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Published Online: 5 April 2019

Longitudinal Metabolite Changes after Traumatic Brain Injury: A Prospective Pediatric Magnetic Resonance Spectroscopic Imaging Study

Publication: Journal of Neurotrauma
Volume 36, Issue Number 8

Abstract

The aims of this study were to evaluate longitudinal metabolite changes in traumatic brain injury (TBI) subjects and determine whether early magnetic resonance spectroscopic imaging (MRSI) changes in discrete brain regions predict 1-year neuropsychological outcomes. Three-dimensional (3D) proton MRSI was performed in pediatric subjects with complicated mild (cMild), moderate, and severe injury, acutely (6–17 days) and 1-year post-injury along with neurological and cognitive testing. Longitudinal analysis found that in the cMild/Moderate group, all MRSI ratios from 12 regions returned to control levels at 1 year. In the severe group, only cortical gray matter regions fully recovered to control levels whereas N-acetylaspartate (NAA) ratios from the hemispheric white matter and subcortical regions remained statistically different from controls. A factor analysis reduced the data to two loading factors that significantly differentiated between TBI groups; one included acute regional NAA variables and another consisted of clinically observed variables (e.g., days in coma). Using scores calculated from the two loading factors in a logistic regression model, we found that the percent accuracy for classification of TBI groups was greatest for the dichotomized attention measure (93%), followed by Full Scale Intelligence Quotient at 91%, and the combined memory Z-score measure (90%). Using the acute basal ganglia NAA/creatine (Cr) ratio alone achieved a higher percent accuracy of 94.7% for the attention measure whereas the acute thalamic NAA/Cr ratio alone achieved a higher percent accuracy of 91.9% for the memory measure. These results support the conclusions that reduced NAA is an early indicator of tissue injury and that measurements from subcortical brain regions are more predictive of long-term cognitive outcome.

