Effect of Aortic Valve Disease on 3D Hemodynamics in Patients With Aortic Dilation and Trileaflet Aortic Valve Morphology.

BACKGROUND: The effect of different expressions of aortic valve disease on 3D aortic hemodynamics is unclear. PURPOSE: To investigate changes in aortic hemodynamics in patients with dilated ascending aorta (AAo) but different severity of aortic valve stenosis (AS) and/or regurgitation (AR). STUDY TYPE: Retrospective. POPULATION: A total of 111 subjects (86 patients with AAo diameter ≥ 40 mm and 25 healthy controls, all with trileaflet aortic valve [TAV]). Patients were further stratified by TAV dysfunction: n = 9 with combined moderate or severe AS and AR (ASR, 56 ± 13 years), n = 14 with moderate or severe AS (AS, 64 ± 14 years), n = 33 with moderate or severe AR (AR, 62 ± 14 years), n = 30 with neither AS nor AR (no AS/AR, 63 ± 9 years). FIELD STRENGTH/SEQUENCE: 4D flow MRI on 1.5/3T systems for the in vivo analysis of aortic blood flow dynamics. ASSESSMENT: Data analysis included grading of 3D AAo vortex/helix flow and AAo flow eccentricity as well as quantification of systolic peak velocities and wall shear stress (WSS). STATISTICAL TESTS: Continuous variables were compared by one-way analysis of variance or Kruskal-Wallis, followed by a pairwise Tukey or Dunn test if there was a significant difference. RESULTS: All patients demonstrated markedly elevated vortex and helix flow compared with controls (P < 0.05). Peak velocities were significantly elevated in ASR, AS, and AR patients compared with controls (P < 0.05). Increased flow eccentricity was observed in entire AAo for AR, at the mid and distal AAo for ASR and AS, and at the proximal AAo for no AS/AR. Compared with controls, WSS in the AAo was significantly elevated in ASR and AS patients (P < 0.05) and reduced in no AS/AR patients (P < 0.05). DATA CONCLUSION: The presence of TAV dysfunction is associated with aberrant hemodynamics and altered WSS, which may play a role in the development of aortopathy. LEVEL OF EVIDENCE: 3 Technical Efficacy Stage: 3 J. Magn. Reson. Imaging 2020;51:481-491.

The role of initial chest X-ray in triaging patients with suspected COVID-19 during the pandemic.

PURPOSE: The purpose of our research is to evaluate the usefulness of chest X-ray for triaging patients with suspected COVID-19 infection. METHODS: IRB approval was obtained to allow a retrospective review of adult patients who presented to the Emergency Department with a complaint of fever, cough, dyspnea or hypoxia and had a chest X-ray between 12 March 2020 and 26 March 2020. The initial chest X-ray was graded on a scale of 0-3 with grade 0 representing no alveolar opacities, grade 1: < 1/3 alveolar opacities of the lung, Grade 2: 1/3 to 2/3 lung with alveolar opacities and grade 3: > 2/3 alveolar opacities of the lung. Past medical history of diabetes and hypertension, initial oxygen saturation, COVID-19 testing results, intubation, and outcome were also collected. RESULTS: Four hundred ten patient chest X-rays were reviewed. Oxygen saturation and X-ray grade were both significantly associated with the length of stay in hospital, the hazard ratio (HR) of discharge was 1.05 (95% CI [1.01, 1.09], p = 0.017) and 0.61 (95% CI [0.51, 0.73], p < 0.001), respectively. In addition, oxygen saturation and X-ray grade were significant predictors of intubation (odds ratio (OR) of intubation is 0.88 (95% CI [0.81, 0.96], p = 0.004) and 3.69 (95% CI [2.25, 6.07], p < 0.001). CONCLUSIONS: Initial chest X-ray is a useful tool for triaging those subjects who might have poor outcomes with suspected COVID-19 infection and benefit most from hospitalization.

Reproducibility and Changes in Vena Caval Blood Flow by Using 4D Flow MRI in Pulmonary Emphysema and Chronic Obstructive Pulmonary Disease (COPD): The Multi-Ethnic Study of Atherosclerosis (MESA) COPD Substudy.

