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Published Online: 6 November 2020

Early Increase in Cortical T2 Relaxation Is a Prognostic Biomarker for the Evolution of Severe Cortical Damage, but Not for Epileptogenesis, after Experimental Traumatic Brain Injury

Publication: Journal of Neurotrauma
Volume 37, Issue Number 23

Abstract

Prognostic biomarkers for post-injury outcome are necessary for the development of neuroprotective and antiepileptogenic treatments for traumatic brain injury (TBI). We hypothesized that T2 relaxation magnetic resonance imaging (MRI) predicts the progression of perilesional cortical pathology and epileptogenesis. The EPITARGET animal cohort used for MRI analysis included 120 adult male Sprague-Dawley rats with TBI induced by lateral fluid-percussion injury and 24 sham-operated controls. T2 MRI was performed at days 2, 7, and 21 post-TBI. The lesioned cortex was outlined, and the T2 value of each imaging voxel within the lesion area was scored using a five-grade pathology classification. Analysis of 1-month video-electroencephalography recordings initiated 5 months post-TBI indicated that 27% (31 of 114) of the animals with TBI developed epilepsy. Multiple linear regression analysis indicated that T2-based classification of lesion volume at day 2 and day 7 post-TBI explained the necrotic lesion volume with greatly increased T2 (>102 ms) at day 21 post-TBI (F(13,103) = 52.5; p < 0.001; R2 =  0.87; adjusted R2 = 0.85). The volume of moderately increased (78–102 ms) T2 at day 7 post-TBI predicted the evolution of large (>12 mm3) cortical lesions (area under the curve, 0.92; p < 0.001; cutoff, 1.9 mm3; false positive rate, 0.10; true positive rate, 0.62). Logistic regression analysis, however, showed that the different severities of T2 lesion volumes at days 2, 7, and 21 post-TBI did not explain the development of epilepsy (χ2(18,95) = 18.4; p = 0.427). In addition, the location of the T2 abnormality within the cortex did not correlate with epileptogenesis. A single measurement of T2 relaxation MRI in the acute post-TBI phase is useful for identifying post-TBI subjects at highest risk of developing large cortical lesions, and thus, in the greatest need of neuroprotective therapies after TBI, but not the development of post-traumatic epilepsy.

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cover image Journal of Neurotrauma
Journal of Neurotrauma
Volume 37Issue Number 23December 1, 2020
Pages: 2580 - 2594
PubMed: 32349620

History

Published in print: December 1, 2020
Published online: 6 November 2020
Published ahead of print: 26 June 2020
Published ahead of production: 29 April 2020

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Eppu Manninen
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Karthik Chary
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Niina Lapinlampi
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Pedro Andrade
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Tomi Paananen
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Alejandra Sierra
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Jussi Tohka
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Olli Gröhn
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
Asla Pitkänen [email protected]
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.

Notes

Address correspondence to: Asla Pitkänen, MD, PhD, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, PO Box 1627, FI-70211 Kuopio, Finland [email protected]

Author Disclosure Statement

No competing financial interests exist.

Funding Information

This study was supported by the Medical Research Council of the Academy of Finland (grants 272249 and 273909) and by the European Union's Seventh Framework Programme (FP7/2007-2013) under grant agreement no. 602102 (EPITARGET). Alejandra Sierra wants to thank Academy of Finland for funding support (#284544; #312686, and #275453).

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