Noninvasive methods to measure and predict ultrasound effects on cells are needed to realize applications of ultrasound-mediated drug delivery to improve chemotherapy, gene therapy and targeted delivery. This study tested the hypothesis that (i) cellular bioeffects of ultrasound correlate with cavitation dose, (ii) broadband noise provides a measure of cavitation dose, and, thus, (iii) cellular bioeffects can be predicted by noninvasively measuring broadband noise. After exposing cell suspensions to ultrasound and measuring intracellular molecular uptake and loss of cell viability (bioeffects), a broad range of bioeffects were achieved by varying frequency, pressure, exposure time, cavitation nucleation site (Optison) concentration, and cell type. As a measure of cavitation activity, broadband noise measurements from acoustic spectra were collected during cell sonication and shown to be larger at elevated pressure and, after a high initial value, sharply decayed to a constant, background value at long exposure times. Combining these results, we found that broadband noise correlated well with molecular uptake and viability over the broad range of experimental conditions used (p-value <0.0001). This indicates that acoustic spectrum analysis provides a unifying parameter to correlate with bioeffects over a wide range of acoustic and experimental conditions. [Work supported by NIH, EKOS, DoEd GAANN Program.]
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