Multiyear Interval Changes in Aortic Wall Shear Stress in Patients with Bicuspid Aortic Valve Assessed by 4D Flow MRI.

BACKGROUND: In patients with bicuspid aortic valve (BAV), 4D flow MRI can quantify regions exposed to abnormal aortic hemodynamics, including high wall shear stress (WSS), a known stimulus for arterial wall dysfunction. However, the long-term multiscan reproducibility of 4D flow MRI-derived hemodynamic parameters is unknown. PURPOSE: To investigate the long-term stability of 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps in patients with BAV undergoing multiyear surveillance imaging. STUDY TYPE: Retrospective. POPULATION: 20 BAV patients (mean age 48.4 ± 13.9 years; 14 males) with five 4D flow MRI scans, with intervals of at least 6 months between scans, and 125 controls (mean age: 50.7 ± 15.8 years; 67 males). FIELD STRENGTH/SEQUENCE: 1.5 and 3.0T, prospectively ECG and respiratory navigator-gated aortic 4D flow MRI. ASSESSMENT: Automated AI-based 4D flow analysis pipelines were used for data preprocessing, aorta 3D segmentation, and quantification of ascending aorta (AAo) peak velocity, peak systolic WSS, and heatmap-derived relative area of elevated WSS compared to WSS ranges in age and sex-matched normative control populations. Growth rate was derived from the maximum AAo diameters measured on the first and fifth MRI scans. STATISTICAL TESTS: One-way repeated measures analysis of variance. P < 0.05 indicated significance. RESULTS: One hundred 4D flow MRI exams (five per patient) were analyzed. The mean total follow-up duration was 5.5 ± 1.1 years, and the average growth rate was 0.3 ± 0.2 mm/year. Peak velocity, peak systolic WSS, and relative area of elevated WSS did not change significantly over the follow-up period (P = 0.64, P = 0.69, and P = 0.35, respectively). The patterns and areas of elevated WSS demonstrated good reproducibility on semiquantitative assessment. CONCLUSION: 4D flow MRI-derived peak velocity, WSS, and WSS-derived heatmaps showed good multiyear and multiscan stability in BAV patients with low aortic growth rates. These findings underscore the reliability of these metrics in monitoring BAV patients for potential risk of dilation. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 1.

Global Aortic Pulse Wave Velocity is Unchanged in Bicuspid Aortopathy With Normal Valve Function but Elevated in Patients With Aortic Valve Stenosis: Insights From a 4D Flow MRI Study of 597 Subjects.

BACKGROUND: Aortopathy is common with bicuspid aortic valve (BAV), and underlying intrinsic tissue abnormalities are believed causative. Valve-mediated hemodynamics are altered in BAV and may contribute to aortopathy and its progression. The contribution of intrinsic tissue defects versus altered hemodynamics to aortopathy progression is not known. PURPOSE: To investigate relative contributions of tissue-innate versus hemodynamics in progression of BAV aortopathy. STUDY TYPE: Retrospective. SUBJECTS: Four hundred seventy-three patients with aortic dilatation (diameter ≥40 mm; comprised of 281 BAV with varied AS severity, 192 tricuspid aortic valve [TAV] without AS) and 124 healthy controls. Subjects were 19-91 years (141/24% female). FIELD STRENGTH/SEQUENCE: 1.5T, 3T; time-resolved gradient-echo 3D phase-contrast (4D flow) MRI. ASSESSMENT: A surrogate measure for global aortic wall stiffness, pulse wave velocity (PWV), was quantified from MRI by standardized, automated technique based on through-plane flow cross-correlation maximization. Comparisons were made between BAV patients with aortic dilatation and varying aortic valve stenosis (AS) severity and healthy subjects and aortopathy patients with normal TAV. STATISTICAL TESTS: Multivariable regression, analysis of covariance (ANCOVA), Tukey's, student's (t), Mann-Whitney (U) tests, were used with significance levels P < 0.05 or P < 0.01 for post-hoc Bonferroni-corrected t/U tests. Bland-Altman and ICC calculations were performed. RESULTS: Multivariable regression showed age with the most significant association for increased PWV in all groups (increase 0.073-0.156 m/sec/year, R2  = 0.30-48). No significant differences in aortic PWV were observed between groups without AS (P = 0.20-0.99), nor were associations between PWV and regurgitation or Sievers type observed (P = 0.60, 0.31 respectively). In contrast, BAV AS patients demonstrated elevated PWV and a significant relationship for AS severity with increased PWV (covariate: age, R2  = 0.48). BAV and TAV patients showed no association between aortic diameter and PWV (P = 0.73). DATA CONCLUSION: No significant PWV differences were observed between BAV patients with normal valve function and control groups. However, AS severity and age in BAV patients were directly associated with PWV increases. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.

Fully-automated deep learning-based flow quantification of 2D CINE phase contrast MRI.

