Here we propose to adapt a well known and well established technique, two-color pump-probe absorption spectroscopy, for high resolution 3-D optical molecular imaging of biological systems. Pump-probe absorption spectroscopy has been used extensively in experimental molecular physics to measure the molecular properties of poorly fluorescing molecular species. Optical coherence tomography (OCT) is an emerging high resolution optical imaging modality which harnesses the power of low coherence interferometry to measure the 3-D spatially resolved reflectivity of a tissue sample. By melding these two techniques we will establish a new high resolution 3-D optical molecular imaging technique which can directly probe the large number of poorly fluorescing biomolecular species. An early application of this new technology and an excellent test bed is the mapping and monitoring of blood oxygen saturation in tissue microvasculature. Both oxy and deoxy hemoglobin are extremely poor fluorophores making this a formidable if not impossible task for fluorescence based techniques. Blood oxygen saturation is an important biometric for numerous human diseases and conditions including tumor growth and response to treatment, diseases of the nervous system, and wound healing. In addition we plan to combine the developed technique with Doppler OCT, in order to simultaneously measure the blood flow rate. In summary, the hybrid imaging system proposed here will have the capacity to noninvasively and without molecular tags, map the tissue morphology and microvasculature down to the smallest vessels (~10 ?m), measure the blood oxygen saturation at physiologically relevant levels, and measure blood flow at physiologically relevant flow rates We believe the technological advances proposed here will provide an invaluable tool for the in vivo measure of biochemical concentration and dynamics in cells and small animals which may lead to advances in the understanding of the origins and treatment of human disease. There is also the potential for application in humans for noninvasive monitoring and diagnosis of diseases and conditions which occur in the epithelium and retina. Since the proposed technique does not require tagging of target molecules either chemically or genetically it has a strong potential for dramatically extending the impact of optical molecular imaging in both the clinical and research environment.
| Applegate, Brian E; Shelton, Ryan L; Gao, Simon S et al. (2011) Imaging high-frequency periodic motion in the mouse ear with coherently interleaved optical coherence tomography. Opt Lett 36:4716-8 |
| Jacob, Desmond; Shelton, Ryan L; Applegate, Brian E (2010) Fourier domain Pump-Probe Optical Coherence Tomography imaging of melanin. Opt Express 18:12399-410 |
| Shelton, Ryan L; Applegate, Brian E (2010) Off-axis photoacoustic microscopy. IEEE Trans Biomed Eng 57:1835-8 |
