Riti Mahadevia

Bicuspid Aortic Cusp Fusion Morphology Alters Aortic Three-Dimensional Outflow Patterns, Wall Shear Stress, and Expression of Aortopathy

Background— Aortic 3-dimensional blood flow was analyzed to investigate altered ascending aorta (AAo) hemodynamics in bicuspid aortic valve (BAV) patients and its association with differences in cusp fusion patterns (right-left, RL versus right-noncoronary, RN) and expression of aortopathy. Methods and Results— Four-dimensional flow MRI measured in vivo 3-dimensional blood flow in the aorta of 75 subjects: BAV patients with aortic dilatation stratified by leaflet fusion pattern (n=15 RL-BAV, mid AAo diameter=39.9±4.4 mm; n=15 RN-BAV, 39.6±7.2 mm); aorta size controls with tricuspid aortic valves (n=30, 41.0±4.4 mm); healthy volunteers (n=15, 24.9±3.0 mm). Aortopathy type (0–3), systolic flow angle, flow displacement, and regional wall shear stress were determined for all subjects. Eccentric outflow jet patterns in BAV patients resulted in elevated regional wall shear stress (P<0.0125) at the right-anterior walls for RL-BAV and right-posterior walls for RN-BAV in comparison with aorta size controls. Dilatation of the aortic root only (type 1) or involving the entire AAo and arch (type 3) was found in the majority of RN-BAV patients (87%) but was mostly absent for RL-BAV patients (87% type 2). Differences in aortopathy type between RL-BAV and RN-BAV patients were associated with altered flow displacement in the proximal and mid AAo for type 1 (42%–81% decrease versus type 2) and distal AAo for type 3 (33%–39% increase versus type 2). Conclusions— The presence and type of BAV fusion was associated with changes in regional wall shear stress distribution, systolic flow eccentricity, and expression of BAV aortopathy. Hemodynamic markers suggest a physiological mechanism by which the valve morphology phenotype can influence phenotypes of BAV aortopathy.

Evaluation of aortic stenosis severity using 4D flow jet shear layer detection for the measurement of valve effective orifice area.

AIMS The objective of this study was to evaluate the potential of 4D flow MRI to assess valve effective orifice area (EOA) in patients with aortic stenosis as determined by the jet shear layer detection (JSLD) method. METHODS AND RESULTS An in-vitro stenosis phantom was used for validation and in-vivo imaging was performed in 10 healthy controls and 40 patients with aortic stenosis. EOA was calculated by the JSLD method using standard 2D phase contrast MRI (PC-MRI) and 4D flow MRI measurements (EOAJSLD-2D and EOAJSLD-4D, respectively). As a reference standard, the continuity equation was used to calculate EOA (EOACE) with the 2D PC-MRI velocity field and compared to the EOAJSLD measurements. The in-vitro results exhibited excellent agreement between flow theory (EOA=0.78cm(2)) and experimental measurement (EOAJSLD-4D=0.78±0.01cm(2)) for peak velocities ranging from 0.9 to 3.7m/s. In-vivo results showed good correlation and agreement between EOAJSLD-2D and EOACE (r=0.91, p<0.001; bias: -0.01±0.38cm(2); agreement limits: 0.75 to -0.77cm(2)), and between EOAJSLD-4D and EOACE (r=0.95, p<0.001; bias: -0.09±0.26cm(2); limits: 0.43 to -0.62cm(2)). CONCLUSION This study demonstrates the feasibility of measuring EOAJSLD using 4D flow MRI. The technique allows for optimization of the EOA measurement position by visualizing the 3D vena contracta, and avoids potential sources of EOACE measurement variability.

Matrix metalloproteinase levels in early HIV infection and relation to in vivo brain status

Matrix metalloproteinases (MMPs) have been implicated in human immunodeficiency virus (HIV)-associated neurological injury; however, this relationship has not been studied early in infection. Plasma levels of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 measured using Luminex technology (Austin, TX, USA) were compared in 52 HIV and 21 seronegative participants of the Chicago Early HIV Infection study. MMP levels were also examined in HIV subgroups defined by antibody reactivity, viremia, and antiretroviral status, as well as in available cerebrospinal fluid (CSF) samples (n = 9). MMPs were evaluated for patterns of relationship to cognitive function and to quantitative magnetic resonance measurements of the brain derived in vivo. Plasma MMP-2 levels were significantly reduced in early HIV infection and correlated with altered white matter integrity and atrophic brain changes. MMP-9 levels were higher in the treated subgroup than in the naïve HIV subgroup. Only MMP-2 and MMP-9 were detected in the CSF; CSF MMP-2 correlated with white matter integrity and with volumetric changes in basal ganglia. Relationships with cognitive function were also identified. MMP-2 levels in plasma and in CSF correspond to early changes in brain structure and function. These findings establish a link between MMPs and neurological status previously unidentified in early HIV infection.