OBJECTIVES: Time-resolved, 2D-phase-contrast MRI (2D-CINE-PC-MRI) enables in vivo blood flow analysis. However, accurate vessel contour delineation (VCD) is required to achieve reliable results. We sought to evaluate manual analysis (MA) compared to the performance of a deep learning (DL) application for fully-automated VCD and flow quantification and corrected semi-automated analysis (corSAA). METHODS: We included 97 consecutive patients (age = 52.9 ± 16 years, 41 female) with 2D-CINE-PC-MRI imaging on 1.5T MRI systems at sinotubular junction (STJ), and 28/97 also received 2D-CINE-PC at main pulmonary artery (PA). A cardiovascular radiologist performed MA (reference) and corSAA (built-in tool) in commercial software for all cardiac time frames (median: 20, total contours per analysis: 2358 STJ, 680 PA). DL-analysis automatically performed VCD, followed by net flow (NF) and peak velocity (PV) quantification. Contours were compared using Dice similarity coefficients (DSC). Discrepant cases (> ± 10 mL or > ± 10 cm/s) were reviewed in detail. RESULTS: DL was successfully applied to 97% (121/125) of the 2D-CINE-PC-MRI series (STJ: 95/97, 98%, PA: 26/28, 93%). Compared to MA, mean DSC were 0.91 ± 0.02 (DL), 0.94 ± 0.02 (corSAA) at STJ, and 0.85 ± 0.08 (DL), 0.93 ± 0.02 (corSAA) at PA; this indicated good to excellent DL-performance. Flow quantification revealed similar NF at STJ (p = 0.48) and PA (p > 0.05) between methods while PV assessment was significantly different (STJ: p < 0.001, PA: p = 0.04). A detailed review showed noisy voxels in MA and corSAA impacted PV results. Overall, DL analysis compared to human assessments was accurate in 113/121 (93.4%) cases. CONCLUSIONS: Fully-automated DL-analysis of 2D-CINE-PC-MRI provided flow quantification at STJ and PA at expert level in > 93% of cases with results being available instantaneously. KEY POINTS: • Deep learning performed flow quantification on clinical 2D-CINE-PC series at the sinotubular junction and pulmonary artery at the expert level in > 93% of cases. • Location detection and contouring of the vessel boundaries were performed fully-automatic with results being available instantaneously compared to human assessments which approximately takes three minutes per location. • The evaluated tool indicates usability in daily practice.

Deep learning-based velocity antialiasing of 4D-flow MRI.

PURPOSE: To develop a convolutional neural network (CNN) for the robust and fast correction of velocity aliasing in 4D-flow MRI. METHODS: This study included 667 adult subjects with aortic 4D-flow MRI data with existing velocity aliasing (n = 362) and no velocity aliasing (n = 305). Additionally, 10 controls received back-to-back 4D-flow scans with systemically varied velocity-encoding sensitivity (vencs) at 60, 100, and 175 cm/s. The no-aliasing data sets were used to simulate velocity aliasing by reducing the venc to 40%-70% of the original, alongside a ground truth locating all aliased voxels (153 training, 152 testing). The 152 simulated and 362 existing aliasing data sets were used for testing and compared with a conventional velocity antialiasing algorithm. Dice scores were calculated to quantify CNN performance. For controls, the venc 175-cm/s scans were used as the ground truth and compared with the CNN-corrected venc 60 and 100 cm/s data sets RESULTS: The CNN required 176 ± 30 s to perform compared with 162 ± 14 s for the conventional algorithm. The CNN showed excellent performance for the simulated data compared with the conventional algorithm (median range of Dice scores CNN: [0.89-0.99], conventional algorithm: [0.84-0.94], p < 0.001, across all simulated vencs) and detected more aliased voxels in existing velocity aliasing data sets (median detected CNN: 159 voxels [31-605], conventional algorithm: 65 [7-417], p < 0.001). For controls, the CNN showed Dice scores of 0.98 [0.95-0.99] and 0.96 [0.87-0.99] for venc = 60 cm/s and 100 cm/s, respectively, while flow comparisons showed moderate-excellent agreement. CONCLUSION: Deep learning enabled fast and robust velocity anti-aliasing in 4D-flow MRI.

Aortic Pulse Wave Velocity Evaluated by 4D Flow MRI Across the Adult Lifespan.

