The location of the lines separating these opposing shear directions shifts back-and-forth in a sweeping motion over the course of the cardiac cycle, moving more proximal during peak-systole and more distal during the diastolic phase

of the pulse. In contrast, the line demarcating the reattachment and realignment of WSS in the main flow direction in the distal PSR is more distal during peak-systole and becomes more proximal during diastole. In case Inhibitors,research,lifescience,medical 6, a vortex of WSS vectors pointing into a retrograde direction is found in the proximal portion (circle a) and the midportion of the stenosis (circle b), where they change size and shape over the course of the pulse, in addition to another area of retrograde WSS that sweeps the distal portion of the stenosis in cyclic fashion (circle c, Fig. 2C). Rapid temporal

change of regional shear stress distributions This phenomenon of migrating zones of reversal of the WSS direction was further characterized by examining Inhibitors,research,lifescience,medical the PXD101 temporal evolution of the axial WSS magnitude along a cutline through the stenosis throat (X-Y line, Fig. 3). In each case, we were able to identify a region along the chosen cutline that displayed a reversal of the direction Inhibitors,research,lifescience,medical of the WSS, typically between peak systole (t2) and the deceleration phase (t3) (cases 1–4 and 7), which is exposed to extreme directional changes of nearly 1412 ± 1037 dyn/cm2 in the short time between peak systole and deceleration phases of the cardiac cycle (green arrows in Fig. 3). The length of the portion of the chosen cutplane that shows a shear reversal was variable in length between

0.1 (case 5) and 1 mm (case 4). Complex temporospatial WSSG patterns The spatial WSS Gradient (WSSG) magnitude, Inhibitors,research,lifescience,medical averaged over the course of the cardiac cycle, exhibited a visible increase in the area of the stenosis (Fig. 4A); in cases with concentric stenosis two distinct bands were found with increased axial component of the WSSG pointing in opposite directions (Fig. 4B). The previously defined three regions of interest (see insert Fig. 4C) were analyzed and the WSSG vectors were Inhibitors,research,lifescience,medical averaged spatially and temporally and the mean over Astemizole all cases in this study was taken. The average WSSG magnitude at the throat of the stenosis was 1425 ± 1012 dyn/cm3, significantly increased from 8 ± 17 dyn/cm3 in the healthy CCA segment upstream (P < 0.002). In the PSR, the average WSSG magnitude was 140 ± 109 dyn/cm3 (Fig. 4C). The averaged axial WSSG components differed considerably from the averaged WSSG magnitude: in the stenosis the axial WSS component was 36 ± 273 dyn/cm3 (P < 0.002), and in the PSR the axial component was −6 ± 12 dyn/cm3 (P < 0.002). The axial component of the spatial gradient of the WSSG along the vessel changes direction rapidly from positive to negative at the throat of the stenosis, corresponding to the peak axial WSS (line a to line b in Fig.