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Contrast enhanced pulmonary vein magnetic resonance angiography (PV CE-MRA) has value in atrial ablation pre-procedural planning. We aimed to provide high fidelity, ECG gated PV CE-MRA accelerated by variable density Cartesian sampling (VD-CASPR) with image navigator (iNAV) respiratory motion correction acquired in under 4 min. We describe its use in part during the global iodinated contrast shortage. VD-CASPR/iNAV framework was applied to ECG-gated inversion and saturation recovery gradient recalled echo PV CE-MRA in 65 patients (66 exams) using .15 mmol/kg Gadobutrol. Image quality was assessed by three physicians, and anatomical segmentation quality by two technologists. Left atrial SNR and left atrial/myocardial CNR were measured. 12 patients had CTA within 6 months of MRA. Two readers assessed PV ostial measurements versus CTA for intermodality/interobserver agreement. Inter-rater/intermodality reliability, reproducibility of ostial measurements, SNR/CNR, image, and anatomical segmentation quality was compared. The mean acquisition time was 3.58 ± 0.60 min. Of 35 PV pre-ablation datasets (34 patients), mean anatomical segmentation quality score was 3.66 ± 0.54 and 3.63 ± 0.55 as rated by technologists 1 and 2, respectively (p = 0.7113). Good/excellent anatomical segmentation quality (grade 3/4) was seen in 97% of exams. Each rated one exam as moderate quality (grade 2). 95% received a majority image quality score of good/excellent by three physicians. Ostial PV measurements correlated moderate to excellently with CTA (ICCs range 0.52-0.86). No difference in SNR was observed between IR and SR. High quality PV CE-MRA is possible in under 4 min using iNAV bolus timing/motion correction and VD-CASPR., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Dark-blood late gadolinium enhancement (LGE) has been shown to improve the visualization and quantification of areas of ischemic scar compared to standard bright-blood LGE. Recently, the performance of various semi-automated quantification methods has been evaluated for the assessment of infarct size using both dark-blood LGE and conventional bright-blood LGE with histopathology as a reference standard. However, the impact of this sequence on different quantification strategies in vivo remains uncertain. In this study, various semi-automated scar quantification methods were evaluated for a range of different ischemic and non-ischemic pathologies encountered in clinical practice. A total of 62 patients referred for clinical cardiovascular magnetic resonance (CMR) were retrospectively included. All patients had a confirmed diagnosis of either ischemic heart disease (IHD; n = 21), dilated/non-ischemic cardiomyopathy (NICM; n = 21), or hypertrophic cardiomyopathy (HCM; n = 20) and underwent CMR on a 1.5 T scanner including both bright- and dark-blood LGE using a standard PSIR sequence. Both methods used identical sequence settings as per clinical protocol, apart from the inversion time parameter, which was set differently. All short-axis LGE images with scar were manually segmented for epicardial and endocardial borders. The extent of LGE was then measured visually by manual signal thresholding, and semi-automatically by signal thresholding using the standard deviation (SD) and the full width at half maximum (FWHM) methods. For all quantification methods in the IHD group, except the 6 SD method, dark-blood LGE detected significantly more enhancement compared to bright-blood LGE (p < 0.05 for all methods). For both bright-blood and dark-blood LGE, the 6 SD method correlated best with manual thresholding (16.9% vs. 17.1% and 20.1% vs. 20.4%, respectively). For the NICM group, no significant differences between LGE methods were found. For bright-blood LGE, the 5 SD method agreed best with manual thresholding (9.3% vs. 11.0%), while for dark-blood LGE the 4 SD method agreed best (12.6% vs. 11.5%). Similarly, for the HCM group no significant differences between LGE methods were found. For bright-blood LGE, the 6 SD method agreed best with manual thresholding (10.9% vs. 12.2%), while for dark-blood LGE the 5 SD method agreed best (13.2% vs. 11.5%). Semi-automated LGE quantification using dark-blood LGE images is feasible in both patients with ischemic and non-ischemic scar patterns. Given the advantage in detecting scar in patients with ischemic heart disease and no disadvantage in patients with non-ischemic scar, dark-blood LGE can be readily and widely adopted into clinical practice without compromising on quantification., (© 2024. The Author(s).)

Background: Incomplete atrial lesions resulting in pulmonary vein-left atrium reconnection after pulmonary vein antrum isolation (PVAI), are related to atrial fibrillation (AF) recurrence. Unfortunately, during the PVAI procedure, fluoroscopy and electroanatomic mapping cannot accurately determine the location and size of the ablation lesions in the atrial wall and this can result in incomplete PVAI lesions (PVAI-L) after radiofrequency catheter ablation (RFCA)., Aim: We seek to evaluate whether cardiac magnetic resonance (CMR), immediately after RFCA of AF, can identify PVAI-L by characterizing the left atrial tissue., Methods: Ten patients (63.1 ± 5.7 years old, 80% male) receiving a RFCA for paroxysmal AF underwent a CMR before (<1 week) and after (<1 h) the PVAI. Two-dimensional dark-blood T2-weighted short tau inversion recovery (DB-STIR), Three-dimensional inversion-recovery prepared long inversion time (3D-TWILITE) and three-dimensional late gadolinium enhancement (3D-LGE) images were performed to visualize PVAI-L., Results: The PVAI-L was visible in 10 patients (100%) using 3D-TWILITE and 3D-LGE. Conversely, On DB-STIR, the ablation core of the PAVI-L could not be identified because of a diffuse high signal of the atrial wall post-PVAI. Microvascular obstruction was identified in 7 (70%) patients using 3D-LGE., Conclusion: CMR can visualize PVAI-L immediately after the RFCA of AF even without the use of contrast agents. Future studies are needed to understand if the use of CMR for PVAI-L detection after RFCA can improve the results of ablation procedures., (© 2023 Wiley Periodicals LLC.)

Aims: 18F-sodium fluoride ([18F]fluoride) and gadobutrol are promising probes for positron emission tomography (PET) and magnetic resonance imaging (MRI) characterizing coronary artery disease (CAD) activity. Unlike [18F]fluoride-PET/computed tomography (CT), the potential of PET/MR using [18F]fluoride and gadobutrol simultaneously, has so far not been evaluated. This study assessed feasibility and diagnostic potential of [18F]fluoride and gadobutrol enhanced dual-probe PET/MR in patients with CAD., Methods and Results: Twenty-one patients (age, 66.7 ± 6.7 years) with CAD scheduled for invasive coronary angiography (XCA) underwent simultaneous [18F]fluoride (mean activity/effective dose: 157.2 ± 29.7 MBq/3.77 ± 0.72 mSv) and gadobutrol enhanced PET/MR on an integrated PET/MRI (3 T) scanner. Optical coherence tomography (OCT) was used as reference. Target-to-background ratio (TBR, [18F]fluoride-PET) and contrast-to-noise ratio (CNR) values (MRI, gadobutrol) were calculated for each coronary segment. Previously suggested PET/CT-TBR thresholds for adverse coronary events were evaluated. High-risk plaques, i.e. calcified and non-calcified thin-cap fibroatheromas (TCFAs) were predominantly located in segments with a TBR >1.28 (P = 0.012). Plaques containing a lipid core on OCT, were more frequently detected in segments with a TBR >1.25 (P < 0.001). TBR values significantly correlated with maximum calcification thickness (P = 0.009), while fibrous cap thickness was significantly less in segments with a TBR >1.28 (P = 0.044). Above a TBR threshold of >1.28, CNR values significantly correlated with the presence of calcified TCFAs (P = 0.032)., Conclusion: Simultaneous [18F]fluoride and gadobutrol dual-probe PET/MRI is feasible in clinical practice and may facilitate the identification of high-risk patients. The combination of coronary MR-derived CNR values post gadobutrol and [18F]fluoride based TBR values may improve identification of high-risk plaque features., Competing Interests: Conflict of interest: none declared., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

The incidence of abdominal aortic aneurysms (AAAs) has substantially increased during the last 20 years and their rupture remains the third most common cause of sudden death in the cardiovascular field after myocardial infarction and stroke. The only established clinical parameter to assess AAAs is based on the aneurysm size. Novel biomarkers are needed to improve the assessment of the risk of rupture. ADAMTS4 (A Disintegrin And Metalloproteinase with ThromboSpondin motifs 4) is a strongly upregulated proteoglycan cleaving enzyme in the unstable course of AAAs. In the screening of a one-bead-one-compound library against ADAMTS4, a low-molecular-weight cyclic peptide is discovered with favorable properties for in vivo molecular magnetic resonance imaging applications. After identification and characterization, it's potential is evaluated in an AAA mouse model. The ADAMTS4-specific probe enables the in vivo imaging-based prediction of aneurysm expansion and rupture., (© 2022. The Author(s).)