BACKGROUND: Evaluation of aortic stiffness by pulse wave velocity (PWV) across the adult lifespan is needed to better understand normal aging in women and men. PURPOSE: To characterize PWV in the thoracic aorta using 4D flow MRI in an age- and sex-stratified cohort of healthy adults. STUDY TYPE: Retrospective. POPULATION: Ninety nine healthy participants (age: 46 ± 15 [19-79] years, 50% female), divided into young adults (<45 years) (N = 48), midlife (45-65 years) (N = 37), and later life (>65 years) (N = 14) groups. FIELD STRENGTH/SEQUENCE: 1.5 T or 3 T, 2D cine bSSFP, 4D flow MRI. ASSESSMENT: Cardiac functional parameters of end-diastolic volume (EDV), end-systolic volume (ESV), stroke volume (SV) and myocardial mass were assessed by 2D cine bSSFP. PWV and aortic blood flow velocity were assessed by 4D flow MRI. Reproducibility of PWV was evaluated in a subset of nine participants. STATISTICAL TESTS: Analysis of variance, Pearson's correlation coefficient (r), linear regression, intraclass correlation coefficient (ICC). A P value < 0.05 was considered statistically significant. RESULTS: PWV increased significantly with age (young adults: 5.4 ± 0.9 m/sec, midlife: 7.2 ± 1.1 m/sec, and later life: 9.4 ± 1.8 m/sec) (r = 0.79, slope = 0.09 m/sec/year). PWV did not differ in women and men in entire sample (P = 0.40) or within age groups (young adults: P = 0.83, midlife: P = 0.17, and later life: P = 0.96). PWV was significantly correlated with EDV (r = -0.29), ESV (r = -0.23), SV (r = -0.28), myocardial mass (r = 0.21), and mean aortic blood flow velocity (r = -0.62). In the test-retest subgroup (N = 9), PWV was 6.7 ± 1.5 [4.4-9.3] m/sec and ICC = 0.75. DATA CONCLUSION: 4D flow MRI quantified higher aortic PWV with age, by approximately 1 m/sec per decade, and significant differences between young adults, midlife and later life. Reproducibility analysis showed good test-retest agreement. Increased PWV was associated with decline in cardiac function and reduced aortic blood flow velocity. This study demonstrates the utility of 4D flow MRI-derived aortic PWV for studying aging. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Segmentation of the Aorta and Pulmonary Arteries Based on 4D Flow MRI in the Pediatric Setting Using Fully Automated Multi-Site, Multi-Vendor, and Multi-Label Dense U-Net.

BACKGROUND: Automated segmentation using convolutional neural networks (CNNs) have been developed using four-dimensional (4D) flow magnetic resonance imaging (MRI). To broaden usability for congenital heart disease (CHD), training with multi-institution data is necessary. However, the performance impact of heterogeneous multi-site and multi-vendor data on CNNs is unclear. PURPOSE: To investigate multi-site CNN segmentation of 4D flow MRI for pediatric blood flow measurement. STUDY TYPE: Retrospective. POPULATION: A total of 174 subjects across two sites (female: 46%; N = 38 healthy controls, N = 136 CHD patients). Participants from site 1 (N = 100), site 2 (N = 74), and both sites (N = 174) were divided into subgroups to conduct 10-fold cross validation (10% for testing, 90% for training). FIELD STRENGTH/SEQUENCE: 3 T/1.5 T; retrospectively gated gradient recalled echo-based 4D flow MRI. ASSESSMENT: Accuracy of the 3D CNN segmentations trained on data from single site (single-site CNNs) and data across both sites (multi-site CNN) were evaluated by geometrical similarity (Dice score, human segmentation as ground truth) and net flow quantification at the ascending aorta (Qs), main pulmonary artery (Qp), and their balance (Qp/Qs), between human observers, single-site and multi-site CNNs. STATISTICAL TESTS: Kruskal-Wallis test, Wilcoxon rank-sum test, and Bland-Altman analysis. A P-value <0.05 was considered statistically significant. RESULTS: No difference existed between single-site and multi-site CNNs for geometrical similarity in the aorta by Dice score (site 1: 0.916 vs. 0.915, P = 0.55; site 2: 0.906 vs. 0.904, P = 0.69) and for the pulmonary arteries (site 1: 0.894 vs. 0.895, P = 0.64; site 2: 0.870 vs. 0.869, P = 0.96). Qs site-1 medians were 51.0-51.3 mL/cycle (P = 0.81) and site-2 medians were 66.7-69.4 mL/cycle (P = 0.84). Qp site-1 medians were 46.8-48.0 mL/cycle (P = 0.97) and site-2 medians were 76.0-77.4 mL/cycle (P = 0.98). Qp/Qs site-1 medians were 0.87-0.88 (P = 0.97) and site-2 medians were 1.01-1.03 (P = 0.43). Bland-Altman analysis for flow quantification found equivalent performance. DATA CONCLUSION: Multi-site CNN-based segmentation and blood flow measurement are feasible for pediatric 4D flow MRI and maintain performance of single-site CNNs. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Highly accelerated aortic 4D flow MRI using compressed sensing: Performance at different acceleration factors in patients with aortic disease.

