It is the purpose of the proposed study to investigate the ultrasound nonlinearity parameter B/A in vivo (B and A being the coefficients of the second and first terms, respectively, of the equation of state relating acoustic pressure and material density). Our preliminary studies have concerned in vitro determinations of the parameter for biological materials, including tissue models. We have determined by two independent methods, viz., the finite amplitude method involving the measurement of harmonics and the thermodynamic method involving the measurement of the speed of sound as a function of hydrostatic pressure, the following: (1) B/A increases nearly linearly with solute concentration for aqueous solutions of proteins, (2) B/A is relatively insensitive to the molecular weight of the solute at fixed concentrations, (3) B/A ranges from 6.5 to 11 for various soft mammalian tissues, and (4) B/A decreases significantly with destruction of the supracellular architectural features of tissue and with destruction of cellular structure. Thus significant information regarding the state of the tissue is believed to be contained in the nonlinear ultrasonic propagation parameter B/A. It is proposed to determine B/A in vivo for a number of tissues and organs and for different pathological states thereof. This is considered essential before the parameter can be used for diagnostic imaging purposes and for therapeutic treatment planning as it is presently not known how the vascular system is involved in determining B/A. Initial studies will involve determining B/A as a function of path length utilizing exteriorized organs, for the purpose of developing a data base. Subsequent studies will deal with more advanced methods not requiring surgical preparations. Pathological conditions will be introduced to examine the range of variation of B/A from normal to diseased organs. The study requires that appropriate transducer systems be designed and fabricated to make the measurements. The results of this study will be details of in vivo values of B/A of normal and pathological tissues, with the long range goal of being able to utilize this information for diagnostic and therapeutic purposes.
