CP #8: Quantitative MRI and 1H-MRS in Traumatic Brain Injury
You are here
Home / CP #8: Quantitative MRI and 1H-MRS in Traumatic BrSignificance:
This project aims at elucidating the role of brain iron in mild traumatic brain injury (MTBI), also known as concussion, as a first step in developing new treatments. Traumatic brain injury (TBI) is a growing public health problem with annual U.S. incidence of 1.7 million, ~90% of cases being MTBI. In 2011, the journal Nature described MTBI an “epidemic of brain damage [and] a major challenge for scientists” [1]. Despite typically normal conventional imaging, patients may suffer a combination of physical, cognitive and behavioral deficits leading to an array of persistent symptoms termed Post-Concussive Syndrome (PCS) [2,3] with up to 22% of patients symptomatic 12 months after injury [4]. In addition, Chronic Traumatic Encephalopathy (CTE) is associated with multiple MTBI and is reported to occur even after a single concussive episode [5]. Our group has found measurable regional brain atrophy after a single concussion[6]. The effects on the brain are incompletely known and no good medical treatments or means of predicting outcome exist. It is thus vital to identify disease markers for early stratification of patients and development and monitoring of targeted therapy.
Advances in imaging, including work from our group, now reveal evidence of white matter injury after MTBI with one of most commonly implicated regions being the anterior corona radiata/cingulum [7-15]. Substantial evidence also exists that the thalamus is abnormal after MTBI with alterations in functional connectivity, perfusion and diffusion [12,16-22]. In the previous funding period, using Magnetic Field Correlation (MFC), we demonstrated abnormal thalamic iron levels after MTBI without co-existent evidence of hemorrhage [20] (see Figure 1). Though vital to neurons, excess iron is toxic via the production of free radicals. A growing body of work suggests that abnormal iron plays a significant role in secondary injury after TBI. Secondary injury cascades are increasingly felt to be important in the pathogenesis of persistent symptoms [20,23,24]. Identifying and quantifying such mechanisms will provide novel pathways for treatment which are currently lacking.
Aims:
The goal of this study is to observe frontal white matter and thalamic iron levels after MBTI in a longitudinal study to determine whether the iron abnormalities can predict further brain injury and dysfunction.
Approach:
A cohort of 90 MBTI patients and 45 matched controls will undergo MR imaging and neuropsychological testing soon after injury and again at 6 and 12 months. Iron levels will be assessed using MFC and R2* measurements. Structural imaging (T2-weighted fast spin-echo, high-resolution SWI and 3D T1-weighted MPRAGE) will be performed to assess changes in frontal white matter and thalamic volume. Diffusion kurtosis acquisitions will be used to assess microstructural changes and resting-state fMRI will assess functional connectivity. Clinical and neuropsychological assessments will be performed within 1 day of MR imaging.
Push-Pull Relationship with TR&D Projects 1 & 2:
TR&D#1: Dr. Lui and her team are currently working with BTRC staff to improve T2* mapping and modeling (e.g. to determine the key length scales involved), as well as to tailor diffusion acquisitions and modeling. Needs of this CP will push TR&D #1 toward developments in these areas. Use of the EMC-based T2 mapping approach described in TR&D #1 is now being explored to separate T2 and T2* components for this project. Ultimately, there will also be great value in combining the various anatomical, functional, and parametric mapping acquisitions called for in this project, which currently occupy at least an hour of scan time. Therefore, this CP will serve as a test bed for evaluation of our rapid comprehensive imaging paradigm in Specific Aim 3 of TR&D #1.
TR&D#2: Quantification of the effects of iron is expected to improve with increasing field strength. Work on this CP has begun at 3T because of the ready availability of 3T scanners for clinical studies, but the project is well suited for extension to 7T as a research and clinical platform. Indeed, the approved IRB protocol for the project includes 7T imaging, and preliminary data have already been gathered at 7T in boxers. T2* assessment using the plug and play parallel transmission technique described in TR&D #2 will be explored for this project, which will also benefit from tailored RF coils for improved SNR and spatial resolution.
- Weinberger S. Bombs' hidden impact: the brain war. Nature;477(7365):390-393.
- Veterans Administration Department of Defense Clinical Practice Guideline for Mangement of Concussion / Mild Traumatic Brain Injury. Volume 2011: Department of Veteran Affairs / Department of Defense; 2009.
- Robinson S, Barth M, Jovicich J. Fast, high resolution T2* mapping using 3D MGE and 3D EPI with 3D correction for macroscopic dephasing effects. Proc Intl Soc Mag Reson Med 2009;17:4525.
- Roe C, Sveen U, Alvsaker K, Bautz-Holter E. Post-concussion symptoms after mild traumatic brain injury: influence of demographic factors and injury severity in a 1-year cohort study. Disabil Rehabil 2009;31(15):1235-1243.
- Assaf Y, Cohen Y. Assignment of the water slow-diffusing component in the central nervous system using q-space diffusion MRS: implications for fiber tract imaging. Magn Reson Med 2000;43(2):191-199.