PURPOSE: To systematically assess the feasibility and performance of a highly accelerated compressed sensing (CS) 4D flow MRI framework at three different acceleration factors (R) for the quantification of aortic flow dynamics and wall shear stress (WSS) in patients with aortic disease. METHODS: Twenty patients with aortic disease (58 ± 15 y old; 19 M) underwent four 4D flow scans: one conventional (GRAPPA, R = 2) and three CS 4D flows with R = 5.7, 7.7, and 10.2. All scans were acquired with otherwise equivalent imaging parameters on a 1.5T scanner. Peak-systolic velocity (Vmax ), peak flow (Qmax ), and net flow (Qnet ) were quantified at the ascending aorta (AAo), arch, and descending aorta (DAo). WSS was calculated at six regions within the AAo and arch. RESULTS: Mean scan times for the conventional and CS 4D flows with R = 5.7, 7.7, and 10.2 were 9:58 ± 2:58 min, 3:40 ± 1:19 min, 2:50 ± 0:56 min, and 2:05 ± 0:42 min, respectively. Vmax , Qmax , and Qnet were significantly underestimated by all CS protocols (underestimation ≤ -7%, -9%, and -10% by CS, R = 5.7, 7.7, and 10.2, respectively). WSS measurements showed the highest underestimation by all CS protocols (underestimation ≤ -9%, -12%, and -14% by CS, R = 5.7, 7.7, and 10.2). CONCLUSIONS: Highly accelerated aortic CS 4D flow at R = 5.7, 7.7, and 10.2 showed moderate agreement with the conventional 4D flow, despite systematically underestimating various hemodynamic parameters. The shortened scan time may enable the clinical translation of CS 4D flow, although potential hemodynamic underestimation should be considered when interpreting the results.

Chest radiograph at admission predicts early intubation among inpatient COVID-19 patients.

OBJECTIVE: The 2019 Coronavirus (COVID-19) results in a wide range of clinical severity and there remains a need for prognostic tools which identify patients at risk of rapid deterioration and who require critical care. Chest radiography (CXR) is routinely obtained at admission of COVID-19 patients. However, little is known regarding correlates between CXR severity and time to intubation. We hypothesize that the degree of opacification on CXR at time of admission independently predicts need and time to intubation. METHODS: In this retrospective cohort study, we reviewed COVID-19 patients who were admitted to an urban medical center during March 2020 that had a CXR performed on the day of admission. CXRs were divided into 12 lung zones and were assessed by two blinded thoracic radiologists. A COVID-19 opacification rating score (CORS) was generated by assigning one point for each lung zone in which an opacity was observed. Underlying comorbidities were abstracted and assessed for association. RESULTS: One hundred forty patients were included in this study and 47 (34%) patients required intubation during the admission. Patients with CORS ≥ 6 demonstrated significantly higher rates of early intubation within 48 h of admission and during the hospital stay (ORs 24 h, 19.8, p < 0.001; 48 h, 28.1, p < 0.001; intubation during hospital stay, 6.1, p < 0.0001). There was no significant correlation between CORS ≥ 6 and age, sex, BMI, or any underlying cardiac or pulmonary comorbidities. CONCLUSIONS: CORS ≥ 6 at the time of admission predicts need for intubation, with significant increases in intubation at 24 and 48 h, independent of comorbidities. KEY POINTS: • Chest radiography at the time of admission independently predicts time to intubation within 48 h and during the hospital stay in COVID-19 patients. • More opacities on chest radiography are associated with several fold increases in early mechanical ventilation among COVID-19 patients. • Chest radiography is useful in identifying COVID-19 patients whom may rapidly deteriorate and help inform clinical management as well as hospital bed and ventilation allocation.

Impact of age, sex, and global function on normal aortic hemodynamics.

PURPOSE: To examine the effects of age, sex, and left ventricular global function on velocity, helicity, and 3D wall shear stress (3D-WSS) in the aorta of N = 100 healthy controls. METHODS: Fifty female and 50 male volunteers with no history of cardiovascular disease, with 10 volunteers per age group (18-30, 31-40, 41-50, 51-60, and 61-80 years) underwent aortic 4D-flow MRI. Quantification of systolic aortic peak velocity, helicity, and 3D-WSS distribution and the calculation of age group-averaged peak systolic velocity and 3D-WSS maps ("atlases") were computed. Age-related and sex-related changes in peak velocity, helicity, and 3D-WSS were computed and correlated with standard metrics of left ventricular function derived from short-axis cine MRI. RESULTS: No significant differences were found in peak systolic velocity or 3D-WSS based on sex except for the 18- to 30-year-old group (males 8% higher velocity volume and 3D-WSS surface area). Between successively older groups, systolic velocity decreased (13%, <1%, 7%, and 55% of the aorta volume) and 3D-WSS decreased (21%, 2%, 30%, and 62% of the aorta surface area). Mean velocity, mean 3D-3D-WSS, and median helicity increased with cardiac output (r = 0.27-0.43, all P < .01), and mean velocity and 3D-WSS decreased with increasing diameter (r > 0.35, P < .001). Arch and descending aorta systolic mean velocity, mean 3D-WSS, and median helicity increased with normalized left ventricular volumes: end diastolic volume (r = 0.31-0.37, P < .01), end systolic volume (r = 0.27-0.35, P < .01), and stroke volume (r = 0.28-0.35, P < .01). CONCLUSION: Healthy aortic hemodynamics are dependent on subject age, and correlate with vessel diameter and cardiac function.

