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In Vivo Neurological Signatures of Chronic Traumatic Encephalopathy: An MRI study of QSM and MRS.

Poster No:

171

Submission Type:

Abstract Submission

Authors:

Pamela González Méndez¹^,2, Elías Alfaro Nasta¹^,2, Aline Xavier³, Marisleydis García-Saborit³^,4^,5, Carlos Juri Clavería¹, Juan Tichauer⁶, Carlos Milovic⁷, Marcelo Andía Kohnenkampf¹^,2^,5, Maximiliano Rovegno Echavarría¹^,6, Waldo Cerpa Nebott⁸

Institutions:

¹School of Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile, ²Millennium Institute for Intelligent Healthcare Engineering - iHEALTH, Santiago, Chile, ³Faculty of Engineering, Universidad de Santiago de Chile, Santiago, Chile, ⁴Department of Electrical Engineering, Pontificia Universidad Catolica de Chile, Santiago, Chile, ⁵Biomedical Imaging Center, Pontificia Universidad Catolica de Chile, Santiago, Chile, ⁶Department of Intensive Care Medicine, Pontificia Universidad Catolica de Chile, Santiago, Chile, ⁷School of Electrical Engineering, Pontificia Universidad Catolica de Valparaiso, Valparaiso, Chile, ⁸Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile, Santiago, Chile

First Author:

Pamela González Méndez
School of Medicine, Pontificia Universidad Catolica de Chile|Millennium Institute for Intelligent Healthcare Engineering - iHEALTH
Santiago, Chile|Santiago, Chile

Co-Author(s):

Elías Alfaro Nasta
School of Medicine, Pontificia Universidad Catolica de Chile|Millennium Institute for Intelligent Healthcare Engineering - iHEALTH
Santiago, Chile|Santiago, Chile

Aline Xavier
Faculty of Engineering, Universidad de Santiago de Chile
Santiago, Chile

Marisleydis García-Saborit
Faculty of Engineering, Universidad de Santiago de Chile|Department of Electrical Engineering, Pontificia Universidad Catolica de Chile|Biomedical Imaging Center, Pontificia Universidad Catolica de Chile
Santiago, Chile|Santiago, Chile|Santiago, Chile

Carlos Juri Clavería
School of Medicine, Pontificia Universidad Catolica de Chile
Santiago, Chile

Juan Tichauer
Department of Intensive Care Medicine, Pontificia Universidad Catolica de Chile
Santiago, Chile

Carlos Milovic
School of Electrical Engineering, Pontificia Universidad Catolica de Valparaiso
Valparaiso, Chile

Marcelo Andía Kohnenkampf
School of Medicine, Pontificia Universidad Catolica de Chile|Millennium Institute for Intelligent Healthcare Engineering - iHEALTH|Biomedical Imaging Center, Pontificia Universidad Catolica de Chile
Santiago, Chile|Santiago, Chile|Santiago, Chile

Maximiliano Rovegno Echavarría
School of Medicine, Pontificia Universidad Catolica de Chile|Department of Intensive Care Medicine, Pontificia Universidad Catolica de Chile
Santiago, Chile|Santiago, Chile

Waldo Cerpa Nebott
Faculty of Biological Sciences, Pontificia Universidad Catolica de Chile
Santiago, Chile

E-Poster

Introduction:

Chronic Traumatic Encephalopathy (CTE) is a neurodegenerative condition associated with repeated brain trauma, often seen in former players of contact sports including soccer. It presents a range of symptoms, such as cognitive impairments and behavioral changes. The diagnosing of CTE is challenging due to the absence of definitive in vivo biomarkers, relying on postmortem confirmation (McKee A.C., Acta Neuropathol. 2023). This limitation has hindered the comprehension of CTE's progression and the development of proactive intervention strategies.
Advanced Magnetic Resonance Imaging (MRI) techniques, such as Quantitative Susceptibility Mapping (QSM) and Magnetic Resonance Spectroscopy (MRS) have the potential to address this challenge. QSM is used to quantify iron deposition in the brain, which may indicate oxidative stress, a crucial element in neurodegenerative diseases (Ward R.J., Lancet Neurol. 2014). MRS assesses metabolic alterations, offering insights into cellular pathophysiology, particularly in the diffuse brain injury common in CTE.
We aim to enhance our understanding of CTE's in vivo pathology and contribute to the development of non-invasive diagnostic approaches. This research carries significant implications for early detection and management of CTE in populations at high risk.

