Virtual Biopsy: Distinguishing Post-traumatic Stress from Mild Traumatic Brain Injury Using Magnetic Resonance Spectroscopy

Post-Traumatic Stress Disorder (PTSD) and mild Traumatic Brain Injury (mTBI) affect soldiers returning from recent conflicts at an elevated rate. Our study focuses on the use of magnetic resonance spectroscopy (MRS) measurements to distinguish subjects having mTBI, PTSD, or both, with the goal of identifying biomarkers for of these specific disorders from the MRS data. MRS provides a non-invasive in vivo technique for measuring the concentration of metabolites in the brain, thus serving as a “virtual biopsy” that can be used to monitor a range of neurological diseases. The traditional method for analyzing MRS data assumes that the signal arises from a known set of metabolites and finds the best fit to a collection of pre-defined basis functions representing this set. Our novel approach makes no assumptions about the underlying metabolite population, and instead extracts a rich set of wavelet-based features from the entire MRS signal. Capturing the structure of all significant peaks in the signal allows for the discovery of previously unknown signatures related to disease state. We applied this approach to MRS data from 100 participants across five categories: civilian control subjects, military control subjects, military with PTSD, military with mTBI, and military with both PTSD and mTBI. After signal processing to remove artifacts, features were extracted from each signal using a wavelet decomposition approach, and MRS features from subjects with PTSD, mTBI, or both, were compared to both military and civilian control subjects. Our analysis identified significant changes in many different regions of the MR spectrum, including regions corresponding to glutamate, glutamine, GABA, Creatine, and Lactate. Classifiers based on these features exhibit correct classification rates of 80% or better in cross-validation, demonstrating the value of MRS as a non-invasive means of measuring biochemical signatures associated with PTSD and mTBI in military service men and women.

[1]  N. Osório,et al.  Glutathione in multiple sclerosis , 2013, British journal of biomedical science.

[2]  B J Soher,et al.  Quantitation of proton NMR spectra of the human brain using tissue water as an internal concentration reference , 1993, NMR in biomedicine.

[3]  Yvonne Tran,et al.  Neuro magnetic resonance spectroscopy using wavelet decomposition and statistical testing identifies biochemical changes in people with spinal cord injury and pain , 2010, NeuroImage.

[4]  S. Bouix,et al.  Neuroimaging in repetitive brain trauma , 2014, Alzheimer's Research & Therapy.

[5]  J. Harp,et al.  The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans. , 2015, Journal of neurotrauma.

[6]  L. Shutter,et al.  Proton MRS in acute traumatic brain injury: role for glutamate/glutamine and choline for outcome prediction. , 2004, Journal of neurotrauma.

[7]  R. Kreis Issues of spectral quality in clinical 1H‐magnetic resonance spectroscopy and a gallery of artifacts , 2004, NMR in biomedicine.

[8]  N. Fayed,et al.  Conversion from mild cognitive impairment to probable Alzheimer's disease predicted by brain magnetic resonance spectroscopy. , 2005, The American journal of psychiatry.

[9]  D. Leibfritz,et al.  Regulation of intracellular pH in neuronal and glial tumour cells, studied by multinuclear NMR spectroscopy , 1994, NMR in biomedicine.

[10]  Isabelle Guyon,et al.  An Introduction to Variable and Feature Selection , 2003, J. Mach. Learn. Res..

[11]  Daubechies,et al.  Ten Lectures on Wavelets Volume 921 , 1992 .

[12]  S. Provencher Estimation of metabolite concentrations from localized in vivo proton NMR spectra , 1993, Magnetic resonance in medicine.

[13]  Robin A. de Graaf,et al.  In Vivo NMR Spectroscopy , 2019 .

[14]  D. van Ormondt,et al.  SVD-based quantification of magnetic resonance signals , 1992 .

[15]  Michael R Galarneau,et al.  Traumatic brain injury during Operation Iraqi Freedom: findings from the United States Navy-Marine Corps Combat Trauma Registry. , 2008, Journal of neurosurgery.

[16]  B. Ross,et al.  Changes in the neurochemistry of athletes with repetitive brain trauma: preliminary results using localized correlated spectroscopy , 2015, Alzheimer's Research & Therapy.

[17]  M. Robson,et al.  Receive array magnetic resonance spectroscopy: Whitened singular value decomposition (WSVD) gives optimal Bayesian solution , 2010, Magnetic resonance in medicine.

[18]  Peter Jezzard,et al.  Frequency and phase drift correction of magnetic resonance spectroscopy data by spectral registration in the time domain , 2015, Magnetic resonance in medicine.

[19]  M. Wyss,et al.  Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: the 'phosphocreatine circuit' for cellular energy homeostasis. , 1992, The Biochemical journal.

[20]  S. Williams,et al.  Glutathione in the human brain: Review of its roles and measurement by magnetic resonance spectroscopy. , 2017, Analytical biochemistry.

[21]  F. Jiru Introduction to post-processing techniques. , 2008, European journal of radiology.

[22]  Y. Lui,et al.  Myoinositol and glutamate complex neurometabolite abnormality after mild traumatic brain injury , 2014, Neurology.