Detection of cardiomyopathic changes induced by doxorubicin based on quantitative analysis of ultrasonic backscatter

Ultrasonic measurements are valuable in characterizing cardiac dimensions and structure. Recently, analysis of ultrasonic properties of tissue has proved useful in detecting morphologic changes such as those accompanying myocardial infarction. This study was undertaken to determine whether acoustic properties of tissue can be utilized to detect cardiomyopathic changes as well. Cardiomyopathy was induced by prolonged administration of doxorubicin (Adriamycin) (1.2 mg/kg twice weekly) in 25 rabbits and results were compared with those in normal control rabbits, housed identically. The 15 surviving treated animals were killed at selected intervals to 10 to 18 weeks after initiation of drug administration and the hearts were analyzed for collagen content based on hydroxyproline. Regional ultrasonic backscatter was assessed with a frequency-averaging procedure to minimize effects of phase cancellation and with an independent method employing spectral display over the frequency range of 1 to 11 megahertz from which an index of backscatter at a single frequency (2.25 megahertz) could be calculated. In hearts from treated animals, collagen content was significantly increased (p less than 0.05). Integrated ultrasonic backscatter was markedly increased (by more than 500 percent, that is, equivalent to 7 decibels) in fibrotic regions and significantly, although less markedly, in myopathic regions without marked collagen deposition. Thus, increased backscatter correlated with collagen deposition. Backscatter at 2.25 megahertz was significantly increased (by more than 500 percent, that is, equivalent to 7 decibels) in fibrotic regions. These results indicate that alterations in acoustic properties occur in cardiomyopathic tissue and that such alterations can be detected with the use of reflected ultrasound. Accordingly, assessment of integrated backscatter offers a promising approach for early clinical detection and characterization of evolution of cardiomyopathy induced by doxorubicin or of other causes.