The goal of this proposal is to establish a multi-user Brain Imaging Core at the VA Portland Health Care System facility (VAPORHCS) using ultrafast ultrasound in freely behaving animals. VAPORHCS has a long history of strong research within its facility, and currently has over 175 investigators and more than 570 active protocols. In 2018, Portland VA scientists produced nearly 500 research publications, were awarded over $33 million in research grants from the VA, NIH, DoD and other sources, and VAPORHCS ranks in the top 10 nationwide among VA Medical Centers in grant support from the Department of Veterans Affairs. Research is conducted in nearly ~100,000 square feet of wet and dry lab space that supports programs in basic science, clinical research, health services, cooperative studies, epidemiology and outcomes research. The VAPORHCS houses several funded neuroscience-related centers reflecting expertise in specific research areas, including: 1) NIH-funded Portland Alcohol Research Center (PARC), 2) National Center for Rehabilitative Auditory Research, 3) Mental Illness Research Education and Clinical Center, 4) Research Enhancement Awards Program in Multiple Sclerosis, 5) Parkinson's Disease Research Education and Clinical Center, 6) Multiple Sclerosis Center of Excellence, 7) Epilepsy Center of Excellence, 8) Hepatitis C Virus (HCV) Resource Center, 9) NIH-funded Methamphetamine Abuse Research Center, 10) VA Health Services Research and Development Center of Innovation (COIN), and 11) Agency for Healthcare Research and Quality Evidence Based Practice Center. The plan is to purchase the Ultrafast Ultrasound brain imaging system and to establish a core laboratory to service the needs of VA-funded scientists for brain imaging in freely behaving rodents. This request is for an instrument made by ICONEUS, the first and only developer of this novel technology, which will enable researchers to non-invasively acquire and tomographically reconstruct changes in cerebral blood flow perfusion to brain areas in coronal slices as well as 3D reconstruction of the whole brain. The technique has high temporal (100 frames per second) and spatial resolution (sub-millimeter range) and facilitates high throughput longitudinal study designs of the nature contemplated by Portland VA scientists. The technology offers an extremely powerful 3D in vivo screening method yielding quantitative and calibrated temporal and spatial/anatomical data while animals are fully awake and freely behaving in behavioral tasks of interest. Planned studies by the 8 VA-Funded PI's include: 1) Measure brain regions involved in chronic progressive MPTP model of Parkinsons disease in mice and response to treatments (Meshul), 2) Measure brain regions involved in alcohol-use disorder in mice and mechanisms of novel immunotherapies (Loftis), 3) Measure brain regions involved in mouse model of Alzheimer's disease and response to treatment with the botanical Centella asiatica (Quinn), 4) Measure brain regions involved in methamphetamine addiction in high and low administration mouse strains and mechanisms involving glutamatergic balance (Richards), 5) Measure brain regions involved in the Experimental Autoimmune Encephalitis model of multiple sclerosis in mice and response to treatments (Vandenbark), 6) Measure brain regions involved in post-traumatic epilepsy and control of seizure spread by opioids and other neuropeptides (Schnell), 7) Measure brain regions involved in sleep and cognitive deficits following TBI in mice and response to dietary intervention with branched chain amino acids (Lim), and 8) Measure brain regions involved in binge drinking and ethanol withdrawal (Ozburn).
The ICONEUS Ultrafast Ultrasound will allow VA-funded researchers to establish an in vivo brain imaging core for animals with the goal of advancing preclinical and translational research. Research programs at the Portland VA will benefit greatly from the acquisition of this novel, highly versatile equipment, which can be used in tandem with several other research techniques. This device would be used to advance findings in ongoing VA-funded studies including preclinical models of Parkinson's disease, traumatic brain injury, substance use disorders, multiple sclerosis, Alzheimer's Disease, and epilepsy, among other disorders that greatly impact the Veteran population. Furthermore, the ability of the ICONEUS Ultrasound to collect real-time recordings of regional brain activity in freely behaving animals is unprecedented, positioning the VA as a trailblazer nationwide in perform innovative experiments of this nature.
