Multimodal Magnetic Resonance Imaging After Experimental Moderate and Severe Traumatic Brain Injury: a Longitudinal Correlative Assessment of Structural and Cerebral Blood Flow Changes

Juliana Sanchez-Molano, Meghan O. Blaya, Kyle R. Padgett, William J. Moreno, Weizhao Zhao, W. Dalton Dietrich, Helen M. Bramlett


Traumatic brain injury (TBI) is a worldwide problem that results in death or disability for millions of people every year. Progressive neurological complications and long-term impairment can significantly disrupt quality of life. We demonstrated the feasibility of multiple magnetic resonance imaging (MRI) modalities to investigate and predict aberrant changes and progressive atrophy of gray and white matter tissue at several acute and chronic time points after moderate and severe parasagittal fluid percussion TBI. T2-weighted imaging, diffusion tensor imaging (DTI), and perfusion weighted imaging (PWI) were performed. Adult Sprague-Dawley rats were imaged sequentially on days 3, 14, and 1, 4, 6, 8, and 12 months following surgery.


Traumatic brain injury (TBI) is a critical global health problem that results in death or disability for millions of people every year [1]. TBI is a causal factor in 34 percent of all injury-related deaths in the United States [2]. In addition, The Center for Disease Control and Prevention [3] reported that 2.8 million individuals sustain a TBI each year. Falls, motor vehicle collisions, sports-related injuries, abuse/assault, and blast-induced high-pressure waves are the primary causes of TBI [2].

Materials and method

Adult 3- to 4-month-old male Sprague Dawley rats (Rattus norvegicus; n = 26) were randomly assigned to 1 of 3 groups: uninjured sham (n = 10), moderate TBI (n = 8), or severe TBI (n = 8). Blocking randomization and standardization strategies were used to enhance scientific rigor and to control for variables that could potentially bias the results and ensure balanced numbers in each treatment group [48]. Females were not utilized in the present study as hormonal fluctuations associated with the female reproductive cycle may introduce biological variability. To standardize TBI models, monitoring and controlling for physiological and metabolic variables is important to reduce variability.


Vulnerable regions are affected in TBI, resulting in hallmark sequelae across patients. We investigated key ROIs susceptible to functional and structural damage after brain injury (Fig 1, top). After undergoing moderate or severe fluid-percussion TBI or sham surgery, animals were imaged longitudinally 7 consecutive times using described multiple MRI modalities.


In the current study, we evaluated how DTI and CBF PWI measurements evolved over time in a preclinical model of moderate and severe TBI, as well as the degree of chronic cerebral atrophy at 1 year after injury. Furthermore, we sought to establish whether there was a significant correlative relationship between MRI parameters and 12-month histopathology at various time points over the course of the study.


We would like to thank Ofelia Alonso-Furones for her surgical expertise and support.

Citation: Sanchez-Molano J, Blaya MO, Padgett KR, Moreno WJ, Zhao W, Dietrich WD, et al. (2023) Multimodal magnetic resonance imaging after experimental moderate and severe traumatic brain injury: A longitudinal correlative assessment of structural and cerebral blood flow changes. PLoS ONE 18(8): e0289786.

Editor: Firas H. Kobeissy, University of Florida, UNITED STATES

Received: May 4, 2023; Accepted: July 25, 2023; Published: August 7, 2023

This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

Data Availability: All relevant data are within the paper and its Supporting information files.

Funding: The present study was supported by Department of Defense grant DAMD-17-02-1-0190, NIH/NINDS5P50NS030291-20, and NIH/NINDSRF1NS125578 awarded to WDD. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing interests: The authors have declared that no competing interests exist.


Harvard Medical School - Leadership in Medicine Southeast Asia47th IHF World Hospital CongressHealthcare CNO Summit - USAHealthcare CMO Summit - USA