Abstract This study reports first application of biodynamic imaging (BDI), a novel Doppler imaging technology, in studies of ovarian cancer xenografts and preclinical trials of canine multicentric lymphoma responding to doxorubicin. In a study of A2780 human ovarian cell lines implanted in mice, an unexpected and large difference was discovered between mouse tumor explants versus A2780 cells grown as 3D tumor spheroids. The biopsied explants from mice were three times more sensitive to platinum, applied in vitro, than were multicellular tumor spheroids. A preclinical trial has been completed for canine non-Hodgkins lymphoma using BDI to predict patient outcome under doxorubicin therapy. The 3D imaging capability of BDI enabled the measurement of tumor heterogeneity in response to the therapy. The biodynamic assay took only 24 hours to complete, while the clinical outcome was often unknown for one to several months. The therapeutic efficacy of doxorubicin was predicted by BDI with 90% accuracy. Based on this success, biodynamic imaging is entering human pilot trials in ovarian, pancreatic, and esophageal cancer. Biodynamic imaging is a radically different approach to the prediction of therapeutic efficacy for personalized medicine with higher accuracy and more biological relevance than standard cell-based assays. Supported in part by NIH NIBIB 1R01EB016582-01. Citation Format: John J. Turek, Dan Merrill, Michelle Custead, Michael Childress, David D. Nolte, Bakhtiyor Yakubov, Ran An, Daniela Matei. Novel intracellular Doppler imaging predicts therapeutic efficacy for personalized medicine. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 208. doi:10.1158/1538-7445.AM2015-208