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Defense of DissertationReal-time quantitative assessment of tissue oxygen metabolism and hemodynamics using coherent light

Michael Ghijsen, MD PhD Student

Tissue metabolism and hemodynamicas are known to be abnormal in several pathological processes including cancer and atherosclerosis. Peripheral Arterial Disease (PAD) is one such example in which tissue metabolism is reduced as an adaptive mechanism to hypoxia, and pulsatile hemodynamic signatures are deteriorated by progressive arterial obstruction. Interrogating tissue with coherent light sources offers a simple and effective means for noninvasive measurement of metabolism and hemodynamics, providing a strategy for treatment monitoring in PAD. In this work we develop a wide-field noncontact imaging technique that utilizes coherent light and pixel-based detectors in order to map metabolism and blood flow at high speeds. First, we expand upon previous work on Coherent Spatial Frequency Domain Imaging (cSFDI) by mitigating bottlenecks in data acquisition. Adapting advanced image demodulation techniques along with simplified projection optics, we are able to recover the tissue absorption and reduced-scattering coefficients (µa and µs’, respectively), in addition to speckle contrast from a single snapshot. Next, we extend this technique to two wavelengths allowing for the recovery blood flow, oxyhemoglobin and deoxyhemoglobin at up to 25 frames per second. We then implement a framework for extracting the absolute rate of oxygen consumption (MRO2) from dual-wavelength cSFDI output parameters. We validate MRO2 measurements using yeast-hemoglobin phantoms in which oxygen is extracted from bovine hemoglobin using baker’s yeast. Next, we perform a series of in vivo arterial occlusion protocols and demonstrate sensitivity to metabolic changes caused by transient tissue ischemia. At the same time, we investigate pulsatile signals due to the cardiac cycle using a novel device that measures coherent speckle patterns in transmission geometry. From a single coherent light source we are able to obtain two signals, one related to blood flow and one related to vascular compliance. We are able to demonstrate sensitivity to arterial stiffness and vascular tone using novel processing methods aimed at characterizing timing offsets between the signals along with embedded harmonic content. Using high speed single wavelength (852 nm) cSFDI measurements at 100 frames per second we are able to extract pulsatile time domain components of µa, µs’ and speckle flow from 2-dimensional images. Our results show that due to its unique spatiotemporal information content and sensitivity to multiple contrast features, cSFDI can play an important role as a bedside metabolic imaging technology for managing patients with peripheral arterial disease

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