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. 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. Aging ; Algorithms ; Animal Experimentation ; Animal Experimental Use ; Animal Research ; Animals ; Biomedical Research ; Brain ; Brain Nervous System ; Encephalon ; Brain Neoplasms ; Brain Neoplasia ; Brain Tumors ; tumors in the brain ; Calibration ; Cerebrovascular Circulation ; brain blood flow ; cerebral blood flow ; cerebral circulation ; cerebrocirculation ; cerebrovascular blood flow ; Cerebrovascular Disorders ; Brain Vascular Disorders ; Cerebrovascular Disease ; Intracranial Vascular Diseases ; Intracranial Vascular Disorders ; brain vascular disease ; brain vascular dysfunction ; cerebral vascular disease ; cerebral vascular dysfunction ; cerebrovascular dysfunction ; intracranial vascular dysfunction ; Dyes ; Coloring Agents ; Feedback ; Fluorescence ; Future ; Head ; hemodynamics ; Homeostasis ; Autoregulation ; Physiological Homeostasis ; Human ; Modern Man ; Industrialization ; Infant ; instrumentation ; Kentucky ; Laboratories ; Magnetic Resonance Imaging ; MR Imaging ; MR Tomography ; MRI ; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance ; NMR Imaging ; NMR Tomography ; Nuclear Magnetic Resonance Imaging ; Zeugmatography ; Metabolism ; Intermediary Metabolism ; Metabolic Processes ; Methodology ; Mus ; Mice ; Mice Mammals ; Murine ; United States National Institutes of Health ; NIH ; National Institutes of Health ; nervous system disorder ; Nervous System Diseases ; Neurologic Disorders ; Neurological Disorders ; neurological disease ; Neurons ; Nerve Cells ; Nerve Unit ; Neural Cell ; Neurocyte ; neuronal ; Neurosciences ; Noise ; Optics ; optical ; Oxygen ; O element ; O2 element ; Oxygen Consumption ; Legal patent ; Patents ; Pathology ; Perfusion ; Positron-Emission Tomography ; PET ; PET Scan ; PET imaging ; PETSCAN ; PETT ; Positron Emission Tomography Medical Imaging ; Positron Emission Tomography Scan ; Rad.-PET ; positron emission tomographic (PET) imaging ; positron emission tomographic imaging ; positron emitting tomography ; Rattus ; Common Rat Strains ; Rat ; Rats Mammals ; Research Personnel ; Investigators ; Researchers ; Rodent ; Rodentia ; Rodents Mammals ; Signal Transduction ; Cell Communication and Signaling ; Cell Signaling ; Intracellular Communication and Signaling ; Signal Transduction Systems ; Signaling ; biological signal transduction ; Computer software ; Software ; Stress ; Stroke ; Apoplexy ; Brain Vascular Accident ; Cerebral Stroke ; Cerebrovascular Apoplexy ; Cerebrovascular Stroke ; brain attack ; cerebral vascular accident ; cerebrovascular accident ; Technology ; Testing ; Time ; Tissues ; Body Tissues ; tomography ; Universities ; Work ; Measures ; base ; density ; human subject ; Brain imaging ; brain visualization ; Acute ; Chronic ; Clinical ; Diffuse ; Penetration ; Phase ; Variant ; Variation ; Histologic ; Histologically ; Medical ; Neurologic ; Neurological ; Evaluation ; Recovery ; Hypoxia ; Hypoxic ; Oxygen Deficiency ; Cerebrum ; cerebral ; Measurement ; Funding ; Collaborations ; Metabolic ; lightweight ; light weight ; tool ; instrument ; Investigation ; Techniques ; System ; 3-D ; 3D ; three dimensional ; 3-Dimensional ; experience ; Performance ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; neural ; relating to nervous system ; Devices ; intervention therapy ; Therapeutic Intervention ; Property ; response ; tissue oxygen saturation ; tissue oxygenation ; portability ; Intervention Strategies ; interventional strategy ; Intervention ; 3-D Imaging ; 3D imaging ; Three-Dimensional Imaging ; Optical Tomography ; image-based method ; imaging method ; imaging modality ; Ultrasonic ; Ultrasonics ; Imaging Instrument ; Imaging Tool ; Imaging Device ; Resolution ; in vivo ; Functional Imaging ; Physiologic Imaging ; physiological imaging ; Neurosciences Research ; Rodent Model ; Small Business Innovation Research Grant ; SBIR ; Small Business Innovation Research ; Small Business Technology Transfer Research ; STTR ; Pathologic ; Monitor ; Development ; developmental ; Image ; imaging ; pre-clinical ; preclinical ; neonate ; cost ; design ; designing ; Neonatal Brain Injury ; Outcome ; Neonatal ; Imaging technology ; innovation ; innovate ; innovative ; clinical application ; clinical applicability ; user-friendly ; commercialization ; tissue phantom ; multimodality ; multi-modality ; effective intervention ; Biological Markers ; bio-markers ; biologic marker ; biomarker ; phase 1 study ; Phase I Study ; phase 2 study ; phase II study ; stress disorder ; Algorithmic Software ; Algorithmic Tools ; Software Algorithm ; non-invasive imaging ; noninvasive imaging ; metabolic rate ; brain health ; human imaging ; serial imaging ; longitudinal imaging ; stroke model ; imager ; neonatal brain development ; therapeutically effective ;
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.