- Zhou Y, Kierans A, Kenul D, Ge Y, Rath J, Reaume J, Grossman RI, Lui YW. Longitudinal Regional Brain Volume Changes in Mild Traumatic Brain Injury Patients. Radiology 2013.
- Kiselev VG, Posse S. Analytical theory of susceptibility induced NMR signal dephasing in a cerebrovascular network. Phys Rev Lett 1998;81(25):5696-5699.
- Novikov DS, Kiselev VG. Transverse NMR relaxation in magnetically heterogeneous media. J Magn Reson 2008;195(1):33-39.
- Kraus MF, Susmaras T, Caughlin BP, Walker CJ, Sweeney JA, Little DM. White matter integrity and cognition in chronic traumatic brain injury: a diffusion tensor imaging study. Brain 2007;130(Pt 10):2508-2519.
- Potts MB, Koh SE, Whetstone WD, Walker BA, Yoneyama T, Claus CP, Manvelyan HM, Noble-Haeusslein LJ. Traumatic injury to the immature brain: inflammation, oxidative injury, and iron-mediated damage as potential therapeutic targets. NeuroRx : the journal of the American Society for Experimental NeuroTherapeutics 2006;3(2):143-153.
- Okanishi T, Saito Y, Fujii S, Maegaki Y, Fukuda C, Tomita Y, Ohno K. Low signal intensity and increased anisotropy on magnetic resonance imaging in the white matter lesion after head trauma: unrecognized findings of diffuse axonal injury. J Neurol Sci 2007;263(1-2):218-222.
- Bogner J, Corrigan JD. Reliability and predictive validity of the Ohio State University TBI identification method with prisoners. J Head Trauma Rehabil 2009;24(4):279-291.
- Mayer AR, Ling J, Mannell MV, Gasparovic C, Phillips JP, Doezema D, Reichard R, Yeo RA. A prospective diffusion tensor imaging study in mild traumatic brain injury. Neurology;74(8):643-650.
- Niogi SN, Mukherjee P, Ghajar J, Johnson C, Kolster RA, Sarkar R, Lee H, Meeker M, Zimmerman RD, Manley GT, McCandliss BD. Extent of microstructural white matter injury in postconcussive syndrome correlates with impaired cognitive reaction time: a 3T diffusion tensor imaging study of mild traumatic brain injury. AJNR Am J Neuroradiol 2008;29(5):967-973.
- Rutgers DR, Toulgoat F, Cazejust J, Fillard P, Lasjaunias P, Ducreux D. White matter abnormalities in mild traumatic brain injury: a diffusion tensor imaging study. AJNR Am J Neuroradiol 2008;29(3):514-519.
- Anderson CV, Wood DM, Bigler ED, Blatter DD. Lesion volume, injury severity, and thalamic integrity following head injury. J Neurotrauma 1996;13(1):35-40.
- Ge Y, Patel MB, Chen Q, Grossman EJ, Zhang K, Miles L, Babb JS, Reaume J, Grossman RI. Assessment of thalamic perfusion in patients with mild traumatic brain injury by true FISP arterial spin labelling MR imaging at 3T. Brain Inj 2009;23(7):666-674.
- Grossman EJ, Ge Y, Jensen JH, Babb JS, Miles L, Reaume J, Silver JM, Grossman RI, Inglese M. Thalamus and Cognitive Impairment in Mild Traumatic Brain Injury: A Diffusional Kurtosis Imaging Study. J Neurotrauma.
- Miles L, Grossman RI, Johnson G, Babb JS, Diller L, Inglese M. Short-term DTI predictors of cognitive dysfunction in mild traumatic brain injury. Brain Inj 2008;22(2):115-122.
- Raz E, Jensen JH, Ge Y, Babb JS, Miles L, Reaume J, Grossman RI, Inglese M. Brain Iron Quantification in Mild Traumatic Brain Injury: A Magnetic Field Correlation Study. AJNR Am J Neuroradiol 2011.
- 21. Tang L, Ge Y, Sodickson DK, Miles L, Zhou Y, Reaume J, Grossman RI. Thalamic resting-state functional networks: disruption in patients with mild traumatic brain injury. Radiology;260(3):831-840.
- Wood DM, Bigler ED. Diencephalic changes in traumatic brain injury: relationship to sensory perceptual function. Brain Res Bull 1995;38(6):545-549.
- Long DA, Ghosh K, Moore AN, Dixon CE, Dash PK. Deferoxamine improves spatial memory performance following experimental brain injury in rats. Brain Res 1996;717(1-2):109-117.
- Negri L, Lattanzi R, Tabacco F, Melchiorri P. Respiratory and cardiovascular effects of the mu-opioid receptor agonist [Lys7]dermorphin in awake rats. Br J Pharmacol 1998;124(2):345-355.
Latest Updates
Philanthropic Support
We gratefully acknowledge generous support for radiology research at NYU Langone Health from:
• The Big George Foundation
• Bernard and Irene Schwartz
© 2021 Center for Advanced Imaging Innovation and Research. All rights reserved. This content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Additional disclaimers.