Time-efficient patient-specific quantification of regional carotid artery fluid dynamics and spatial correlation with plaque burden.

PURPOSE: Low wall shear stress (WSS) and high oscillatory shear index (OSI) influence plaque formation, yet little is known about their role in progression/regression of established plaques because of lack of practical means to calculate them in individual patients. Our aim was to use computational fluid dynamics (CFD) models of patients with carotid plaque undergoing statin treatment to calculate WSS and OSI in a time-efficient manner, and determine their relationship to plaque thickness (PT), plaque composition (PC), and regression. METHODS: Eight patients (68 +/- 9 yr, one female) underwent multicontrast 3 T MRI at baseline and six-month post statin treatment. PT and PC were measured in carotid segments (common-CC, bifurcation-B, internal-IC) and circumferentially in nonoverlapping 600 angles and correlated with CFD models created from MRI, ultrasound, and blood pressure. RESULTS: PT was highest in B (2.42 +/- 0.98 versus CC: 1.60 +/- 0.47, IC: 1.62 +/- 0.52 mm, p < 0.01). Circumferentially, plaque was greatest opposite the flow divider (p < 0.01), where the lowest WSS and highest OSI were observed. In B and IC, PT was inversely related to WSS (R = -0.28 and -0.37, p < 0.01) and directly related to OSI (R = 0.22 and 0.52, p < 0.05). The total plaque volume changed from 1140 +/- 437 to 974 +/- 587 mm3 at six months (p = 0.1). Baseline WSS, but not OSI, correlated with changes in PT, necrotic tissue, and hemorrhage in B and IC, but not CC. CFD modeling took 49 +/- 18 h per patient. CONCLUSIONS: PT and PC correspond to adverse WSS and OSI in B and IC, and WSS is modestly but significantly related to changes in PT after short-term statin treatment. Regional hemodynamics from CFD can feasibly augment routine clinical imaging for comprehensive plaque evaluation.

10 Gy total body irradiation increases risk of coronary sclerosis, degeneration of heart structure and function in a rat model.

PURPOSE: To determine the impact of 10 Gy total body irradiation (TBI) or local thorax irradiation, a dose relevant to a radiological terrorist threat, on lipid and liver profile, coronary microvasculature and ventricular function. MATERIALS AND METHODS: WAG/RijCmcr rats received 10 Gy TBI followed by bone marrow transplantation, or 10 Gy local thorax irradiation. Age-matched, non-irradiated rats served as controls. The lipid profile and liver enzymes, coronary vessel morphology, nitric oxide synthase (NOS) isoforms, protease activated receptor (PAR)-1 expression and fibrinogen levels were compared. Two-dimensional strain echocardiography assessed global radial and circumferential strain on the heart. RESULTS: TBI resulted in a sustained increase in total and low density lipoprotein (LDL) cholesterol (190 +/- 8 vs. 58 +/- 6; 82 +/- 8 vs. 13 +/- 3 mg/dl, respectively). The density of small coronary arterioles was decreased by 32%. Histology revealed complete blockage of some vessels while cardiomyocytes remained normal. TBI resulted in cellular peri-arterial fibrosis whereas control hearts had symmetrical penetrating vessels with less collagen and fibroblasts. TBI resulted in a 32 +/- 4% and 28 +/- 3% decrease in endothelial NOS and inducible NOS protein, respectively, and a 21 +/- 4% and 35 +/- 5% increase in fibrinogen and PAR-1 protein respectively, after 120 days. TBI reduced radial strain (19 +/- 8 vs. 46 +/- 7%) and circumferential strain (-8 +/- 3 vs. -15 +/- 3%) compared to controls. Thorax-only irradiation produced no changes over the same time frame. CONCLUSIONS: TBI with 10 Gy, a dose relevant to radiological terrorist threats, worsened lipid profile, injured coronary microvasculature, altered endothelial physiology and myocardial mechanics. These changes were not manifest with local thorax irradiation. Non-thoracic circulating factors may be promoting radiation-induced injury to the heart.