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References

1. Farkas O., and Povlishock J.T. (2007). Cellular and subcellular change evoked by diffuse traumatic brain injury: a complex web of change extending far beyond focal damage. Prog. Brain Res. 161, 43–59.
2. Dennis E.L., Babikian T., Giza C.C., Thompson P.M., and Asarnow R.F. (2018). Neuroimaging of the injured pediatric brain: methods and new lessons. Neuroscientist Feb 1. [Epub ahead of print].
3. Astrakas LG, Argyropoulou MI. (2016). Key concepts in MR spectroscopy and practical approaches to gaining biochemical information in children. Pediatr. Radiol. 46, 941–951.
4. Croall I., Smith F.E., and Blamire A.M. (2015). Magnetic resonance spectroscopy for traumatic brain injury. Top. Magn. Reson. Imaging 24, 267–274.
5. Chang L, Munsaka SM, Kraft-Terry S, and Ernst T. (2013). Magnetic resonance spectroscopy to assess neuroinflammation and neuropathic pain. J. Neuroimmune Pharmacol. 8, 576–593.
6. Ariza M., Junque C., Mataro M., Poca M.A., Bargallo N., Olondo M., and Sahuquillo J. (2004). Neuropsychological correlates of basal ganglia and medial temporal lobe NAA/Cho reductions in traumatic brain injury. Arch. Neurol. 61, 541–544.
7. Brooks W.M., Stidley C.A., Petropoulos H., Jung R.E., Weers D.C., Friedman S.D., Barlow M.A., Sibbitt W.L. Jr., and Yeo R.A. (2000). Metabolic and cognitive response to human traumatic brain injury: a quantitative proton magnetic resonance study. J. Neurotrauma 17, 629–640.
8. Friedman S.D., Brooks W.M., Jung R.E., Hart B.L., and Yeo R.A. (1998). Proton MR spectroscopic findings correspond to neuropsychological function in traumatic brain injury. AJNR Am. J. Neuroradiol. 19, 1879–1885.
9. Shutter L., Tong K.A., Lee A., and Holshouser B.A. (2006). Prognostic role of proton magnetic resonance spectroscopy in acute traumatic brain injury. J. Head Trauma Rehabil. 21, 334–349.
10. Sivak S., Bittsansky M., Grossmann J., Nosal V., Kantorova E., Sivakova J., Demkova A., Hnilicova P., Dobrota D., and Kurca E. (2014). Clinical correlations of proton magnetic resonance spectroscopy findings in acute phase after mild traumatic brain injury. Brain Inj. 28, 341–346.
11. Ashwal S., Holshouser B.A., Shu S.K., Simmons P.L., Perkin R.M., Tomasi L.G., Knierim D.S., Sheridan C., Craig K., Andrews G.H., and Hinshaw D.B. (2000). Predictive value of proton magnetic resonance spectroscopy in pediatric closed head injury. Pediatr. Neurol. 23, 114–125.
12. Holshouser B.A., Ashwal S., Shu S., and Hinshaw D.B. Jr. (2000). Proton MR spectroscopy in children with acute brain injury: comparison of short and long echo time acquisitions. J. Magn. Reson. Imaging 11, 9–19.
13. Brenner T., Freier M.C., Holshouser B.A., Burley T., and Ashwal S. (2003). Predicting neuropsychologic outcome after traumatic brain injury in children. Pediatr. Neurol. 28, 104–114.
14. Gasparovic C., Yeo R., Mannell M., Ling J., Elgie R., Phillips J., Doezema D., and Mayer A.R. (2009). Neurometabolite concentrations in gray and white matter in mild traumatic brain injury: an 1H-magnetic resonance spectroscopy study. J. Neurotrauma 26, 1635–1643.
15. Yeo R.A., Phillips J.P., Jung R.E., Brown A.J., Campbell R.C., and Brooks W.M. (2006). Magnetic resonance spectroscopy detects brain injury and predicts cognitive functioning in children with brain injuries. J. Neurotrauma 23, 1427–1435.
16. Holshouser B.A., Tong K.A., and Ashwal S. (2005). Proton MR spectroscopic imaging depicts diffuse axonal injury in children with traumatic brain injury. AJNR Am. J. Neuroradiol. 26, 1276–1285.
17. Babikian T., Freier M.C., Tong K.A., Nickerson J.P., Wall C.J., Holshouser B.A., Burley T., Riggs M.L., and Ashwal S. (2005). Susceptibility weighted imaging: neuropsychologic outcome and pediatric head injury. Pediatr. Neurol. 33, 184–194.
18. Babikian T., Alger J.R., Ellis-Blied M.U., Giza C.C., Dennis E., Olsen A., Mink R., Babbitt C., Johnson J., Thompson P.M., and Asarnow R.F. (2018). Whole brain magnetic resonance spectroscopic determinants of functional outcomes in pediatric moderate/severe traumatic brain injury. J. Neurotrauma 35, 1637–1645.
