Project Grant R01NS134712
- This federal Project Grant award of $452,561 from the National Institute on Aging (CFDA 93.866 Aging Research) aims to utilize a novel magnetic resonance imaging (MRI) technique, known as multi-delay arterial spin labeling (ASL) with T2 preparation (T2PREP-ASL), to non-invasively measure blood-brain barrier (BBB) integrity in a cohort of ethnically diverse individuals genetically susceptible to Alzheimer's disease. The project will validate the T2PREP-ASL imaging technique against existing...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the federal Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, aims to establish the feasibility of cell-type specific modulation of the blood-brain barrier (BBB) using a novel "MagnetoBBB" approach. The total award amount is $447,501.00 with a project period from September 1, 2024 to August 31, 2026. The key objectives are to: 1)...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) will provide $794,981 to the University of California, San Diego (UCSD) to investigate the use of blood-brain barrier permeability and brain microstructure as biomarkers for predicting and monitoring amyloid-related imaging abnormalities (ARIA) and treatment outcomes in Alzheimer's disease patients prescribed anti-amyloid immunotherapies. The study aims to integrate advanced MRI techniques into...
- This Project Grant award from the National Institute on Aging (CFDA 93.866 - Aging Research) totaling $2,317,887 will be used by Indiana University Indianapolis to map paravascular cerebrospinal fluid (PCSF) signatures associated with healthy aging, aging with hypertension, and Alzheimer's disease (AD). The researchers will leverage dynamic diffusion-weighted imaging, a novel neuroimaging technique, to quantify PCSF dynamics and volume near major arteries - a key component of the glymphatic...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under CFDA 93.853 Extramural Research Programs in the Neurosciences and Neurological Disorders will support research to understand the mechanisms underlying brain-immune interactions at the blood-brain barrier. The overarching goal is to generate novel targets for immunotherapy in neuroinflammatory conditions. The $230,580 award to Brigham & Women's Hospital, a subsidiary of Partners...
- The National Institute on Aging (NIA), through its Aging Research federal grant program (CFDA 93.866), awarded the University of Washington a $303,614 Project Grant (R03AG081836) to develop a computational model for accurately calculating cerebrospinal fluid (CSF) velocities and brain tissue deformation. The goal is to create novel, non-invasive biomarkers for early detection of Alzheimer's disease by measuring impairment of CSF flow and brain tissue stiffness, which are linked to the...
- The U.S. National Institute of Biomedical Imaging and Bioengineering (NIBIB) awarded a $349,908 Project Grant under the Discovery and Applied Research for Technological Innovations to Improve Human Health program (CFDA 93.286) to Evanesc Therapeutics, Inc. to develop a non-invasive medical device designated "EvaPERMEA" that uses low-power radio frequency evanescent waves to temporarily permeabilize the blood-brain barrier. This innovation aims to improve the delivery of therapeutic...
- This Project Grant award, totaling $1,491,482, was provided by the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242). The project aims to investigate the neurobiological correlates of increased extracellular water volume (free water) observed in schizophrenia patients, particularly during early phases of the disease. The research will leverage a validated animal model (GCLM knockout mice) to test the relationship between oxidative stress,...
- The National Institute of Neurological Disorders and Stroke (NINDS) awarded a $147,486 Project Grant under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) to the Massachusetts Institute of Technology (MIT) from July 1, 2025 to June 30, 2027. The grant funds the development of a novel Magnetic Resonance Imaging (MRI) method to concurrently measure brain tissue displacement, blood dynamics, and cerebrospinal fluid (CSF) flow in humans. This research...
- This Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS) under CFDA 93.853 "Extramural Research Programs in the Neurosciences and Neurological Disorders" provides $404,100.00 to The General Hospital Corporation, doing business as Massachusetts General Hospital (MGH), to study the mechanisms of chronic blood-brain barrier dysfunction after traumatic brain injury (TBI). The research aims to identify a signaling pathway involving the...
