Super Pixel Diffuse Optical Tomography

Optical imaging has long held promise as a clinical, bedside neuroimaging tool; however, the performance has been lacking compared to functional Magnetic Resonance Imaging (fMRI), the gold standard of functional brain imaging. Recently, High-Density Diffuse Optical Tomography (HD-DOT) has matched image resolution with fMRI and has adapted an fMRI technique which assays cerebral function without requiring task performance, known as resting-state functional connectivity, for use with optical data. HD-DOT uses safe, near-infrared light delivered via optical fibers to the head to measure oxygenation changes in the brain. The system performance of HD-DOT has been validated using tasks and resting-state functional connectivity in healthy adults but has not yet transitioned to a bedside neuroimaging tool. The final limitations are ergonomic in nature, including large console sizes and heavy caps. In this dissertation, we utilize advances in CMOS camera sensor designs to improve the ergonomics of HD-DOT systems for use in clinical care settings. The primary advantage we are leveraging to improve HD-DOT ergonomics is the increased sensitivity of CMOS sensors compared to previously used detectors. This increased sensitivity allows for a reduction in the optical fiber diameters without compromising data quality. The reduced fiber diameters significantly decrease the weight of the cap, improving wearability. The secondary advantage of CMOS sensors are their small form factors which allow for a significantly reduced console size, improving the portability of the system. The disadvantage of CMOS sensors are the low dynamic ranges (DNR), which are 100-fold lower than the DNR necessary for HD-DOT neuroimaging. To combat this disadvantage, we have developed a Super Pixel HD-DOT (SP-DOT) algorithm which uses pixel binning and electronic noise reduction to meet the required specifications for HD-DOT neuroimaging. This dissertation reports the development, testing, and validation of the SP-DOT system. Collectively, this dissertation demonstrates that advanced SP-DOT offers a practical solution to imaging brain activity in the clinic with fMRI-comparable spatial resolution. As a preliminary investigation into the utility of HD-DOT in the clinic, we imaged acute stroke patients at the bedside using a first generation, APD-based HD-DOT system with large optical fibers. By optimizing the location of the cap, we were able to image key areas of the brain while maintaining system portability and moderate cap wearability. We had success collecting resting-state data from these acute stroke patients for use in functional connectivity analysis. We developed a “Similarity” metric for each stroke patient, which is a measure of how similar the stroke patients’ connectivity maps are to a healthy cohort. This similarity metric is significantly reduced over the damaged hemisphere in stroke patients and also correlates with neurological impairment