BackgroundChronic obstructive pulmonary disease (COPD) is associated with hemodynamic changes in the pulmonary vasculature. However, cardiac effects are not fully understood and vary by phenotype of chronic lower respiratory disease.PurposeTo use four-dimensional (4D) flow MRI for comprehensive assessment of the right-sided cardiovascular system, assess its interrater and intraobserver reproducibility, and examine associations with venous return to the right heart in individuals with chronic COPD and emphysema.Materials and MethodsThe Multi-Ethnic Study of Atherosclerosis COPD substudy prospectively recruited participants who smoked and who had COPD and nested control participants from population-based samples. Electrocardiography and respiratory gated 4D flow 1.5-T MRI was performed at three sites with full volumetric coverage of the thoracic vessels in 2014-2017 with postbronchodilator spirometry and inspiratory chest CT to quantify percent emphysema. Net flow, peak velocity, retrograde flow, and retrograde fraction were measured on 14 analysis planes. Interrater reproducibility was assessed by two independent observers, and the principle of conservation of mass was employed to evaluate the internal consistency of flow measures. Partial correlation coefficients were adjusted for age, sex, race/ethnicity, height, weight, and smoking status.ResultsAmong 70 participants (29 participants with COPD [mean age, 73.5 years ± 8.1 {standard deviation}; 20 men] and 41 control participants [mean age, 71.0 years ± 6.1; 22 men]), the interrater reproducibility of the 4D flow MRI measures was good to excellent (intraclass correlation coefficient range, 0.73-0.98), as was the internal consistency. There were no statistically significant differences in venous flow parameters according to COPD severity (P > .05). Greater percent emphysema at CT was associated with greater regurgitant flow in the superior and inferior caval veins and tricuspid valve (adjusted r = 0.28-0.55; all P < .01), particularly in the superior vena cava.ConclusionFour-dimensional flow MRI had good-to-excellent observer variability and flow consistency. Percent emphysema at CT was associated with statistically significant differences in retrograde flow, greatest in the superior vena cava.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Choe in this issue.

Accelerated dual-venc 4D flow MRI for neurovascular applications.

PURPOSE: To improve velocity-to-noise ratio (VNR) and dynamic velocity range of 4D flow magnetic resonance imaging (MRI) by using dual-velocity encoding (dual-venc) with k-t generalized autocalibrating partially parallel acquisition (GRAPPA) acceleration. MATERIALS AND METHODS: A dual-venc 4D flow MRI sequence with k-t GRAPPA acceleration was developed using a shared reference scan followed by three-directional low- and high-venc scans (repetition time / echo time / flip angle = 6.1 msec / 3.4 msec / 15°, temporal/spatial resolution = 43.0 msec/1.2 × 1.2 × 1.2 mm3 ). The high-venc data were used to correct for aliasing in the low-venc data, resulting in a single dataset with the favorable VNR of the low-venc but without velocity aliasing. The sequence was validated with a 3T MRI scanner in phantom experiments and applied in 16 volunteers to investigate its feasibility for assessing intracranial hemodynamics (net flow and peak velocity) at the major intracranial vessels. In addition, image quality and image noise were assessed in the in vivo acquisitions. RESULTS: All 4D flow MRI scans were acquired successfully with an acquisition time of 20 ± 4 minutes. The shared reference scan reduced the total acquisition time by 12.5% compared to two separate scans. Phantom experiments showed 51.4% reduced noise for dual-venc compared to high-venc and an excellent agreement of velocities (ρ = 0.8, P < 0.001). The volunteer data showed decreased noise in dual-venc data (54.6% lower) compared to high-venc, and improved image quality, as graded by two observers: fewer artifacts (P < 0.0001), improved vessel conspicuity (P < 0.0001), and reduced noise (P < 0.0001). CONCLUSION: Dual-venc 4D flow MRI exhibits the superior VNR of the low-venc acquisition and reliably incorporates low- and high-velocity fields simultaneously. In vitro and in vivo data demonstrate improved flow visualization, image quality, and image noise. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2017;46:102-114.

Longitudinal Evaluation of Aortic Hemodynamics in Marfan Syndrome: New Insights from a 4D Flow Cardiovascular Magnetic Resonance Multi-Year Follow-Up Study.

