Introduction Intracranial 4D flow MRI enables quantitative assessment of hemodynamics in patients with intracranial atherosclerotic disease (ICAD). However, quantitative assessments are still challenging due to the time-consuming vessel segmentation, especially in the presence of stenoses, which can often result in user variability. To improve the reproducibility and robustness as well as to accelerate data analysis, we developed an accurate, fully automated segmentation for stenosed intracranial vessels using deep learning. Methods 154 dual-VENC 4D flow MRI scans (68 ICAD patients with stenosis, 86 healthy controls) were retrospectively selected. Manual segmentations were used as ground truth for training. For automated segmentation, deep learning was performed using a 3D U-Net. 20 randomly selected cases (10 controls, 10 patients) were separated and solely used for testing. Cross-sectional areas and flow parameters were determined in the Circle of Willis (CoW) and the sinuses. Furthermore, the flow conservation error was calculated. For statistical comparisons, Dice scores (DS), Hausdorff distance (HD), average symmetrical surface distance (ASSD), Bland-Altman analyses, and interclass correlations were computed using the manual segmentations from two independent observers as reference. Finally, three stenosis cases were analyzed in more detail by comparing the 4D flow-based segmentations with segmentations from black blood vessel wall imaging (VWI). Results Training of the network took approximately 10 h and the average automated segmentation time was 2.2 ± 1.0 s. No significant differences in segmentation performance relative to two independent observers were observed. For the controls, mean DS was 0.85 ± 0.03 for the CoW and 0.86 ± 0.06 for the sinuses. Mean HD was 7.2 ± 1.5 mm (CoW) and 6.6 ± 3.7 mm (sinuses). Mean ASSD was 0.15 ± 0.04 mm (CoW) and 0.22 ± 0.17 mm (sinuses). For the patients, the mean DS was 0.85 ± 0.04 (CoW) and 0.82 ± 0.07 (sinuses), the HD was 8.4 ± 3.1 mm (CoW) and 5.7 ± 1.9 mm (sinuses) and the mean ASSD was 0.22 ± 0.10 mm (CoW) and 0.22 ± 0.11 mm (sinuses). Small bias and limits of agreement were observed in both cohorts for the flow parameters. The assessment of the cross-sectional lumen areas in stenosed vessels revealed very good agreement (ICC: 0.93) with the VWI segmentation but a consistent overestimation (bias ± LOA: 28.1 ± 13.9%). Discussion Deep learning was successfully applied for fully automated segmentation of stenosed intracranial vasculatures using 4D flow MRI data. The statistical analysis of segmentation and flow metrics demonstrated very good agreement between the CNN and manual segmentation and good performance in stenosed vessels. To further improve the performance and generalization, more ICAD segmentations as well as other intracranial vascular pathologies will be considered in the future.

Cerebrovascular imaging assessments are particularly challenging in adolescent cohorts, where not all modalities are appropriate, and rapid brain maturation alters hemodynamics at both macro- and microvascular scales. In a preliminary sample of healthy adolescents (n=12, 8-25 years), we investigated relationships between 4D flow MRI-derived blood velocity and blood flow in bilateral anterior, middle, and posterior cerebral arteries and BOLD cerebrovascular reactivity in associated vascular territories. As hypothesized, higher velocities in large arteries are associated with an earlier response to a vasodilatory stimulus (cerebrovascular reactivity delay) in the downstream territory. Higher blood flow through these arteries is associated with a larger BOLD response to a vasodilatory stimulus (cerebrovascular reactivity amplitude) in the associated territory. These trends are consistent in a case study of adult moyamoya disease. In our small adolescent cohort, macrovascular-microvascular relationships for velocity/delay and flow/CVR change with age, though underlying mechanisms are unclear. Our work emphasizes the need to better characterize this key stage of human brain development, when cerebrovascular hemodynamics are changing, and standard imaging methods offer limited insight into these processes. We provide important normative data for future comparisons in pathology, where combining macro- and microvascular assessments may better help us prevent, stratify, and treat cerebrovascular disease.

