# Technology to Realize the Full Potential of UHF MRI (Supplement)

> **NIH NIH P41** · UNIVERSITY OF MINNESOTA · 2021 · $377,216

## Abstract

ABSTRACT
The pathophysiology of Alzheimer’s disease involves a plethora of structural and functional abnormalities of
multiple brain structures and related circuits, including neurodegeneration of the hippocampus, a critical hub
responsible for memory and executive function. While progress has been made in documenting the hallmarks
of the disease’s pathophysiology, the sequence of events that lead to hippocampus atrophy, loss of memory,
and loss of executive function with disease progression remain insufficiently characterized due to the lack of in-
vivo markers sensitive to the process of neurodegeneration. To address this unmet need our goal is to establish
rotating frame MRI relaxation mapping based on Frequency Swept (FS) pulses, adiabatic T1ρ and RAFFn, as
novel, non-invasive biomarkers of neurodegeneration and demyelination. This goal is supported by the fact that
the rotation frame relaxation parameters that will be investigated, allow us to probe slow motional components
of the spectral density function unlike standard free-precession MRI metrics. This slow motional regime is most
relevant to characterize multiple biological processes at the molecular and cellular levels in tissue as we and
others have demonstrated in other pathologies. As such, our overarching hypothesis is that adiabatic T1ρ will
serve as an early marker of neural degeneration of the hippocampus, while RAFFn will be able to detect
demyelination, and both markers will correlate with neural network dysfunction at different stages of Alzheimer’s
disease, as detected by resting state functional MRI. Three specific aims will be pursued to investigate this
hypothesis: 1) optimization of parameters for obtaining high-resolution mapping of rotating frame MRI metrics
from hippocampal subregions and layers, 2) identify rotating frame MRI markers of brain tissue abnormalities
in a rat model of Alzheimer’s disease as compared to age-matched wile-type rats and 3) uncover the Alzheimer’s
disease pathophysiological substrates that best correlate with the novel rotating frame MRI biomarkers, as
revealed by resting-state fMRI, histology and spatial genomics. Accomplishing these aims will establish the
potential of rotating frame MRI markers as novel biomarkers of neurodegeneration in Alzheimer’s disease by
extending technical developments proposed in the parent grant. Spatial genomic analysis will allow us to identify
the molecular basis of the MRI outcomes, thus providing an invaluable validation needed for optimizing
therapies, monitoring treatment response and supporting subsequent applications in humans.

## Key facts

- **NIH application ID:** 10285102
- **Project number:** 3P41EB027061-03S1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Gregory John Metzger
- **Activity code:** P41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,216
- **Award type:** 3
- **Project period:** 2019-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10285102

## Citation

> US National Institutes of Health, RePORTER application 10285102, Technology to Realize the Full Potential of UHF MRI (Supplement) (3P41EB027061-03S1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10285102. Licensed CC0.

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