BACKGROUND: The aim of this 4D flow cardiovascular magnetic resonance (CMR) follow-up study was to investigate longitudinal changes in aortic hemodynamics in adolescent patients with Marfan syndrome (MFS). METHODS: 4D flow CMR for the assessment of in-vivo 3D blood flow with full coverage of the thoracic aorta was performed twice (baseline scan t1/follow-up scan t2) in 19 adolescent MFS patients (age at t1: 12.7 ± 3.6 years, t2: 16.2 ± 4.3 years) with a mean follow-up duration of 3.5 ± 1.2 years. Ten healthy volunteers (24 ± 3.8 years) served as a control group. Data analysis included aortic blood flow visualization by color-coded 3D pathlines, and grading of flow patterns (helices/vortices) on a 3-point scale (none, moderate, severe; blinded reading, 2 observers). Regional aortic peak systolic velocities and systolic 3D wall shear stress (WSS) along the entire aortic wall were quantified. Z-Scores of the aortic root and proximal descending aorta (DAo) were assessed. RESULTS: Regional systolic WSS was stable over the follow-up duration, except for a significant decrease in the proximal inner DAo segment (p = 0.02) between t1 and t2. MFS patients revealed significant lower mean systolic WSS in the proximal inner DAo compared with volunteers (0.78 ± 0.15 N/m2) at baseline t1 (0.60 ± 0.18 N/m2; p = 0.01) and follow-up t2 (0.55 ± 0.16 N/m2; p = 0.001). There were significant relationships (p < 0.01) between the segmental WSS in the proximal inner DAo, DAo Z-scores (r = -0.64) and helix/vortex pattern grading (r = -0.55) at both t1 and t2. The interobserver agreement for secondary flow patterns assessment was excellent (Cohen's k = 0.71). CONCLUSIONS: MFS patients have lower segmental WSS in the inner proximal DAo segment which correlates with increased localized aberrant vortex/helix flow patterns and an enlarged diameter at one of the most critical sites for aortic dissection. General aortic hemodynamics are stable but these subtle localized DAo changes are already present at young age and tend to be more pronounced in the course of time.

Interval changes in aortic peak velocity and wall shear stress in patients with bicuspid aortic valve disease.

Bicuspid aortic valve (BAV) is associated with abnormal valve-mediated hemodynamics including high velocity jets and elevated wall shear stress (WSS). This study investigated interval changes in flow and WSS in a multi-year follow-up study. This cross-sectional study included n = 44 patients with BAV (age = 44.9 ± 12 years), n = 17 patients with tricuspid aortic valve and thoracic aortic dilatation (TAV with dilation, age = 54.6 ± 16.5 years), and n = 9 healthy controls (age = 49.3 ± 14.7 years) underwent baseline and serial aortic 4D flow MRI (follow-up duration: BAV: 2.6 ± 0.7 years, TAV with dilation: 2.7 ± 0.5 years, controls: 1.1 ± 0.5 years). Data analysis included quantification of aortic dimensions, peak systolic velocities, as well as regional 3D WSS in the ascending aorta. At baseline, BAV patients demonstrated uniformly elevated peak velocity and WSS compared to TAV with dilation and control groups (peak velocity 2.2 m/s vs. 1.6 m/s vs. 1.5 m/s, p < 0.004; WSS: 0.74 Pa vs. 0.45 Pa vs. 0.55 Pa, p < 0.001). For BAV, peak velocity increased from baseline to follow up (2.2 ± 0.8 to 2.3 ± 0.9 m/s, p < 0.001) while WSS decreased (0.74 ± 0.22 to 0.65 ± 0.21 Pa, p < 0.001). Aortic growth was minimal for both BAV (0.05 cm/year) and TAV with dilation (0.03-0.04 cm/year) patients. For BAV patients, increase of ascending aorta peak velocities indicated worsening of valve function at follow-up. Compared to TAV with dilation patients, BAV patients demonstrated a reduction in WSS which may indicate a compensatory mechanism to reduce elevated WSS forces by aortic remodeling.

Perioperative evaluation of regional aortic wall shear stress patterns in patients undergoing aortic valve and/or proximal thoracic aortic replacement.

OBJECTIVES: To assess in patients with aortopathy perioperative changes in thoracic aortic wall shear stress (WSS), which is known to affect arterial remodeling, and the effects of specific surgical interventions. METHODS: Presurgical and postsurgical aortic 4D flow MRI were performed in 33 patients with aortopathy (54 ± 14 years; 5 women; sinus of Valsalva (d_SOV)/midascending aortic (d_MAA) diameters = 44 ± 5/45 ± 6 mm) scheduled for aortic valve (AVR) and/or root (ARR) replacement. Control patients with aortopathy who did not have surgery were matched for age, sex, body size, and d_MAA (n = 20: 52 ± 14 years; 3 women; d_SOV/d_MAA = 42 ± 4/42 ± 4 mm). Regional aortic 3D systolic peak WSS was calculated. An atlas of WSS normal values was used to quantify the percentage of at-risk tissue area with abnormally high WSS, excluding the area to be resected/graft. RESULTS: Peak WSS and at-risk area showed low interobserver variability (≤0.09 [-0.3; 0.5] Pa and 1.1% [-7%; 9%], respectively). In control patients, WSS was stable over time (follow-up-baseline differences ≤0.02 Pa and 0.0%, respectively). Proximal aortic WSS decreased after AVR (n = 5; peak WSS difference ≤-0.41 Pa and at-risk area ≤-10%, P < .05 vs controls). WSS was increased after ARR in regions distal to the graft (peak WSS difference ≥0.16 Pa and at-risk area ≥4%, P < .05 vs AVR). Follow-up duration had no significant effects on these WSS changes, except when comparing ascending aortic peak WSS between ARR and AVR (P = .006). CONCLUSIONS: Serial perioperative 4D flow MRI investigations showed distinct patterns of postsurgical changes in aortic WSS, which included both reductions and translocations. Larger longitudinal studies are warranted to validate these findings with clinical outcomes and prediction of risk of future aortic events.

