# Development of Novel Functional Markers for TBI Using Molecular MRI

> **NIH NIH UH3** · JOHNS HOPKINS UNIVERSITY · 2021 · $420,672

## Abstract

ABSTRACT
 Traumatic brain injury (TBI) is an important public health problem. Currently, the ability to objectively
assess TBI is a critical research gap. CT and conventional structural MRI have proven to be highly effective in
identifying macroscopic lesions. However, these standard imaging techniques have clear limitations in
assessing important microscopic lesions and neurologic pathology. The clinical diagnosis of TBI via imaging,
particularly mild TBI, remains controversial, because the brain often appears quite normal on conventional CT
and MRI. Therefore, new sensitive surrogate biomarkers for TBI are greatly needed in routine clinical practice.
Amide proton transfer (APT) imaging is an important molecular MRI technique that can generate contrast
based on tissue pH or concentrations of endogenous mobile proteins and peptides. In our preliminary study,
we have applied the APTw-MRI approach to a rat TBI model, induced by controlled cortical impact (CCI). Our
preliminary results have demonstrated unique APTw-MRI signal characteristics at different time points after
injury that are associated with ischemia (at a few hours) and neuroinflammation (at 2-3 days). Notably, APT
imaging revealed an acidosis-based ischemic penumbra around the impacted area at a few hours post-injury.
These initial results are very promising. However, further development and radiographic-histopathologic
validation with different TBI models and at other research sites is crucial for translating this innovative
technology and these important results to the clinic. The overall goal of this application is to demonstrate the
feasibility, potential, and reproducibility of protein-based APT-MRI signals as functional markers for TBI using
animal models of mild, moderate, or severe TBI. We hypothesize that molecular imaging using APT-MRI can
sensitively and non-invasively visualize ischemic damage, inflammatory responses, and several other key
pathological processes in TBI, thus improving the capability of MRI to objectively assess TBI. Our three
specific aims are: (i) to assess APT-MRI spatio-temporal evolution characteristics of TBI and the underlying
pathological mechanisms in rat CCI models; (ii) to assess whether APT-MRI predicts therapeutic outcomes in
rat CCI models; and (iii) to validate the sensitivity and reliability of APT-MRI in assessing TBI at external sites.
Molecular imaging of TBI using APT-MRI opens up a new research area of APT imaging that could address
many unmet clinical needs. If our aims in this preclinical study are achieved, the results will provide the solid
foundation required to translate this important MRI technology to clinical studies in patients with TBI.

## Key facts

- **NIH application ID:** 10256740
- **Project number:** 5UH3NS106937-04
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** RAYMOND Charles KOEHLER
- **Activity code:** UH3 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $420,672
- **Award type:** 5
- **Project period:** 2018-04-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10256740

## Citation

> US National Institutes of Health, RePORTER application 10256740, Development of Novel Functional Markers for TBI Using Molecular MRI (5UH3NS106937-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10256740. Licensed CC0.

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