Current research is focused on the medical applications of Intracellular Doppler Imaging (Biodynamic Imaging-BDI) with a focus in drug discovery and personalized cancer therapy selection.
Accurate phenotyping of patient resistance or sensitivity to anticancer therapies (cytotoxins, targeted drugs, or immunotherapy) has been a significant challenge. The NCI MATCH Trial (Molecular Analysis for Therapy Choices) showed that only 15% of the patients had druggable targets and only one-third of the patients responded to the molecularly chosen treatment. Genetics alone has proven inadequate for predicting patient phenotype. The phenotype of the tumor is a combined effect of the genetics, proteomics, etc., and the extracellular environment (the stromal connective tissue cells, the immune cells, and the extracellular matrix). As soon as the tumor cells are removed from this environment and cultured, the true phenotype is lost or drifts from what is in the patient. For that reason ex vivo culture methods have low phenotypic predictive accuracy. Culturing cells in 2-dimensions (2-D) in plastic culture dishes is ineffective. Efforts to maintain phenotype by 3-dimensional (3-D) culture, the use of artificial matrices, or implantation in nude mice (xenografts) is an improvement over 2-D, but these methods can be very expensive and time consuming requiring months of work. Intracellular Doppler spectroscopy (biodynamic imaging) is a new, label-free, predictive screening technology that is fundamentally different than any other method since it uses non-cultured, intact tumor tissue rather than isolated cells. Maintaining the 3D structure and environment of the tumor is essential for preservation of drug response phenotype. Biodynamic imaging uses diverse intracellular motions as a novel suite of biomarkers that provide endogenous phenotypic imaging contrast and are highly sensitive to the efficacy of drugs on cellular metabolism, nuclear morphology, mitochondrial membrane potential and cell proliferation. BDI can accurately assess drug response phenotype from intact patient tumor tissue within 24-48 hours (time for assay + analysis).
The Doppler effect is used in weather radar to analyze the speed and motion of wind and moisture in the atmosphere using microwave radiation. Similarly, intracellular Doppler imaging uses near-infrared light to analyze the motion of the parts of a cell. A cell is like a small machine with many moving parts. The organelles, vesicles, nucleus, and cell membranes all move at well-defined speeds in a normal healthy cell. Addition of some outside agent (i.e., drug, toxin, cytokine, etc.) begins to alter the speed of various subcellular components that alters the spectral signal. If a particular cell/tissue is more or less susceptible to the effects of the exogenous agent then this will be reflected in the spectrum. The cause of the spectral shifts could be due to metabolism (hyper- or hypo- metabolism), levels of receptor expression for the agent, membrane pumps that clear the agent from the tissue, drug inactivation, or any of the other known mechanisms for drug sensitivity or resistance.
Dr. Turek is a co-founder of Animated Dynamics (Anidyn) Inc, a company commercializing the BDI technology.