MR imaging with an albumin-binding probe enables the visualization of endothelial permeability and damage in the arterial system. The goal of this study was to compare signal enhancement of lesions with different grades of stenosis segments on molecular CMR in combination with the albumin-binding probe gadofosveset. This prospective clinical study included patients with symptoms suggestive of coronary artery disease (CAD). Patients underwent gadofosveset-enhanced cardiovascular magnetic resonance (CMR) imaging and x-ray angiography (QCA) within 24 h. CMR imaging was performed prior to and 24 h following the administration of gadofosveset. Contrast-to-noise ratios (CNRs) between segments with different grades of stenosis were compared. Overall, n = 203 segments of 26 patients were included. Lesions with more than > 70% stenosis demonstrated significantly higher CNRs compared to lesions < 70% (7.6 ± 8.3 vs. 2.5 ± 4.9; p < 0.001). Post-stenotic segments of lesions > 70% stenosis showed significant higher signal enhancement compared to segments located upstream of these lesions (7.3 ± 8.8 vs. 2.8 ± 2.2; p = 0.02). No difference in signal enhancement between segments proximal and distal of lesions with stenosis greater than 50% was measured (3.3 ± 2.8 vs. 2.4 ± 2.7; p = 0.18). ROC analysis for the detection of lesions ≥ 70% revealed an area under the curve of 0.774 (95% CI 0.681-0.866). This study suggests that relevant coronary stenosis and their down-stream segments are associated with increased signal enhancement on Gadofosveset-enhanced CMR, suggesting a higher endothelial permeability in these lesions. An albumin-binding MR probe could represent a novel in vivo biomarker for the identification and characterization of these vulnerable coronary segments., (© 2021. The Author(s).)

Atherosclerosis is a progressive inflammatory vascular disease characterized by endothelial dysfunction and plaque burden. Extracellular matrix (ECM)-associated plasma proteins play an important role in disease development. Our magnetic resonance imaging (MRI) study investigates the feasibility of using two different molecular MRI probes for the simultaneous assessment of ECM-associated intraplaque albumin deposits caused by endothelial damage and progressive inflammation in atherosclerosis. Male apolipoprotein E-deficient ( ApoE -/- )-mice were fed a high-fat diet (HFD) for 2 or 4 months. Another ApoE -/- -group was treated with pravastatin and received a HFD for 4 months. T1- and T2*-weighted MRI was performed before and after albumin-specific MRI probe (gadofosveset) administration and a macrophage-specific contrast agent (ferumoxytol). Thereafter, laser ablation inductively coupled plasma mass spectrometry and histology were performed. With advancing atherosclerosis, albumin-based MRI signal enhancement and ferumoxytol-induced signal loss areas in T2*-weighted MRI increased. Significant correlations between contrast-to-noise-ratio (CNR) post-gadofosveset and albumin stain (R 2 = 0.78, p < 0.05), and signal loss areas in T2*-weighted MRI with Perls' Prussian blue stain (R 2 = 0.83, p < 0.05) were observed. No interference of ferumoxytol with gadofosveset enhancement was detectable. Pravastatin led to decreased inflammation and intraplaque albumin. Multi-target MRI combining ferumoxytol and gadofosveset is a promising method to improve diagnosis and treatment monitoring in atherosclerosis.

Simultaneous PET-MR imaging has shown potential for the comprehensive assessment of myocardial health from a single examination. Furthermore, MR-derived respiratory motion information has been shown to improve PET image quality by incorporating this information into the PET image reconstruction. Separately, MR-based anatomically guided PET image reconstruction has been shown to perform effective denoising, but this has been so far demonstrated mainly in brain imaging. To date the combined benefits of motion compensation and anatomical guidance have not been demonstrated for myocardial PET-MR imaging. This work addresses this by proposing a single cardiac PET-MR image reconstruction framework which fully utilises MR-derived information to allow both motion compensation and anatomical guidance within the reconstruction. Methods: Fifteen patients underwent a 18 F-FDG cardiac PET-MR scan with a previously introduced acquisition framework. The MR data processing and image reconstruction pipeline produces respiratory motion fields and a high-resolution respiratory motion-corrected MR image with good tissue contrast. This MR-derived information was then included in a respiratory motion-corrected, cardiac-gated, anatomically guided image reconstruction of the simultaneously acquired PET data. Reconstructions were evaluated by measuring myocardial contrast and noise and compared to images from several comparative intermediate methods using the components of the proposed framework separately. Results: Including respiratory motion correction, cardiac gating, and anatomical guidance significantly increased contrast. In particular, myocardium-to-blood pool contrast increased by 143% on average (p<0.0001) compared to conventional uncorrected, non-guided PET images. Furthermore, anatomical guidance significantly reduced image noise compared to non-guided image reconstruction by 16.1% (p<0.0001). Conclusion: The proposed framework for MR-derived motion compensation and anatomical guidance of cardiac PET data was shown to significantly improve image quality compared to alternative reconstruction methods. Each component of the reconstruction pipeline was shown to have a positive impact on the final image quality. These improvements have the potential to improve clinical interpretability and diagnosis based on cardiac PET-MR images., (Copyright © 2021 by the Society of Nuclear Medicine and Molecular Imaging, Inc.)

Background: Currently, there is no reliable nonsurgical treatment for abdominal aortic aneurysm (AAA). This study, therefore, investigates if doxycycline reduces AAA growth and the number of rupture-related deaths in a murine ApoE-/- model of AAA and whether gadofosveset trisodium-based MRI differs between animals with and without doxycycline treatment., Methods: Nine ApoE-/- mice were implanted with osmotic minipumps continuously releasing angiotensin II and treated with doxycycline (30 mg/kg/d) in parallel. After four weeks, MRI was performed at 3T with a clinical dose of the albumin-binding probe gadofosveset (0.03 mmol/kg). Results were compared with previously published wild-type control animals and with previously studied ApoE-/- animals without doxycycline treatment. Differences in mortality were also investigated between these groups., Results: In a previous study, we found that approximately 25% of angiotensin II-infused ApoE-/- mice died, whereas in the present study, only one out of 9 angiotensin II-infused and doxycycline-treated ApoE-/- mice (11.1%) died within 4 weeks. Furthermore, doxycycline-treated ApoE-/- mice showed significantly lower contrast-to-noise (CNR) values ( p =0.017) in MRI compared to ApoE-/- mice without doxycycline treatment. In vivo measurements of relative signal enhancement (CNR) correlated significantly with ex vivo measurements of albumin staining ( R 2  = 0.58). In addition, a strong visual colocalization of albumin-positive areas in the fluorescence albumin staining with gadolinium distribution in LA-ICP-MS was shown. However, no significant difference in aneurysm size was observed after doxycycline treatment., Conclusion: The present experimental in vivo study suggests that doxycycline treatment may reduce rupture-related deaths in AAA by slowing endothelial damage without reversing aneurysm growth., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Lisa C. Adams et al.)

Background: Dixon cardiac magnetic resonance fingerprinting (MRF) has been recently introduced to simultaneously provide water T 1 , water T 2 , and fat fraction (FF) maps., Purpose: To assess Dixon cardiac MRF repeatability in healthy subjects and its clinical feasibility in a cohort of patients with cardiovascular disease., Population: T1MES phantom, water-fat phantom, 11 healthy subjects and 19 patients with suspected cardiovascular disease., Study Type: Prospective., Field Strength/sequence: 1.5T, inversion recovery spin echo (IRSE), multiecho spin echo (MESE), modified Look-Locker inversion recovery (MOLLI), T 2 gradient spin echo (T 2 -GRASE), 6-echo gradient rewound echo (GRE), and Dixon cardiac MRF., Assessment: Dixon cardiac MRF precision was assessed through repeated scans against conventional MOLLI, T 2 -GRASE, and PDFF in phantom and 11 healthy subjects. Dixon cardiac MRF native T 1 , T 2 , FF, postcontrast T 1 and synthetic extracellular volume (ECV) maps were assessed in 19 patients in comparison to conventional sequences. Measurements in patients were performed in the septum and in late gadolinium enhanced (LGE) areas and assessed using mean value distributions, correlation, and Bland-Altman plots. Image quality and diagnostic confidence were assessed by three experts using 5-point scoring scales., Statistical Tests: Paired Wilcoxon rank signed test and paired t-tests were applied. Statistical significance was indicated by *(P < 0.05)., Results: Dixon cardiac MRF showed good overall precision in phantom and in vivo. Septal average repeatability was ~23 msec for T 1 , ~2.2 msec for T 2 , and ~1% for FF. Biases in healthy subjects/patients were measured at +37 msec*/+60 msec* and -8.8 msec*/-8 msec* when compared to MOLLI and T 2 -GRASE, respectively. No statistically significant differences in postcontrast T 1 (P = 0.17) and synthetic ECV (P = 0.19) measurements were observed in patients., Data Conclusion: Dixon cardiac MRF attained good overall precision in phantom and healthy subjects, while providing coregistered T 1 , T 2 , and fat fraction maps in a single breath-hold scan with similar or better image quality than conventional methods in patients., Level of Evidence: 2., Technical Efficacy Stage: 2., (© 2020 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Non-rigid motion-corrected reconstruction has been proposed to account for the complex motion of the heart in free-breathing 3D coronary magnetic resonance angiography (CMRA). This reconstruction framework requires efficient and accurate estimation of non-rigid motion fields from undersampled images at different respiratory positions (or bins). However, state-of-the-art registration methods can be time-consuming. This article presents a novel unsupervised deep learning-based strategy for fast estimation of inter-bin 3D non-rigid respiratory motion fields for motion-corrected free-breathing CMRA. The proposed 3D respiratory motion estimation network (RespME-net) is trained as a deep encoder-decoder network, taking pairs of 3D image patches extracted from CMRA volumes as input and outputting the motion field between image patches. Using image warping by the estimated motion field, a loss function that imposes image similarity and motion smoothness is adopted to enable training without ground truth motion field. RespME-net is trained patch-wise to circumvent the challenges of training a 3D network volume-wise which requires large amounts of GPU memory and 3D datasets. We perform 5-fold cross-validation with 45 CMRA datasets and demonstrate that RespME-net can predict 3D non-rigid motion fields with subpixel accuracy (0.44 ± 0.38 mm) within ~10 seconds, being ~20 times faster than a GPU-implemented state-of-the-art non-rigid registration method. Moreover, we perform non-rigid motion-compensated CMRA reconstruction for 9 additional patients. The proposed RespME-net has achieved similar motion-corrected CMRA image quality to the conventional registration method regarding coronary artery length and sharpness.

