Photoacoustic Imaging Probes
Photoacoustic imaging is a revolutionary imaging modality that is characterized by the conversion of absorbed light into ultrasound. Compared to other techniques where the readout is light, photoacoustic imaging is superior in terms of resolution and imaging depth because the sound waves that are generated can readily pass through the body with minimal interference. A major advance in this field, which our group helped to pioneer, is the development of analyte-responsive photoacoustic probes featuring novel activity-based sensing designs. Beyond their broad utility to answer fundamental biological questions, our photoacoustic probes have tremendous potential to directly impact human health as reliable diagnostic agents and surgical guidance tools. Representative projects in this research area are highlighted below.
We envision the application of photoacoustic probes for biopsy-free assessment (BFA) of disease biomarkers can replace invasive medical procedures such as liver biopsies which are employed to measure hepatic copper levels in Wilson's disease (a rare genetic disorder). To this end, we recently developed PACu-1, a safe and sensitive, copper-responsive photoacoustic probe (PNAS 2021). We demonstrate that we can correctly identify animals with Wilson's disease from a cohort of healthy control mice with 100% accuracy when our probe was assessed in unbiased blind studies. Current projects are focused on developing new imaging agents to replace other invasive procedures.
Hypoxia is described as a condition where the demand for oxygen in tissue outweighs the available supply. Numerous studies in humans have shown that the extent of oxygen deficiency is correlated to the clinical stage of prostate cancer. Thus, the goal of this project is to synthesize photoacoustic probes that can be applied to noninvasively measure tumor hypoxia in prostate cancer patients. Toward this goal we have developed several hypoxia-responsive probes including HyP-1 (Nat Commun 2017), rHyP-1 (ACS Chem Biol 2018) and CRaB-HyP (JACS 2019) which were applied to various murine models to map tumor hypoxia. Current efforts will be to develop new congeners with improved properties and to conduct testing in larger mammals.
Companion diagnostics (CDx) are powerful tests that can provide physicians with crucial biomarker information that can improve treatment outcomes by matching therapies to patients. In this project, we report a photoacoustic imaging-based CDx (PACDx) for the selective detection of elevated glutathione in multiple lung cancer models (Nat Chem 2021). A key feature of our study was the design of an unprecedented blind study where photoacoustic imaging alone was employed to identify mice bearing lung xenografts. Beyond this work, we are interested in expanding the utility of imaging-based CDx by targeting other cancer types and disease states.
Researchers working on projects in the 'Photoacoustic Imaging Probes' area will experience synthetic chemistry, photophysical characterization, UV-Vis-NIR spectroscopy, physical organic chemistry techniques, photoacoustic imaging, and animal work.