Aortic Volumetry at Contrast-Enhanced Magnetic Resonance Angiography: Feasibility as a Sensitive Method for Monitoring Bicuspid Aortic Valve Aortopathy.

OBJECTIVES: Bicuspid aortic valve patients can develop thoracic aortic aneurysms and therefore require serial imaging to monitor aortic growth. This study investigates the reliability of contrast-enhanced magnetic resonance angiography (CEMRA) volumetry compared with 2-dimensional diameter measurements to identify thoracic aortic aneurysm growth. MATERIALS AND METHODS: A retrospective, institutional review board-approved, and Health Insurance Portability and Accountability Act-compliant study was conducted on 20 bicuspid aortic valve patients (45 ± 8.9 years, 20% women) who underwent serial CEMRA with a minimum imaging follow-up of 11 months. Magnetic resonance imaging was performed at 1.5 T with electrocardiogram-gated, time-resolved CEMRA. Independent observers measured the diameter at the sinuses of Valsalva (SOVs) and mid ascending aorta (MAA) as well as ascending aorta volume between the aortic valve annulus and innominate branch. Intraobserver/interobserver coefficient of variation (COV) and intraclass correlation coefficient (ICC) were computed to assess reliability. Growth rates were calculated and assessed by Student t test (P < 0.05, significant). The diameter of maximal growth (DMG), defined as the diameter at SOV or MAA with the faster growth rate, was recorded. RESULTS: The mean time of follow-up was 2.6 ± 0.82 years. The intraobserver COV was 0.01 for SOV, 0.02 for MAA, and 0.02 for volume (interobserver COV: 0.02, 0.03, 0.04, respectively). The ICC was 0.83 for SOV, 0.86 for MAA, 0.90 for DMG, and 0.95 for volume. Average aortic measurements at baseline and (follow-up) were 42 ± 3 mm (42 ± 3 mm, P = 0.11) at SOV, 46 ± 4 mm (47 ± 4 mm, P < 0.05) at MAA, and 130 ± 23 mL (144 ± 24 mL, P < 0.05). Average size changes were 0.2 ± 0.6 mm/y (1% ± 2%) at SOV, 0.5 ± 0.8 mm/y (1% ± 2%) at MAA, 0.7 ± 0.7 mm/y (2% ± 2%) at DMG, and 6 ± 3 mL/y (4% ± 3%) with volumetry. CONCLUSIONS: Three-dimensional CEMRA volumetry exhibited a larger effect when examining percentage growth, a better ICC, and a marginally lower COV. Volumetry may be more sensitive to growth and possibly less affected by error than diameter measurements.

Rosemary (Rosmarinus officinalis) extract modulates CHOP/GADD153 to promote androgen receptor degradation and decreases xenograft tumor growth.

The Mediterranean diet has long been attributed to preventing or delaying the onset of cardiovascular disease, diabetes and various solid organ cancers. In this particular study, a rosemary extract standardized to carnosic acid was evaluated for its potential in disrupting the endoplasmic reticulum machinery to decrease the viability of prostate cancer cells and promote degradation of the androgen receptor. Two human prostate cancer cell lines, 22Rv1 and LNCaP, and prostate epithelial cells procured from two different patients undergoing radical prostatectomy were treated with standardized rosemary extract and evaluated by flow cytometry, MTT, BrdU, Western blot and fluorescent microscopy. A significant modulation of endoplasmic reticulum stress proteins was observed in cancer cells while normal prostate epithelial cells did not undergo endoplasmic reticulum stress. This biphasic response suggests that standardized rosemary extract may preferentially target cancer cells as opposed to "normal" cells. Furthermore, we observed standardized rosemary extract to decrease androgen receptor expression that appears to be regulated by the expression of CHOP/GADD153. Using a xenograft tumor model we observed standardized rosemary extract when given orally to significantly suppress tumor growth by 46% compared to mice not receiving standardized rosemary extract. In the last several years regulatory governing bodies (e.g. European Union) have approved standardized rosemary extracts as food preservatives. These results are especially significant as it is becoming more likely that individuals will be receiving standardized rosemary extracts that are a part of a natural preservative system in various food preparations. Taken a step further, it is possible that the potential benefits that are often associated with a "Mediterranean Diet" in the future may begin to extend beyond the Mediterranean diet as more of the population is consuming standardized rosemary extracts.