Doppler Spectroscopy of Intracellular Dynamics in Esophageal Cancer Biopsies*

We perform depth-resolved Doppler light scattering from intracellular transport inside living tissue to monitor phenotypic responses of patient biopsies to anti-cancer drugs. Near infrared optical coherence tomography, combined with digital holography coherence-gated read-out, provides rich speckle dynamics from light scattered inside the living tissue.  This novel technique, called biodynamic imaging (BDI), uses fluctuation spectroscopy to extract the Doppler spectra associated with active transport of organelles, membranes and cell movements.  We have completed a 28-patient pilot clinical trial of BDI applied to platinum-based chemotherapy in human esophageal cancer.  Living biopsies were stabilized and immobilized into multi-well plates where the Doppler spectra were monitored as different chemotherapy agents were applied to different wells.  Doppler drug-response spectrograms are converted to a feature space that was analyzed using triplet-loss neural network machine learning to reduce the dimensionality to a low-dimensional latent space.  Patients who were sensitive or resistant to the platinum chemotherapy could be distinguished by their different spectral responses to therapy.  Biodynamic imaging, probing therapy-induced changes in intracellular transport, promises a new form of precision functional medicine for personalized therapy selection.