Four-dimensional Virtual Catheter: Noninvasive Assessment of Intra-aortic Hemodynamics in Bicuspid Aortic Valve Disease.

Background Four-dimensional (4D) flow MRI enables the evaluation of blood flow alterations in patients with congenital bicuspid aortic valve (BAV). However, current analysis methods are cumbersome and lack the use of the volumetric data from 4D MRI. Purpose To investigate the feasibility and reproducibility of a technique that uses a catheter-like mathematical model (virtual catheter) to assess volumetric intra-aortic hemodynamics from 4D flow MRI in patients with BAV. Materials and Methods In this retrospective study, data were collected from adult patients with BAV and healthy participants who underwent aortic 4D flow MRI from November 2011 through August 2014. Reproducibility was tested in healthy study participants who underwent test-retest examinations within 2 weeks. Patients were grouped on the basis of the severity of aortic valve regurgitation (AVR) and aortic valve stenosis (AVS). A 4D virtual catheter mathematical model for probing intra-aortic hemodynamic flow was constructed as a tube with an automatically derived radius along the entire thoracic aorta centerline. Volumetric intra-aortic hemodynamics were computed from 4D flow MRI only within the virtual catheter, and the following volume-normalized systolic peaks were derived: kinetic energy (KE), viscous energy loss rate (VELR), and vorticity. Hemodynamic data were presented as medians with interquartile ranges and compared by using Mann-Whitney U test and Kruskal-Wallis test. Results The study included 91 participants (57 patients [mean age, 46 years ± 12], 18 women; 34 healthy participants [mean age: 44 years ± 14], 12 women; 15 healthy participants underwent test-retest examinations). Patients showed higher VELR values compared with healthy participants (median, 31 W/m3 [interquartile range, 21-72] vs 23 W/m3 [interquartile range, 17-30], respectively; P < .001) and vorticity (69 sec-1 [interquartile range, 59-87] vs 60 sec-1 [interquartile range, 50-67], respectively; P < .001). Four-dimensional virtual catheter showed differences among different AVS and AVR grades with the highest VELR (120 W/m3; interquartile range, 99-166; P < .001) and vorticity (108 sec-1; interquartile range, 84-151; P < .001) found in severe AVS. High test-retest reproducibility was found for all virtual catheter-derived metrics (intraclass correlation, 0.80 ± 0.07; coefficient of variation, 9% ± 3). Conclusion The proposed four-dimensional (4D) virtual catheter technique enabled reproducible automated evaluation of volumetric intra-aortic hemodynamics alterations from 4D flow MRI in patients with bicuspid aortic valve. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Mitsouras and Hope in this issue.

Dihydromyricetin prevents fetal alcohol exposure-induced behavioral and physiological deficits: the roles of GABAA receptors in adolescence.

Fetal alcohol exposure (FAE) can lead to a variety of behavioral and physiological disturbances later in life. Understanding how alcohol (ethanol, EtOH) affects fetal brain development is essential to guide the development of better therapeutics for FAE. One of EtOH's many pharmacological targets is the γ-aminobutyric acid type A receptor (GABAAR), which plays a prominent role in early brain development. Acute EtOH potentiates inhibitory currents carried by certain GABAAR subtypes, whereas chronic EtOH leads to persistent alterations in GABAAR subunit composition, localization and function. We recently introduced a flavonoid compound, dihydromyricetin (DHM), which selectively antagonizes EtOH's intoxicating effects in vivo and in vitro at enhancing GABAAR function as a candidate for alcohol abuse pharmacotherapy. Here, we studied the effect of FAE on physiology, behavior and GABAAR function of early adolescent rats and tested the utility of DHM as a preventative treatment for FAE-induced disturbances. Gavage administration of EtOH (1.5, 2.5, or 5.0 g/kg) to rat dams on day 5, 8, 10, 12, and 15 of pregnancy dose-dependently reduced female/male offspring ratios (largely through decreased numbers of female offspring) and offspring body weights. FAE (2.5 g/kg) rats tested on postnatal days (P) 25-32 also exhibited increased anxiety and reduced pentylenetetrazol (PTZ)-induced seizure threshold. Patch-clamp recordings from dentate gyrus granule cells (DGCs) in hippocampal slices from FAE (2.5 g/kg) rats at P25-35 revealed reduced sensitivity of GABAergic miniature inhibitory postsynaptic currents (mIPSCs) and tonic current (Itonic) to potentiation by zolpidem (0.3 µM). Interestingly, potentiation of mIPSCs by gaboxadol increased, while potentiation of Itonic decreased in DGCs from FAE rats. Co-administration of EtOH (1.5 or 2.5 g/kg) with DHM (1.0 mg/kg) in pregnant dams prevented all of the behavioral, physiological, and pharmacological alterations observed in FAE offspring. DHM administration alone in pregnant rats had no adverse effect on litter size, progeny weight, anxiety level, PTZ seizure threshold, or DGC GABAAR function. Our results indicate that FAE induces long-lasting alterations in physiology, behavior, and hippocampal GABAAR function and that these deficits are prevented by DHM co-treatment of EtOH-exposed dams. The absence of adverse side effects and the ability of DHM to prevent FAE consequences suggest that DHM is an attractive candidate for development as a treatment for prevention of fetal alcohol spectrum disorders.

