High-density optical tomography of cerebral blood flow and metabolism in small animals

ABSTRACT
Many clinical situations, including stroke, expose the brain to insufficient cerebral blood flow (CBF) that cannot
maintain normal cerebral metabolic rate of oxygen consumption (CMRO2) requirements, thereby leading to
cerebral ischemic/hypoxic stresses and neurological disorders. Effective interventions are dependent on the
findings of CBF/CMRO2 improvement and eventually neural recovery. Rodents (mice and rats) make up 95% of
research animals. However, one major limitation with neuroscience research in rodent models is lack of
affordable noninvasive imaging technologies for continuous and longitudinal monitoring of CBF and CMRO2
variations. Large imaging modalities (e.g., CT, PET, and MRI) require expensive instrumentation, and are difficult
to use for longitudinal monitoring. Portable, inexpensive optical/ultrasonic technologies greatly expand choices
for 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 available
techniques enable simultaneous imaging of CBF, cerebral tissue oxygen saturation (StO2), and CMRO2. To
overcome these limitations, researchers at University of Kentucky (UK) have developed an innovative
CCD/CMOS based speckle contrast diffuse correlation tomography (scDCT: US Patent #9861319) technique
to 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 commercialization
in terms of imaging performance (signal-to-noise ratio, temporal-spatial resolution, accuracy, easy-to-use), and
instrument 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. New
methodologies and algorithms will be developed to achieve a nearly real-time, high-density, 3D imaging of
cerebral function. The MW-scDCT will be rigorously tested and optimized using head-simulating phantoms with
known optical and hemodynamic properties (Aim 1). In vivo calibration and evaluation of absolute measurements
with MW-scDCT will be conducted against standard perfusion MRI and histological examination in rats with or
without stroke (Aim 2). Finally, optimized MW-scDCT devices will be disseminated to several neuroscience
researchers 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 improvements
needed for the MW-scDCT in a continued Phase-II study to produce an optimal product-level device for
commercialization. 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 for
commercializing the device, thereby paving the way for future commercialization of clinical-level devices.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.