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To define the impact of age on microscopic structural remodeling after myocardial infarction, the physical properties of infarct scar tissue and viable remote zone tissues in young (3 months) and older adult (18 months) Fischer rats were quantified with the use of high-frequency (50 MHz) high-resolution acoustic microscopy 3 months after coronary artery occlusion. We observed that integrated backscatter increased by 100% in the viable zones of old animals after infarction, but remained relatively unaffected in the same regions of younger animals. Mathematical models of myocardial scattering behavior indicated that a 25% increase in stiffness of the extracellular matrix materials in viable zones likely occurred in the older animals. Alterations in gross tissue collagen content were not responsible for this increased stiffness. These observations are compatible with the hypothesis that progressive age-related changes in the quality of the collagen (e.g., excessive age-related crosslinking) rather than its amount per se may have altered the stiffness of the extracellular matrix of remodeled viable tissue in older animals.

The cardiac aging process is accompanied by global mechanical dysfunction that reflects increased myocardial stiffness. Accordingly, age-related changes in microscopic material properties of myocardium were delineated with high-frequency ultrasound (US) (30 to 44 MHz) tissue characterization methods for aging Fischer 344 rats at 6 (adult), 18 (aged), and 24 (senescent) months of age. The excised lateral wall of the left ventricle of rats (n = 10 per group) was insonified with a 50-MHz acoustic microscope for determination of integrated backscatter, backscatter coefficient and attenuation coefficient. Histological and biochemical analyses for collagen content and cardiac myocyte diameter were performed. Collagen concentration increased progressively with age, with the greatest increments occurring from 6 to 18 months (38.0 ± 6.3 to 53.0 ± 7.1 mg/g dry wt), and leveling off at 24 months (60.0 ± 7.4 mg/g dry wt). Tissue microscopic material properties also changed progressively from 6 to 24 months of age, as determined by US methods: integrated backscatter increased (−44.7 ± 1.8 vs. –40.8 ± 1.9 dB, p < 0.05), attenuation increased (47.1 ± 5.9 to 65.3 ± 7.8 dB/cm, p < 0.05), and the backscatter coefficient increased (0.73 ± 0.16 × 10−5 to 3.76 ± 1.6 × 10−5 cm-1, p < 0.05), from 6 to 24 months of age in each case. Age-related alterations in indices of cardiac microscopic material properties were closely correlated with the changes in cardiac microstructure. Ultrasonic tissue characterization may prove to be a sensitive tool to monitor changes in the cardiac microstructure, such as increased collagen deposition, that occur within age-related diastolic dysfunction. (E-mail: saw@howdy.wustl.edu)

Elastic arteries consist of three primary components: elastin fibers, extracellular collagen matrix and smooth muscle cells. However, the relative contribution of elastin and collagen fibers to overall ultrasonic scattering from an intact arterial wall is poorly understood. To define the principal source of extracellular scattering from the medial layer of elastic arteries, canine ascending aortas (n = 10) were excised, fixed and sectioned for insonification. Subsequently, aortic specimens were restudied after treatment to dissolve all tissue components except extracellular collagen matrix (n = 5) and elastin fibers (n = 5). Histological staining revealed very few elastin fibers and sparse intact collagen in collagen-isolated and elastin-isolated tissues, respectively. Integrated backscatter, attenuation and backscatter coefficients differentiated these two treated tissues. The backscatter coefficient for elastin-isolated tissue demonstrated a fivefold increase over collagen-isolated tissue, suggesting that elastin fibers represent a primary scattering component within elastic arteries, and the collagen fibers may provide a secondary component of scattering.

Myocardial edema has been associated with impaired ventricular compliance and diastolic filling. To determine the sensitivity of high-frequency (40 MHz) ultrasound to myocardial edema, we employed a model in which myocardial edema was induced by immersion of tissue in isotonic saline. The effect of freezing tissue on edema formation was also evaluated. Rat hearts were arrested at end-diastole and insonified fresh within 15 min of excision (n = 5) or following being frozen for 24 h and thawed (n = 4). Measurements of attenuation, backscatter, tissue thickness and speed of sound were performed at baseline and hourly for 4 h, and compared with direct measurements of myocardial edema. Fresh tissue demonstrated a greater propensity for the development of edema than frozen tissue. Integrated backscatter increased in both tissues, whereas the magnitude and slope of attenuation decreased as edema evolved. We conclude that high-frequency ultrasound sensitively detects myocardial edema, and we propose that the extension of these methods to clinical frequencies may prove useful for monitoring and treatment of cardiac edematous disease states.