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Development of Non-Invasive, Functional, Optical Imaging for Monitoring and Detecting Cardiovascular Disease

Robert Warren

Cardiovascular disease (CVD) is the number one killer in the world, yet one third of CVD-related deaths occur in asymptomatic individuals and one fifth of these individuals bear no previous diagnosis of CVD. New methods that provide a better understanding of CVD risk factors and detect asymptomatic disease could save many lives. In this work, I introduce diffuse optical spectroscopic imaging (DOSI) as a new method for non-invasively assessing “silent” CVD and CVD risk. DOSI is a quantitative, model-based technique that utilizes a broadband wavelength range, corrects for light scattering, and probes several centimeters into tissue. DOSI is particularly relevant for cardiovascular disease research because it measures absolute concentrations of the primary light absorber in blood, hemoglobin, as well as the oxygenation state of hemoglobin, lipid content, and water content. These features of DOSI allow for hemodynamic measurements, compositional analysis, and reliable comparisons across operators, instruments, and even separate institutions.
I demonstrate a diffuse optical spectroscopic vascular health assessment which samples three important features of vascular health: body composition, tissue metabolism, and vascular reactivity. In a pilot study of body composition assessment, DOSI is used to track alterations in human muscle tissue following 5-weeks of resistance training. These assessments of muscle are compared to dual-energy x-ray absorptiometry (DXA), a standard body composition assessment technique. A similar approach is used in a study of 103 individuals but is extended to sample the whole body. Using DOSI assessments at 12 anatomical locations, a method is developed to predict whole-body fat and lean soft tissue percentage. Next, I study hemodynamics in a cohort of healthy volunteers using a vascular occlusion technique. This study characterizes the range of tissue metabolism we expect to see in healthy individuals and identifies how adipose tissue thickness affects DOSI assessments. Finally, preliminary data on vascular reactivity from patients with confirmed vascular disease is presented and I propose a framework for future vascular health assessments with DOSI.

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