Methods:

Using a cross-sectional design, we analyzed 10 former professional soccer players under 65 yrs, retired for +8 yrs, with a history of repeated head trauma. We reconstructed QSM and R2* maps from a 3D Gradient Recalled Echo sequence. QSM pipeline: ROMEO (Dymerska B., Magn Res Med. 2021) unwrapping, PDF background field removal (Liu T., NMR Biomed. 2011), and FANSI dipole inversion (Milovic C., Magn Res Med. 2018). Both, QSM and R2* are used to confirm iron deposition (Yan F., JMRI 2018). For registration and segmentation, we used SPM 12 (WCHN, UCL) and FSL (FMRIB, Oxford), respectively. Single Voxel Spectroscopy (PRESS, TE = 35 ms, voxel size 3x3x3 cm) was acquired at the posterior cingulate gyrus (PCG) and used for metabolite quantification using LCModel (Provencher). We also included the Up and Go motor test and the telephonic Montreal Cognitive Assessment (MOCA). We examined QSM maps in 15 subcortical areas and metabolite concentrations at the PCG, a region key for cognition and part of the default mode network (Leech and Sharp, BRAIN 2014). We used Spearman's correlations to associate MRI findings with cognitive and motor function, and descriptive statistics to identify patterns. Using data from QSM and MRS, we performed a dimensionality reduction analysis with the Robust-PCA methodology through the rpca library of the R statistical package (RStudio 2023) and analyzed the data separated into two groups (high and low risk by position on the playing field). Funding: ANID-ICN2021_004.

Results:

We found a correlation between higher QSM values at the left pallidum and reduced cognitive function (Spearman's r = -0.67). Also, a positive correlation between QSM and R2* values (Spearman's r = 0.78) was observed. We described a metabolic pattern; particularly, low NAA+NAAG was linked to poor motor performance (Spearman's r = -0.75). Notably, the data are distributed into 2 clusters, the first of them only with high-risk individuals, and the second with a predominance of lower-risk individuals. High risk: central defense. (Fig.1-2)

·Figure 1. In vivo MRI in Former Soccer Players. a. Tissue susceptibility (QSM), ≥0.2 ppm high QSM values. b. QSM vs R2*(all regions). c. MRS, metabolites concentration /tCr (NAA, NAA+NAAG <1.5). n=10.

·Figure 2. a. NAA+NAAG vs Up and Go (<10s normal). b. QSM vs MOCA (≤ 10 mild cognitive impairment). n=10. c. Corr. only central defenders. d. High risk: position on the playing field: central defense.

Conclusions:

We explored CTE signatures in vivo using MRI. QSM values at the left pallidum were higher than the ones found in control brains and similar to those seen in Parkinson's disease (Shahmaei V., Eur. J. Radiol. 2019). Lower NAA/tCr and NAA+NAAG/tCr at the PCG suggested neuronal damage compared with healthy subjects (Wijtenburg S.A., NMR Biomed. 2019). We found signatures correlated with motor and cognitive changes. The R-PCA analysis suggests that our in-vivo methodology would be able to differentiate high and lower-risk groups. Our study aims to advance a better understanding of CTE and the development of early detection methods.

Disorders of the Nervous System:

Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) ¹

Novel Imaging Acquisition Methods:

MR Spectroscopy

Imaging Methods Other ²

Keywords:

Degenerative Disease

Magnetic Resonance Spectroscopy (MRS)

MRI

Trauma

Other - Quantitative Susceptibility Mapping, Chronic Traumatic Encephalopathy, Soccer, Football

^1|2Indicates the priority used for review

Provide references using author date format

Dymerska B. (2021), 'Phase unwrapping with a rapid opensource minimum spanning tree algorithm (ROMEO) '. Magnetic Resonance in Medicine. Apr;85(4):2294–308.

Leech R. and Sharp D.J. (2014), 'The role of the posterior cingulate cortex in cognition and disease'. Brain. Jan;137(Pt 1):12–32.

Liu T. (2011), 'A novel background field removal method for MRI using projection onto dipole fields (PDF)'. NMR in Biomedicine. Nov;24(9):1129–36.

McKee A.C. (2023), 'Chronic traumatic encephalopathy (CTE): criteria for neuropathological diagnosis and relationship to repetitive head impacts', Acta Neuropathology. Apr;145(4):371–94.

Milovic C. (2018), 'Fast nonlinear susceptibility inversion with variational regularization'. Magnetic Resonance in Medicine. Aug;80(2):814–21.

Shahmaei V. (2019), 'Evaluation of iron deposition in brain basal ganglia of patients with Parkinson’s disease using quantitative susceptibility mapping'. European Journal of Radiology Open. 6:169–74.

Ward R.J. (2014), 'The role of iron in brain ageing and neurodegenerative disorders'. Lancet Neurology. Oct;13(10):1045–60.

Wijtenburg S.A. (2019), 'Reproducibility of brain MRS in older healthy adults at 7T'. NMR in Biomedicine. Feb;32(2):e4040.

Yan F. (2018), 'Iron deposition quantification: Applications in the brain and liver'. Journal of Magnetic Resonance Imaging. Aug;48(2):301–17.