Purpose: Quantitative T 1 , T 2 , T 2 *, and fat fraction (FF) maps are promising imaging biomarkers for the assessment of liver disease, however these are usually acquired in sequential scans. Here we propose an extended MR fingerprinting (MRF) framework enabling simultaneous liver T 1 , T 2 , T 2 *, and FF mapping from a single ~14 s breath-hold scan., Methods: A gradient echo (GRE) liver MRF sequence with nine readouts per TR, low flip angles (5-15°), varying magnetisation preparation and golden angle radial trajectory is acquired at 1.5T to encode T 1 , T 2 , T 2 *, and FF simultaneously. The nine-echo time-series are reconstructed using a low-rank tensor constrained reconstruction and used to fit T 2 *, B 0 and to separate the water and fat signals. Water- and fat-specific T 1 , T 2, and M 0 are obtained through dictionary matching, whereas FF estimation is extracted from the M 0 maps. The framework was evaluated in a standardized T 1 /T 2 phantom, a water-fat phantom, and 12 subjects in comparison to reference methods. Preliminary clinical feasibility is shown in four patients., Results: The proposed water T 1 , water T 2 , T 2 *, and FF maps in phantoms showed high coefficients of determination (r 2 > 0.97) relative to reference methods. Measured liver MRF values in vivo (mean ± SD) for T 1 , T 2 , T 2 *, and FF were 671 ± 60 ms, 43.2 ± 6.8 ms, 29 ± 6.6 ms, and 3.2 ± 2.6% with biases of 92 ms, -7.1 ms, -1.4 ms, and 0.63% when compared to conventional methods., Conclusion: A nine-echo liver MRF sequence allows for quantitative multi-parametric liver tissue characterization in a single breath-hold scan of ~14 s. Future work will aim to validate the proposed approach in patients with liver disease., (© 2020 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease with an up to 80% mortality in case of rupture. Current biomarkers fail to account for size-independent risk of rupture. By combining the information of different molecular probes, multi-target molecular MRI holds the potential to enable individual characterization of AAA. In this experimental study, we aimed to examine the feasibility of simultaneous imaging of extracellular collagen and inflammation for size-independent prediction of risk of rupture in murine AAA. The study design consisted of: (1) A outcome-based longitudinal study with imaging performed once after one week with follow-up and death as the end-point for assessment of rupture risk. (2) A week-by-week study for the characterization of AAA development with imaging after 1, 2, 3 and 4 weeks. For both studies, the animals were administered a type 1 collagen-targeted gadolinium-based probe (surrogate marker for extracellular matrix (ECM) remodeling) and an iron oxide-based probe (surrogate marker for inflammatory activity), in one imaging session. In vivo measurements of collagen and iron oxide probes showed a significant correlation with ex vivo histology (p < 0.001) and also corresponded well to inductively-coupled plasma-mass spectrometry and laser-ablation inductively-coupled plasma mass spectrometry. Combined evaluation of collagen-related ECM remodeling and inflammatory activity was the most accurate predictor for AAA rupture (sensitivity 80%, specificity 100%, area under the curve 0.85), being superior to information from the individual probes alone. Our study supports the feasibility of a simultaneous assessment of collagen-related extracellular matrix remodeling and inflammatory activity in a murine model of AAA.

Objective: Evidence from preclinical and clinical studies has demonstrated that myocardial infarction promotes atherosclerosis progression. The impact of focal vascular inflammation on the progression and phenotype of remote atherosclerosis remains unknown. Approach and Results: We used a novel ApoE -/- knockout mouse model of sustained arterial inflammation, initiated by mechanical injury in the abdominal aorta. Using serial in vivo molecular MRI and ex vivo histology and flow cytometry, we demonstrate that focal arterial inflammation triggered by aortic injury, accelerates atherosclerosis in the remote brachiocephalic artery. The brachiocephalic artery atheroma had distinct histological features including increased plaque size, plaque permeability, necrotic core to collagen ratio, infiltration of more inflammatory monocyte subsets, and reduced collagen content. We also found that arterial inflammation following focal vascular injury evoked a prolonged systemic inflammatory response manifested as a persistent increase in serum IL-6 (interleukin 6). Finally, we demonstrate that 2 therapeutic interventions-pravastatin and minocycline-had distinct anti-inflammatory effects at the plaque and systemic level., Conclusions: We show for the first time that focal arterial inflammation in response to vascular injury enhances systemic vascular inflammation, accelerates remote atheroma progression and induces plaques more inflamed, lipid-rich, and collagen-poor in the absence of ischemic myocardial injury. This inflammatory cascade is modulated by pravastatin and minocycline treatments, which have anti-inflammatory effects at both plaque and systemic levels that mitigate atheroma progression.

Abdominal aortic aneurysm (AAA) remains a fatal disease. Its development encompasses a complex interplay between hemodynamic stimuli on and changes in the arterial wall. Currently available biomarkers fail to predict the risk of AAA rupture independent of aneurysm size. Therefore, novel biomarkers for AAA characterization are needed. In this study, we used a mouse model of AAA to investigate the potential of magnetic resonance imaging (MRI) with an albumin-binding probe to assess changes in vascular permeability at different stages of aneurysm growth. Two imaging studies were performed: a longitudinal study with follow-up and death as endpoint to predict rupture risk and a week-by-week study to characterize AAA development. AAAs, which eventually ruptured, demonstrated a significantly higher in vivo MR signal enhancement from the albumin-binding probe (p = 0.047) and a smaller nonenhancing thrombus area compared to intact AAAs (p = 0.001). The ratio of albumin-binding-probe enhancement of the aneurysm wall to size of nonenhancing-thrombus-area predicted AAA rupture with high sensitivity/specificity (100%/86%). More advanced aneurysms with higher vascular permeability demonstrated an increased uptake of the albumin-binding-probe. These results indicate that MRI with an albumin-binding probe may enable noninvasive assessment of vascular permeability in murine AAAs and prediction of rupture risk.

Background: There is limited knowledge about morphological molecular-imaging-derived parameters to further characterize hemodynamically relevant coronary lesions., Objective: The aim of this study was to describe and differentiate specific parameters between hemodynamically significant and non-significant coronary lesions using various invasive and non-invasive measures., Methods: This clinical study analyzed patients with symptoms suggestive of coronary artery disease (CAD) who underwent native T1-weighted CMR and gadofosveset-enhanced CMR as well as invasive coronary angiography. OCT of the culprit vessel to determine the plaque type was performed in a subset of patients. Functional relevance of all lesions was examined using quantitative flow reserve (QFR-angiography). Hemodynamically significant lesions were defined as lesions with a QFR <0.8. Signal intensity (contrast-to-noise ratios; CNRs) on native T1-weighted CMR and gadofosveset-enhanced CMR was defined as a measure for intraplaque hemorrhage and endothelial permeability, respectively., Results: Overall 29 coronary segments from 14 patients were examined. Segments containing lesions with a QFR <0.8 (n = 9) were associated with significantly higher signal enhancement on Gadofosveset-enhanced CMR as compared to segments containing a lesions without significant stenosis (lesion-QFR>0.8; n = 19) (5.32 (4.47-7.02) vs. 2.42 (1.04-5.11); p = 0.042). No differences in signal enhancement were seen on native T1-weighted CMR (2.2 (0.68-6.75) vs. 2.09 (0.91-6.57), p = 0.412). 66.7% (4 out of 6) of all vulnerable plaque and 33.3% (2 out of 6) of all non-vulnerable plaque (fibroatheroma) as assessed by OCT were hemodynamically significant lesions., Conclusion: The findings of this pilot study suggest that signal enhancement on albumin-binding probe-enhanced CMR but not on T1-weighted CMR is associated with hemodynamically relevant coronary lesions., Competing Interests: The authors have declared that no competing interests exist.

Molecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE -/- ) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R 2  = 0.83, p < 0.05; Perls' Prussian-blue-stain: y = 834.1 + 0.67, R 2  = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.

