings suggest that diminished patellofemoral cartilage composition is not associated with PFP., (© 2016 The Author(s).)

Aim: To investigate whether preoperative chest computed tomography (CT) decreases postoperative mortality and stroke rate in cardiac surgery by detection of calcifications and visualization of postoperative anatomy in redo cardiac surgery which can be used to optimize the surgical approach., Methods: The PubMed, EMBASE and Cochrane databases were searched and articles concerning preoperative CT in cardiac surgery were included. Articles not reporting mortality, stroke rate or change in surgical approach were excluded. Studies concerning primary cardiac surgery as well as articles concerning redo cardiac surgery were both included., Results: Eighteen studies were included (n=4057 patients) in which 2584 patients received a preoperative CT. Seven articles (n=1754 patients) concerned primary surgery and eleven articles (n=2303 patients) concerned redo cardiac surgery. None of the studies was randomized but 8 studies provided a comparison to a control group. Stroke rate decreased with 77-96% (primary surgery) and 18-100% (redo surgery) in patients receiving a preoperative CT. Mortality decreased up to 66% in studies investigating primary surgery while the effect on mortality in redo surgery varied widely. Change in surgical approach based on CT-findings consisted of choosing a different cannulation site, opting for off-pump surgery and cancellation of surgery., Conclusions: Current evidence suggests that preoperative CT imaging may lead to decreased stroke and mortality rate in patients undergoing primary cardiac surgery by optimizing surgical approach. In patients undergoing redo cardiac surgery stroke rate is also decreased but the effect on mortality is unclear. However, evidence is weak and included studies were of moderate quality., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

White matter microstructural integrity has been related to cognition. Yet, the potential role of specific white matter tracts on top of a global white matter effect remains unclear, especially when considering specific cognitive domains. Therefore, we determined the tract-specific effect of white matter microstructure on global cognition and specific cognitive domains. In 4400 nondemented and stroke-free participants (mean age 63.7 years, 55.5% women), we obtained diffusion magnetic resonance imaging parameters (fractional anisotropy and mean diffusivity) in 14 white matter tracts using probabilistic tractography and assessed cognitive performance with a cognitive test battery. Tract-specific white matter microstructure in all supratentorial tracts was associated with poorer global cognition. Lower fractional anisotropy in association tracts, primarily the inferior fronto-occipital fasciculus, and higher mean diffusivity in projection tracts, in particular the posterior thalamic radiation, most strongly related to poorer cognition. Altered white matter microstructure related to poorer information processing speed, executive functioning, and motor speed, but not to memory. Tract-specific microstructural changes may aid in better understanding the mechanism of cognitive impairment and neurodegenerative diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cationic liposomes carrying high [Gd] can be used as efficient cell-labeling agents. In a compartmentalized state, Gd can cause signal loss (relaxivity quenching). The contributions of liposomal [Gd], size and compartmentalization state to relaxivity quenching were assessed. The dependency of signal intensity (SI) on intraliposomal [Gd] was assessed comparing three different [Gd] (0.3, 0.6 and 1.0 M Gd) in both small (80 nm) and large (120 nm) cationic liposomes. In addition, five compartmentalization states were compared: free Gd, intact Gd liposomes, ruptured Gd liposomes, Gd liposomes in intact cells and Gd liposomes in ruptured cells (simulating cell death). Gd also causes R2 effects, which is often overlooked. Therefore, both R1 and R2 relaxation rates of a dilution range were measured by T1 and T2 mapping on a 7 T clinical scanner. Less is more. As the unidirectional water efflux rate (outbound across the liposome membrane, κle) is proportional to the surface:volume ratio, smaller liposomes yielded a consistently higher R1 than larger liposomes. For equal voxel [Gd] less concentrated liposomes (0.3 M Gd) yielded higher R1/R2 ratio because of the higher extraliposomal water fraction (vl ). Gd exhibits a dualistic behavior: from hypointensity to hyperintensity to hypointensity, with decreasing [Gd]. Regarding compartmentalization, fewer membrane barriers means a higher R1 /R2 ratio. Gd liposomes exhibit a versatile contrast behavior, dependent on the compartmentalization state, liposomal size, intraliposomal [Gd] and liposome number. Both R1 and R2 effects contribute to this. The versatility allows one to tailor the optimal liposomal formulation to desired goals in cell labeling and tracking., (Copyright © 2015 John Wiley & Sons, Ltd.)

