Early Increase in Cortical T <sub>2</sub> Relaxation Is a Prognostic Biomarker for the Evolution of Severe Cortical Damage, but Not for Epileptogenesis, after Experimental Traumatic Brain Injury
Eppu Manninen, Karthik Chary, Niina Lapinlampi, Pedro Andrade, Tomi Paananen, Alejandra Sierra, Jussi Tohka, Olli Gröhn, Asla Pitkänen
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 T 2 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. T 2 MRI was performed at days 2, 7, and 21 post-TBI. The lesioned cortex was outlined, and the T 2 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 T 2 -based classification of lesion volume at day 2 and day 7 post-TBI explained the necrotic lesion volume with greatly increased T 2 (>102 ms) at day 21 post-TBI ( F (13,103) = 52.5; p < 0.001; R 2 = 0.87; adjusted R 2 = 0.85). The volume of moderately increased (78–102 ms) T 2 at day 7 post-TBI predicted the evolution of large (>12 mm 3 ) cortical lesions (area under the curve, 0.92; p < 0.001; cutoff, 1.9 mm 3 ; false positive rate, 0.10; true positive rate, 0.62). Logistic regression analysis, however, showed that the different severities of T 2 lesion volumes at days 2, 7, and 21 post-TBI did not explain the development of epilepsy (χ 2 (18,95) = 18.4; p = 0.427). In addition, the location of the T 2 abnormality within the cortex did not correlate with epileptogenesis. A single measurement of T 2 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.