Biodynamic digital holography of chemoresistance in a pre-clinical trial of canine B-cell lymphoma

Abstract

Biodynamic digital holography was used to obtain phenotypic profiles of canine non-Hodgkin B-cell lymphoma biopsies treated with standard-of-care chemotherapy. Biodynamic signatures from the living 3D tissues were extracted using fluctuation spectroscopy from intracellular Doppler light scattering in response to the molecular mechanisms of action of therapeutic drugs that modify a range of internal cellular motions. The standard-of-care to treat B-cell lymphoma in both humans and dogs is a combination CHOP therapy that consists of doxorubicin, prednisolone, cyclophosphamide and vincristine. The proportion of dogs experiencing durable cancer remission following CHOP chemotherapy was 68%, with 13 out of 19 dogs responding favorably to therapy and 6 dogs failing to have progression-free survival times greater than 100 days. Biodynamic signatures were found that correlate with inferior survival times, and biomarker selection was optimized to identify specific Doppler signatures related to chemoresistance. A machine learning classifier was constructed based on feature vector correlations and linear separability in highdimensional feature space. Hold-out validation predicted patient response to therapy with 84% accuracy. These results point to the potential for biodynamic profiling to contribute to personalized medicine by aiding the selection of chemotherapy for cancer patients.

Intracellular Optical Doppler Phenotypes of Chemosensitivity in Human Epithelial Ovarian Cancer

“…By penetrating volumetrically into tissue up to 1 mm deep, BDI maps out heterogeneous tissue layers. BDI has previously been applied to drug screening [20][21][22] , phenotypic profiling 23 , and preclinical chemosensitivity testing on ovarian xenografts in mice and canine B-cell lymphoma 19,24,25 . Light scattering of near-infrared light from living ex vivo tissue biopsies displays Doppler frequency shifts caused by intracellular motion 9 .…”

An optical study of drug resistance detection in endometrial cancer cells by dynamic and quantitative phase imaging

“…Furthermore, no labeling or staining is necessary for DHM measurement. Due to advances in living cell monitoring, DHM has been widely used in biomedical research [23][24][25][26][27], especially for measuring on morphological changes in living cells [28][29][30][31][32][33].…”

Intracellular optical doppler phenotypes of chemosensitivity in human epithelial ovarian cancer

“…There has been growing recognition of the importance of intracellular dynamics for functional imaging on intact tissue [10][11][12][13][14][15][16] . Biodynamic imaging is a form of full-frame optical coherence tomography (FF-OCT) 17,18 based on off-axis digital holography that uses principles of coherent laser ranging that can quantify the dynamic response of tumors to chemotherapy treatment 19 . Cellular motions are unusual but specific biomarkers of cellular health and response.…”

“…xenografts in mice and canine B-cell lymphoma 19,24,25 . Light scattering of near-infrared light from living ex vivo tissue biopsies displays Doppler frequency shifts caused by intracellular motion 9 .…”