Purpose: To develop a framework for respiratory motion-corrected 3D whole-heart water/fat coronary MR angiography (CMRA) at 3T with reduced and predictable scan time., Methods: A 3D dual-echo acquisition and respiratory motion-corrected reconstruction framework for water/fat CMRA imaging was developed. The acquisition sequence integrates a 2D dual-echo image navigator (iNAV), enabling 100% respiratory scan efficiency. Respiratory motion estimated from both the 2D iNAVs and the 3D data itself is used to produce nonrigid motion-corrected water/fat CMRA images. A first study to investigate which iNAV (water, fat, in-phase or out-of-phase) provides the best translational motion estimation was performed in 10 healthy subjects. Subsequently, nonrigid motion-corrected water/fat images were compared to a diaphragmatic navigator gated and tracked water/fat CMRA acquisition. Image quality metrics included visible vessel length and vessel sharpness for both the left anterior descending and right coronary arteries., Results: Average vessel sharpness achieved with water, fat, in-phase and out-of-phase iNAVs was 33.8%, 29.6%, 32.2%, and 38.5%, respectively. Out-of-phase iNAVs were therefore used for estimating translational respiratory motion for the remainder of the study. No statistically significant differences in vessel length and sharpness (P > 0.01) were observed between the proposed nonrigid motion correction approach and the reference images, although data acquisition was significantly shorter (P < 2.6×10 -4 ). Motion correction improved vessel sharpness by 60.4% and vessel length by 47.7%, on average, in water CMRA images in comparison with no motion correction., Conclusion: The feasibility of a novel motion-corrected water/fat CMRA approach has been demonstrated at 3T, producing images comparable to a reference gated acquisition, but in a shorter and predictable scan time., (© 2019 The Authors. Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Fibrosis is the common endpoint and currently the best predictor of progression of chronic kidney diseases (CKDs). Despite several drawbacks, biopsies remain the only available means to specifically assess the extent of renal fibrosis. Here, we show that molecular imaging of the extracellular matrix protein elastin allows for noninvasive staging and longitudinal monitoring of renal fibrosis. Elastin was hardly expressed in healthy mouse, rat, and human kidneys, whereas it was highly up-regulated in cortical, medullar, and perivascular regions in progressive CKD. Compared to a clinically relevant control contrast agent, the elastin-specific magnetic resonance imaging agent ESMA specifically detected elastin expression in multiple mouse models of renal fibrosis and also in fibrotic human kidneys. Elastin imaging allowed for repetitive and reproducible assessment of renal fibrosis, and it enabled longitudinal monitoring of therapeutic interventions, accurately capturing anti-fibrotic therapy effects. Last, in a model of reversible renal injury, elastin imaging detected ensuing fibrosis not identifiable via routine assessment of kidney function. Elastin imaging thus has the potential to become a noninvasive, specific imaging method to assess renal fibrosis., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Purpose: To develop a framework for efficient and simultaneous acquisition of motion-compensated whole-heart coronary MR angiography (CMRA) and left ventricular function by MR and myocardial integrity by PET on a 3T PET-MR system., Methods: An acquisition scheme based on a dual-phase CMRA sequence acquired simultaneously with cardiac PET data has been developed. The framework is integrated with a motion-corrected image reconstruction approach, so that non-rigid respiratory and cardiac deformation fields estimated from MR images are used to correct both the CMRA (respiratory motion correction for each cardiac phase) and the PET data (respiratory and cardiac motion correction). The proposed approach was tested in a cohort of 8 healthy subjects and 6 patients with coronary artery disease. Left ventricular (LV) function estimated from motion-corrected dual-phase CMRA was compared to the gold standard estimated from a stack of 2D CINE images for the healthy subjects. Relative increase of signal in motion-corrected PET images compared to uncorrected images was computed for standard 17-segment polar maps for each patient., Results: Motion-corrected dual-phase CMRA images allow for visualization of the coronary arteries in both systole and diastole for all healthy subjects and cardiac patients. LV functional indices from healthy subjects result in good agreement with the reference method, underestimating stroke volume by 3.07 ± 3.26 mL and ejection fraction by 0.30 ± 1.01%. Motion correction improved delineation of the myocardium in PET images, resulting in an increased 18 F-FDG signal of up to 28% in basal segments of the myocardial wall compared to uncorrected images., Conclusion: The proposed motion-corrected dual-phase CMRA and cardiac PET produces co-registered good quality images in both modalities in a single efficient examination of ~13 min., (© 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Background: Molecular magnetic resonance imaging is a promising modality for the characterization of abdominal aortic aneurysms (AAAs). The combination of different molecular imaging biomarkers may improve the assessment of the risk of rupture. This study investigates the feasibility of imaging inflammatory activity and extracellular matrix degradation by concurrent dual-probe molecular magnetic resonance imaging in an AAA mouse model., Methods: Osmotic minipumps with a continuous infusion of Ang II (angiotensin II; 1000 ng/[kg·min]) to induce AAAs were implanted in apolipoprotein-deficient mice (N=58). Animals were assigned to 2 groups. In group 1 (longitudinal group, n=13), imaging was performed once after 1 week with a clinical dose of a macrophage-specific iron oxide-based probe (ferumoxytol, 4 mgFe/kg, surrogate marker for inflammatory activity) and an elastin-specific gadolinium-based probe (0.2 mmol/kg, surrogate marker for extracellular matrix degradation). Animals were then monitored with death as end point. In group 2 (week-by-week-group), imaging with both probes was performed after 1, 2, 3, and 4 weeks (n=9 per group). Both probes were evaluated in 1 magnetic resonance session., Results: The combined assessment of inflammatory activity and extracellular matrix degradation was the strongest predictor of AAA rupture (sensitivity 100%; specificity 89%; area under the curve, 0.99). Information from each single probe alone resulted in lower predictive accuracy. In vivo measurements for the elastin- and iron oxide-probe were in good agreement with ex vivo histopathology (Prussian blue-stain: R 2 =0.96, P<0.001; Elastica van Giesson stain: R 2 =0.79, P<0.001). Contrast-to-noise ratio measurements for the iron oxide and elastin-probe were in good agreement with inductively coupled mass spectroscopy ( R 2 =0.88, R 2 =0.75, P<0.001) and laser ablation coupled to inductively coupled plasma-mass spectrometry., Conclusions: This study demonstrates the potential of the concurrent assessment of inflammatory activity and extracellular matrix degradation by dual-probe molecular magnetic resonance imaging in an AAA mouse model. Based on the combined information from both molecular probes, the rupture of AAAs could reliably be predicted.

The aim of this study was to compare endothelial permeability, which is considered a hallmark of coronary artery disease, between patients with different HbA 1c levels using an albumin-binding magnetic resonance (MR) probe. This cross-sectional study included 26 patients with clinical indication for X-ray angiography who were classified into three groups according to HbA 1c level (<5.7% [<39 mmol/mol], 5.7-6.4% [39-47 mmol/mol], and ≥6.5% [48 mmol/mol]). Subjects underwent gadofosveset-enhanced coronary magnetic resonance and X-ray angiography including optical coherence within 24 h. Contrast-to-noise ratios (CNRs) were assessed to measure the probe uptake in the coronary wall by coronary segment, excluding those with culprit lesions in X-ray angiography. In the group of patients with HbA 1c levels between 5.7 and 6.4%, 0.30 increased normalized CNR values were measured, compared with patients with HbA 1c levels <5.7% (0.30 [95% CI 0.04, 0.57]). In patients with HbA 1c levels ≥6.5%, we found 0.57 higher normalized CNR values compared with patients with normal HbA 1c levels (0.57 [95% CI 0.28, 0.85]) and 0.26 higher CNR values for patients with HbA 1c level ≥6.5% compared with patients with HbA 1c levels between 5.7 and 6.4% (0.26 [95% CI -0.04, 0.57]). Additionally, late atherosclerotic lesions were more common in patients with high HbA 1c levels (HbA 1c ≥6.5%, n = 14 [74%]; HbA 1c 5.7-6.4%, n = 6 [60%]; and HbA 1c <5.7%, n = 10 [53%]). In conclusion, coronary MRI in combination with an albumin-binding MR probe suggests that both patients with intermediate and patients with high HbA 1c levels are associated with a higher extent of endothelial damage of the coronary arteries compared with patients with HbA 1c levels <5.7%., (© 2018 by the American Diabetes Association.)

