Functional Optical Imaging to Measure Drug Response in Cancer and Study Infrared Light Effects in Neurons

Optical imaging techniques are advantageous for studying cellular behaviors due to the unique sources of contrast, non-invasive and non-damaging nature of light, and high spatial resolution. This talk will present two projects that utilize functional optical imaging techniques.  First, optical metabolic imaging (OMI) was developed to detect drug-induced metabolism changes in cancer.  OMI probes the auto-fluorescence intensity and lifetime of NADH and FAD, coenzymes of metabolism, to quantify fluorophore concentration and protein-binding dynamics.  For optimal clinical utility, an OMI drug screen was developed to test drug response on patient-specific organoids. Second, fluorescence imaging techniques were used to study infrared light effects in neurons. Short pulses (micro to milli-seconds in duration) of infrared light (1400-2100 nm) have been shown to stimulate and inhibit action potentials in neurons, but the mechanism remains unknown.  Direct action potential block by infrared light was observed in neurons for several seconds using optogenetic proteins in primary rat hippocampal neurons for non-contact and reliable action potential stimulation and recording.  Novel image acquisition and analysis techniques enabled time-correlated single photon counting fluorescence lifetime imaging at ~80 Hz to investigate calcium-induced-calcium release as a possible mechanism for infrared light effects in neurons.