NON-INVASIVE MRI MAPPING OF BBB WATER EXCHANGE RATE AND PERMEABILITY - PROJECT SUMMARY/ABSTRACT THE BLOOD-BRAIN BARRIER (BBB) PLAYS A CRUCIAL ROLE IN PROTECTING THE CENTRAL NERVOUS SYSTEM (CNS) FROM HARMFUL SUBSTANCES SUCH AS PLASMA PROTEINS AND INORGANIC SOLUTES. A NON-INVASIVE MRI TECHNIQUE TO DETECT SUBTLE BBB DYSFUNCTION COULD BE AN EXTREMELY VALUABLE TOOL FOR EARLY DIAGNOSIS OF NEURODEGENERATIVE DISORDERS. OUR TEAM HAS DEVELOPED A DIFFUSION PREPARED PSEUDO-CONTINUOUS ARTERIAL SPIN LABELING (OP-PCASL) TECHNIQUE FOR MAPPING BBB WATER EXCHANGE RATE (KW), WHICH HAS BEEN VALIDATED BY PRECLINICAL STUDIES AND FOUND TO BE ASSOCIATED WITH AGING, SMALL VASCULAR DISEASE, APOE EPSILON4 GENOTYPE, AMYLOID PET, AND CSF AB-42 IN COGNITIVELY NORMAL SUBJECTS. HOWEVER, THE OP-PCASL TECHNIQUE CURRENTLY HAS LOW SPATIAL RESOLUTION AND CANNOT ESTIMATE THE PERMEABILITY SURFACE AREA PRODUCT OF WATER (PSW) DUE TO A LACK OF VENOUS COMPARTMENT IN ITS MODELING. MAPPING BOTH KW AND PSW IS SIGNIFICANT BECAUSE THEY ASSESS DIFFERENT ASPECTS OF THE BBB AND PROVIDE COMPREHENSIVE INFORMATION ABOUT ITS FUNCTION. CHANGES IN PSW CAN INDICATE A COMBINATION OF CHANGES IN CAPILLARY SURFACE AND PERMEABILITY, MAKING IT A POTENTIAL BIOMARKER FOR SUBTLE BBB LEAKAGE ACROSS ENDOTHELIAL CELLS. IN CONTRAST, KW MEASURES THE EXCHANGE RATE BETWEEN BLOOD AND TISSUE AND CAN BE MORE SENSITIVE TO TRANSPORT MECHANISMS, E.G. AQP4 FUNCTION, AND POTENTIALLY LINKED TO THE GLYMPHATIC FUNCTION. HOWEVER, THE EXACT NEUROPHYSIOLOGICAL MECHANISMS OF KW AND PSW ARE STILL UNCLEAR. THE PROPOSED PROJECT AIMS TO DEVELOP AND OPTIMIZE A HIGHRESOLUTION DIFFUSION-WEIGHTED ARTERIAL SPIN LABELING (OW-ASL) TECHNIQUE AND MATHEMATICAL MODELS TO NON-INVASIVELY QUANTIFY BBB KW AND PSW SIMULTANEOUSLY. THE INDIVIDUAL BBB KW AND PSW MEASUREMENTS WILL BE EVALUATED FOR TEST-RETEST REPEATABILITY. THE AGE-RELATED CHANGES OF BBB FUNCTION AND BBB DYSFUNCTION IN CEREBRAL SMALL VESSEL DISEASE (CSVO) WILL BE INVESTIGATED BY MEASURING KW AND PSW IN A COHORT OF HEALTHY SUBJECTS ACROSS THE LIFESPAN OF 18-90 YEARS AND ELDERLY SUBJECTS (AGE> 60 YEARS) WITH CSVO FROM USC VCIO STUDY. FINALLY, THE MECHANISMS OF BBB WATER EXCHANGE WILL BE STUDIED IN AQP4-KNOCKOUT MICE AND IN MODELS OF MANNITOL-INDUCED BBB DISRUPTION. THE OUTCOME OF THIS PROJECT WILL BE A CUTTING-EDGE OW-ASL PULSE SEQUENCE AND POST-PROCESSING PIPELINE THAT ALLOWS FOR HIGH-RESOLUTION MAPPING OF KW AND PSW, WITH AN UNDERSTANDING OF THEIR NEUROPHYSIOLOGICAL MECHANISMS.
Mod # | Description | ReasonForModification | Federal Obligation | Date |
|---|---|---|---|---|
| Not listed | $689.5k | 5/29/25 | ||
| Not listed | $0 | 10/29/24 | ||
| Not listed | $0 | 10/29/24 | ||
| Not listed | $691.1k | 7/19/24 | ||
| Not listed | $691.1k | 7/19/24 |