QUANTIFICATION OF ATHEROSCLEROTIC PLAQUE COMPOSITION IN CHOLESTEROL-FED RABBITS WITH 50-MHZ ACOUSTIC MICROSCOPY

To determine whether high-frequency ultrasound could distinguish normal from pathological vascular structure and to elucidate the determinants of ultrasonic backscatter in different layers of normal and atherosclerotic arteries, high-resolution acoustic microscopy at 50 MHz was used to characterize aortic plaque in six New Zealand White rabbits fed a 2% cholesterol diet for 3.5 months. Four rabbits were fed a standard diet for 3.5 months to provide normal control data. Segments of aortas were excised, fixed in formalin, opened longitudinally, and mounted flat for insonification. For each specimen, backscattered radio frequency (rf) data were acquired from 30 to 100 independent sites separated by 500 mum. Portions of rf data were gated from discrete layers of the vessel wall for computation of integrated backscatter. Results of histological and immunocytochemical analyses of vessel wall thickness and composition were compared with those of ultrasonic analysis. Normal aortas manifested prominent but homogeneous backscatter (average integrated backscatter, -28.5+/-2.9 dB) throughout the vessel wall, with no clear distinction between intimal and medial layers. The atherosclerotic aortas manifested substantially reduced integrated backscatter from the thickened intima (-47.5+/-3.2 dB, p<0.000) but relatively normal integrated backscatter from the media (-31.2+/-1.6 dB; p=NS versus normal aortas). The thickness of the media for both normal and atherosclerotic rabbits was approximately 300 mum. Histological characteristics of atherosclerotic aortas confirmed the presence of substantial intimal thickening, with prominent foam cell and lipid infiltration abutting a more normal medial layer. Two of the six cholesterol-fed rabbits did not develop atherosclerotic plaque despite marked elevations in blood cholesterol levels, and their aortas manifested rf backscatter patterns identical to those from normal aortas. Thus, quantitative high-frequency, high-resolution ultrasound differentiates normal from pathological vascular structure in diet-induced atherosclerosis.