19. Govind V., Gold S., Kaliannan K., Saigal G., Falcone S., Arheart K.L., Harris L., Jagid J., and Maudsley A.A. (2010). Whole-brain proton MR spectroscopic imaging of mild-to-moderate traumatic brain injury and correlation with neuropsychological deficits. J. Neurotrauma 27, 483–496.
20. Maudsley A.A., Domenig C., Govind V., Darkazanli A., Studholme C., Arheart K., and Bloomer C. (2009). Mapping of brain metabolite distributions by volumetric proton MR spectroscopic imaging (MRSI). Magn. Reson. Med. 61, 548–559.
21. Malec J.F., Brown A.W., Leibson C.L., Flaada J.T., Mandrekar J.N., Diehl N.N., and Perkins P.K. (2007). The Mayo Classification System for traumatic brain injury severity. J. Neurotrauma 24, 1417–1424.
22. Ghosh N., Holshouser B., Oyoyo U., Barnes S., Tong K., and Ashwal S. (2017). Combined diffusion tensor and magnetic resonance spectroscopic imaging methodology for automated regional brain analysis: application in a normal pediatric population. Dev. Neurosci. 39, 413–429.
23. Mohamed M.A., Lentz M.R., Lee V., Halpern E.F., Sacktor N., Selnes O., Barker P.B., and Pomper MG. (2010). Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia. Radiology 254, 577–586.
24. Dennis E.L., Babikian T., Alger J., Rashid F., Villalon-Reina J.E., Jin Y., Olsen A., Mink R., Babbitt C., Johnson J., Giza C.C., Thompson P.M., and Asarnow R.F. (2018). Magnetic resonance spectroscopy of fiber tracts in children with traumatic brain injury: a combined MRS-diffusion MRI study. Hum. Brain Mapp. May 10. [Epub ahead of print]
25. Robertson C.L., Scafidi S., McKenna M.C., and Fiskum G. (2009). Mitochondrial mechanisms of cell death and neuroprotection in pediatric ischemic and traumatic brain injury. Exp. Neurol. 218, 371–380.
26. Marmarou A., Signoretti S., Fatouros P., Aygok G.A.,. and Bullock R. (2005). Mitochondrial injury measured by proton magnetic resonance spectroscopy in severe head trauma patients. Acta Neurochir. Suppl. 95, 149–151.
27. Signoretti S., Vagnozzi R., Tavazzi B., and Lazzarino G. (2010). Biochemical and neurochemical sequelae following mild traumatic brain injury: summary of experimental data and clinical implications. Neurosurg. Focus 29, E1.
28. Bigler E.D., and Maxwell W.L. (2011). Neuroimaging and neuropathology of TBI. NeuroRehabilitation 28, 63–74.
29. Wu T.C., Wilde E.A., Bigler E.D., Li X., Merkley T.L., Yallampalli R., McCauley S.R., Schnelle K.P., Vasquez A.C., Chu Z., Hanten G., Hunter J.V., and Levin H.S. (2010). Longitudinal changes in the corpus callosum following pediatric traumatic brain injury. Dev. Neurosci. 32, 361–373.
30. Ommaya A.K., and Gennarelli TA. (1974). Cerebral concussion and traumatic unconsciousness. Correlation of experimental and clinical observations of blunt head injuries. Brain 97, 633–654.
31. Adams J.H., Doyle D., Ford I., Gennarelli T.A., Graham D.I., and McLellan D.R. (1989). Diffuse axonal injury in head injury: definition, diagnosis and grading. Histopathology 15, 49–59.
32. Grados M.A., Slomine B.S., Gerring J.P., Vasa R., Bryan N., and Denckla M.B. (2001). Depth of lesion model in children and adolescents with moderate to severe traumatic brain injury: use of SPGR MRI to predict severity and outcome. J. Neurol. Neurosurg. Psychiatry 70, 350–358.
33. Babikian T., and Asarnow R. (2009). Neurocognitive outcomes and recovery after pediatric TBI: meta-analytic review of the literature. Neuropsychology 23, 283–296.
34. Catroppa C., Anderson V.A., Morse S.A., Haritou F., and Rosenfeld J.V. (2007). Children's attentional skills 5 years post-TBI. J. Pediatr. Psychol. 32, 354–369.
35. Fay G.C., Jaffe K.M., Polissar N.L., Liao S., Rivara J.B., and Martin K.M. (1994). Outcome of pediatric traumatic brain injury at three years: a cohort study. Arch. Phys. Med. Rehabil. 75, 733–741.
36. Beck L.H., Bransome E.D. Jr., Mirsky A.F., Rosvold H.E., and Sarason I. (1956). A continuous performance test of brain damage. J. Consult. Psychol. 20, 343–350.
37. Penfield W., and Jasper H.H. (1954). Epilepsy and the Functional Anatomy of the Human Brain. Little, Brown: Oxford, UK.
38. Van der Werf Y.D., Jolles J., Witter M.P., and Uylings H.B. (2003). Contributions of thalamic nuclei to declarative memory functioning. Cortex 39, 1047–1062.