Purpose: Develop a method for rigid body motion-corrected magnetic resonance fingerprinting (MRF)., Methods: MRF has shown some robustness to abrupt motion toward the end of the acquisition. Here, we study the effects of different types of rigid body motion during the acquisition on MRF and propose a novel approach to correct for this motion. The proposed method (MC-MRF) follows 4 steps: (1) sliding window reconstruction is performed to produce high-quality auxiliary dynamic images; (2) rotation and translation motion is estimated from the dynamic images by image registration; (3) estimated motion is used to correct acquired k-space data with corresponding rotations and phase shifts; and (4) motion-corrected data are reconstructed with low-rank inversion. MC-MRF was validated in a standard T 1 /T 2 phantom and 2D in vivo brain acquisitions in 7 healthy subjects. Additionally, the effect of through-plane motion in 2D MC-MRF was investigated., Results: Simulation results show that motion in MRF can introduce artifacts in T 1 and T 2 maps, depending when it occurs. MC-MRF improved parametric map quality in all phantom and in vivo experiments with in-plane motion, comparable to the no-motion ground truth. Reduced parametric map quality, even after motion correction, was observed for acquisitions with through-plane motion, particularly for smaller structures in T 2 maps., Conclusion: Here, a novel method for motion correction in MRF (MC-MRF) is proposed, which improves parametric map quality and accuracy in comparison to no-motion correction approaches. Future work will include validation of 3D MC-MRF to enable also through-plane motion correction., (© 2018 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: This study sought to investigate the potential of the noninvasive albumin-binding probe gadofosveset-enhanced cardiac magnetic resonance (GE-CMR) for detection of coronary plaques that can cause acute coronary syndromes (ACS)., Background: ACS are frequently caused by rupture or erosion of coronary plaques that initially do not cause hemodynamically significant stenosis and are therefore not detected by invasive x-ray coronary angiography (XCA)., Methods: A total of 25 patients with ACS or symptoms of stable coronary artery disease underwent GE-CMR, clinically indicated XCA, and optical coherence tomography (OCT) within 24 h. GE-CMR was performed approximately 24 h following a 1-time application of gadofosveset-trisodium. Contrast-to-noise ratio (CNR) was quantified within coronary segments in comparison with blood signal., Results: A total of 207 coronary segments were analyzed on GE-CMR. Segments containing a culprit lesion in ACS patients (n = 11) showed significant higher signal enhancement (CNR) following gadofosveset-trisodium application than segments without culprit lesions (n = 196; 6.1 [3.9 to 16.5] vs. 2.1 [0.5 to 3.5]; p < 0.001). GE-CMR was able to correctly identify culprit coronary lesions in 9 of 11 segments (sensitivity 82%) and correctly excluded culprit coronary lesions in 162 of 195 segments (specificity 83%). Additionally, segmented areas of thin-cap fibroatheroma (n = 22) as seen on OCT demonstrated significantly higher CNR than segments without coronary plaque or segments containing early atherosclerotic lesions (n = 185; 9.2 [3.3 to 13.7] vs. 2.1 [0.5 to 3.4]; p = 0.001)., Conclusions: In this study, we demonstrated for the first time the noninvasive detection of culprit coronary lesions and thin-cap fibroatheroma of the coronary arteries in vivo by using GE-CMR. This method may represent a novel approach for noninvasive cardiovascular risk prediction., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: The purpose of this paper is to review current and new modalities to image key biological processes in ischemic heart disease and after myocardial infarction non-invasively., Recent Findings: New imaging targets have been developed to detect and quantify myocardial damage after ischemia. Although positron emission tomography (PET) has been leading the development of new probes in the past, continuous improvements of magnetic resonance imaging (MRI) together with the development of new novel MRI contrast agents opens new research avenues including the combination of both PET and MRI to obtain anatomic, functional, and molecular information simultaneously, which is not possible from a single imaging session., Summary: This review summarizes the state of art of non-invasive molecular imaging of the myocardium during ischemia and after myocardial infarction using PET and MRI. We also describe the different contrast agents that have been developed to image the different phases of cardiac healing and the biological processes associated with each of those phases. Importantly, here we focus on imaging of inflammation as it is the key biological process that orchestrates clearance of dead cells, tissue remodeling, cardiac repair, and future outcome. We also focus on clinical translation of some of the novel contrast agents that have been tested in patients and discuss the need for larger, multi-center patient studies to fully validate the applicability of new imaging probes., Competing Interests: Conflict of InterestAll authors declare that they have no conflict of interest.

Objectives: The aim of this study was to test the potential of a new elastin-specific molecular agent for the performance of contrast-enhanced first-pass and 3D magnetic resonance angiography (MRA), compared to a clinically used extravascular contrast agent (gadobutrol) and based on clinical MR sequences., Materials and Methods: Eight C57BL/6J mice (BL6, male, aged 10 weeks) underwent a contrast-enhanced first-pass and 3D MR angiography (MRA) of the aorta and its main branches. All examinations were on a clinical 3 Tesla MR system (Siemens Healthcare, Erlangen, Germany). The clinical dose of 0.1 mmol/kg was administered in both probes. First, a time-resolved MRA (TWIST) was acquired during the first-pass to assess the arrival and washout of the contrast agent bolus. Subsequently, a high-resolution 3D MRA sequence (3D T1 FLASH) was acquired. Signal-to-noise ratios (SNRs) and contrast-to-noise ratios (CNRs) were calculated for all sequences., Results: The elastin-specific MR probe and the extravascular imaging agent (gadobutrol) enable high-quality MR angiograms in all animals. During the first-pass, the probes demonstrated a comparable peak enhancement (300.6 ± 32.9 vs. 288.5 ± 33.1, p > 0.05). Following the bolus phase, both agents showed a comparable intravascular enhancement (SNR: 106.7 ± 11 vs. 102.3 ± 5.3; CNR 64.5 ± 7.4 vs. 61.1 ± 7.2, p > 0.05). Both agents resulted in a high image quality with no statistical difference ( p > 0.05)., Conclusion: The novel elastin-specific molecular probe enables the performance of first-pass and late 3D MR angiography with an intravascular contrast enhancement and image quality comparable to a clinically used extravascular contrast agent.

Background: Dual-phase 3-dimensional whole-heart acquisition allows simultaneous imaging during systole and diastole. Respiratory navigator gating and tracking of the diaphragm is used with limited accuracy. Prolonged scan time is common, and navigation often fails in patients with erratic breathing. Image-navigation (iNAV) tracks movement of the heart itself and is feasible in single phase whole heart imaging. To evaluate its diagnostic ability in congenital heart disease, we sought to apply iNAV to dual-phase sequencing., Methods: Healthy volunteers and patients with congenital heart disease underwent dual-phase imaging using the conventional diaphragmatic-navigation (dNAV) and iNAV. Acquisition time was recorded and image quality assessed. Sharpness and length of the right coronary (RCA), left anterior descending (LAD), and circumflex (LCx) arteries were measured in both cardiac phases for both approaches. Qualitative and quantitative analyses were performed in a blinded and randomized fashion., Results: In volunteers, there was no significant difference in vessel sharpness between approaches (p > 0.05). In patients, analysis showed equal vessel sharpness for LAD and RCA (p > 0.05). LCx sharpness was greater with dNAV (p < 0.05). Visualized length with iNAV was 0.5 ± 0.4 cm greater than that with dNAV for LCx in diastole (p < 0.05), 1.0 ± 0.3 cm greater than dNAV for LAD in diastole (p < 0.05), and 0.8 ± 0.7 cm greater than dNAV for RCA in systole (p < 0.05). Qualitative scores were similar between modalities (p = 0.71). Mean iNAV scan time was 5:18 ± 2:12 min shorter than mean dNAV scan time in volunteers (p = 0.0001) and 3:16 ± 1:12 min shorter in patients (p = 0.0001)., Conclusions: Image quality of iNAV and dNAV was similar with better distal vessel visualization with iNAV. iNAV acquisition time was significantly shorter. Complete cardiac diagnosis was achieved. Shortened acquisition time will improve clinical applicability and patient comfort.

Purpose: Develop a framework for efficient free-breathing simultaneous whole-heart coronary magnetic resonance angiography (CMRA) and cardiac positron emission tomography (PET) on a 3 Tesla PET-MR system., Methods: An acquisition that enables nonrigid motion correction of both CMRA and PET has been developed. The proposed method estimates translational motion from low-resolution 2D MR image navigators acquired at each heartbeat and 3D nonrigid respiratory motion between different respiratory bins from the CMRA data itself. Estimated motion is used for correcting the CMRA as well as the emission and attenuation PET data sets to the same respiratory position. The CMRA approach was studied in 10 healthy subjects and compared for both left and right coronary arteries (LCA, RCA) against a reference scan with diaphragmatic navigator gating and tracking. The PET-CMRA approach was tested in 5 oncology patients with 18 F-FDG myocardial uptake. PET images were compared against uncorrected and gated PET reconstructions., Results: For the healthy subjects, no statistically significant differences in vessel length and sharpness (P > 0.01) were observed between the proposed approach and the reference acquisition with navigator gating and tracking, although data acquisition was significantly shorter. The proposed approach improved CMRA vessel sharpness by 37.9% and 49.1% (LCA, RCA) and vessel length by 48.0% and 36.7% (LCA, RCA) in comparison with no motion correction for all the subjects. Motion-corrected PET images showed improved sharpness of the myocardium compared to uncorrected reconstructions and reduced noise compared to gated reconstructions., Conclusion: Feasibility of a new respiratory motion-compensated simultaneous cardiac PET-CMRA acquisition has been demonstrated. Magn Reson Med 79:339-350, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited., (© 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

The development of abdominal aortic aneurysm (AAA) associated thrombi plays an important role during the onset and progression of AAAs. The aim of this study was to evaluate the potential of high-frequency ultrasound for characterization of AAA associated thrombi in an apolipoprotein-E-deficient mouse-model. Ultrasound measurements were performed using a high-resolution ultrasound system (Vevo770, FUJIFILM VisualSonics, Inc., Toronto, ON, Canada) with a 30 MHz linear-array transducer (RMV707 B). Magnetic resonance imaging with a 3 Tesla scanner (Achieva MR system, Philips Healthcare, Best, The Netherlands) and a single-loop microscopy coil was performed as a reference standard. All stages of aneurysm development were evaluated by histologic analyses. The "signal-thrombus-matrix" to "signal-blood" ratio on high-frequency ultrasound measurements showed a strong correlation (R 2  = 0.81, p <0.05) with the state of extracellular matrix remodeling. Furthermore, size measurements derived from the high-frequency ultrasound correlated well with magnetic resonance imaging and histology. This study demonstrated that high-frequency ultrasound enables the reliable in vivo quantification of extracellular matrix remodeling at various stages of thrombus development, based on the thrombus echogenicity., (Copyright © 2017 World Federation for Ultrasound in Medicine and Biology. Published by Elsevier Inc. All rights reserved.)