A classification approach to improve out of sample predictability of structure-based constitutive models for ascending thoracic aortic tissue.

In this research, a pipeline was developed to assess the out-of-sample predictive capability of structure-based constitutive models of ascending aortic aneurysmal tissue. The hypothesis being tested is that a biomarker can help establish similarities among tissues sharing the same level of a quantifiable property, thus enabling the development of biomarker-specific constitutive models. Biomarker-specific averaged material models were constructed from biaxial mechanical tests of specimens that shared similar biomarker properties such as level of blood-wall shear stress or microfiber (elastin or collagen) degradation in the extracellular matrix. Using a cross-validation strategy commonly used in classification algorithms, biomarker-specific averaged material models were assessed in contrast to individual tissue mechanics of out of sample specimens that fell under the same category but did not contribute to the averaged model's generation. The normalized root means square errors (NRMSE) calculated on out-of-sample data were compared with average models when no categorization was performed versus biomarker-specific models and among different level of a biomarker. Different biomarker levels exhibited statistically different NRMSE when compared among each other, indicating more common features shared by the specimens belonging to the lower error groups. However, no specific biomarkers reached a significant difference when compared to the average model created when No Categorization was performed, possibly on account of unbalanced number of specimens. The method developed could allow for the screening of different biomarkers or combinations/interactions in a systematic manner leading the way to larger datasets and to more individualized constitutive approaches.

Valvular and ascending aortic hemodynamics of the On-X aortic valved conduit by same-day echocardiography and 4D flow MRI.

This study aims to assess whether the On-X aortic valved conduit better restores normal valvular and ascending aortic hemodynamics than other commonly used bileaflet mechanical valved conduit prostheses from St. Jude Medical and Carbomedics by using same-day transthoracic echocardiography (TTE) and 4D flow magnetic resonance imaging (MRI) examinations. TTE and 4D flow MRI were performed back-to-back in 10 patients with On-X, six patients with St. Jude (two) and Carbomedics (four) prostheses, and 36 healthy volunteers. TTE evaluated valvular hemodynamic parameters: transvalvular peak velocity (TPV), mean and peak transvalvular pressure gradient (TPG), and effective orifice area (EOA). 4D flow MRI evaluated the peak systolic 3D viscous energy loss rate (VELR) density and mean vorticity magnitude in the ascending aorta (AAo). While higher TPV and mean and peak TPG were recorded in all patients compared to healthy subjects, the values in On-X patients were closer to those in healthy subjects (TPV 1.9 ± 0.3 vs. 2.2 ± 0.3 vs. 1.2 ± 0.2 m/s, mean TPG 7.4 ± 1.9 vs. 9.2 ± 2.3 vs. 3.1 ± 0.9 mmHg, peak TPG 15.3 ± 5.2 vs. 18.9 ± 5.2 vs. 6.1 ± 1.8 mmHg, p < 0.001). Likewise, while higher VELR density and mean vorticity magnitude were recorded in all patients than in healthy subjects, the values in On-X patients were closer to those in healthy subjects (VELR: 50.6 ± 20.1 vs. 89.8 ± 35.2 vs. 21.4 ± 9.2 W/m3, p < 0.001) and vorticity (147.6 ± 30.0 vs. 191.2 ± 26.0 vs. 84.6 ± 20.5 s-1, p < 0.001). This study demonstrates that the On-X aortic valved conduit may produce less aberrant hemodynamics in the AAo while maintaining similar valvular hemodynamics to St. Jude Medical and Carbomedics alternatives.

Impact of Holocene environmental change on the evolutionary ecology of an Arctic top predator.

The Arctic is among the most climatically sensitive environments on Earth, and the disappearance of multiyear sea ice in the Arctic Ocean is predicted within decades. As apex predators, polar bears are sentinel species for addressing the impact of environmental variability on Arctic marine ecosystems. By integrating genomics, isotopic analysis, morphometrics, and ecological modeling, we investigate how Holocene environmental changes affected polar bears around Greenland. We uncover reductions in effective population size coinciding with increases in annual mean sea surface temperature, reduction in sea ice cover, declines in suitable habitat, and shifts in suitable habitat northward. Furthermore, we show that west and east Greenlandic polar bears are morphologically, and ecologically distinct, putatively driven by regional biotic and genetic differences. Together, we provide insights into the vulnerability of polar bears to environmental change and how the Arctic marine ecosystem plays a vital role in shaping the evolutionary and ecological trajectories of its inhabitants.

Polyphenols: Bioavailability, Microbiome Interactions and Cellular Effects on Health in Humans and Animals.

