# Diffusion-weighted fMRI for presurgical mapping of primary motor cortex in the presence of neurovascular uncoupling (NVU)

> **NIH NIH R03** · JOHNS HOPKINS UNIVERSITY · 2021 · $163,750

## Abstract

Project Summary/Abstract
Current state-of-art for preoperative noninvasive planning of tumor resection is to perform task-based blood
oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). During scanning, a patient
performs a specific task to localize brain functional regions related to the task. BOLD fMRI detects alterations in
deoxyhemoglobin concentration influenced by hemodynamic factors that occur in response to neuronal activity.
The reliance on BOLD signal to represent activity in the brain comes with limitations. One major limitation is that
brain activation mapping using BOLD fMRI relies on the tight coupling between hemodynamic changes and
neuronal activity. In the presence of brain tumors or other focal brain lesions, the coupling between neuronal
activity and the hemodynamic changes occurring in the adjacent vasculature is often disrupted, which is referred
as neurovascular uncoupling (NVU). NVU is a major problem in the interpretation of task-based BOLD fMRI
maps in the settings of focal brain lesions, as it may lead to spuriously decreased or even absent activation in
electrically active, essential functional cortex. As a result, surgical resection of eloquent cortex may occur with
resultant postsurgical morbidity. Another limitation of BOLD fMRI, due to its indirect measure of neuronal activity,
is that there is a several second offset in both initiation and cessation of the hemodynamic response with respect
to actual timing of neural activity. Such a lag in the temporal profile of the BOLD fMRI response becomes more
critical in the case of brain tumors. As a result, the BOLD signal is susceptible to “hemodynamic modulations”
which decreases the spatial and temporal accuracy of the BOLD signal. To overcome these limitations of BOLD
fMRI, a method which is immune to the hemodynamic changes and is more direct representation of neural activity
is needed. A promising alternative approach is the use of activation-associated decreases in brain apparent
diffusion constant (ADC) observed using diffusion-weighted MRI (DWI). The use of DWI for functional imaging
is referred as ‘diffusion-weighted fMRI (dfMRI)’. DWI is sensitized to water diffusion of underlying tissues in brain.
Prior work has shown that brain ADC decreases in activated cortical areas, occurring several seconds before
the hemodynamic response detected by BOLD fMRI. These observations therefore suggest that dfMRI is more
directly linked to brain activation than traditional BOLD fMRI, and furthermore may be independent of
hemodynamic response factors. However, to date there have been no studies of dfMRI in the evaluation of
patients with brain tumors. In the current proposal, we aim to investigate dfMRI in the presence of brain lesion-
induced disruption of coupling between neuronal activity and hemodynamic changes. We hypothesize that dfMRI
may enhance detectability of primary motor cortex activation in the vicinity of brain lesions.

## Key facts

- **NIH application ID:** 10301967
- **Project number:** 1R03NS120323-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Shruti Agarwal
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $163,750
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301967

## Citation

> US National Institutes of Health, RePORTER application 10301967, Diffusion-weighted fMRI for presurgical mapping of primary motor cortex in the presence of neurovascular uncoupling (NVU) (1R03NS120323-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10301967. Licensed CC0.

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