Objective: To investigate the achievable radiation dose reduction for coronary CT angiography (CCTA) with iterative reconstruction (IR) in adults and the effects on image quality., Methods: PubMed and EMBASE were searched, and original articles concerning IR for CCTA in adults using prospective electrocardiogram triggering were included. Primary outcome was the effective dose using filtered back projection (FBP) and IR. Secondary outcome was the effect of IR on objective and subjective image quality., Results: The search yielded 1616 unique articles, of which 10 studies (1042 patients) were included. The pooled routine effective dose with FBP was 4.2 mSv [95% confidence interval (CI) 3.5-5.0]. A dose reduction of 48% to a pooled effective dose of 2.2 mSv (95% CI 1.3-3.1) using IR was reported. Noise, contrast-to-noise ratio and subjective image quality were equal or improved in all but one study, whereas signal-to-noise ratio was decreased in two studies with IR at reduced dose., Conclusion: IR allows for CCTA acquisition with an effective dose of 2.2 mSv with preserved objective and subjective image quality.

Cardiovascular CT acquisition protocol optimization in pediatric patients, including newborns is often challenging. This might be due to non-cooperative patients, the complexity and variety of diseases and the need for stringent dose minimization. Motion artifacts caused by voluntary and involuntary motion are most frequently seen in cardiac imaging with high heart and respiratory rates. Dual source scanners of the second and third generation are particularly well suited to respond to these challenges. This can be accomplished with advanced scan options, such as high pitch scanning, short rotation times, automated tube voltage selection, tube current modulation and iterative reconstruction., (Copyright © 2016 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Familial hypercholesterolemia is typically caused by LDL receptor (LDLR) mutations that result in elevated levels of LDL cholesterol (LDL-C). In homozygous FH, the prevalence of aortic valve calcification (AoVC) reaches 100% and is often symptomatic., Objectives: The objective of this study was to investigate the prevalence, extent, and risk-modifiers of AoVC in heterozygous FH (he-FH) that are presently unknown., Methods: Asymptomatic patients with he-FH and 131 non-familial hypercholesterolemia controls underwent CT computed tomography calcium scoring. AoVC was defined as the presence of calcium at the aortic valve leaflets. The extent of AoVC was expressed in Agatston units, as the AoVC-score. We compared the prevalence and extent of AoVC between cases and controls. In addition, we investigated risk modifiers of AoVC, including the presence of LDLR mutations without residual function (LDLR-negative mutations), maximum untreated LDL-cholesterol (maxLDL), LDL-C, blood pressure, and coronary artery calcification (CAC)., Results: We included 145 asymptomatic patients with he-FH (93 men; mean age 52 ± 8 years) and 131 non-familial hypercholesterolemia controls. The prevalence (%) and AoVC-score (median, IQR) were higher in he-FH patients than in controls: 41%, 51 (9-117); and 21%, 21 (3-49) (p < 0.001 and p = 0.007). Age, untreated maxLDL, CAC, and diastolic blood pressure were independently associated with AoVC. LDLR-negative mutational he-FH was the strongest predictor of the AoVC-score (OR: 4.81; 95% CI: 2.22 to 10.40; p = <0.001)., Conclusions: Compared to controls, he-FH is associated with a high prevalence and a large extent of subclinical AoVC, especially in patients with LDLR-negative mutations, highlighting the critical role of LDL-C metabolism in AoVC etiology., (Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose: The aim of the study was to evaluate the prevalence of collateral findings detected in computed tomography coronary angiography (CTCA) in a multi-center registry., Materials and Methods: We performed a retrospective review of 4303 patients (2719 males, mean age 60.3 ± 10.2 years) undergoing 64-slice CTCA for suspected or known coronary artery disease (CAD) at various academic institutions between 01/2006 and 09/2010. Collateral findings were recorded and scored as: non-significant (no signs of relevant pathology, not necessary to be reported), significant (clear signs of pathology, mandatory to be reported), or major (remarkable pathology, mandatory to be reported and further investigated)., Results: We detected 6886 non-cardiac findings (1.6 non cardiac finding per patient). Considering all centers, only 865/4303 (20.1 %) patients were completely without any additional finding. Overall, 2095 (30.4 %) non-significant, 4486 (65.2 %) significant, and 305 (4.4 %) major findings were detected. Among major findings, primary lung cancer was reported in 21 cases. In every center, most prevalent significant findings were mediastinal lymph nodes >1 cm. In 256 patients, collateral findings were clinically more relevant than coexisting CAD and justified the symptoms of patients., Conclusions: The prevalence of significant and major collateral findings in CTCA is high. Radiologists should carefully evaluate the entire scan volume in each patient.