Purpose: X-ray coronary angiography (XCA) is the current gold standard for the assessment of lumen encroaching coronary stenosis but XCA does not allow for early detection of rupture-prone vulnerable plaques, which are thought to be the precursor lesions of most acute myocardial infarctions (AMI) and sudden death. The aim of this study was to investigate the potential of delayed contrast-enhanced magnetic resonance coronary vessel wall imaging (CE-MRCVI) for the detection of culprit lesions in the coronary arteries., Methods: 16 patients (13 male, age 61.9±8.6 years) presenting with sub-acute MI underwent CE-MRCVI within 24-72h prior to invasive XCA. CE-MRCVI was performed using a T1-weighted 3D gradient echo inversion recovery sequence (3D IR TFE) 40±4 minutes following the administration of 0.2 mmol/kg gadolinium-diethylenetriamine-pentaacetic acid (DTPA) on a 3T MRI scanner equipped with a 32-channel cardiac coil., Results: 14 patients were found to have culprit lesions (7x LAD, 1xLCX, 6xRCA) as identified by XCA. Quantitative CE-MRCVI correctly identified the culprit lesion location with a sensitivity of 79% and excluded culprit lesion formation with a specificity of 99%. The contrast to noise ratio (CNR) of culprit lesions (9.7±4.1) significantly exceeded CNR values of segments without culprit lesions (2.9±1.9, p<0.001)., Conclusion: CE-MRCVI allows the selective visualization of culprit lesions in patients immediately after myocardial infarction (MI). The pronounced contrast uptake in ruptured plaques may represent a surrogate biomarker of plaque activity and/or vulnerability.

Objectives: The aim of this study was to investigate the impact of BMI on late gadolinium enhancement (LGE) of the coronary artery wall in identical monozygous twins discordant for BMI. Coronary LGE represents a useful parameter for the detection and quantification of atherosclerotic coronary vessel wall disease., Methods: Thirteen monozygote female twin pairs (n = 26) with significantly different BMIs (>1.6 kg/m2) were recruited out of >10,000 twin pairs (TwinsUK Registry). A coronary 3D-T2prep-TFE MR angiogram and 3D-IR-TFE vessel wall scan were performed prior to and following the administration of 0.2 mmol/kg of Gd-DTPA on a 1.5 T MR scanner. The number of enhancing coronary segments and contrast to noise ratios (CNRs) of the coronary wall were quantified., Results: An increase in BMI was associated with an increased number of enhancing coronary segments (5.3 ± 1.5 vs. 3.5 ± 1.6, p < 0.0001) and increased coronary wall enhancement (6.1 ± 1.1 vs. 4.8 ± 0.9, p = 0.0027) compared to matched twins with lower BMI., Conclusions: This study in monozygous twins indicates that acquired factors predisposing to obesity, including lifestyle and environmental factors, result in increased LGE of the coronary arteries, potentially reflecting an increase in coronary atherosclerosis in this female study population., Key Points: • BMI-discordant twins allow the investigation of the influence of lifestyle factors independent from genetic confounders. • Only thirteen obesity-discordant twins were identified underlining the strong genetic component of BMI. • In female twins, a BMI increase is associated with increased coronary late gadolinium enhancement. • Increased late gadolinium enhancement in the coronary vessel wall potentially reflects increased atherosclerosis.

Background: The use of coronary MR angiography (CMRA) in patients with coronary artery disease (CAD) remains limited due to the long scan times, unpredictable and often non-diagnostic image quality secondary to respiratory motion artifacts. The purpose of this study was to evaluate CMRA with image-based respiratory navigation (iNAV CMRA) and compare it to gold standard invasive x-ray coronary angiography in patients with CAD., Methods: Consecutive patients referred for CMR assessment were included to undergo iNAV CMRA on a 1.5 T scanner. Coronary vessel sharpness and a visual score were assigned to the coronary arteries. A diagnostic reading was performed on the iNAV CMRA data, where a lumen narrowing >50% was considered diseased. This was compared to invasive x-ray findings., Results: Image-navigated CMRA was performed in 31 patients (77% male, 56 ± 14 years). The iNAV CMRA scan time was 7 min:21 s ± 0 min:28 s. Out of a possible 279 coronary segments, 26 segments were excluded from analysis due to stents or diameter less than 1.5 mm, resulting in a total of 253 coronary segments. Diagnostic image quality was obtained for 98% of proximal coronary segments, 94% of middle segments, and 91% of distal coronary segments. The sensitivity and specificity was 86% and 83% per patient, 80% and 92% per vessel and 73% and 95% per segment., Conclusion: In this study, iNAV CMRA offered a very good diagnostic performance when compared against invasive x-ray angiography. Due to the short and predictable scan time it can add clinical value as a part of a comprehensive CAD assessment protocol.

Purpose: To develop a respiratory motion correction framework to accelerate free-breathing three-dimensional (3D) whole-heart coronary lumen and coronary vessel wall MRI., Methods: We developed a 3D flow-independent approach for vessel wall imaging based on the subtraction of data with and without T2-preparation prepulses acquired interleaved with image navigators. The proposed method corrects both datasets to the same respiratory position using beat-to-beat translation and bin-to-bin nonrigid corrections, producing coregistered, motion-corrected coronary lumen and coronary vessel wall images. The proposed method was studied in 10 healthy subjects and was compared with beat-to-beat translational correction (TC) and no motion correction for the left and right coronary arteries. Additionally, the coronary lumen images were compared with a 6-mm diaphragmatic navigator gated and tracked scan., Results: No significant differences (P > 0.01) were found between the proposed method and the gated and tracked scan for coronary lumen, despite an average improvement in scan efficiency to 96% from 59%. Significant differences (P < 0.01) were found in right coronary artery vessel wall thickness, right coronary artery vessel wall sharpness, and vessel wall visual score between the proposed method and TC., Conclusion: The feasibility of a highly efficient motion correction framework for simultaneous whole-heart coronary lumen and vessel wall has been demonstrated. Magn Reson Med 77:1894-1908, 2017. © 2016 International Society for Magnetic Resonance in Medicine., (© 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine.)

This review summarizes the current status of molecular imaging of the extracellular matrix (ECM) in the context of atherosclerosis. Apart from cellular components, the ECM of the atherosclerotic plaque plays a relevant role during the initiation of atherosclerosis and its' subsequent progression. Important structural and signaling components of the ECM include elastin, collagen and fibrin. However, the ECM not only plays a structural role in the arterial wall but also interacts with different cell types and has important biological signaling functions. Molecular imaging of the ECM has emerged as a new diagnostic tool to characterize biological aspects of atherosclerotic plaques, which cannot be characterized by current clinically established imaging techniques, such as X-ray angiography. Different types of molecular probes can be detected in vivo by imaging modalities such as magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT). The modality specific signaling component of the molecular probe provides information about its spatial location and local concentration. The successful introduction of molecular imaging into clinical practice and guidelines could open new pathways for an earlier detection of disease processes and a better understanding of the disease state on a biological level. Quantitative in vivo molecular parameters could also contribute to the development and evaluation of novel cardiovascular therapeutic interventions and the assessment of response to treatment., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Pulse wave velocity (PWV) is a biomarker for the intrinsic stiffness of the aortic wall, and has been shown to be predictive for cardiovascular events. It can be assessed using cardiovascular magnetic resonance (CMR) from the delay between phase-contrast flow waveforms at two or more locations in the aorta, and the distance on CMR images between those locations. This study aimed to investigate the impact of different distance measurement methods on PWV. We present and evaluate an algorithm for automated centreline tracking in 3D images, and compare PWV calculations using distances derived from 3D images to those obtained from a conventional 2D oblique-sagittal image of the aorta., Methods: We included 35 patients from a twin cohort, and 20 post-coarctation repair patients. Phase-contrast flow was acquired in the ascending, descending and diaphragmatic aorta. A 3D centreline tracking algorithm is presented and evaluated on a subset of 30 subjects, on three CMR sequences: balanced steady-state free precession (SSFP), black-blood double inversion recovery turbo spin echo, and contrast-enhanced CMR angiography. Aortic lengths are subsequently compared between measurements from a 2D oblique-sagittal plane, and a 3D geometry., Results: The error in length of automated 3D centreline tracking compared with manual annotations ranged from 2.4 [1.8-4.3] mm (mean [IQR], black-blood) to 6.4 [4.7-8.9] mm (SSFP). The impact on PWV was below 0.5m/s (<5%). Differences between 2D and 3D centreline length were significant for the majority of our experiments (p < 0.05). Individual differences in PWV were larger than 0.5m/s in 15% of all cases (thoracic aorta) and 37% when studying the aortic arch only. Finally, the difference between end-diastolic and end-systolic 2D centreline lengths was statistically significant (p < 0.01), but resulted in small differences in PWV (0.08 [0.04 - 0.10]m/s)., Conclusions: Automatic aortic centreline tracking in three commonly used CMR sequences is possible with good accuracy. The 3D length obtained from such sequences can differ considerably from lengths obtained from a 2D oblique-sagittal plane, depending on aortic curvature, adequate planning of the oblique-sagittal plane, and patient motion between acquisitions. For accurate PWV measurements we recommend using 3D centrelines.