Mechanisms underlying heart-brain hemodynamic coupling and effects on the brain remain unclear due to challenges of measuring both heart and brain in a single MRI exam. We have developed a comprehensive MRI protocol that incorporates 1) 4D flow MRI of chest, 2) 4D flow MRI of head and 3) structural neuroimaging into one MRI exam to assess cardiovascular and cerebrovascular flow as well as white matter lesions and brain atrophy. This study demonstrates the utility of heart-brain MRI as viable new tool for in vivo evaluation of hemodynamic coupling along the entire heart-brain pathway.

Cardiovascular risk factors have been linked with dementia risk in aging adults. However, mechanisms underlying heart-brain hemodynamic coupling and effects on the brain remain unclear. 4D flow MRI is uniquely poised to systematically evaluate complex hemodynamics along the heart-brain pathway. Owing to advancements yielding shorter scan times, 4D flow MRI can be acquired in approximately 7 minutes (heart) and 10 minutes (brain). This supports practical add-on of 4D flow MRI to neuroimaging scans for comprehensive heart-brain MRI evaluation in under an hour. We aimed to build a heart-brain MRI acquisition and analysis framework to study relationships between hemodynamics and brain structure with age. 17 healthy participants (age = 53.5±16.3[24-76] years) underwent heart-brain MRI at 3T (MAGNETOM Prisma, Siemens, Erlangen, Germany), including a free-breathing whole-chest 4D flow MRI research sequence, intracranial dual-venc 4D flow MRI research sequence, and T1- and T2-weighted structural neuroimaging. Participants were cognitively healthy and screened for history of cardiovascular and cerebrovascular problems that may influence blood flow. 4D flow MRI was used to evaluate blood flow velocities in the aorta and Circle of Willis (Figure 1: left). Mean velocity was determined on a voxel-wise basis over the entire cardiac cycle. Volumetric and cortical thickness analysis was performed with FreeSurfer (v7.3; Figure 1: right). Left and right hippocampal and amygdala volumes were averaged and corrected for intracranial head size. We examined relationships between hemodynamics, volume and thickness measures, and age using Pearson correlations and multiple regression. Mean aortic velocity was associated with age (r = -0.59, p = 0.012), hippocampal volume (r = 0.68, p = 0.003), amygdala volume (r = 0.59, p = 0.012), and inferior temporal thickness (r = 0.49, p = 0.044). Figure 2. Mean velocity in the Circle of Willis (r = -0.49, p = 0.048), amygdala volume (r = -0.66, p = 0.004) and inferior temporal thickness (r = -0.60, p = 0.010) were also associated with age. Using multiple regression, mean aortic velocity was associated with hippocampal volume (p = 0.018) adjusting for age. This study demonstrates capture of comprehensive heart and brain data in a single imaging exam for assessment of age-related relationships in hemodynamics and brain structure. Heart-brain MRI is a promising tool for evaluation of hemodynamic coupling along the entire heart-brain pathway. Grant support: NIH NIA P30AG059988, P30AG072977, K01AG080070; NINDS R21NS122511:

BackgroundPulmonary hypertension (PH) contributes to restricted flow through the pulmonary circulation characterized by elevated mean pulmonary artery pressure acquired from invasive right heart catheterization (RHC). MRI may provide a noninvasive alternative for diagnosis and characterization of PH.PurposeTo characterize PH via quantification of regional pulmonary transit times (rPTT).Study TypeRetrospective.PopulationA total of 43 patients (58% female); 24 controls (33% female). RHC‐confirmed patients classified as World Health Organization (WHO) subgroups 1–4.Field Strength/SequenceA 1.5 T/time‐resolved contrast‐enhanced MR Angiography (CE‐MRA).AssessmentCE‐MRA data volumes were combined into a 4D matrix (3D resolution + time). Contrast agent arrival time was defined as the peak in the signal‐intensity curve generated for each voxel. Average arrival times within a vessel region of interest (ROI) were normalized to the main pulmonary artery ROI (t0) for eight regions to define rPTT for all subjects. Subgroup analysis included grouping the four arterial and four venous regions. Intraclass correlation analysis completed for reproducibility.Statistical TestsAnalysis of covariance with age as covariate. A priori Student's t‐tests or Wilcoxon rank‐sum test; α = 0.05. Results compared to controls unless noted. Significant without listing P value. ICC ran as two‐way absolute agreement model with two observers.ResultsPH patients demonstrated elevated rPTT in all vascular regions; average rPTT increase in arterial and venous branches was 0.85 ± 0.15 seconds (47.7%) and 1.0 ± 0.18 seconds (16.9%), respectively. Arterial rPTT was increased for all WHO subgroups; venous regions were elevated for subgroups 2 and 4 (group 1, P = 0.86; group 3, P = 0.32). No significant rPTT differences were found between subgroups (P = 0.094–0.94). Individual vessel ICC values ranged from 0.58 to 0.97.Data ConclusionNoninvasive assessment of PH using standard‐of‐care time‐resolved CE‐MRA can detect increased rPTT in PH patients of varying phenotypes compared to controls.Level of Evidence1Technical EfficacyStage 3.