To estimate the probability of ≥ 50% coronary stenoses based on computed tomography (CT) segmental calcium score (SCS) and clinical factors. The Institutional Review Board approved the study. A training sample of 201 patients underwent CT calcium scoring and conventional coronary angiography (CCA). All patients consented to undergo CT before CCA after being informed of the additional radiation dose. SCS and calcification morphology were assessed in individual coronary segments. We explored the predictive value of patient's symptoms, clinical history, SCS and calcification morphology. We developed a prediction model in the training sample based on these variables then tested it in an independent test sample. The odds ratio (OR) for ≥ 50% coronary stenosis was 1.8-fold greater (p = 0.006) in patients with typical chest pain, twofold (p = 0.014) greater in patients with acute coronary syndromes, twofold greater (p < 0.001) in patients with prior myocardial infarction. Spotty calcifications had an OR for ≥ 50% stenosis 2.3-fold (p < 0.001) greater than the absence of calcifications, wide calcifications 2.7-fold (p < 0.001) greater, diffuse calcifications 4.6-fold (p < 0.001) greater. In middle segments, each unit of SCS had an OR 1.2-fold (p < 0.001) greater than in distal segments; in proximal segments the OR was 1.1-fold greater (p = 0.021). The ROC curve area of the prediction model was 0.795 (0.95 confidence interval 0.602-0.843). Validation in a test sample of 201 independent patients showed consistent diagnostic performance. In conjunction with calcification morphology, anatomical location, patient's symptoms and clinical history, SCS can be helpful to estimate the probability of ≥ 50% coronary stenosis.

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from 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. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study.

Objectives: Iterative reconstruction (IR) allows for dose reduction with maintained image quality in CT imaging. In this systematic review the reported effective dose reductions for chest CT and the effects on image quality are investigated., Methods: A systematic search in PubMed and EMBASE was performed. Primary outcome was the reported local reference and reduced effective dose and secondary outcome was the image quality with IR. Both non contrast-enhanced and enhanced studies comparing reference dose with reduced dose were included., Results: 24 studies were included. The median number of patients per study was 66 (range 23-200) with in total 1806 patients. The median reported local reference dose of contrast-enhanced chest CT with FBP was 2.6 (range 1.5-21.8) mSv. This decreased to 1.4 (range 0.4-7.3) mSv at reduced dose levels using IR. With non contrast-enhanced chest CT the dose decreased from 3.4 (range 0.7-7.8) mSv to 0.9 (range 0.1-4.5) mSv. Objective mage quality and diagnostic confidence and acceptability remained the same or improved with IR compared to FBP in most studies while data on diagnostic accuracy was limited., Conclusion: Radiation dose can be reduced to less than 2 mSv for contrast-enhanced chest CT and non contrast-enhanced chest CT is possible at a submillisievert dose using IR algorithms., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The question remains whether reduced cerebral blood flow (CBF) leads to brain atrophy or vice versa. We studied the longitudinal relation between CBF and brain volume in a community-dwelling population. In the Rotterdam Study, 3011 participants (mean age 59.6 years (s.d. 8.0)) underwent repeat brain magnetic resonance imaging to quantify brain volume and CBF at two time points. Adjusted linear regression models were used to investigate the bidirectional relation between CBF and brain volume. We found that smaller brain volume at baseline was associated with a steeper decrease in CBF in the whole population (standardized change per s.d. increase of total brain volume (TBV)=0.296 (95% confidence interval (CI) 0.200; 0.393)). Only in persons aged ⩾65 years, a lower CBF at baseline was associated with steeper decline of TBV (standardized change per s.d. increase of CBF=0.003 (95% CI -0.004; 0.010) in the whole population and 0.020 (95% CI 0.004; 0.036) in those aged ⩾65 years of age). Our results indicate that brain atrophy causes CBF to decrease over time, rather than vice versa. Only in persons aged >65 years of age did we find lower CBF to also relate to brain atrophy.

In vivo cell tracking has emerged as a much sought after tool for design and monitoring of cell-based treatment strategies. Various techniques are available for pre-clinical animal studies, from which much has been learned and still can be learned. However, there is also a need for clinically translatable techniques. Central to in vivo cell imaging is labelling of cells with agents that can give rise to signals in vivo, that can be detected and measured non-invasively. The current imaging technology of choice for clinical translation is MRI in combination with labelling of cells with magnetic agents. The main challenge encountered during the cell labelling procedure is to efficiently incorporate the label into the cell, such that the labelled cells can be imaged at high sensitivity for prolonged periods of time, without the labelling process affecting the functionality of the cells. In this respect, nanoparticles offer attractive features since their structure and chemical properties can be modified to facilitate cellular incorporation and because they can carry a high payload of the relevant label into cells. While these technologies have already been applied in clinical trials and have increased the understanding of cell-based therapy mechanism, many challenges are still faced.

