The valve morphology of bicuspid aortic valve (BAV) patients will alter transvalvular blood flow patterns and aortic wall shear stress (WSS). These hemodynamic changes are associated with the regional expression of BAV aortopathy¹, which manifests in the form of ascending aorta dilation, aneurysm formation or dissection. Two dominant patterns of aortic dilation are known to occur, that is: a ‘type 1’ pattern involving the proximal portion of the ascending aorta; or a ‘type 2’ involving the distal AAo and arch. Compared to the normal aortic valve, blood flow through the BAV is altered as a function of the valve fusion phenotype, the most commonly of which are the right-left or right-noncoronary leaflet fusion patterns. These BAV phenotypes are postulated to change downstream 3D WSS expression in aortic regions known to be at risk of dilation. Previous studies investigating these effects were based on small cohorts and the confounding role of aortic stenosis (AS) was not systematically studied. This study uses 4D flow MRI to understand the role of BAV morphology and AS on the expression of 3D WSS in the ascending aorta of a large control and BAV patient cohort (n=312).56 healthy volunteers (43±13 years) with no known history of cardiovascular disease and 256 BAV patients (48±14 years) underwent ECG and respiratory navigator gated 4D flow MRI exams on 1.5 and 3T MAGNETOM Avanto, Espree, Aera and Skyra MRI systems (Siemens Healthcare, Erlangen, Germany). The BAV patients also underwent CE-MRA and bSSFP cine imaging for surveillance of aortic disease or valve degeneration. Valve morphology was determined via bSSFP and the fusion phenotype was recorded as either right-left coronary or right-noncoronary leaflet fusion. 4D flow imaging paremeters were as follows: spatial resolution=1.7-3.6x1.8–2.4x2.2–3.0mm³; temporal resolution=37–42ms, (14-25 phases); TE/TR/FA=2.2-2.8ms/4.6-5.3ms/7-15°; VENC=1.5–4.5m/s. The thoracic aorta was segmented using a commercial software package (Mimics, Materialise, Leuven, Belgium). The time frame with the maximum average absolute velocity in the segmentation was defined as peak systole. Peak velocity was assessed in a velocity maximum intensity projection (MIP) to determine subjects with significant stenosis (>3m/s). The sinus of Valsalva (SOV) and mid-ascending aortic (MAA) diameters were measured using CE-MRA. Peak systolic 3D WSS was computed along the segmented wall and WSS atlases were created using a previously published methodology^2-3. In short, each aorta segmentation for a given cohort was registered to a common probability mask. This allowed for 3D WSS to be averaged across subjects and the subsequent generation of WSS atlases. Each atlas was stratified by valve morphology group (RL or RN) and presence or absence of stenosis (AS is designated as ‘+’ and no AS ’-‘). Confidence intervals were plotted using the inter-subject standard deviation (SD) of WSS on a voxel by voxel basis.Table 1 summarizes the subject demographics, aortic geometry and peak velocity. Figure 1 summarizes the results for each 3D WSS atlas group and Figure 2 displays the associated confidence intervals. The outflow patterns were fairly consistent for the controls and across the unobstructed patients, as seen by the low magnitude of the SD maps. 41 RL and 22 RN patients were found to be significantly stenotic. In the stenotic groups, the outflow patterns varied markedly as evaluated by the confidence interval maps (Figure 2c,e where SD>1.0 in a number of locations). Markedly higher WSS was observed in the stenosis cohorts. Aortic size was similar between all four groups by Wilcoxon rank sum testing (P>0.05).This is the first study in a large cohort (>250 patients) that confirms that there are clear differences in 3D WSS based on BAV phenotype and which correspond to the known differences in aortopathy expression. This further strengthens previous findings and shows that 4D flow and 3D WSS can detect patient specific changes in aortic hemodynamics. However, AS has a significant impact on these patterns and thus must be treated as a separate clinical entity for risk-stratification and patient specific resection purposes.A consistent pattern of elevated WSS was found in a large cohort of BAV patients with unobstructed RL (at the root and tubular ascending aorta) and RN (in the distal ascending aorta) valve fusion patterns, which matches with regions of known dilation patterns. Aortic valve stenosis was found to introduce marked variability in the WSS atlases. Thus, regions thought to be at-risk for further aortopathy development as determined solely by valve morphology may be altered by the presence of AS, and thus confound longitudinal outcome studies or prophylactic surgical efforts.