Individual Markers Of Brain Inflammation in Acute Mild Traumatic Brain Injury: A Case Series

2382 

Abstract Submission 

Mayan Bedggood¹, Christi Essex¹, Samantha Holdsworth^2,3, Amabelle Voice-Powell¹, Richard Faull³, Alice Theadom¹, Mangor Pedersen¹

¹Auckland University of Technology, Auckland, New Zealand, ²Mātai Medical Research Institute, Gisborne, New Zealand, ³Centre for Brain Research, University of Auckland, Auckland, New Zealand

Mayan Bedggood  
Auckland University of Technology
Auckland, New Zealand

Christi Essex  
Auckland University of Technology
Auckland, New Zealand

Samantha Holdsworth, Associate Professor  
Mātai Medical Research Institute|Centre for Brain Research, University of Auckland
Gisborne, New Zealand|Auckland, New Zealand

Amabelle Voice-Powell  
Auckland University of Technology
Auckland, New Zealand

Richard Faull, Professor Sir  
Centre for Brain Research, University of Auckland
Auckland, New Zealand

Alice Theadom, Professor  
Auckland University of Technology
Auckland, New Zealand

Mangor Pedersen, Associate Professor  
Auckland University of Technology
Auckland, New Zealand

Magnetic resonance imaging (MRI)-based T2 relaxometry is a quantitative technique measuring transverse components of the magnetisation dephase during an MRI scan. Importantly, T2 relaxation time increases as tissue water content increases (Liu et al., 2018). This indication of elevated fluid can indicate things such as gliosis (the proliferation of glial cells in injured brain areas), and increased inflammation (Cheng et al., 2012). This novel method can assess microstructural tissue alterations, such as inflammation, accompanying neurological conditions, such as mild traumatic brain injury (mTBI) (Pedersen et al., 2020). In the current study we aim to (1) investigate the utility of this objective method in discovering potential indicators of inflammation in individuals with acute mTBI (compared to healthy control estimates), and (2) link the findings to what their clinical radiologist report indicates about their brain health.

This is a case series with two groups of male participants: those with acute sports-related mTBI sustained within 14 days, (mean age = 21.4 years, n = 20) and controls with no mTBI in the last 12 months (mean age = 22.4 years, n = 44). MR images were acquired using a 3T Siemens MAGNETOM Vida fit scanner located at the Centre for Advanced Magnetic Resonance Imaging at The University of Auckland. T2 maps were acquired using a multi-echo relaxometry sequence and with 8 echoes (TE = 29.0, 58.0, 87.0, 120.0, 140.0, 170.0, 200.0, 230.0 ms, TR = 6s, voxel size = 2x 2x 2mm, FA = 180°. T1-weighted anatomical images were collected for quality control and normalisation using a magnetization-prepared rapid gradient echo (MPRAGE) sequence (TR = 1.94s, TE = 2.49ms, voxel size = 0.9x 0.9x 0.9 mm, FA = 9°). Processing and analyses were conducted using Matlab version 9.13.0 (R2022b; MathWorks Inc., Natick, MA), including skullstripping, coregistering and normalising the images to MNI152 space. A monoexponential function with a baseline at each voxel was fitted to calculate the T2 relaxation time for each participant (Pedersen et al., 2020; Pell et al., 2004). Voxel-wise z-scores were obtained reflecting T2 relaxometry times between single mTBI participants and average T2 relaxometry times of all 44 controls, after applying a rank-based normalisation invariant algorithm. A False Discovery Rate at p < .05 was applied to derive statistically significant voxels for individual mTBI participants.

19/20 (95%) of mTBI participants had at least one voxel cluster with significantly higher T2 relaxometry times than controls (Figure 1). Although the majority of significant regions were unique to specific participants, we also observed areas common to several individuals, including the cingulate cortex, insula and superior parietal cortex (seen across ~1/3 of mTBI individuals, Figure 2). Furthermore, these potential pathologies were not aligned with the radiologist reports, that were all indicated to have either (a) no findings, or (b) incidental findings were not deemed to be clinically significant.

Increased T2 relaxometry in individuals with mTBI suggests the presence of acute inflammatory processes, despite no gross brain abnormalities on radiologist reports. As well as individual variation in T2 relaxometry times, there were significant voxel clusters that multiple participants had in common, including the cingulate cortex, insula, cerebellum and superior partietal cortex. This could indicate that certain regions are more susceptible to accumulated fluid content following mTBI. Understanding the role that inflammation plays acutely post-mTBI could have implications for individualised treatment and improved recovery outcome. T2 relaxometry provides individual, detailed maps of potential brain abnormalities and may offer new insights into a patient's injury. Future research would benefit from repeating all MRI scans to evaluate whether T2 relaxometry normalises at clinical recovery.

Anatomy and Functional Systems

Cortical Anatomy and Brain Mapping

Neuroanatomy Other

Imaging Methods Other ¹

Neurophysiology of Imaging Signals ²

MRI

Neurological

STRUCTURAL MRI

Structures

Trauma

Other - Neuroinflammation