Background: Loss of brain white matter microstructure is presumed to be an early sign of neurodegenerative disease. Yet, little is known on microstructural changes of various white matter tracts with normal aging., Methods: In 4532 nondemented elderly persons, we studied age-related changes in tract-specific diffusion characteristics for 25 tracts using probabilistic tractography. We studied how diffusion differs across tracts with aging, whether this depends on macrostructural white matter changes, and whether cardiovascular risk factors affect microstructure., Results: With increasing age, loss of microstructural organization occurred in association, commissural and limbic tracts. White matter lesions and atrophy each partially explained this loss. We observed worse microstructure with severe hypertension, current smoking and diabetes mellitus, independent from age and macrostructural white matter changes., Conclusions: Microstructure of white matter tracts changes with age, and may mark neurodegeneration more sensitively than white matter lesion load and atrophy. Cardiovascular factors relate to loss in microstructural organization., (Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.)

To establish clinical utility, we need to understand the consequences of extracellular volume (ECV) changes on cardiac function and adverse events, understand its incremental value compared with pre- and postprocedural clinical risk and serum biomarkers, and define how this knowledge will affect therapeutic management.

Objectives: The purpose of this study was to estimate the myocardial area at risk (MAAR) using coronary computed tomography angiography (CTA) and Voronoi algorithm-based myocardial segmentation in comparison with single-photon emission computed tomography (SPECT)., Methods: Thirty-four patients with coronary artery disease underwent 128-slice coronary CTA, stress/rest thallium-201 SPECT, and coronary angiography (CAG). CTA-based MAAR was defined as the sum of all CAG stenosis (>50%) related territories (the ratio of the left ventricular volume). Using automated quantification software (17-segment model, 5-point scale), SPECT-based MAAR was defined as the number of segments with a score above zero as compared to the total 17 segments by summed stress score (SSS), difference (SDS) score map, and comprehensive SPECT interpretation with either SSS or SDS best correlating CAG findings (SSS/SDS). Results were compared using Pearson's correlation coefficient., Results: Forty-nine stenoses were observed in 102 major coronary territories. Mean value of CTA-based MAAR was 28.3 ± 14.0%. SSS-based, SDS-based, and SSS/SDS-based MAAR was 30.1 ± 6.1%, 20.1 ± 15.8%, and 26.8 ± 15.7%, respectively. CTA-based MAAR was significantly related to SPECT-based MAAR (r = 0.531 for SSS; r = 0.494 for SDS; r = 0.814 for SSS/SDS; P < 0.05 in each)., Conclusions: CTA-based Voronoi algorithm myocardial segmentation reliably quantifies SPECT-based MAAR., Key Points: • Voronoi algorithm allows for three-dimensional myocardial segmentation of coronary CT angiography • Stenosis-related CT myocardial territories correlate to SPECT based area at risk • CT angiography myocardial segmentation may assist in clinical decision-making.

Background: There is a growing amount of evidence suggesting that the composition of carotid atherosclerotic plaques may be of clinical relevance. Yet, little is known on the coexistence of potentially vulnerable and stabilizing components within asymptomatic plaques. Therefore, in this study we set out to investigate the coexistence of intraplaque calcification, hemorrhage and lipid core within the carotid artery using a multi-modality imaging approach., Methods: In 329 subjects from the population-based Rotterdam Study, all with ultrasound-confirmed carotid wall thickening, we performed a multi-detector CT and a high-resolution MRI of the carotid artery bifurcation at both sides. On the CT examinations, we quantified the volume of intraplaque calcification, and using the MRI examinations we rated the presence of intraplaque hemorrhage and of lipid core. In total, we investigated 611 carotid arteries with plaques. With logistic regression models we investigated the relationship of calcification volume - as a potential stabilizing component - with the presence of potential vulnerable components (intraplaque hemorrhage and lipid core) within each carotid plaque. We adjusted all analyses for age, sex and maximal plaque thickness. Next, we stratified on degree of stenosis (≤ or >30%) to evaluate effect modification by atherosclerotic burden., Results: We found that a larger calcification volume was associated with a higher prevalence of intraplaque hemorrhage, and a lower prevalence of lipid core (fully-adjusted odds ratio (OR) per standard deviation (SD) increase in calcification volume: 2.04 (95% confidence intervals (CI): 1.49; 2.78) and 0.72 (95% CI: 0.58; 0.90), respectively). Stratification on the degree of stenosis showed no difference in the association between calcification volume and hemorrhage over strata, while the relationship between a larger calcification volume and a lower prevalence of lipid seemed more pronounced in persons with a high degree of stenosis., Conclusions: In this population-based setting, we found that there is a complex relationship between calcification, intraplaque hemorrhage and lipid core within the carotid atherosclerotic plaque. Plaques with a higher load of calcification contain more often hemorrhagic components, but less often lipid core. Our results suggest that both in small and large plaques, intraplaque calcification may not be a stabilizing factor per se. These findings create an urge for conducting prospective studies investigating the interrelation of these different plaque components with regard to future cerebrovascular events., (© 2015 S. Karger AG, Basel.)