Combined modality PET/MR may be a sensitive modality to detect severe large vessel vasculitis. To distinguish severe large vessel vasculitis, a qualitative review of PET imaging findings appears more useful than standardized uptake values of a patient’s highest-uptake vessel. Inflammatory marker levels and trends, as well as single-modality scan findings, were not significantly different between severe and non-severe large vessel vasculitis patients.

Background Gadobutrol (GB) and gadoterate meglumine (GM) are contrast agents used for contrast‐enhanced magnetic resonance angiography (CEMRA). Supraaortic vasculature (SAV) CEMRAs are used to evaluate stroke risk and neurologic symptoms. There is a need to compare the SAV CEMRA image quality obtained with GB and GM. Purpose To intra‐individually compare MRA images obtained with equimolar GB and GM at 1.5 T in the SAV. Study Type Prospective, crossover. Population Twenty‐eight subjects (54 ± 13 years; 17 female). Field Strength/Sequence 1.5 T ; three‐dimensional ( 3D) gradient recalled echo. Assessment Quantitative image quality was measured by normalized signal intensity (SI n ) [SI n = SI blood/SD blood] and contrast ratio (CR) [CR = SI blood/SI muscle], determined by an observer (JWC) with 1 year of vascular imaging experience. Three radiologists (AS, PA, and MU) with (5, 5, and 6 years of) vascular imaging experience evaluated image quality by Likert‐scale ratings (of image impression, wall conspicuity, and artifact absence). Statistical Tests SI n and CR were compared with paired t ‐tests or Wilcoxon signed‐rank tests and Bland–Altman plots. Qualitative ratings were compared with Wilcoxon signed‐rank test. Results No significant difference in SI n was found between GB and GM. CRs with GB were significantly higher than GM at the right common carotid (6.9 ± 2.5 vs. 4.8 ± 1), left internal carotid (7.3 ± 2 vs. 4.4 ± 1.2), right internal carotid (7.7 ± 2.2 vs. 5 ± 1.1), and left vertebral (6.6 ± 2.2 vs. 4.5 ± 1.1) arteries. Bland–Altman plots showed relatively greater differences between GB and GM at higher CRs and SI n s. GM showed significantly higher artifact than GB (3.56 ± 0.52 vs. 3.36 ± 0.46) and significantly lower overall image quality (10.73 ± 1.45 vs. 11.26 ± 1.58) at the left vertebral artery. Data Conclusion At 1.5 T and equimolar demonstration, GB (0.1 mL/kg, i.e., 0.1 mmol/kg) showed higher CRs in the SAV compared to GM (0.2 mL/kg, i.e., 0.1 mmol/kg) at most vessels. Subjective image quality was not significantly different between the two agents for most vessels. Level of Evidence 2 Technical Efficacy Stage 2

Twenty-one novel carbohydrate surfactants were synthesised and characterised. Some formed rare elongated aggregates in water which, when entangled, cause the solution to become thick at low concentrations. The aggregates were studied in detail to optimise and maximise their thickening properties. These bio-resourced thickeners have many potential applications in academia and industry as alternatives to current petrochemical-based products.