Polyphenolic compounds have a variety of functions in plants including protecting them from a range of abiotic and biotic stresses such as pathogenic infections, ionising radiation and as signalling molecules. They are common constituents of human and animal diets, undergoing extensive metabolism by gut microbiota in many cases prior to entering circulation. They are linked to a range of positive health effects, including anti-oxidant, anti-inflammatory, antibiotic and disease-specific activities but the relationships between polyphenol bio-transformation products and their interactions in vivo are less well understood. Here we review the state of knowledge in this area, specifically what happens to dietary polyphenols after ingestion and how this is linked to health effects in humans and animals; paying particular attention to farm animals and pigs. We focus on the chemical transformation of polyphenols after ingestion, through microbial transformation, conjugation, absorption, entry into circulation and uptake by cells and tissues, focusing on recent findings in relation to bone. We review what is known about how these processes affect polyphenol bioactivity, highlighting gaps in knowledge. The implications of extending the use of polyphenols to treat specific pathogenic infections and other illnesses is explored.

4D flow MRI derived aortic hemodynamics multi-year follow-up in repaired coarctation with bicuspid aortic valve.

PURPOSE: The purpose of this study was to investigate the relationships between hemodynamic parameters and longitudinal changes in aortic dimensions on four-dimensional (4D) flow magnetic resonance imaging (MRI) in patients with bicuspid aortic valve (BAV) and repaired coarctation. MATERIALS AND METHODS: The study retrospectively included patients with BAV and childhood coarctation repair who had at least two cardiothoracic MRI examinations including 4D flow MRI at baseline and follow-up. Analysis included the calculation of aortic peak velocities, wall shear stress (WSS), pulse wave velocity (PWV), aortic dimensions and annual growth rates. Differences between examinations were assessed using paired t-test or Wilcoxon signed rank test. Relationships between growth rate and 4D flow metrics were assessed using Pearson or Spearman correlation tests. RESULTS: The cohort included 15 patients (mean age 35 ± 8 [SD] years, 9 men) with a median follow-up time of 3.98 years (Q1: 2.10; Q3: 4.96). There were no significant differences in aortic mean WSS, peak velocities, and PWV between baseline and follow-up values. Greater baseline peak velocities at the site of the coarctation were strongly associated with aortic narrowing (follow-up vs. baseline diameter) at coarctation zone (r = -0.64; P = 0.010) and moderately in descending aorta (r = -0.53; P = 0.042). In addition, increased baseline WSS in the aortic arch was strongly related with narrowing of the coarctation zone at follow-up (r = -0.64, P = 0.011). CONCLUSION: Measures of aortic hemodynamics and aortic WSS are stable over time in patients with BAV with coarctation repair. Increased peak velocity was associated with a progressive narrowing at the site of the coarctation repair.

Association of Regional Wall Shear Stress and Progressive Ascending Aorta Dilation in Bicuspid Aortic Valve.

OBJECTIVES: The aim of this study was to evaluate the role of wall shear stress (WSS) as a predictor of ascending aorta (AAo) growth at 5 years or greater follow-up. BACKGROUND: Aortic 4-dimensional flow cardiac magnetic resonance (CMR) can quantify regions exposed to high WSS, a known stimulus for arterial wall dysfunction. However, its association with longitudinal changes in aortic dilation in patients with bicuspid aortic valve (BAV) is unknown. METHODS: This retrospective study identified 72 patients with BAV (age 45 ± 12 years) who underwent CMR for surveillance of aortic dilation at baseline and ≥5 years of follow-up. Four-dimensional flow CMR analysis included the calculation of WSS heat maps to compare regional WSS in individual patients with population averages of healthy age- and sex-matched subjects (database of 136 controls). The relative areas of the AAo and aorta (in %) exposed to elevated WSS (outside the 95% CI of healthy population averages) were quantified. RESULTS: At a median follow-up duration of 6.0 years, the mean AAo growth rate was 0.24 ± 0.20 mm/y. The fraction of the AAo exposed to elevated WSS at baseline was increased for patients with higher growth rates (>0.24 mm/y, n = 32) compared with those with growth rates <0.24 mm/y (19.9% [IQR: 10.2%-25.5%] vs 5.7% [IQR: 1.5%-21.3%]; P = 0.008). Larger areas of elevated WSS in the AAo and entire aorta were associated with higher rates of AAo dilation >0.24 mm/y (odds ratio: 1.51; 95% CI: 1.05-2.17; P = 0.026 and odds ratio: 1.70; 95% CI: 1.01-3.15; P = 0.046, respectively). CONCLUSIONS: The area of elevated AAo WSS as assessed by 4-dimensional flow CMR identified BAV patients with higher rates of aortic dilation and thus might determine which patients require closer follow-up.

Effect of age and sex on fully automated deep learning assessment of left ventricular function, volumes, and contours in cardiac magnetic resonance imaging.