19 F-magnetic resonance imaging (MRI) is a promising technique that may allow us to measure the concentration of exogenous fluorinated imaging probes quantitatively in vivo. Here, we describe the synthesis and characterisation of a novel geminal bisphosphonate ( 19 F-BP) that contains chemically-equivalent fluorine atoms that show a single and narrow 19 F resonance and a bisphosphonate group that may be used for labelling inorganic materials based in calcium phosphates and metal oxides. The potential of 19 F-BP to provide contrast was analysed in vitro and in vivo using 19 F-MRI . In vitro studies demonstrated the potential of 19 F-BP as an MRI contrast agent in the millimolar concentration range with signal-to-noise ratios (SNR) comparable to previously reported fluorinated probes. The preliminary in vivo MRI study reported here allowed us to visualise the biodistribution of 19 F-BP, showing uptake in the liver and in the bladder/urinary system areas. However, bone uptake was not observed. In addition, 19 F-BP showed undesirable toxicity effects in mice that prevent further studies with this compound at the required concentrations for MRI contrast. This study highlights the importance of developing 19 F MRI probes with the highest signal intensity achievable.

Background: The purpose of this study was to evaluate a recently developed two-dimensional (2D) image-based navigation approach (iNAVG+C ) combined with respiratory bellows gating for CMRA in patients with congenital heart disease., Methods: Nine healthy volunteers (mean age 32 ± 6 years [standard deviation]) and 29 patients (28 ± 9 years) were scanned on a 1.5 Tesla clinical scanner using iNAV(G+C) motion compensated T2prepared CMRA, and the conventional 1D NAV approach. Scan time was recorded for each CMRA scan. An image quality score was given to each coronary artery from (0, uninterpretable; to 4, excellent image quality). Additionally, vessel sharpness of each coronary artery was measured., Results: Average scan time was significantly shorter (P < 0.01) using the proposed iNAVC+G approach (7:57 ± 1:34) compared with 1D NAV (9:15 ± 3:02). Improved visual scores of the right coronary artery (iNAV(G+C) : 4,3,4 (median, 25th percentile, 75th percentile) versus 1D NAV: 3,3,4; P < 0.001) and left anterior descending artery (iNAV(G+C) : 3,3,4 versus 1D NAV: 3,2,3; P < 0.001) were obtained using iNAV(G+C) compared with 1D NAV as well as an increased vessel sharpness of the right coronary artery (iNAV(G+C) : 65.3% ± 6.6% (mean ± standard deviation) versus 1D NAV: 60.2% ± 11.4%; P < 0.05) and left anterior descending artery (iNAV(G+C) : 63.2% ± 6.7% versus 1D NAV: 58.3% ± 9.5%; P < 0.05)., Conclusion: Image-based navigation in combination with respiratory bellows gating allows for more robust suppression of respiratory motion artifacts for whole-heart CMRA compared with conventional 1D NAV as images can be acquired in a shorter time and with improved image quality., (© 2015 Wiley Periodicals, Inc.)

Combining Positron Emission Tomography (PET) with Magnetic Resonance Imaging (MRI) results in a promising hybrid molecular imaging modality as it unifies the high sensitivity of PET for molecular and cellular processes with the functional and anatomical information from MRI. Digital Silicon Photomultipliers (dSiPMs) are the digital evolution in scintillation light detector technology and promise high PET SNR. DSiPMs from Philips Digital Photon Counting (PDPC) were used to develop a preclinical PET/RF gantry with 1-mm scintillation crystal pitch as an insert for clinical MRI scanners. With three exchangeable RF coils, the hybrid field of view has a maximum size of 160 mm × 96.6 mm (transaxial × axial). 0.1 ppm volume-root-mean-square B 0-homogeneity is kept within a spherical diameter of 96 mm (automatic volume shimming). Depending on the coil, MRI SNR is decreased by 13% or 5% by the PET system. PET count rates, energy resolution of 12.6% FWHM, and spatial resolution of 0.73 mm (3) (isometric volume resolution at isocenter) are not affected by applied MRI sequences. PET time resolution of 565 ps (FWHM) degraded by 6 ps during an EPI sequence. Timing-optimized settings yielded 260 ps time resolution. PET and MR images of a hot-rod phantom show no visible differences when the other modality was in operation and both resolve 0.8-mm rods. Versatility of the insert is shown by successfully combining multi-nuclei MRI ((1)H/(19)F) with simultaneously measured PET ((18)F-FDG). A longitudinal study of a tumor-bearing mouse verifies the operability, stability, and in vivo capabilities of the system. Cardiac- and respiratory-gated PET/MRI motion-capturing (CINE) images of the mouse heart demonstrate the advantage of simultaneous acquisition for temporal and spatial image registration.

Background: The purpose of this study was to see how coronary magnetic resonance angiography (CMRA) compared to echocardiography for the detection of coronary artery origins and to compare CMRA measurements for coronary dimensions in children with published echocardiographic reference values., Methods: Enrolled patients underwent dual cardiac phase CMRA and echocardiography under the same anesthetic. Echocardiographic measurements of the right coronary artery (RCA), left anterior descending (LAD) and left main (LM) were made. CMRA dimensions were assessed manually at the same points as the echocardiographic measurements. The number of proximal LAD branches imaged was also recorded in order to give an estimate of distal coronary tree visualization., Results: Fifty patients (24 boys, mean age 4.0 years (range 18 days to 18 years)) underwent dual-phase CMRA. Coronary origins were identified in 47/50 cases for CMRA (remaining 3 were infants aged 3, 9 and 11 months). In comparison, origins were identified in 41/50 cases for echo (remaining were all older children). CMRA performed better than echocardiography in terms of distal visualization of the coronary tree (median 1 LAD branch vs. median 0; p = 0.001). Bland-Altman plots show poor agreement between echocardiography and CMRA for coronary measurements. CMRA measurements did vary according to cardiac phase (systolic mean 1.90, s.d. 0.05 mm vs. diastolic mean 1.84, s.d. 0.05 mm; p = 0.002)., Conclusions: Dual-phase CMRA has an excellent (94 %) success rate for the detection of coronary origins in children. Newborn infants remain challenging and echocardiography remains the accepted imaging modality for this age group. Echocardiographic reference ranges are not applicable to CMRA measurements as agreement was poor between modalities. Future coronary reference values, using any imaging modality, should quote the phase in which it was measured.

Purpose: To develop a flexible image navigator for 3D coronary MR angiography that allows respiratory motion of variable complexity to be compensated for on different temporal scales., Methods: A two-dimensional (2D) golden radial image navigator is proposed; translational motion is compensated for on a beat-to-beat basis, and residual affine motion is compensated for on a bin-to-bin basis in a two-step procedure. The method does not use a respiratory gating window and therefore achieves 100% scan efficiency and a predictable scan time. The proposed method was tested in 11 healthy volunteers and compared against a navigator-gated and tracked acquisition., Results: The proposed method achieved comparable quantitative and qualitative image quality to a 6-mm navigator-gated and tracked scan while reducing the scan time by a factor of approximately 2. Combined motion correction using image navigators improved visualization of the coronary arteries in four of 11 subjects in comparison with translational correction only, and image quality was maintained in the remaining cases. In one case, visualization of the left anterior descending coronary artery was degraded using combined correction compared with translation correction only., Conclusions: The feasibility of correcting for 2D translational motion on a beat-to-beat basis as well as affine motion on a bin-to-bin basis has been demonstrated., (© 2014 The Authors. Magnetic Resonance in Medicine Published by Wiley Periodicals, Inc. on behalf of International Society of Medicine in Resonance.)

Background: Well-defined inflammation, proliferation, and maturation phases orchestrate the remodeling of the injured myocardium after myocardial infarction (MI) by controlling the formation of new extracellular matrix. The extracellular matrix consists mainly of collagen but also fractions of elastin. It is thought that elastin is responsible for maintaining elastic properties of the myocardium, thus reducing the risk of premature rupture. An elastin/tropoelastin-specific contrast agent (Gd-ESMA) was used to image tropoelastin and mature elastin fibers for in vivo assessment of extracellular matrix remodeling post-MI., Methods and Results: Gd-ESMA enhancement was studied in a mouse model of myocardial infarction using a 7 T MRI scanner and results were compared to those achieved after injection of a nonspecific control contrast agent, gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA). In the infarcted tissue, Gd-ESMA uptake (measured as R1 relaxation rate) steadily increased from day 3 to day 21 as a result of the synthesis of elastin/tropoelastin. R1 values were in good agreement with histological findings. A similar R1 behavior was observed in the remote myocardium. No mature cross-linked elastin was found at any time point. In contrast, Gd-DTPA uptake was only observed in the infarct with no changes in R1 values between 3 and 21 days post-MI., Conclusions: We demonstrate the feasibility of in vivo imaging of extracellular matrix remodeling post-MI using a tropoelastin/elastin binding MR contrast agent, Gd-ESMA. We found that tropoelastin is the main contributor to the increased MRI signal at late stages of MI where its augmentation in areas of infarction was in good agreement with the R1 increase., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Background and Purpose: There are conflicting data regarding whether netrin-1 retards or accelerates atherosclerosis progression, as it can lead either to monocyte repulsion from or retention within plaques depending on its cellular source. We investigated the effect of aspirin, which is widely used in cardiovascular prophylaxis, on the synthesis of different isoforms of netrin-1 by endothelial cells under pro-inflammatory conditions, and defined the net effect of aspirin-dependent systemic modulation of netrin-1 on atherosclerosis progression., Experimental Approach: Netrin-1 synthesis was studied in vitro using human endothelial cells stimulated with TNF-α, with or without aspirin treatment. In vivo experiments were conducted in ApoE(-/-) mice fed with a high-fat diet (HFD), receiving either aspirin or clopidogrel., Key Results: TNF-α-induced NF-κB activation up-regulated the nuclear isoform of netrin-1, while simultaneously reducing secreted netrin-1. Down-regulation of the secreted isoform compromised the chemorepellent action of the endothelium against monocyte chemotaxis. Aspirin counteracted TNF-α-mediated effects on netrin-1 synthesis by endothelial cells through COX-dependent inhibition of NF-κB and concomitant histone hyperacetylation. Administration of aspirin to ApoE(-/-) mice on HFD increased blood and arterial wall levels of netrin-1 independently of its effects on platelets, accompanied by reduced plaque size and content of monocytes/macrophages, compared with untreated or clopidogrel-treated mice. In vivo blockade of netrin-1 enhanced monocyte plaque infiltration in aspirin-treated ApoE(-/-) mice., Conclusions and Implications: Aspirin counteracts down-regulation of secreted netrin-1 induced by pro-inflammatory stimuli in endothelial cells. The aspirin-dependent increase of netrin-1 in ApoE(-/-) mice exerts anti-atherogenic effects by preventing arterial accumulation of monocytes., (© 2015 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society.)

