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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 To compare the diagnostic performance and radiation exposure of 128-slice dual-source CT coronary angiography (CTCA) protocols to detect coronary stenosis with more than 50 % lumen obstruction. Methods We prospectively included 459 symptomatic patients referred for CTCA. Patients were randomized between high-pitch spiral vs. narrow-window sequential CTCA protocols (heart rate below 65 bpm, group A), or between wide-window sequential vs. retrospective spiral protocols (heart rate above 65 bpm, group B). Diagnostic performance of CTCA was compared with quantitative coronary angiography in 267 patients. Results In group A (231 patients, 146 men, mean heart rate 58 ± 7 bpm), high-pitch spiral CTCA yielded a lower per-segment sensitivity compared to sequential CTCA (89 % vs. 97 %, P  = 0.01). Specificity, PPV and NPV were comparable (95 %, 62 %, 99 % vs. 96 %, 73 %, 100 %, P  > 0.05) but radiation dose was lower (1.16 ± 0.60 vs. 3.82 ± 1.65 mSv, P  < 0.001). In group B (228 patients, 132 men, mean heart rate 75 ± 11 bpm), per-segment sensitivity, specificity, PPV and NPV were comparable (94 %, 95 %, 67 %, 99 % vs. 92 %, 95 %, 66 %, 99 %, P  > 0.05). Radiation dose of sequential CTCA was lower compared to retrospective CTCA (6.12 ± 2.58 vs. 8.13 ± 4.52 mSv, P  < 0.001). Diagnostic performance was comparable in both groups. Conclusion Sequential CTCA should be used in patients with regular heart rates using 128-slice dual-source CT, providing optimal diagnostic accuracy with as low as reasonably achievable (ALARA) radiation dose. Key Points • 128-slice dual-source CT coronary angiography offers several different acquisition protocols. • Randomized comparison of protocols reveals an optimal protocol selection strategy. • Appropriate CTCA protocol selection lowers radiation dose, while maintaining high quality. • CTCA protocol selection should be based on individual patient characteristics. • A prospective sequential protocol is preferred for CTCA.

To evaluate the frequency of total-body CT and MR features of postmortem change in in-hospital deaths. 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. 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). 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.

Background To assess diagnostic accuracy of quantitative double-echo in steady-state (qDESS) MRI for detecting synovitis in knee osteoarthritis (OA). Methods Patients with different degrees of radiographic knee OA were included prospectively. All underwent MRI with both qDESS and contrast-enhanced T1-weighted magnetic resonance imaging (CE-MRI). A linear combination of the two qDESS images can be used to create an image that displays contrast between synovium and the synovial fluid. Synovitis on both qDESS and CE-MRI was assessed semi-quantitatively, using a whole-knee synovitis sum score, indicating no/equivocal, mild, moderate, and severe synovitis. The correlation between sum scores of qDESS and CE-MRI (reference standard) was determined using Spearman’s rank correlation coefficient and intraclass correlation coefficient for absolute agreement. Receiver operating characteristic analysis was performed to assess the diagnostic performance of qDESS for detecting different degrees of synovitis, with CE-MRI as reference standard. Results In the 31 patients included, very strong correlation was found between synovitis sum scores on qDESS and CE-MRI ( ρ  = 0.96, p  < 0.001), with high absolute agreement (0.84 (95%CI 0.14–0.95)). Mean sum score (SD) values on qDESS 5.16 (3.75) were lower than on CE-MRI 7.13 (4.66), indicating systematically underestimated synovitis severity on qDESS. For detecting mild synovitis or higher, high sensitivity and specificity were found for qDESS (1.00 (95%CI 0.80–1.00) and 0.909 (0.571–1.00), respectively). For detecting moderate synovitis or higher, sensitivity and specificity were good (0.727 (95%CI 0.393–0.927) and 1.00 (0.800–1.00), respectively). Conclusion qDESS MRI is able to, however with an underestimation, detect synovitis in patients with knee OA.

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.

Autopsy rates worldwide have dropped significantly over the last decades and imaging-based autopsies are increasingly used as an alternative to conventional autopsy. Our aim was to evaluate the clinical performance and cost of minimally invasive autopsy. This study was part of a prospective cohort study evaluating a newly implemented minimally invasive autopsy consisting of MRI, CT, and biopsies. We calculated diagnostic yield and clinical utility-defined as the percentage successfully answered clinical questions-of minimally invasive autopsy. We performed minimally invasive autopsy in 46 deceased (30 men, 16 women; mean age 62.9±17.5, min-max: 18-91). Ninety-six major diagnoses were found with the minimally invasive autopsy of which 47/96 (49.0%) were new diagnoses. CT found 65/96 (67.7%) major diagnoses and MRI found 82/96 (85.4%) major diagnoses. Eighty-four clinical questions were asked in all cases. Seventy-one (84.5%) of these questions could be answered with minimally invasive autopsy. CT successfully answered 34/84 (40.5%) clinical questions; in 23/84 (27.4%) without the need for biopsies, and in 11/84 (13.0%) a biopsy was required. MRI successfully answered 60/84 (71.4%) clinical questions, in 27/84 (32.1%) without the need for biopsies, and in 33/84 (39.8%) a biopsy was required. The mean cost of a minimally invasive autopsy was €1296 including brain biopsies and €1087 without brain biopsies. Mean cost of CT was €187 and of MRI €284. A minimally invasive autopsy, consisting of CT, MRI and CT-guided biopsies, performs well in answering clinical questions and detecting major diagnoses. However, the diagnostic yield and clinical utility were quite low for postmortem CT and MRI as standalone modalities.

