QSM for identification of microstructural pathology in sports-related mild Traumatic Brain Injury

2631 

Abstract Submission 

Christi Essex¹, Catherine Morgan², Samantha Holdsworth², Kieran O'Brien³, Mayan Bedggood¹, Amabelle Voice-Powell¹, Richard Faull², Alice Theadom¹, Mangor Pedersen¹

¹Auckland University of Technology, Auckland, New Zealand, ²The University of Auckland, Auckland, New Zealand, ³Siemens Healthineers, Brisbane, Australia

Christi Essex  
Auckland University of Technology
Auckland, New Zealand

Catherine Morgan, Doctor  
The University of Auckland
Auckland, New Zealand

Samantha Holdsworth, Associate Professor  
The University of Auckland
Auckland, New Zealand

Kieran O'Brien, Doctor  
Siemens Healthineers
Brisbane, Australia

Mayan Bedggood  
Auckland University of Technology
Auckland, New Zealand

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

Richard Faull, Professor Sir  
The 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

Brain iron accumulation is a putative biomarker of dementias and other neuropathological processes (Zecca et al., 2004). Despite evidence linking exposure to head trauma and risk factors for premature neuropathy (Daglas & Adlard, 2018), little is known about iron levels following sports-related mild Traumatic Brain Injury (sr-mTBI). Quantitative susceptibility mapping (QSM), an advanced MRI method, measures an intrinsic magnetic property of biomaterials (including iron, calcium, and myelin) (Wei et al., 2023) related to tissue composition. Recent advances in QSM image reconstruction have streamlined and simplified this process but require further validation. The aims of this study were to 1) investigate the presence of iron in subcortical grey matter as a marker of cellular pathology in acute sr-mTBI using QSM; and 2) assess the utility of developments in QSM processing for clinical research.

An observational, case-control study design was used to investigate differences in tissue magnetic susceptibility in basal ganglia sub-regions of 13 male contact sports players aged 16-35 years (M = 22.80, SD = 4.90) with acute sr-mTBI (< 14 days) and twelve age-matched male controls (M = 20.70, SD = 3.68). QSM was used to quantify iron deposition at high spatial resolution (1mm isotropic voxels) using data acquired on a Siemens MAGNETOM Vida Fit scanner (Siemens Healthcare, Erlangen, Germany) at 3 Tesla with a 3D Gradient Echo (GRE) sequence (TR = 30ms, TE = 20ms, FA= 15°, slice thickness = 1mm). Image processing with Morphology Enabled Dipole Inversion (MEDI) (Liu et al., 2012) was performed in-line on the scanner using a prototype sequence (Siemens Healthineers) which automates QSM image reconstruction. Images were skullstripped, coregistered and normalised to MNI152 standard space using FSL and fitted with the CIT168 mask (Pauli et al., 2018) to identify and partition the basal ganglia into 16 functionally and structurally distinct regions of interest (ROI). Maximum voxel-wise susceptibility values were extracted from each ROI with MATLAB version 9.13.0 (R2022b; MathWorks Inc., Natick, MA) and compared between groups using Bonferroni-adjusted Mann-Whitney U tests. Spearman's rho correlation coefficients were used to investigate the expected relationship between brain iron and age (Li et al., 2014).

No significant difference in magnetic susceptibility was observed in participants with sr-mTBI compared to controls for any ROI after post-hoc correction (p > 0.003). A trend for elevated susceptibility in the Globus Pallidus externus (GPe) of participants with sr-mTBI was noted (U = 38, p = 0.03) (see Figure 1). Susceptibility values were moderately, but not significantly, correlated with age for most basal nuclei (p > 0.003).

The lack of significant findings suggests this study was underpowered to detect changes in brain iron composition likely to be subtle at acute-stage mTBI. This is particularly salient given the association of iron deposition with age (Li et al., 2014) and exposure to repeated mTBI (Juan at al., 2023). However, the trend for increased GPe susceptibility in the sr-mTBI cohort hints at a possible role for iron accumulation shortly after injury. The Globus Pallidus is abnormally in iron and ferritin (Rouault, 2013), and appears particularly vulnerable to iron-mediated cellular pathology in neurodegenerative disease (Kruer et al., 2012). Prior research has evidenced increased iron in Pallidal nuclei at 6 (Lu et al., 2015) and 18 months (Raz et al., 2011) post-mTBI. Our observed MRI-based susceptibility values were consistent and comparable between groups and fell within expected range for the relative iron content of each ROI; suggesting our current imaging protocol may be used not only to research effects of sr-mTBI but other disorders of the central nervous system. Together, results indicate further research and increased study power is necessary to elucidate the underlying pathophysiological mechanisms of acute sr-mTBI.

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s)

Methods Development

Subcortical Structures

Anatomical MRI ²

Physiology, Metabolism and Neurotransmission Other ¹

Acquisition

Basal Ganglia

Cellular

MRI

Neurological

Neuron

STRUCTURAL MRI

Sub-Cortical

Other - Biomarker