Evaluation of the Threshold for Lung Hemorrhage by Diagnostic Ultrasound and a Proposed New Safety Index

In a recent report (O'Brien et al. (2006b), it was suggested that the current expression for the mechanical index (MI) was not well suited to its function of quantifying the likelihood of an adverse biological effect after exposure of the gas-filled lung to diagnostic ultrasound. The purpose of this study was to analyze the relatively large database of experimental thresholds for the induction of lung hemorrhage to: (i) determine which variable(s) best describe the data and (ii) use the resulting equation to obtain a new formulation for the MI for lung exposures. Data from 14 studies of lung hemorrhage in four common laboratory animals (mouse, rat, rabbit and pig) were tabulated with regard to five common acoustic variables: center frequency (fc), pulse repetition frequency (PRF), pulse duration (PD), exposure duration (ED) and the threshold in situ peak rarefactional pressure (pr). The 34 threshold data points were fit by linear regression to: (i) a multiplicative model of the other variables, pr = AfcBPRFCPDDEDE, where A is a constant; (ii) 14 “reduced” models in which one or more variables were not included in the analysis; (iii) four models in which a multiplicative combination of variables has a common name e.g., duty factor; and (iv) the general form of the current expression for the MI. The MI was shown to provide a poor fit to the threshold data (r2 = 0.382), as were three of the four named models. The best fits were found for the complete model and for three reduced models, all of which contain the exposure duration. Because the implementation of a time-dependent safety parameter would present significant practical difficulties, a different model, pr = AfcBPRFCPDD, was chosen as the basis for the new MI. Thus, the expression for the lung-specific mechanical index, MILung, includes several, rather than only one, of the relevant acoustic variables. This is the first potential safety index developed as a direct result of experimental measurements rather than theoretical analysis. (E-mail: cchurch@olemiss.edu)