# Implementing a novel, multimodal technique for monitoring cerebrovascular hemodynamics in mice as a diagnostic and prognostic tool for single and repeated mild TBI

> **NIH NIH R21** · UNIVERSITY OF KENTUCKY · 2020 · $420,750

## Abstract

Project Summary
Traumatic brain injuries (TBIs) are a major societal and public health concern with over 2.8 million TBIs
reported each year in the US. Mild TBIs (mTBIs), accounting for over 80% of TBIs, can be difficult to diagnose.
Because no FDA-approved therapeutic intervention for mTBI exists, a period of rest to allow symptom
resolution is the primary treatment approach. It is imperative that while symptomatic, a person recovering from
mTBI avoid sustaining a second mTBI, as multiple mTBIs greatly increases the risk for prolonged disability.
The period of brain vulnerability after mTBI, however, extends beyond the resolution of clinical symptoms,
underscoring the vital need for accurate assessment of neurophysiological recovery in order to mitigate the
risks associated with repeated head injury. Unlike moderate and severe TBI, which are typically associated
with neuron death and vascular disruption, mTBI results in more subtle physiological and cellular changes,
such as metabolic distress and alterations in cerebral blood flow (CBF). We hypothesize that mTBI induces
acute, transient changes in CBF that, coupled with metabolic dysregulation, form the basis of the window of
vulnerability to repeated mTBI. We predict, therefore, that a second injury induced during the period of acute
CBF alteration will result in worsened outcome as reflected by greater perturbations in CBF and metabolism.
Our group has developed a novel multiple-wavelength speckle contrast diffuse correlation tomography (MW-
scDCT) technique that yields non-invasive, longitudinal, regional mapping of CBF and oxygenation in mice. We
have validated our technique against established methods and demonstrated its utility in detecting CBF
changes in rodents. In Aim 1, we will first use MW-scDCT to measure cortical and hippocampal CBF and
oxygenation after single closed head injury (CHI) to monitor temporal changes and determine the time to
recovery. We will then determine whether normalization of CBF is required to prevent synergistic effects of a
second CHI on cerebral hemodynamics. Neurovascular coupling and cerebrovascular reactivity will be
assessed at selected time points to inform potential mechanisms underlying CBF changes. Finally,
quantitative analysis of cerebrovascular structure and communication will be performed to identify anatomical
plasticity or damage. In Aim 2, a targeted metabolomics approach will be used to identify metabolite profiles in
cortical tissue and plasma which are unique to mice with single or repeated mTBI. We will further test whether
restoration of the metabolome coincides with normalization of CBF after mTBI. Such a finding would support a
dual-pronged approach for assessing concussion recovery through noninvasive CBF monitoring and
assessment of plasma metabolite biomarkers. These studies will pair metabolomics with our innovative MW-
scDCT technique for monitoring cerebral hemodynamics to provide new insights into the neurophysiological
determin...

## Key facts

- **NIH application ID:** 10056044
- **Project number:** 1R21NS114771-01A1
- **Recipient organization:** UNIVERSITY OF KENTUCKY
- **Principal Investigator:** KATHRYN E SAATMAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $420,750
- **Award type:** 1
- **Project period:** 2020-06-01 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10056044

## Citation

> US National Institutes of Health, RePORTER application 10056044, Implementing a novel, multimodal technique for monitoring cerebrovascular hemodynamics in mice as a diagnostic and prognostic tool for single and repeated mild TBI (1R21NS114771-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10056044. Licensed CC0.

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