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

Manninen, Eppu; Chary, Karthik; Lapinlampi, Niina; Andrade, Pedro; Paananen, Tomi; Sierra, Alejandra; Tohka, Jussi; Gröhn, Olli; Pitkänen, Asla

doi:10.1089/neu.2019.6796

Cited by 16 publications

(26 citation statements)

References 42 publications

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“…Moreover, the range of impact forces does not correlate with the severity of the cortical lesion area or T2 signal enhancement in magnetic resonance imaging. 31 The lack of correlations likely relates to a relatively narrow range of impact forces administered to the animal cohorts.…”

Section: Discussionmentioning

confidence: 99%

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

et al. 2020

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Section: Discussionmentioning

confidence: 99%

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

et al. 2020

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“…MRI data for T 2 estimation were acquired using Bruker's Multi‐Slice‐Multi‐Echo sequence as described previously 23 . Briefly, six echoes (echo times 14.6–87.6 msec) were recorded with a spatial resolution of 201 × 201 µm 2 and a slice thickness of 500 µm.…”

Section: Methodsmentioning

confidence: 99%

“…The data were derived from the 6‐month behavioral, MRI, and EEG follow‐up of the EPITARGET animal cohort described previously 23,24 . All procedures and measurements were performed in a standardized manner, according to the pre‐set protocol.…”

Section: Methodsmentioning

confidence: 99%

Acute thalamic damage as a prognostic biomarker for post‐traumatic epileptogenesis

et al. 2021

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Objective To identify magnetic resonance imaging (MRI) biomarkers for post‐traumatic epilepsy. Methods The EPITARGET (Targets and biomarkers for antiepileptogenesis, epitarget.eu) animal cohort completing T2 relaxation and diffusion tensor MRI follow‐up and 1‐month‐long video‐electroencephalography monitoring included 98 male Sprague‐Dawley rats with traumatic brain injury and 18 controls. T2 imaging was performed on day (D) 2, D7, and D21 and diffusion tensor imaging (DTI) on D7 and D21 using a 7‐Tesla Bruker PharmaScan MRI scanner. The mean and standard deviation (SD) of the T2 relaxation rate, multiple diffusivity measures, and diffusion anisotropy at each time‐point within the ventroposterolateral and ventroposteromedial thalamus were used as predictor variables in multi‐variable logistic regression models to distinguish rats with and without epilepsy. Results Twenty‐nine percent (28/98) of the rats with traumatic brain injury (TBI) developed epilepsy. The best‐performing logistic regression model utilized the D2 and D7 T2 relaxation time as well as the D7 diffusion tensor data. The model distinguished rats with and without epilepsy (Bonferroni‐corrected p‐value < .001) with a cross‐validated concordance statistic of 0.74 (95% confidence interval [CI] 0.60–0.84). In a cross‐validated classification test, the model exhibited 54% sensitivity and 91% specificity, enriching the epilepsy rate within the study population from the expected 29% to 71%. A model using the D2 T2 data only resulted in a 73% enriched epilepsy rate (regression p‐value .007, cross‐validated concordance 0.70, 95% CI 0.56–0.80, sensitivity 29%, specificity 96%). Significance An MRI parameter set reporting on acute and subacute neuropathologic changes common to experimental and human TBI presents a diagnostic biomarker for post‐traumatic epileptogenesis. Significant enrichment of the study population was achieved even when using a single time‐point measurement, producing an expected epilepsy rate of 73%.

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“…EPITARGET (https://epitarget.eu/) was a European Union Framework 7 -funded, large-scale, multidisciplinary research project aimed at identifying mechanisms and treatment targets for epileptogenesis after various epileptogenic brain insults. The 6-month MRI follow-up of the EPITARGET animal cohort has been described in detail previously [17,18]. We describe only the details that are important for the present study.…”

Section: Epitarget Cohortmentioning

confidence: 99%

“…We hypothesized that the performance of CNNs would not be affected by the presence of lesions to the same extent as registration-based methods as long as a sufficient anatomical variety of lesions is present in the training data. We segmented MRI scans acquired at different time points following experimental TBI, available from our two large preclinical animal cohorts, EpiBioS4Rx [15,16] and EPITARGET [17,18]. We focused on the segmentation of the hippocampus as (a) it is frequently damaged by experimental and human TBI and (b) its damage is associated with the development of posttraumatic epilepsy and cognitive impairment in both animal models and humans [19,20].…”

Section: Introductionmentioning

confidence: 99%

Automatic segmentation of the rat brain hippocampus in MRI after traumatic brain injury

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Hamalainen

Manninen

et al. 2021

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Registration-based methods are commonly used in the anatomical segmentation of magnetic resonance (MR) brain images. However, they are sensitive to the presence of deforming brain pathologies that may interfere with the alignment of the atlas image with the target image. Our goal was to develop an algorithm for automated segmentation of the normal and injured rat hippocampus. We implemented automated segmentation using a U-Net-like Convolutional Neural Network (CNN). of sham-operated experimental controls and rats with lateral-fluid-percussion induced traumatic brain injury (TBI) on MR images and trained ensembles of CNNs. Their performance was compared to three registration-based methods: single-atlas, multi-atlas based on majority voting and Similarity and Truth Estimation for Propagated Segmentations (STEPS). Then, the automatic segmentations were quantitatively evaluated using six metrics: Dice score, Hausdorff distance, precision, recall, volume similarity and compactness using cross-validation. Our CNN and multi-atlas -based segmentations provided excellent results (Dice scores > 0.90) despite the presence of brain lesions, atrophy and ventricular enlargement. In contrast, the performance of singe-atlas registration was poor (Dice scores < 0.85). Unlike registration-based methods, which performed better in segmenting the contralateral than the ipsilateral hippocampus, our CNN-based method performed equally well bilaterally. Finally, we assessed the progression of hippocampal damage after TBI by applying our automated segmentation tool. Our data show that the presence of TBI, time after TBI, and whether the location of the hippocampus was ipsilateral or contralateral to the injury explained hippocampal volume (p=0.029, p< 0.001, and p< 0.001 respectively).

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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

Cited by 16 publications

References 42 publications

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Acute thalamic damage as a prognostic biomarker for post‐traumatic epileptogenesis

Automatic segmentation of the rat brain hippocampus in MRI after traumatic brain injury

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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

Cited by 16 publications

References 42 publications

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Postinjury weight rather than cognitive or behavioral impairment predicts development of posttraumatic epilepsy after lateral fluid‐percussion injury in rats

Acute thalamic damage as a prognostic biomarker for post‐traumatic epileptogenesis

Automatic segmentation of the rat brain hippocampus in MRI after traumatic brain injury

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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