Time-Efficient Black Blood RCA Wall Imaging at 3T Using Improved Motion Sensitized Driven Equilibrium (iMSDE): Feasibility and Reproducibility

The aim of this study was to explore the feasibility and reproducibility of a time-efficient coronary vessel wall measurement approach using an improved motion-sensitized driven equilibrium (iMSDE) pulse sequence.In this study, the iMSDE pulse sequence was first optimized and then applied on a group of healthy volunteers (N = 10) to evaluate its feasibility of vessel wall visualization. The same technique was also applied on a separate group of volunteers (N = 19) for a reproducibility study by scanning the same subject in two separate sessions. The iMSDE sequence was found to provide good coronary vessel wall delineation. It was also found to provide reproducible coronary vessel wall diameter and thickness measurements in both proximal and middle segments of the right coronary artery.The feasibility and reproducibility of iMSDE based coronary vessel wall imaging were demonstrated for the first time, paving the way for further testing in a clinical environment for fast and accurate coronary artery disease detection

Nested star-shaped objects segmentation using diameter annotations

Most current deep learning based approaches for image segmentation require annotations of large datasets, which limits their application in clinical practice. We observe a mismatch between the voxelwise ground-truth that is required to optimize an objective at a voxel level and the commonly used, less time-consuming clinical annotations seeking to characterize the most important information about the patient (diameters, counts, etc.). In this study, we propose to bridge this gap for the case of multiple nested star-shaped objects (e.g., a blood vessel lumen and its outer wall) by optimizing a deep learning model based on diameter annotations. This is achieved by extracting in a differentiable manner the boundary points of the objects at training time, and by using this extraction during the backpropagation. We evaluate the proposed approach on segmentation of the carotid artery lumen and wall from multisequence MR images, thus reducing the annotation burden to only four annotated landmarks required to measure the diameters in the direction of the vessel's maximum narrowing. Our experiments show that training based on diameter annotations produces state-of-the-art weakly supervised segmentations and performs reasonably compared to full supervision. We made our code publicly available at https://gitlab.com/radiology/aim/carotid-artery-image-analysis/nested-star-shaped-objects

Visualization of Coronary Wall Atherosclerosis in Asymptomatic Subjects and Patients with Coronary Artery Disease Using Magnetic Resonance Imaging

Background: Magnetic resonance imaging (MRI) is sensitive to early atherosclerotic changes such as positive remodeling in patients with coronary artery disease (CAD). We assessed prevalence, quality, and extent of coronary atherosclerosis in a group of healthy subjects compared to patients with confirmed CAD. Methodology: Twenty-two patients with confirmed CAD (15M, 7F, mean age 60.4±10.4 years) and 26 healthy subjects without history of CAD (11M, 15F, mean age 56.1±4.4 years) underwent MRI of the right coronary artery (RCA) and vessel wall (MR-CVW) on a clinical 1.5T MR-scanner. Wall thickness measurements of both groups were compared. Principal Findings: Stenoses of the RCA (both < and ≥50% on CAG) were present in all patients. In 21/22 patients, stenoses detected at MRI corresponded to stenoses detected with conventional angiography. In 19/26 asymptomatic subjects, there was visible luminal narrowing in the MR luminography images. Fourteen of these subjects demonstrated corresponding increase in vessel wall thickness. In 4/26 asymptomatic subjects, vessel wall thickening without luminal narrowing was present. Maximum and mean wall thicknesses in patients were significantly higher (2.16 vs 1.92 mm, and 1.38 vs 1.22 mm, both p<0.05). Conclusions: In this cohort of middle-aged individuals, both patients with stable angina and angiographically proven coronary artery disease, as well as age-matched asymptomatic subjects. exhibited coronary vessel wall thickening detectable with MR coronary vessel wall imaging. Maximum and mean wall thicknesses were significantly higher in patients. The vast majority of asymptomatic subjects had either positive remodeling without luminal narrowing, or non-significant stenosis. Trial registration ClinicalTrials.gov NCT00456950

