The long term objective of this program is to identify mechanisms of absorption of ultrasound in biological material at the molecular level. The proposed project includes theoretical, instrumentation development, and experimental aspects. Theoretical analysis is aimed at determining whether a dual-Voigt model of the medium can yield absorption characteristics typical of biological material without invoking a distribution of many relaxation processes. Instrumentation development aspects of the project include development of an automated absorption measurement and analysis system and development of a new single-transducer absorption cell with half the volume previously required and much simpler in design and construction. Hypotheses to be tested are: (1) Biomolecular absorption is a function of molecular weight only in a threshold sense, increasing significantly in the molecular weight range 500-1500. (2) Biomolecular absorption is a function of solute-solvent interactions primarily in the presence of buffer ions which permit proton exchange with histidyl residues. (3) Biomolecular absorption is a function of solute-solute interactions occuring under the conditions of high (Greater than 100 mg/ml) concentration, aggregation, or cross-linking. The proposed experimental approach is to (1) investigate parameters of interest by varying them in a controlled, systematic fashion obtaining absorption data under conditions in which the physicochemical state of the biomolecule is known and (2) evaluate the data in light of the hypotheses. Specific experiments include: study of absorption of molecules in the molecular weight range 300-5,000, chemical blocking of side chain proton transfer, photochemical oxidation of histidyl to aspartyl residues, varying solvent (buffer) characteristics, and collagen absorption measurements in monodisperse, gel-like, and aligned-fiber states. The results of the proposed work will contribute to the knowledge of interaction mechanisms between ultrasound and biological material and thus improve our ability to understand and predict attenuation characteristics and biological effects of ultrasound and efficaciously and safely apply ultrasound clinically both as a diagnostic and as a therapeutic tool.
