# Innovative Non-Invasive Imaging of Traumatic Brain Injury

> **NIH NIH R21** · UNIVERSITY OF FLORIDA · 2022 · $400,685

## Abstract

Project Summary
 Traumatic brain injury (TBI) occurs due to the transient application of mechanical force to the brain, which
causes damage to cellular membranes, axons, and brain vasculature. TBI affects millions of people in the US
each year, resulting in hundreds of thousands of hospitalizations, thousands of deaths, and significant disability
in survivors. In addition to acute injury, TBI leads to progressive pathophysiology, including focal bleeding and
transient opening of the blood brain barrier (BBB). Accurate and fast diagnosis of severity of TBI is necessary to
better prescribe treatments and reduce associated death, morbidity, and disability. However, diagnosis of TBI
often relies on patient history, subjective complaints, and neurophysiological status, and classifying severity
remains challenging. Computed tomography and magnetic resonance imaging are fast and accurate for injuries
requiring emergency surgery but are limited to chronic issues such as excessive brain bleeding and swelling.
Magnetic resonance imaging (MRI) can evaluate white matter micropathology of TBI in cohorts but fail to
evaluate TBI in individuals. Therefore, innovative non-invasive imaging technologies are necessary to
improve TBI diagnosis and accelerate research at the clinical and pre-clinical stage.
 This proposal will apply an innovative imaging modality called magnetic particle imaging (MPI) to monitor
vascular pathophysiology of TBI. MPI enables non-invasive, unambiguous, and quantitative imaging of the
biodistribution of biocompatible superparamagnetic iron oxide (SPION) tracers. Application of MPI to monitor
TBI consists of systemic administration of SPIONs that accumulate at sites of local BBB disruption, resulting in
a signal that is proportional to SPION MPI performance, rate of accumulation, and accumulation time. The PI
developed a new synthesis method resulting in SPIONs with enhanced MPI performance and preliminary results
demonstrate these SPIONs are superior to commercially available nanoparticles and possess long blood
circulation half-life. The PI hypothesizes that MPI using SPIONs optimized for sensitivity and blood circulation
time will be a powerful non-invasive complementary imaging tool to study TBI in pre-clinical rodent models. This
hypothesis will be tested through two specific aims. Studies in Aim 1 will determine SPION accumulation in a
controlled cortical impact (CCI) injury mouse model of TBI as a function of dose and time of administration and
will establish histological factors linked to MPI measures of SPION accumulation. Studies in Aim 2 will compare
MPI measures of SPION accumulation in the CCI injury mouse model against MRI measures of SPION
accumulation and other changes associated with TBI. Together, the proposed studies will test the potential of
MPI for non-invasive, sensitive, and quantitative evaluation of TBI in pre-clinical models by comparison to ground
truth and established non-invasive imaging modalities. The propo...

## Key facts

- **NIH application ID:** 10527640
- **Project number:** 1R21NS125089-01A1
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** Carlos M Rinaldi-Ramos
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $400,685
- **Award type:** 1
- **Project period:** 2022-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527640

## Citation

> US National Institutes of Health, RePORTER application 10527640, Innovative Non-Invasive Imaging of Traumatic Brain Injury (1R21NS125089-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10527640. Licensed CC0.

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