Deep learning algorithms for left ventricle (LV) segmentation are prone to bias towards the training dataset. This study assesses sex- and age-dependent performance differences when using deep learning for automatic LV segmentation. Retrospective analysis of 100 healthy subjects undergoing cardiac MRI from 2012 to 2018, with 10 men and women in the following age groups: 18-30, 31-40, 41-50, 51-60, and 61-80 years old. Subjects underwent 1.5 T, 2D CINE SSFP MRI. 35 pathologic cases from local clinical exams and the SCMR 2015 consensus contours dataset were also analyzed. A fully convolutional network (FCN) similar to U-Net trained on the U.K. Biobank was used to automatically segment LV endocardial and epicardial contours. FCN and manual segmentation were compared using Dice metrics and measurements of end-diastolic volume (EDV), end-systolic volume (ESV), mass (LVM), and ejection fraction (LVEF). Paired t-tests and linear regressions were used to analyze measurement differences with respect to sex and age. Dice metrics (median ± IQR) for n = 135 cases were 0.94 ± 0.04/0.87 ± 0.10 (ED endocardium/ES endocardium). Measurement biases (mean ± SD) among the healthy cohort were - 0.3 ± 10.1 mL for EDV, - 6.7 ± 9.6 mL for ESV, 4.6 ± 6.4% for LVEF, and - 2.2 ± 11.0 g for LVM; biases were independent of sex and age. Biases among the 35 pathologic cases were 0.1 ± 19 mL for EDV, - 4.8 ± 19 mL for ESV, 2.0 ± 7.6% for LVEF, and 1.0 ± 20 g for LVM. In conclusion, automatic segmentation by the Biobank-trained FCN was independent of age and sex. Improvements in end-systolic basal slice detection are needed to decrease bias and improve precision in ESV and LVEF.

Divergence-Free Constrained Phase Unwrapping and Denoising for 4D Flow MRI Using Weighted Least-Squares.

A novel divergence-free constrained phase unwrapping method was proposed and evaluated for 4D flow MRI. The unwrapped phase field was obtained by integrating the phase variations estimated from the wrapped phase data using weighted least-squares. The divergence-free constraint for incompressible blood flow was incorporated to regulate and denoise the resulting phase field. The proposed method was tested on synthetic phase data of left ventricular flow and in vitro 4D flow measurement of Poiseuille flow. The method was additionally applied to in vivo 4D flow measurements in the thoracic aorta from 30 human subjects. The performance of the proposed method was compared to the state-of-the-art 4D single-step Laplacian algorithm. The synthetic phase data were completely unwrapped by the proposed method for all the cases with velocity encoding (venc) as low as 20% of the maximum velocity and signal-to-noise ratio as low as 5. The in vitro Poiseuille flow data were completely unwrapped with a 60% increase in the velocity-to-noise ratio. For the in-vivo aortic datasets with venc ratio less than 0.4, the proposed method significantly improved the success rate by as much as 40% and reduced the velocity error levels by a factor of 10 compared to the state-of-the-art method. The divergence-free constrained method exhibits reliability and robustness on phase unwrapping and shows improved accuracy of velocity and hemodynamic quantities by unwrapping the low-venc 4D flow MRI data.

Four-dimensional Flow Magnetic Resonance Imaging Quantification of Blood Flow in Bicuspid Aortic Valve.

BACKGROUND: Four-dimensional (D) flow magnetic resonance imaging (MRI) is limited by time-consuming and nonstandardized data analysis. We aimed to test the efficiency and interobserver reproducibility of a dedicated 4D flow MRI analysis workflow. MATERIALS AND METHODS: Thirty retrospectively identified patients with bicuspid aortic valve (BAV, age=47.8±11.8 y, 9 male) and 30 healthy controls (age=48.8±12.5 y, 21 male) underwent Aortic 4D flow MRI using 1.5 and 3 T MRI systems. Two independent readers performed 4D flow analysis on a dedicated workstation including preprocessing, aorta segmentation, and placement of four 2D planes throughout the aorta for quantification of net flow, peak velocity, and regurgitant fraction. 3D flow visualization using streamlines was used to grade aortic valve outflow jets and extent of helical flow. RESULTS: 4D flow analysis workflow time for both observers: 5.0±1.4 minutes per case (range=3 to 10 min). Valve outflow jets and flow derangement was visible in all 30 BAV patients (both observers). Net flow, peak velocity, and regurgitant fraction was significantly elevated in BAV patients compared with controls except for regurgitant fraction in plane 4 (91.1±29.7 vs. 62.6±19.6 mL/s, 37.1% difference; 121.7±49.7 vs. 90.9±26.4 cm/s, 28.9% difference; 9.3±10.1% vs. 2.0±3.4%, 128.0% difference, respectively; P<0.001). Excellent intraclass correlation coefficient agreement for net flow: 0.979, peak velocity: 0.931, and regurgitant fraction: 0.928. CONCLUSION: Our study demonstrates the potential of an efficient data analysis workflow to perform standardized 4D flow MRI processing in under 10 minutes and with good-to-excellent reproducibility for flow and velocity quantification in the thoracic aorta.