Cardiac lipid content is unresponsive to a physical activity training intervention in type 2 diabetic patients, despite improved ejection fraction

Background: Increased cardiac lipid content has been associated with diabetic cardiomyopathy. We recently showed that cardiac lipid content is reduced after 12 weeks of physical activity training in healthy overweight subjects. The beneficial effect of exercise training on cardiovascular risk is well established and the decrease in cardiac lipid content with exercise training in healthy overweight subjects was accompanied by improved ejection fraction. It is yet unclear whether diabetic patients respond similarly to physical activity training and whether a lowered lipid content in the heart is necessary for improvements in cardiac function. Here, we investigated whether exercise training is able to lower cardiac lipid content and improve cardiac function in type 2 diabetic patients. Methods: Eleven overweight-to-obese male patients with type 2 diabetes mellitus (age: 58.4 +/- 0.9 years, BMI: 29.9 +/- 0.01 kg/m(2)) followed a 12-week training program (combination endurance/strength training, three sessions/week). Before and after training, maximal whole body oxygen uptake (VO2max) and insulin sensitivity (by hyperinsulinemic, euglycemic clamp) was determined. Systolic function was determined under resting conditions by CINE-MRI and cardiac lipid content in the septum of the heart by Proton Magnetic Resonance Spectroscopy. Results: VO2max increased (from 27.1 +/- 1.5 to 30.1 +/- 1.6 ml/min/kg, p = 0.001) and insulin sensitivity improved upon training (insulin stimulated glucose disposal (delta Rd of glucose) improved from 5.8 +/- 1.9 to 10.3 +/- 2.0 mu mol/kg/min, p = 0.02. Left-ventricular ejection fraction improved after training (from 50.5 +/- 2.0 to 55.6 +/- 1.5%, p = 0.01) as well as cardiac index and cardiac output. Unexpectedly, cardiac lipid content in the septum remained unchanged (from 0.80 +/- 0.22% to 0.95 +/- 0.21%, p = 0.15). Conclusions: Twelve weeks of progressive endurance/strength training was effective in improving VO(2)max, insulin sensitivity and cardiac function in patients with type 2 diabetes mellitus. However, cardiac lipid content remained unchanged. These data suggest that a decrease in cardiac lipid content in type 2 diabetic patients is not a prerequisite for improvements in cardiac function.Cardiovascular Aspects of Radiolog

Biliverdin Reductase B Is a Plasma Biomarker for Intraplaque Hemorrhage and a Predictor of Ischemic Stroke in Patients with Symptomatic Carotid Atherosclerosis

Background: Intraplaque hemorrhage (IPH) is a hallmark of atherosclerotic plaque instability. Biliverdin reductase B (BLVRB) is enriched in plasma and plaques from patients with symptomatic carotid atherosclerosis and functionally associated with IPH. Objective: We explored the biomarker potential of plasma BLVRB through (1) its correlation with IPH in carotid plaques assessed by magnetic resonance imaging (MRI), and with recurrent ischemic stroke, and (2) its use for monitoring pharmacotherapy targeting IPH in a preclinical setting. Methods: Plasma BLVRB levels were measured in patients with symptomatic carotid atherosclerosis from the PARISK study (n = 177, 5 year follow-up) with and without IPH as indicated by MRI. Plasma BLVRB levels were also measured in a mouse vein graft model of IPH at baseline and following antiangiogenic therapy targeting vascular endothelial growth factor receptor 2 (VEGFR-2). Results: Plasma BLVRB levels were significantly higher in patients with IPH (737.32 ± 693.21 vs. 520.94 ± 499.43 mean fluorescent intensity (MFI), p = 0.033), but had no association with baseline clinical and biological parameters. Plasma BLVRB levels were also significantly higher in patients who developed recurrent ischemic stroke (1099.34 ± 928.49 vs. 582.07 ± 545.34 MFI, HR = 1.600, CI [1.092–2.344]; p = 0.016). Plasma BLVRB levels were significantly reduced following prevention of IPH by anti-VEGFR-2 therapy in mouse vein grafts (1189 ± 258.73 vs. 1752 ± 366.84 MFI; p = 0.004). Conclusions: Plasma BLVRB was associated with IPH and increased risk of recurrent ischemic stroke in patients with symptomatic low- to moderate-grade carotid stenosis, indicating the capacity to monitor the efficacy of IPH-preventive pharmacotherapy in an animal model. Together, these results suggest the utility of plasma BLVRB as a biomarker for atherosclerotic plaque instability

DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia (DECONNECT):research protocol for a cross-sectional pilot study

Introduction Pre-eclampsia is a hypertensive disorder affecting up to 8% of pregnancies. After pre-eclampsia, women are at increased risk of cognitive problems, and cerebrovascular and cardiovascular disorders. These sequelae could result from microvascular dysfunction persisting after pre-eclampsia. This study will explore differences in cerebral and myocardial microvascular function between women after pre-eclampsia and women after normotensive gestation. We hypothesise that pre-eclampsia alters cerebral and myocardial microvascular functions, which in turn are related to diminished cognitive and cardiac performance. Methods and analysis The cross-sectional € DEcreased Cognitive functiON, NEurovascular CorrelaTes and myocardial changes in women with a history of pre-eclampsia' (DECONNECT) pilot study includes women after pre-eclampsia and controls after normotensive pregnancy between 6 months and 20 years after gestation. We recruit women from the Queen of Hearts study, a study investigating subclinical heart failure after pre-eclampsia. Neuropsychological tests are employed to assess different cognitive domains, including attention, processing speed, and cognitive control. Cerebral images are recorded using a 7 Tesla MRI to assess blood-brain barrier integrity, perfusion, blood flow, functional and structural networks, and anatomical dimensions. Cardiac images are recorded using a 3 Tesla MRI to assess cardiac perfusion, strain, dimensions, mass, and degree of fibrosis. We assess the effect of a history of pre-eclampsia using multivariable regression analyses. Ethics and dissemination This study is approved by the Ethics Committee of Maastricht University Medical Centre (METC azM/UM, NL47252.068.14). Knowledge dissemination will include scientific publications, presentations at conferences and public forums, and social media. Trial registration number NCT02347540.</p

Dynamic location problems with limited look-ahead

Background Among the most frequently encountered mutations in dilated cardiomyopathy (DCM) are those in the lamin A/C (LMNA) gene. Our goal was to analyze the LMNA gene in patients with DCM and/or conduction disease referred to the cardiogenetics outpatient clinic and to evaluate the prevalence of LMNA mutations and their clinical expression. Methods and Results The LMNA gene was screened in 61 index patients. Eleven mutations (including 6 novel) were identified, mainly in the subgroup of familial DCM with cardiac conduction disease (3/10 index patients) and in patients with DCM and Emery-Dreifuss, Limb-Girdle, or unclassified forms of muscular dystrophy (7/8 index patients). In addition, a mutation was identified in 1 of 4 families with only cardiac conduction disease. We did not identify any large deletions or duplications.Genotype-phenotype relationships revealed a high rate of sudden death and cardiac transplants in carriers of the p.N 195K mutation. Our study confirmed that the p.R225X mutation leads to cardiac conduction disease with late or no development of DCM, underscoring the importance of this mutation in putative familial "lone conduction disease." Nearly one third of LMNA mutation carriers had experienced a thromboembolic event. Conclusions This study highlights the role of LMNA mutations in DCM and related disorders. A severe phenotype in p.N 195K mutation carriers and preferential cardiac conduction disease in p.R225X carriers was encountered. Because of the clinical variability, including the development of associated symptoms in time, LMNA screening should be considered in patients with DCM or familial lone conduction diseas

UR-CarA-Net: A Cascaded Framework with Uncertainty Regularization for Automated Segmentation of Carotid Arteries on Black Blood MR Images

