# Quantitative Sodium MR Imaging and Proton MR Spectroscopy in Traumatic Brain Injury

> **NIH NIH R01** · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · 2020 · $588,531

## Abstract

Project Summary
Traumatic brain injury (TBI) is the world's leading cause of neurological disability in the young adult and
middle-aged population. The role of computed tomography (CT) and magnetic resonance imaging (MRI) in
patient management is limited due to the widespread presence of clinically-relevant, but imaging-occult injury.
We propose new metrics of TBI damage obtained from sodium (23Na) MRI and proton MR
spectroscopy (1H MRS). The central hypothesis is that conjoint 23Na MRI/1H MRS will provide
metabolic imaging markers for loss of ion homeostasis and neurodegeneration, which will predict
patients’ long-term clinical outcome. Sodium MRI is a non-invasive modality based on the direct detection
of Na+ ions using dedicated MRI software and hardware. It can assess loss of Na+ homeostasis, which can be
disturbed by processes where ionic imbalance is the driving force behind the cascade of cell damage. The
Na+/K+ exchange pump can be affected by energy deficits due to mitochondrial dysfunction, as well as by
diffuse axonal injury, the histopathological signature of TBI. This would result in variations of the intracellular
sodium concentration (C1), while inflammation, gliosis and cell loss would be reflected in variations of the
extracellular volume fraction (alpha2). We propose to combine the 23Na metrics C1 and alpha2 with 1H
MRS, from which quantification of N-acetylaspartate (NAA), creatine (Cr), choline (Cho) and myo-inositol (mI)
can be used to infer neuronal health/density (NAA), cellular energy/density (Cr), membrane turnover (Cho) and
astrocytic activation (mI). Specific aims are: AIM 1: Methodology. (1.a) To optimize ultrashort echo-time 23Na
MRI with and without fluid suppression at 3 T. To optimize image reconstruction with denoising and
compressed sensing to increase signal-to-noise ratio, resolution and speed of acquisition. To develop C1 and
alpha2 quantification based on 23Na spin dynamics simulation and reference phantoms. (1.b) To implement
whole-brain 1H MRS acquisition with 4th order shimming. AIM 2: Clinical application. (2.a) To compare C1
and alpha2 in TBI patients and controls at baseline (≤10 days after TBI) and their rates of change over time (2-
month and 1-year follow-ups for TBI, 1-year follow-up for controls), adjusted for MRI (FLAIR, SWI, DTI) and 1H
MRS. (2.b) To correlate the baseline values of the MR metrics, and their rates of change over time, with clinical
outcome at the two follow-ups. To assess the added value of C1 and alpha2 to MRI and 1H MRS. AIM 3:
Mechanistic model. (3.a) Given the interdependence between ATP and both NAA and C1, to determine
whether TBI-related changes in C1 are glial or neuronal. (3.b) To test whether, based on a mechanistic model
of neurodegeneration: (i) baseline 23Na MRI and 1H MRS findings will be moderated by injury severity; (ii)
longitudinal 23Na MRI and 1H MRS changes consistent with neurodegeneration will correlate with worse
clinical outcome at the two follow-ups. (3.c...

## Key facts

- **NIH application ID:** 9921497
- **Project number:** 5R01NS097494-05
- **Recipient organization:** NEW YORK UNIVERSITY SCHOOL OF MEDICINE
- **Principal Investigator:** Ivan Ivanov Kirov
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $588,531
- **Award type:** 5
- **Project period:** 2016-07-15 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9921497

## Citation

> US National Institutes of Health, RePORTER application 9921497, Quantitative Sodium MR Imaging and Proton MR Spectroscopy in Traumatic Brain Injury (5R01NS097494-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9921497. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*