Imaging mild Traumatic Brain Injury (mTBI)
Traumatic Brain Injury (TBI) is a complex disease caused by an impact to the head or body that alters normal brain function [Maas et al. 2017]. TBI is biphasic; the first phase involves the tissue damage from the initial injury to the head and the chronic second phase involves the damage from the biochemical and physiological changes including oxidative stress, disruption of blood brain barrier (BBB), inflammation and mitochondrial dysfunction [Roux et al. 2016, Khatri et al. 2018]. This secondary damage progresses through a patient’s life and causes serious long-term physical, emotional and cognitive disabilities [Maas et al. 2017]. TBI can also increase the risk of cognitive impairment and a variety of neurological disorders [Maas et al. 2017]. Furthermore, TBI can vary in severity, from mild to moderate to severe. Research has largely focused on severe TBI, yet 70-90% of incidents are mild TBI [Maas et al. 2017].
TBI is a significant cause of death and disability worldwide for all ages; 30-40% of all injury related deaths can be attributed to TBI [Maas et al. 2017]. There are more than 50 million TBI incidents worldwide annually and this costs the economy an estimated $400 billion [Maas et al. 2017]. Estimates indicate that half of the global population will experience a TBI in their lifetime [Maas et al. 2017]. Despite its widespread occurrence, there are currently no FDA approved neuroprotective treatments for TBI and no effective diagnosis approaches. Diagnosis is challenging in milder injuries due to the reliance on self-reported criteria in the clinic and lack of effect standardized tests that capture a patients physiological and neurochemical response [Stein et al. 2015]. This lack of advanced treatments and diagnosis is where biomarkers could have a large impact. Lipid biomarkers have the potential to determine TBI severity, track disease progression and aid in treatment decisions [Hogan et al. 2018].
There are various different techniques being used to study TBI including mass spectrometry (MS) and mass spectrometry imaging (MSI), magnetic resonance imaging, nuclear magnetic resonance spectroscopy, and raman spectroscopy. Amongst these techniques, MS stands out as optimal tool to study the metabolic changes associated with TBI because it is a label free method that is able to identify metabolites and determine how their abundance changes after TBI. Once their identity and biological role is uncovered, these metabolites could act as biomarkers and help with diagnosis and treatment of TBI. Moreover, the spatial data that MSI provides will help to localize metabolic changes to various anatomical structures in tissue samples, which helps to better understand the disease pathology and helps to determine the biological role of metabolites.
Figure 1. 11 Rat Brains Images (A) PC 32:0 (m/z 734.5689 +/- 2 ppm); localized to grey matter and (B) PC 36:1 (m/z 788.61738 +/- 2 ppm); localized to white matter. These images reveal anatomical brain structures such as the corpus callosum.
Hogan, S. R.; Phan, J. H.; Alvarado-Velez, M.; Wang, M. D.; Bellamkonda, R. V.; Fernandez, F. M.; LaPlaca, M. C., Discovery of Lipidome Alterations Following Traumatic Brain Injury via High-Resolution Metabolomics. J Proteome Res 2018, 17 (6), 2131-2143.
Khatri, N.; Thakur, M.; Pareek, V.; Kumar, S.; Sharma, S.; Datusalia, A. K., Oxidative Stress: Major Threat in Traumatic Brain Injury. CNS & Neurological Disorders – Drug Targets- CNS & Neurological Disorders) 2018, 17 (9), 689-695.
Maas, A. I. R., et al. Traumatic brain injury: integrated approaches to improve prevention, clinical care, and research. The Lancet Neurology 2017, 16 (12), 987-1048.
Roux, A.; Muller, L.; Jackson, S. N.; Post, J.; Baldwin, K.; Hoffer, B.; Balaban, C. D.; Barbacci, D.; Schultz, J. A.; Gouty, S.; Cox, B. M.; Woods, A. S., Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury. Journal of Neuroscience Methods 2016, 272, 19-32.
Stein, D. G.; Geddes, R. I.; Sribnick, E. A., Recent developments in clinical trials for the treatment of traumatic brain injury. Handb Clin Neurol 2015, 127, 433-51.