We present a fully automated method for carotid artery (CA) outer wall segmentation in black blood MRI using partially annotated data and compare it to the state-of-the-art reference model. Our model was trained and tested on multicentric data of patients (106 and 23 patients, respectively) with a carotid plaque and was validated on different MR sequences (24 patients) as well as data that were acquired with MRI systems of a different vendor (34 patients). A 3D nnU-Net was trained on pre-contrast T1w turbo spin echo (TSE) MR images. A CA centerline sliding window approach was chosen to refine the nnU-Net segmentation using an additionally trained 2D U-Net to increase agreement with manual annotations. To improve segmentation performance in areas with semantically and visually challenging voxels, Monte-Carlo dropout was used. To increase generalizability, data were augmented with intensity transformations. Our method achieves state-of-the-art results yielding a Dice similarity coefficient (DSC) of 91.7% (interquartile range (IQR) 3.3%) and volumetric intraclass correlation (ICC) with ground truth of 0.90 on the development domain data and a DSC of 91.1% (IQR 7.2%) and volumetric ICC with ground truth of 0.83 on the external domain data outperforming top-ranked methods for open-source CA segmentation. The uncertainty-based approach increases the interpretability of the proposed method by providing an uncertainty map together with the segmentation

Quantification of carotid plaque composition with a multi-contrast atherosclerosis characterization (MATCH) MRI sequence

Background and purposeCarotid atherosclerotic plaques with a large lipid-rich necrotic core (LRNC), intraplaque hemorrhage (IPH), and a thin or ruptured fibrous cap are associated with increased stroke risk. Multi-sequence MRI can be used to quantify carotid atherosclerotic plaque composition. Yet, its clinical implementation is hampered by long scan times and image misregistration. Multi-contrast atherosclerosis characterization (MATCH) overcomes these limitations. This study aims to compare the quantification of plaque composition with MATCH and multi-sequence MRI.MethodsMATCH and multi-sequence MRI were used to image 54 carotid arteries of 27 symptomatic patients with ≥2 mm carotid plaque on a 3.0 T MRI scanner. The following sequence parameters for MATCH were used: repetition time/echo time (TR/TE), 10.1/4.35 ms; field of view, 160 mm × 160 mm × 2 mm; matrix size, 256 × 256; acquired in-plane resolution, 0.63 mm2× 0.63 mm2; number of slices, 18; and flip angles, 8°, 5°, and 10°. Multi-sequence MRI (black-blood pre- and post-contrast T1-weighted, time of flight, and magnetization prepared rapid acquisition gradient echo; acquired in-plane resolution: 0.63 mm2 × 0.63 mm2) was acquired according to consensus recommendations, and image quality was scored (5-point scale). The interobserver agreement in plaque composition quantification was assessed by the intraclass correlation coefficient (ICC). The sensitivity and specificity of MATCH in identifying plaque composition were calculated using multi-sequence MRI as a reference standard.ResultsA significantly lower image quality of MATCH compared to that of multi-sequence MRI was observed (p &lt; 0.05). The scan time for MATCH was shorter (7 vs. 40 min). Interobserver agreement in quantifying plaque composition on MATCH images was good to excellent (ICC ≥ 0.77) except for the total volume of calcifications and fibrous tissue that showed moderate agreement (ICC ≥ 0.61). The sensitivity and specificity of detecting plaque components on MATCH were ≥89% and ≥91% for IPH, ≥81% and 85% for LRNC, and ≥71% and ≥32% for calcifications, respectively. Overall, good-to-excellent agreement (ICC ≥ 0.76) of quantifying plaque components on MATCH with multi-sequence MRI as the reference standard was observed except for calcifications (ICC = 0.37–0.38) and fibrous tissue (ICC = 0.59–0.70).Discussion and conclusionMATCH images can be used to quantify plaque components such as LRNC and IPH but not for calcifications. Although MATCH images showed a lower mean image quality score, short scan time and inherent co-registration are significant advantages