# Magnetic susceptibility and volume of microvascular lesions as proof-of concept biomarkers for mixed dementia

> **NIH NIH R21** · WAYNE STATE UNIVERSITY · 2021 · $437,221

## Abstract

Project Summary
The objective of this R21 proposal is to give proof that magnetic susceptibility and volume of cerebral
microbleeds quantified by an innovative MRI technique, CISSCO, and validated by pathological examination
can differentiate postmortem brain samples from control and demented subjects. Microbleeds appear in
varying numbers in images, but they are strongly associated with vascular cognitive impairment (VCI), small
vessel diseases (SVD), and Alzheimer's disease (AD). They also appear in healthy older people at a lower
prevalence. Current clinical diagnosis only counts the number of microbleeds and their mimics from images.
However, the number of these “apparent” micro-objects is subject to imaging parameters (including the MRI
field strength) and does not correlate well with the progression of cognitive decline. As microbleeds with
hemorrhagic components show magnetic susceptibility effects in MRI, these investigators hypothesize that
magnetic properties of microbleeds may help to differentiate certain clinical dementia subtypes. These novel
quantitative parameters may be better markers for incipient dementia. They will advance our current
understanding of the contribution of microbleeds to dementia beyond postmortem analysis and toward living
patients.
To design clinical imaging protocols and parameters, susceptibility values of microbleeds used to distinguish
between control and demented subjects must be known first. The proposed aims are to image and
pathologically examine micro-objects in postmortem samples obtained from the Michigan Brain Bank (MBB),
which will blind these investigators to the clinical and neuropathological diagnosis of each subject until the late
stage of this project. Formalin fixed, paraffin-embedded blocks where microvascular lesions are suspected will
be obtained from subjects who died with no cognitive impairment or mixed dementia (including cases with
high- and intermediate- likelihood of AD pathology). The CISSCO method will be applied to MR images of
postmortem samples for accurate quantification of the magnetic susceptibility and volume of each micro-object.
These micro-objects observed in MRI will then be co-registered and identified histologically in the same
samples. These micro-objects, which are microbleeds and their mimics, will be categorized based on
pathological results and quantified susceptibility values from MRI. They will also be compared between the
diagnostic groups after the investigators are un-blinded. Cox hazard ratios will be calculated for different
categorized results. If different magnetic properties can differentiate the clinical groups, then this outcome
would indicate that magnetic properties of microbleeds is a potential advance in imaging biomarkers for
dementia. With proof from this R21, future clinical testing plans will be proposed to NIH.

## Key facts

- **NIH application ID:** 10209809
- **Project number:** 1R21AG069477-01A1
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** Yu-chung Norman Cheng
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $437,221
- **Award type:** 1
- **Project period:** 2021-05-01 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10209809

## Citation

> US National Institutes of Health, RePORTER application 10209809, Magnetic susceptibility and volume of microvascular lesions as proof-of concept biomarkers for mixed dementia (1R21AG069477-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10209809. Licensed CC0.

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