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Validation of a Novel Magnetic Resonance Imaging (MRI) Technology for both Diagnostic Screening and Quantification of Brain Vascular Physiology in Alzheimer's-Disease-Related Dementias

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R43AG079732-01
Agency Tracking Number: R43AG079732
Amount: $915,931.00
Phase: Phase I
Program: SBIR
Solicitation Topic Code: R
Solicitation Number: PAS19-316
Solicitation Year: 2019
Award Year: 2022
Award Start Date (Proposal Award Date): 2022-09-15
Award End Date (Contract End Date): 2023-02-28
Small Business Information
Medford, MA 02155-4728
United States
DUNS: 081313748
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (857) 222-8879
Business Contact
Phone: (857) 222-8879
Research Institution

Alzheimer’s disease (AD), a degenerative brain disorder, is responsible for 60-70% of all dementia. Currently no
reliable biomarkers exist for precision-medicine-level, single-patient diagnostics for the early detection of
Alzheimer’s disease and related dementias (AD/ADRD). Imaginostics proposes to clinically valdiate novel
magnetic resonance imaging (MRI)-based proprietary biomarkers for the early detection of vascular pathology
that predisposes individuals to develop dementia in patients with mild cognitive impairment (MCI). Further, we
will validate biomarkers for measuring vascular abnormality in Vascular Dementia (VaD), which accounts for
10% of all dementia. Quantitative Ultra-short Time-to-Echo Contrast-Enhanced (QUTE-CE) MRI is unique in that
it generates a quantitative signal directly representative of physiological information.
The overall objective of Phase I proposal: Obtain clinical validation of the QUTE-CE imaging approach for our
panel of biomarkers for measuring microvascular structure, function and leakage. This first validation is targeted
at two groups: 1) MCI: for evaluating the prospects of detecting abnormality before dementia onset and 2) VaD:
for evaluating the prospect of characterizing vascular related cognitive impairment (VCID) in the most pertinent
dementia population. Their ability to detect dementia will be compared to age-matched individuals and also
compared to state-of-the art neuroimaging biomarker approaches to more fully evaluate the potential of QUTE-
Specific Aim 1: Establish the merit and feasibility of QUTE-CE MRI vascular imaging biomarkers for
detecting vascular abnormality in vascular dementia. The study will include (n=24; 12M/12F) Vascular
Dementia subjects and (n=24; 12M/12F) age-matched control subjects.
Specific Aim 2: Establish the merit and feasibility of QUTE-CE MRI vascular imaging biomarkers for
detecting vascular abnormality in Mild Cognitive Impairment (MCI). The study will include (n=24; 12M/12F)
MCI subjects and (n=24; 12M/12F) age-matched control subjects.
Primary Endpoints (Specific Aims 1 and 2):
(1) Structure: Cerebral Blood Volume (QC-CBV) and Small Vessel Density (QC-SVD): (Hypothesis 1) We willtest our hypotheses that QUTE-CE MRI can detect small and large vessel abnormality.
(2) Function: Cerebrovascular reactivity (QC-CVR) and CBV-based Functional MRI (QC-fMRI): (Hypothesis2) We will test our hypotheses that QUTE-CE MRI will outperform EPI-fMRI for cerebrovascular reactivity atthe group level, and that QC-CVR can be mapped in individuals MCI and VaD for precision medicine.
(3) Leakage: Blood-Brain Barrier leakage (QC-BBB): (Hypothesis 3) We will test our hypotheses that QUTE-CE MRI will outperform DCE-MRI for detecting BBB leakage at the group level, and that BBB leakage canbe mapped in individuals MCI and VaD for precision medicine.
Further, we will test our hypothesis (Hypothesis 4) that a multivariate model (CBV, CVR, BBB permeability) of
neurovascular unit dysfunction will provide diagnostic maps indicating abnormality and correlate to cognitive
decline better than any individual imaging measures due to their complementary nature in assessment vascular
related neuropathology.
In addition, fluid-attenuated inversion recovery (FLAIR), susceptibility-weighted imaging (SWI) and diffusion-
weighted imaging (DWI) scans will be acquired to identify white matter hyperintensities (WMHs), cerebral
microbleeds (CMBs) and ischemic lesions to quantify the focal burden of microvascular changes from CBV maps.
Quantitative performance milestones will be comparative whole-brain biomarker analytics and the analysis of
focal burden as identified in FLAIR, SWI and DWI using CBV for identifying the spatial-extent-of-burden, intra-
subject left-right brain comparison, and volume-of-interest comparison to the healthy controls. We will also
perform cognitive testing on all patients to evaluate the correlation to vascular pathology - as measured with
QUTE-CE MRI vascular biomarkers - to clinical measures. We can measure vascular abnormality and metabolic
dysfunction throughout the whole brain, so we should have a gamut of tests that can evaluate all cognitive
domains: memory, language, attention, executive function, visuospatial skills.

* Information listed above is at the time of submission. *

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