Pim van Ooij

Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall Shear Stress Mapping

BACKGROUND Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) have influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients. OBJECTIVES This study assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation. METHODS BAV patients (n = 20) undergoing ascending aortic resection underwent pre-operative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression. RESULTS Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS. CONCLUSIONS Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted.

Volumetric arterial wall shear stress calculation based on cine phase contrast MRI.

To assess the accuracy and precision of a volumetric wall shear stress (WSS) calculation method applied to cine phase contrast magnetic resonance imaging (PC‐MRI) data.

Viscous energy loss in the presence of abnormal aortic flow

To present a theoretical basis for noninvasively characterizing in vivo fluid‐mechanical energy losses and to apply it in a pilot study of patients known to express abnormal aortic flow patterns.

Arterial spin labeling measurement of cerebral perfusion in children with sickle cell disease

To evaluate the applicability of arterial spin labeling (ASL) cerebral blood flow (CBF) measurements in children with sickle cell disease (SCD).

Wall shear stress estimated with phase contrast MRI in an in vitro and in vivo intracranial aneurysm

To evaluate wall shear stress (WSS) estimations in an in vitro and in vivo intracranial aneurysm, WSS was estimated from phase contrast magnetic resonance imaging (PC‐MRI) and compared with computational fluid dynamics (CFD).

Reproducibility and Interobserver Variability of Systolic Blood Flow Velocity and 3D Wall Shear Stress Derived From 4D Flow MRI in the Healthy Aorta

To investigate the reproducibility and interobserver variability of 3D aortic velocity vector fields and wall shear stress (WSS) averaged over five systolic timeframes derived from noncontrast 4D flow magnetic resonance imaging (MRI).

A methodology to detect abnormal relative wall shear stress on the full surface of the thoracic aorta using four-dimensional flow MRI

To compute cohort‐averaged wall shear stress (WSS) maps in the thoracic aorta of patients with aortic dilatation or valvular stenosis and to detect abnormal regional WSS.

Age‐related changes in aortic 3D blood flow velocities and wall shear stress: Implications for the identification of altered hemodynamics in patients with aortic valve disease

To investigate age‐related changes in peak systolic aortic 3D velocity and wall shear stress (WSS) in healthy controls and to investigate the importance of age‐matching for 3D mapping of abnormal aortic hemodynamics in bicuspid aortic valve disease (BAV).

Thoracic Aorta 3D Hemodynamics in Pediatric and Young Adult Patients With Bicuspid Aortic Valve

To evaluate the 3D hemodynamics in the thoracic aorta of pediatric and young adult bicuspid aortic valve (BAV) patients.

Aortic Valve Stenosis Alters Expression of Regional Aortic Wall Shear Stress: New Insights From a 4-Dimensional Flow Magnetic Resonance Imaging Study of 571 Subjects

Background Wall shear stress (WSS) is a stimulus for vessel wall remodeling. Differences in ascending aorta (AAo) hemodynamics have been reported between bicuspid aortic valve (BAV) and tricuspid aortic valve patients with aortic dilatation, but the confounding impact of aortic valve stenosis (AS) is unknown. Methods and Results Five hundred seventy‐one subjects underwent 4‐dimensional flow magnetic resonance imaging in the thoracic aorta (210 right‐left BAV cusp fusions, 60 right‐noncoronary BAV cusp fusions, 245 tricuspid aortic valve patients with aortic dilatation, and 56 healthy controls). There were 166 of 515 (32%) patients with AS. WSS atlases were created to quantify group‐specific WSS patterns in the AAo as a function of AS severity. In BAV patients without AS, the different cusp fusion phenotypes resulted in distinct differences in eccentric WSS elevation: right‐left BAV patients exhibited increased WSS by 9% to 34% (P<0.001) at the aortic root and along the entire outer curvature of the AAo whereas right‐noncoronary BAV patients showed 30% WSS increase (P<0.001) at the distal portion of the AAo. WSS in tricuspid aortic valve patients with aortic dilatation patients with no AS was significantly reduced by 21% to 33% (P<0.01) in 4 of 6 AAo regions. In all patient groups, mild, moderate, and severe AS resulted in a marked increase in regional WSS (P<0.001). Moderate‐to‐severe AS further increased WSS magnitude and variability in the AAo. Differences between valve phenotypes were no longer apparent. Conclusions AS significantly alters aortic hemodynamics and WSS independent of aortic valve phenotype and over‐rides previously described flow patterns associated with BAV and tricuspid aortic valve with aortic dilatation. Severity of AS must be considered when investigating valve‐mediated aortopathy.