Carotid bifurcation atherosclerosis. Quantitative correlation of plaque localization with flow velocity profiles and wall shear stress.

The distribution of nonstenosing, asymptomatic intimal plaques in 12 adult human carotid bifurcations obtained at autopsy was compared with the distribution of flow streamline patterns, flow velocity profiles, and shear stresses in corresponding scale models. The postmortem specimens were fixed while distended to restore normal in vivo length, diameter, and configuration. Angiograms were used to measure branch angles and diameters, and transverse histological sections were studied at five standard sampling levels. Intimal thickness was determined at 15 degrees intervals around the circumference of the vessel sections from contour tracings of images projected onto a digitizing plate. In the models, laser-Doppler anemometry was used to determine flow velocity profiles and shear stresses at levels corresponding to the standard specimen sampling sites under conditions of steady flow at Reynolds numbers of 400, 800, and 1200, and flow patterns were visualized by hydrogen bubble and dye-washout techniques. Intimal thickening was greatest and consistently eccentric in the carotid sinus. With the center of the flow divider as the 0 degree index point, mid-sinus sections showed minimum intimal thickness (0.05 +/- 0.02 mm) within 15 degrees of the index point, while maximum thickness (0.9 +/- 0.1 mm) occurred at 161 +/- 16 degrees, i.e., on the outer wall opposite the flow divider. Where the intima was thinnest, along the inner wall, flow streamlines in the model remain axially aligned and unidirectional, with velocity maxima shifted toward the flow divider apex. Wall shear stress along the inner wall ranged from 31 to 600 dynes/cm2 depending on the Reynolds number. Where the intima was thickest, along the outer wall opposite the flow divider apex, the pattern of flow was complex and included a region of separation and reversal of axial flow as well as the development of counter-rotating helical trajectories. Wall shear stress along the outer wall ranged from 0 to -6 dynes/cm2. Intimal thickening at the common carotid and distal internal carotid levels of section was minimal and was distributed uniformly about the circumference. We conclude that in the human carotid bifurcation, regions of moderate to high shear stress, where flow remains unidirectional and axially aligned, are relatively spared of intimal thickening. Intimal thickening and atherosclerosis develop largely in regions of relatively low wall shear stress, flow separation, and departure from axially aligned, unidirectional flow. Similar quantitative evaluations of other atherosclerosis-prone locations and corresponding flow profile studies in geometrically accurate models may reveal which of these hemodynamic conditions are most consistently associated with the development of intimal disease.

Steady flow in a model of the human carotid bifurcation. Part I--flow visualization.

The geometry of a typical adult human carotid bifurcation, complete with the sinus, was established from a study of a large number of angiograms. A rigid model was constructed from glass and investigations were performed under steady flow conditions using flow visualization techniques over a range of upstream Reynolds numbers and flow division ratios through the branches representative of physiologic conditions expected in the human vasculature. The study reveals a complex flow field in which secondary flows play an important role. The separation regions occurring at the outer corners of the branching are also subjected to much higher shear stress. Comparison with pathologic data on localization of atherosclerotic lesions indicates that zones susceptible to disease experience low or oscillatory shear stress while regions subject to higher shear are free of deposits.

Steady flow in a model of the human carotid bifurcation. Part II--laser-Doppler anemometer measurements.

The evidence for hypothesizing a relationship between hemodynamics and atherogenesis as well as the motivation for selecting the carotid bifurcation for extensive fluid dynamic studies has been discussed in Part I of this two-paper sequence. Part II deals with velocity measurements within the bifurcation model described by Fig. 1 and Table 1 of the previous paper. A plexiglass model conforming to the dimensions of the average carotid bifurcation was machined and employed for velocity measurements with a laser-Doppler anemometer (LDA). The objective of this phase of the study was to obtain quantitative information on the velocity field and to estimate levels and directions of wall shear stress in the region of the bifurcation.

Flow studies in a model carotid bifurcation.

Boundary layer separation in a plexiglass model carotid bifurcation was investigated in relation to the origin of atherosclerotic plaque clinically found in this region. Our model was comparable to a human carotid in both dimensions and geometry. Water flowed through the model at Reynolds numbers from 200 to 1200 under steady and pulsatile flow conditions, with outflow through the external and internal branches varied. The near-wall flow was visualized by slow injection of dye through ports machined in the model. Under steady flow at a physiological Reynolds number of 500 and a flow split at the bifurcation similar to that of a human carotid at rest, boundary layer separation was found to occur in a carotid sinus across from the external carotid origin, forming a shell of slowly moving fluid around the bifurcation. The rapidly moving mainstream impinged directly on the flow divider. The location of atherosclerotic plaque correlates best with the low shear region of separation and not with the region of high shear at the flow divider. Preliminary studies with pulsatile flow demonstrated little change from the steady flow results.