Doppler Spectroscopy of Intracellular Motion in Revived Flash-Frozen Cancer Tissues

Biodynamic imaging is a high-content optical imaging technology based on Doppler spectroscopy and digital holography that uses dynamic speckle as high-content image contrast to probe living tissue. The multimode mixing of Doppler signals produces a fluctuation spectrum that is a function of the acquisition time relative to the persistence time of intracellular transport and hence provides a measure of cellular activity. Creating Doppler spectrograms of tumor tissues responding to anticancer agents usually relies on patient enrollment in IRB-approved trials, which is slow and inefficient. However, if flash-frozen biopsies could be revived and measured, then a large reservoir of tissue-banked samples could become available for phenotypic library building. We have performed biodynamic imaging measurements of flash-frozen canine B-cell cancer tissue and compared the drug-response spectrograms to results from fresh tissues from the same dogs. By compensating for tissue trauma in the frozen sample, we demonstrate a high accuracy for patient clustering between the fresh and frozen samples when correlating with clinical outcomes, identifying resistance or sensitivity to their prescribed chemotherapy.