39. Hall E.D., Sullivan P.G., Gibson T.R., Pavel K.M., Thompson B.M., and Scheff S.W. (2005). Spatial and temporal characteristics of neurodegeneration after controlled cortical impact in mice: more than a focal brain injury. J. Neurotrauma 22, 252–265.
40. Sherman S.M., and Guillery R. W. (2000). Exploring the Thalamus. Academic: New York.
41. Fearing M.A., Bigler E.D., Wilde E.A., Johnson J.L., Hunter J.V., Xiaoqi L., Hanten G., and Levin H.S. (2008). Morphometric MRI findings in the thalamus and brainstem in children after moderate to severe traumatic brain injury. J. Child Neurol. 23, 729–737.
42. Lutkenhoff E.S., McArthur D.L., Hua X., Thompson P.M., Vespa P.M., and Monti M.M. (2013). Thalamic atrophy in antero-medial and dorsal nuclei correlates with six-month outcome after severe brain injury. Neuroimage Clin. 3, 396–404.
43. Lifshitz J., Kelley B.J., and Povlishock J.T. (2007). Perisomatic thalamic axotomy after diffuse traumatic brain injury is associated with atrophy rather than cell death. J. Neuropathol. Exp. Neurol. 66, 218–229.
44. Gooijers J., Chalavi S., Beeckmans K., Michiels K., Lafosse C., Sunaert S., and Swinnen S.P. (2016). Subcortical volume loss in the thalamus, putamen, and pallidum, induced by traumatic brain injury, is associated with motor performance deficits. Neurorehabil. Neural Repair 30, 603–614.
45. De Simoni S., Grover P.J., Jenkins P.O., Honeyfield L., Quest R.A., Ross E., Scott G., Wilson M.H., Majewska P., Waldman A.D., Patel M.C., and Sharp D.J. (2016). Disconnection between the default mode network and medial temporal lobes in post-traumatic amnesia. Brain 139, Pt. 12, 3137–3150.
46. Giacino J.T., Fins J.J., Laureys S., and Schiff N.D. (2014). Disorders of consciousness after acquired brain injury: the state of the science. Nat. Rev. Neurol. 10, 99–114.
47. Scheibel R.S. (2017). Functional magnetic resonance imaging of cognitive control following traumatic brain injury. Front. Neurol. 8, 352.
48. Gratton C., Sun H., and Petersen S.E. (2017). Control networks and hubs. Psychophysiology 55. Epub 2017 Nov 28.
49. Posner M.I., Rothbart M.K., and Voelker P. (2016). Developing brain networks of attention. Curr. Opin. Pediatr. 28, 720–724.
50. Mohan A., Roberto A.J., Mohan A., Lorenzo A., Jones K., Carney M.J., Liogier-Weyback L., Hwang S., and Lapidus K.A. (2016). The Significance of the default mode network (DMN) in neurological and neuropsychiatric disorders: a review. Yale J. Biol. Med. 89, 49–57.
51. Ross B.D., Ernst T., Kreis R., Haseler L.J., Bayer S., Danielsen E., Bluml S., Shonk T., Mandigo J.C., Caton W., Clark C., Jensen S.W., Lehman N.L., Arcinue E., Pudenz R., and Shelden C.H. (1998). 1H MRS in acute traumatic brain injury. J. Magn. Reson. Imaging 8, 829–840.
52. Maudsley A.A., Govind V., Saigal G., Gold S.G., Harris L., and Sheriff S. (2017). Longitudinal MR spectroscopy shows altered metabolism in traumatic brain injury. J. Neuroimaging 27, 562–569.

Information & Authors

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Published In

cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 36Issue Number 8April 15, 2019
Pages: 1352 - 1360
PubMed: 30351247

History

Published in print: April 15, 2019
Published online: 5 April 2019
Published ahead of print: 20 December 2018
Published ahead of production: 23 October 2018

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Authors

Affiliations

Barbara Holshouser [email protected]
Department of Radiology, Loma Linda University School of Medicine, Loma Linda, California.
Jamie Pivonka-Jones
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Joy G. Nichols
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Udo Oyoyo
Department of Radiology, Loma Linda University School of Medicine, Loma Linda, California.
Karen Tong
Department of Radiology, Loma Linda University School of Medicine, Loma Linda, California.
Nirmalya Ghosh
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.
Stephen Ashwal
Department of Pediatrics, Loma Linda University School of Medicine, Loma Linda, California.

Notes

Address correspondence to: Barbara Holshouser, PhD, Department of Radiology, Loma Linda University Health, CSP Room C1025, 11175 Campus Street, Loma Linda, CA 92354 [email protected]

Author Disclosure Statement

No competing financial interests exist.

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