From unicuspid to quadricuspid: influence of aortic valve morphology on aortic three-dimensional hemodynamics.

To assess the impact of aortic valve morphology on aortic hemodynamics between normal tricuspid and congenitally anomalous aortic valves ranging from unicuspid to quadricuspid morphology.

From unicuspid to quadricuspid: the impact of aortic valve morphology on 3D hemodynamics

Background The purpose of this study was to assess the impact of aortic valve morphology on aortic 3D blood flow dynamics and wall shear stress (WSS) in normal and a wide range of congenitally altered aortic valves ranging from unicuspid to quadricuspid morphology. Methods In-vivo aortic 3D hemodynamics were evaluated by MRI in 17 patients with unicuspid (n=3), bicuspid (n=9, 3 true bicuspid, 3 right-left (RL) coronary leaflet fusion, and 3 right-non (RN) coronary leaflet fusion), trileaflet (n=3), and quadricuspid aortic valves (n=2). Valve morphology and dynamics were assessed using 2D CINE MRI. Aortic blood flow was measured using ECG and respiration synchronized 4D flow MRI with full volumetric coverage of the aorta. Data analysis included co-registered visualization of aortic valve morphology with systolic 3D blood flow and grading of valve-specific aortic out-flow patterns. The influence of valve geometry on aortic hemodynamics was quantified by calculation of valve flow angle and segmental distribution of ascending aorta WSS. Results All congenitally altered valves showed marked flow derangement, elevated velocity jets along the aortic wall and distinct flow impingement locations. While all RLBAV valves were associated with flow jets directed towards the right anterior aortic wall, RN-fusion and unicuspid valves showed jet patterns towards the right-posterior wall. Quantitative analysis revealed higher flow angles for unicuspid, true BAV, RN-BAV, RL-BAV, and quadricuspid

4D flow jet shear layer detection method for the measurement of effective orifice area and assessment of aortic stenosis severity

Background Aortic stenosis (AS) is the most common cause of valve replacement and its severity is mainly assessed by transthoracic Doppler echocardiography (TTE) to quantify valve effective orifice area (EOA) as determined by the continuity equation. In a previous study we demonstrated that EOA can be directly determined with 2D flow MRI downstream of the AS using the jet shear layer detection (JSLD) method and the acoustical source term (AST) concept. However, both TTE and 2D flow MRI rely on the measurement of local and single-directional velocities and thus incomplete assessment of the complex post-valve flow dynamics in a significant proportion of patients. 3D CINE phase contrast MRI with 3-directional velocity encoding (4D flow MRI) may improve EOA estimation by the JSLD method coupled with full volumetric coverage of ascending aortic 3D blood flow. The objective of this study was to validate 4D flow MRI based EOA estimation using an in-vitro stenosis phantom and to apply the technique for the in-vivo measurement of the valve EOA compared to the reference standard 2D flow MRI. Methods

Response to Letter Regarding Article, “Bicuspid Aortic Cusp Fusion Morphology Alters Aortic Three-Dimensional Outflow Patterns, Wall Shear Stress, and Expression of Aortopathy”

We thank Hope and colleagues for their interesting and pertinent letter on our recent study in patients with bicuspid aortic valve (BAV), in which the relationship between bicuspid aortic valve morphology, the resulting flow patterns, and the aortopathy phenotype was examined.1 To confirm their initial comment, indeed, the ascending aortic flow displacement parameter was not normalized to the individual vessel diameter. We agree with Hope et al that flow displacement should ideally be normalized by the lumen diameter to account for interindividual differences in aortic geometry. Nonetheless, aortic diameters in the aorta size control group and the BAV patient groups in our study cohort were similar (4.1 versus 4.0 cm, respectively). Thus, the process of normalization did not affect the …

4D flow MRI of the aorta becomes practical: performance and observer variability for a new semi-automated workflow for 3D visualization and quantification of aortic hemodynamics

Background To systematically investigate the performance and interobserver variability of a new standardized workflow for the analysis of aortic hemodynamics based on 4D-flow MRI in a study with 30 subjects. The semi-automated workflow was developed to ensure faster and standardized data analysis including systematic placement of analysis planes, 3D-flow visualization, and quantification of standard clinical flow parameters.

From Unicuspid to Quadricuspid: Influence of Aortic Valve Morphology on Aortic 3D Hemodynamics

To assess the impact of aortic valve morphology on aortic hemodynamics between normal tricuspid and congenitally anomalous aortic valves ranging from unicuspid to quadricuspid morphology.

From unicuspid to quadricuspid: Influence of aortic valve morphology on aortic three-dimensional hemodynamics: Aortic Valve Morphology on 3D Hemodynamics

To assess the impact of aortic valve morphology on aortic hemodynamics between normal tricuspid and congenitally anomalous aortic valves ranging from unicuspid to quadricuspid morphology.