MRI Biomarkers for Post-Traumatic Epileptogenesis

Abstract

The present study tested a hypothesis that early identification of injury severity with quantitative magnetic resonance imaging (MRI) provides biomarkers for predicting increased seizure susceptibility and epileptogenesis after traumatic brain injury (TBI). TBI was induced by lateral fluid percussion injury (FPI) in adult rats. Quantitative T2, T1q, and diffusion were assessed with MRI at 9 days, 23 days, or 2 months post-TBI in the perilesional cortex, thalamus, and hippocampus. Seizure susceptibility was assessed at 12 months after TBI using the pentylenetetrazol seizure-susceptibility test. At 9 and 23 days post-TBI, a change in T1q of the perilesional cortex showed the greatest predictive value for increased seizure susceptibility at 12 months post-TBI [area under the curve (AUC), 0.929 and 0.952, respectively; p < 0.01]. At 2 months post-TBI, Dav in the thalamus was the best of the biomarkers analyzed (AUC, 0.988; p < 0.05). The highest predictive value of all biomarkers was achieved by combining the measurement of Dav in the perilesional cortex and the thalamus at 2 months post-TBI (AUC, 1.000; p < 0.01). Our results provide proof-of-concept evidence that clinically relevant MRI biomarkers predict increased seizure susceptibility after experimental TBI.

Neuroimaging the Epileptogenic Process

“…As shown in Fig. 1, volumetric and morphological changes in the hippocampus and other limbic structures have been reported in both SE [26][27][28][29] and FPI models [11,23,30,31]. However, these changes are typically preceded by abnormalities identified by other more sensitive neuroimaging methods [11,23,[28][29][30][31].…”

“…1, volumetric and morphological changes in the hippocampus and other limbic structures have been reported in both SE [26][27][28][29] and FPI models [11,23,30,31]. However, these changes are typically preceded by abnormalities identified by other more sensitive neuroimaging methods [11,23,[28][29][30][31]. As such, volumetric and morphological changes may not be ideal neuroimaging biomarkers to identify early pathophysiological processes involved in epileptogenesis, but may have more of a role to assess subsequent progressive neurodegenerative changes, in particular atrophy of key structures such as the hippocampus, that may follow an epileptogenic brain insult [11,29,30,32].…”

Susceptibility‐weighted and diffusion kurtosis imaging to evaluate encephalomalacia with epilepsy after traumatic brain injury

“…Let us speculate whether the MRI characteristics of our study evolve over time. After TBI, brain focal encephalomalacia lesions were formed,5 and these changes could reduce the complexity of local brain tissue, leading to a decrease in the MK value 34. Over time, glial hyperplasia was still the main pathological process surrounding the encephalomalacia 35.…”

Epilepsy Related to Traumatic Brain Injury

“…Recently, Schultz et al [67] reported that abnormalities in the surface morphology of the ipsilateral hippocampus present at 1 week after lateral FPI predicted the occurrence of epilepsy 6 months after TBI [67]. We recently investigated whether quantitative T2, T1ρ, and diffusion (Dav) assessed with MRI at 9 days, 23 days, or 2 months after TBI in the peri-lesional cortex, thalamus, and hippocampus would predict seizure susceptibility in the PTZ test at 12 months after TBI [68]. Our data showed that the highest predictive value for the development of seizure susceptibility at 12 months post-TBI was achieved by co-assessment of the Dav in the peri-lesional cortex and the thalamus 2 months after TBI.…”

“…*P≤0.05, **P≤0.01 AUC compared with the area under diagonal line. For details, see [68]. PrhCx = perirhinal cortex; S1 = somatosensory cortex 1, Th=thalamus…”