We present and evaluate a new insight into magnetic resonance imaging (MRI). It is based on the algebraic description of the magnetization during the transient response—including intrinsic magnetic resonance parameters such as longitudinal and transverse relaxation times (T 1 , T 2 ) and proton density (PD) and experimental conditions such as radiofrequency field (B 1 ) and constant/homogeneous magnetic field (B 0 ) from associated scanners. We exploit the correspondence among three different elements: the signal evolution as a result of a repetitive sequence of blocks of radiofrequency excitation pulses and encoding gradients, the continuous Bloch equations and the mathematical description of a sequence as a linear system. This approach simultaneously provides, in a single measurement, all quantitative parameters of interest as well as associated system imperfections. Finally, we demonstrate the in-vivo applicability of the new concept on a clinical MRI scanner.

Articular cartilage has very limited intrinsic regenerative capacity, making cell-based therapy a tempting approach for cartilage repair. Cell tracking can be a major step towards unraveling and improving the repair process of these therapies. We studied superparamagnetic iron oxides (SPIO) for labeling human bone marrow-derived mesenchymal stem cells (hBMSCs) regarding effectivity, cell viability, long term metabolic cell activity, chondrogenic differentiation and hBMSC secretion profile. We additionally examined the capacity of synovial cells to endocytose SPIO from dead, labeled cells, together with the use of magnetic resonance imaging (MRI) for intra-articular visualization and quantification of SPIO labeled cells. Efficacy and various safety aspects of SPIO cell labeling were determined using appropriate assays. Synovial SPIO re-uptake was investigated in vitro by co-labeling cells with SPIO and green fluorescent protein (GFP). MRI experiments were performed on a clinical 3.0T MRI scanner. Two cell-based cartilage repair techniques were mimicked for evaluating MRI traceability of labeled cells: intra-articular cell injection and cell implantation in cartilage defects. Cells were applied ex vivo or in vitro in an intra-articular environment and immediately scanned. SPIO labeling was effective and did not impair any of the studied safety aspects, including hBMSC secretion profile. SPIO from dead, labeled cells could be taken up by synovial cells. Both injected and implanted SPIO-labeled cells could accurately be visualized by MRI in a clinically relevant sized joint model using clinically applied cell doses. Finally, we quantified the amount of labeled cells seeded in cartilage defects using MR-based relaxometry. SPIO labeling appears to be safe without influencing cell behavior. SPIO labeled cells can be visualized in an intra-articular environment and quantified when seeded in cartilage defects.

Objectives We evaluated the influence of sinogram-affirmed iterative reconstruction (SAFIRE) on the coronary artery calcium (CAC) score by computed tomography (CT). Materials and methods Seventy patients underwent CAC imaging by 128-slice dual-source CT. CAC volume, mass and Agatston score were calculated from images reconstructed by filtered back projection (FBP) without and with incremental degrees of the SAFIRE algorithm (10-50 %). We used the repeated measuring test and the Steel-Dwass test for multiple comparisons of values and the difference ratio among different SAFIRE groups using the FBP as reference. Results The median Agatston score (range) decreased with incremental SAFIRE degrees: 163 (0.1 − 3,393.3), 158.4 (0.3 − 3,079.3), 137.7 (0.1 − 2,978.0), 120.6 (0 − 2,783.6), 102.6 (0 − 2,468.4) and 84.1 (0 − 2,186.9) for 0 % (FBP), 10 %, 20 %, 30 %, 40 % and 50 % SAFIRE, respectively ( P  < 0.05). In comparison with FBP, CAC volume (from 8.1 % to 47.7 %), CAC mass (from 5.3 % to 44.7 %) and CAC Agatston score (from 7.3 % to 48.4 %) all decreased with increasing SAFIRE from 10 % to 50 %, respectively ( P  < 0.05). High-grade SAFIRE resulted in the disappearance of detectable calcium in three cases with low calcium burden. Conclusion SAFIRE noise reduction techniques significantly affected the CAC, which potentially alters perceived cardiovascular risk. Key points • Iterative reconstruction reduces the amount of coronary calcium detected. • Iterative reconstruction potentially changes the calcium-based cardiovascular risk estimation. • Incidentally, calcium is no longer detectable using iterative reconstruction.

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