Many clinical situations, including stroke, expose the brain to insufficient cerebral blood flow (CBF) that cannotmaintain normal cerebral metabolic rate of oxygen consumption (CMRO2) requirements, thereby leading tocerebral ischemic/hypoxic stresses and neurological disorders. Effective interventions are dependent on thefindings of CBF/CMRO2 improvement and eventually neural recovery. Rodents (mice and rats) make up 95% ofresearch animals. However, one major limitation with neuroscience research in rodent models is lack ofaffordable noninvasive imaging technologies for continuous and longitudinal monitoring of CBF and CMRO2variations. Large imaging modalities (e.g., CT, PET, and MRI) require expensive instrumentation, and are difficultto use for longitudinal monitoring. Portable, inexpensive optical/ultrasonic technologies greatly expand choicesfor continuous cerebral monitoring although most systems lack the combination of high tempo-spatial resolution,wide field-of-view, and proper penetration depth into deep brains. Moreover, none of currently availabletechniques enable simultaneous imaging of CBF, cerebral tissue oxygen saturation (StO2), and CMRO2. Toovercome these limitations, researchers at University of Kentucky (UK) have developed an innovativeCCD/CMOS based speckle contrast diffuse correlation tomography (scDCT: US Patent #9861319) techniqueto accommodate noninvasive, noncontact, fast, high-density 3D imaging of CBF distributions in mice, rats, piglets,and human neonates. While effective, scDCT has not been optimized for dissemination and commercializationin terms of imaging performance (signal-to-noise ratio, temporal-spatial resolution, accuracy, easy-to-use), andinstrument cost and portability. In collaboration with UK, Bioptics Technology LLC (BOT) proposes to develop,optimize, validate, and commercialize an affordable, portable, easy-to-use, multi-wavelength scDCT (MW-scDCT) technique for repeated, longitudinal imaging of CBF, StO2, and CMRO2 distributions in rodents. Newmethodologies and algorithms will be developed to achieve a nearly real-time, high-density, 3D imaging ofcerebral function. The MW-scDCT will be rigorously tested and optimized using head-simulating phantoms withknown optical and hemodynamic properties (Aim 1). In vivo calibration and evaluation of absolute measurementswith MW-scDCT will be conducted against standard perfusion MRI and histological examination in rats with orwithout stroke (Aim 2). Finally, optimized MW-scDCT devices will be disseminated to several neuroscienceresearchers inside and outside UK to collect feedback regarding instrument applicability and user experience.With preliminary feedback from these selected end-users, we expect to identify refinements and improvementsneeded for the MW-scDCT in a continued Phase-II study to produce an optimal product-level device forcommercialization. The ultimate use will be expanded to larger animal models and human subjects. However,this Phase-I project will begin with rodents as using small animals is easier, more economical and efficient forcommercializing the device, thereby paving the way for future commercialization of clinical-level devices.
Public Health Relevance Statement: PROJECT NARRATIVE
Continuous and longitudinal monitoring of brain blood flow, oxygenation, and metabolism provides an opportunity
to rapidly manage cerebrovascular diseases and neurological disorders. In collaboration with University of
Kentucky, Bioptics Technology LLC proposes to develop, validate, and commercialize an innovative, affordable,
portable/mobile, and ergonomic optical device for noninvasive, noncontact, fast, high-density imaging of brain
blood flow, oxygenation, and metabolism distributions in small animals (rodents). Completion of this STTR
project will provide a unique noninvasive brain monitoring tool for basic neuroscience research in numerous
academic and industrial laboratories.
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