Purpose: To develop an efficient 3D affine respiratory motion compensation framework for Cartesian whole-heart coronary magnetic resonance angiography (MRA)., Materials and Methods: The proposed method achieves 100% scan efficiency by estimating the affine respiratory motion from the data itself and correcting the acquired data in the reconstruction process. For this, a golden-step Cartesian sampling with spiral profile ordering was performed to enable reconstruction of respiratory resolved images at any breathing position and with different respiratory window size. Affine motion parameters were estimated from image-based registration of 3D undersampled respiratory resolved images reconstructed with iterative SENSE and motion correction was performed directly in the reconstruction using a multiple-coils generalized matrix formulation method. This approach was tested on healthy volunteers and compared against a conventional diaphragmatic navigator-gated acquisition using quantitative and qualitative image quality assessment., Results: The proposed approach achieved 47 ± 12% and 59 ± 6% vessel sharpness for the right (RCA) and left (LAD) coronary arteries, respectively. Also, good quality visual scores of 2.4 ± 0.74 and 2.44 ± 0.86 were observed for the RCA and LAD (scores from 0, no to 4, excellent coronary vessel delineation). A not statically significant difference (P = 0.05) was found between the proposed method and an 8-mm navigator-gated and tracked scan, although scan efficiency increased from 61 ± 10% to 100%., Conclusion: We demonstrate the feasibility of a new 3D affine respiratory motion correction technique for Cartesian whole-heart CMRA that achieves 100% scan efficiency and therefore a predictable acquisition time. This approach yields image quality comparable to that of an 8-mm navigator-gated acquisition with lower scan efficiency. Further evaluation of this technique in patients is now warranted to determine its clinical use., (© 2014 Wiley Periodicals, Inc.)

Purpose: To describe a new framework for interleaving scans and demonstrate its usefulness for image-based respiratory motion correction in whole heart coronary MR angiography (CMRA)., Methods: Scan interleaving using the proposed approach was achieved by switching between separately defined, independent scans at arbitrary time points during their execution, using a generic function call. The scan interleaving framework was used to perform scan interleaving for image-based respiratory navigation of CMRA with spiral, radial, and Cartesian echo-planar imaging (EPI) navigator k-space trajectories. Eight healthy volunteers were scanned., Results: Improved coronary vessel sharpness and visual scores were obtained using spiral and Cartesian EPI navigators compared with radial navigators., Conclusion: The usefulness of the proposed scan interleaving framework was demonstrated for image-based respiratory motion correction. It facilitated more direct comparisons of image navigator acquisitions with different k-space trajectories. Furthermore, we could demonstrate that spiral and Cartesian EPI navigators may be particularly suitable for image-based motion correction, as they provide improved motion correction and high navigator apparent signal-to-noise ratio while spending very little magnetization, thereby minimizing saturation effects., (© 2014 Wiley Periodicals, Inc.)

It has been shown that sublingual nitroglycerin (NTG) improves image quality of coronary lumen magnetic resonance angiography. Our aim was to investigate the influence of NTG on coronary lumen and vessel wall image quality using a combined, single sequence approach (i-T2prep), which is able to image both within the known time frame of action of NTG. Ten healthy volunteers underwent right coronary artery lumen and vessel wall imaging using the i-T2prep sequence before and after administration of NTG. Image quality was assessed qualitatively and quantitatively. Diameter, length and wall thickness were also measured using dedicated semi-automatic software. NTG induced coronary vasodilatation (lumen diameter increased from 2.16 ± 0.32 to 2.52 ± 0.59 mm; p = 0.036). As a result, visualized lumen length (9.8 ± 2.6 to 11.4 ± 3.3 cm; p = 0.025) and qualitative lumen image quality (median 3 (interquartile range 2-3.25) vs. median 3 (interquartile range 3-4); p = 0.046) both improved. Vessel wall imaging also demonstrated a significant improvement in vessel wall sharpness after NTG (24.8 vs. 27.3 %; p = 0.036). This study demonstrates the benefits of NTG for coronary lumen and vessel wall imaging using a combined sequence, i-T2prep. The methodology described here has great potential for future pathophysiological studies.

Continued uptake of modified low-density lipoproteins (LDL) by the scavenger receptor, CD68, of activated macrophages is a crucial process in the development of atherosclerotic plaques and leads to the formation of foam cells. Eight-weeks-old male Apolipoprotein E-deficient (ApoE(-/-)) mice (n = 6) were fed a high-fat diet for 12 weeks. C57BL/6J wildtype (WT) mice served as controls (n = 6). Positron emission tomography (PET) with an acquisition time of 1800 s (NanoPET/CT scanner; Mediso, Hungary & Bioscan, USA) was carried out 24h after intravenous tail vein administration of 50 µl (64)Cu-CD68-Fc (~20-30 µg labeled protein/mouse containing approximately 10-12 MBq (64)Cu-CD68-Fc per mouse). Three days after PET/CT, all mice received an intravenous administration of 0.2 mmol/kg body weight of a gadolinium-based elastin-binding contrast agent to assess plaque burden and vessel wall remodeling. Two hours after injection, mice were imaged in a 3T clinical MR scanner (Philips Healthcare, Best, NL) using a dedicated single loop surface coil (23 mm). Enhanced (64)Cu-CD68-Fc uptake was found in the aortic arches of ApoE(-/-) compared to WT mice (ApoE(-/-) mice:10.5 ± 1.5 Bq/cm(3) vs. WT mice: 2.1 ± 0.3 Bq/cm(3); P = 0.002). Higher gadolinium-based elastin-binding contrast agent uptake was also detected in the aortic arch of ApoE(-/-) compared to WT mice using R(1) maps (R(1) = 1.47 ± 0.06 s(-1) vs. 0.92 ± 0.05 s(-1); P <0.001). Radiolabeled scavenger receptor ((64)Cu-CD68-Fc) may help to target foam cell rich plaques with high content of oxidized LDL. This novel imaging biomarker tool may have potential to identify unstable plaques and for risk stratification., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Objectives: This study investigated the feasibility of visual and quantitative assessment of coronary vessel wall contrast enhancement (CE) for detection of symptomatic atherosclerotic coronary artery disease (CAD) and subclinical coronary vasculitis in autoimmune inflammatory disease (systemic lupus erythematosus [SLE]), as well as the association with aortic stiffness, an established marker of risk., Background: Coronary CE by cardiac magnetic resonance (CMR) is a novel noninvasive approach to visualize gadolinium contrast uptake within the coronary artery vessel wall., Methods: A total of 75 subjects (CAD: n = 25; SLE: n = 27; control: n = 23) underwent CMR imaging using a 3-T clinical scanner. Coronary arteries were visualized by a T2-prepared steady state free precession technique. Coronary wall CE was visualized using inversion-recovery T1 weighted gradient echo sequence 40 min after administration of 0.2 mmol/kg gadobutrol. Proximal coronary segments were visually examined for distribution of CE and quantified for contrast-to-noise ratio (CNR) and total CE area., Results: Coronary CE was prevalent in patients (93%, n = 42) with a diffuse pattern for SLE and a patchy/regional distribution in CAD patients. Compared with control subjects, CNR values and total CE area in patients with CAD and SLE were significantly higher (mean CNR: 3.9 ± 2.5 vs. 6.9 ± 2.5 vs. 6.8 ± 2.0, respectively; p < 0.001; total CE area: median 0.8 [interquartile range (IQR): 0.6 to 1.2] vs. 3.2 [IQR: 2.6 to 4.0] vs. 3.3 [IQR: 1.9 to 4.5], respectively; p < 0.001). Both measures were positively associated with aortic stiffness (CNR: r = 0.61, p < 0.01; total CE area: 0.36, p = 0.03), hypercholesterolemia (r = 0.68, p < 0.001; r = 0.61, p < 0.001) and hypertension (r = 0.40, p < 0.01; r = 0.32, p < 0.05)., Conclusions: We demonstrate that quantification of coronary CE by CNR and total CE area is feasible for detection of subclinical and clinical uptake of gadolinium within the coronary vessel wall. Coronary vessel wall CE may become an instrumental novel direct marker of vessel wall injury and remodeling in subpopulations at risk., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)