MRI volumetry and diffusion tensor imaging for diagnosis and follow-up of late post-traumatic injuries.

BACKGROUND: Traumatic Brain Injury (TBI) is a major cause of acquired disability and can cause devastating and progressive post-traumatic encephalopathy. TBI is a dynamic condition that continues to evolve over time. A better understanding of the pathophysiology of these late lesions is important for the development of new therapeutic strategies. OBJECTIVES: The primary objective was to compare the ability of fluid-attenuated reversion recovery (FLAIR) and diffusion tensor imaging (DTI) magnetic resonance imaging (MRI) markers to identify participants with a Glasgow outcome scale extended (GOS-E) score of 7-8, up to 10 years after their original TBI. The secondary objective was to study the brain regionalization of DTI markers. Finally, we analyzed the evolution of late-developing brain lesions using repeated MRI images, also taken up to 10 years after the TBI. METHODS: In this retrospective study, participants were included from a cohort of people hospitalized following a severe TBI. Following their discharge, they were followed-up and clinically assessed, including a DTI-MRI scan, between 2012 and 2016. We performed a cross-sectional analysis on 97 participants at a median (IQR) of 5 years (3-6) post-TBI, and a further post-TBI longitudinal analysis over 10 years on a subpopulation (n = 17) of the cohort. RESULTS: Although the area under the curve (AUC) of FLAIR, fractional anisotropy (FA), and mean diffusivity (MD) were not significantly different, only the AUC of FA was statistically greater than 0.5. In addition, only the FA was correlated with clinical outcomes as assessed by GOS-E score (P<10-4). On the cross-sectional analysis, DTI markers allowed study post-TBI white matter lesions by region. In the longitudinal subpopulation analysis, the observed number of brain lesions increased for the first 5 years post-TBI, before stabilizing over the next 5 years. CONCLUSIONS: This study has shown for the first time that post-TBI lesions can present in a two-phase evolution. These results must be confirmed in larger studies. French Data Protection Agency (Commission nationale de l'informatique et des libertés; CNIL) study registration no: 1934708v0.

Long-term follow-up of neurodegenerative phenomenon in severe traumatic brain injury using MRI.

BACKGROUND: Traumatic brain injury (TBI) lesions are known to evolve over time, but the duration and consequences of cerebral remodelling are unclear. Degenerative mechanisms occurring in the chronic phase after TBI could constitute "tertiary" lesions related to the neurological outcome. OBJECTIVE: The objective of this prospective study of severe TBI was to longitudinally evaluate the volume of white and grey matter structures and white matter integrity with 2 time-point multimodal MRI. METHODS: Longitudinal MRI follow-up was obtained for 11 healthy controls (HCs) and 22 individuals with TBI (mean [SD] 60 [15] months after injury) along with neuropsychological assessments. TBI individuals were classified in the "favourable" recovery group (Glasgow Outcome Scale Extended [GOSE] 6-8) and "unfavourable" recovery group (GOSE 3-5) at 5 years. Variation in brain volumes (3D T1-weighted image) and white matter integrity (diffusion tensor imaging [DTI]) were quantitatively assessed over time and used to predict neurological outcome. RESULTS: TBI individuals showed a marked decrease in volumes of whole white matter (median -11.4% [interquartile range -5.8; -14.6]; p < 0.001) and deep grey nuclear structures (-17.1% [-10.6; -20.5]; p < 0.001). HCs did not show any significant change over the same time period. Median volumetric loss in several brain regions was higher with GOSE 3-5 than 6-8. These lesions were associated with lower fractional anisotropy and higher mean diffusivity at baseline. Volumetric variations were positively correlated with normalized fractional anisotropy and negatively with normalized mean diffusivity at baseline and follow-up. A computed predictive model with baseline DTI showed good accuracy to predict neurological outcome (area under the receiver operating characteristic curve 0.82 [95% confidence interval 0.81-0.83]) CONCLUSIONS: We characterised the striking atrophy of deep brain structures after severe TBI. DTI imaging in the subacute phase can predict the occurrence and localization of these tertiary lesions as well as long-term neurological outcome. TRIAL REGISTRATION: ClinicalTrials.gov: NCT00577954. Registered on October 2006.

Prognostic value of global deep white matter DTI metrics for 1-year outcome prediction in ICU traumatic brain injury patients: an MRI-COMA and CENTER-TBI combined study.

PURPOSE: A reliable tool for outcome prognostication in severe traumatic brain injury (TBI) would improve intensive care unit (ICU) decision-making process by providing objective information to caregivers and family. This study aimed at designing a new classification score based on magnetic resonance (MR) diffusion metrics measured in the deep white matter between day 7 and day 35 after TBI to predict 1-year clinical outcome. METHODS: Two multicenter cohorts (29 centers) were used. MRI-COMA cohort (NCT00577954) was split into MRI-COMA-Train (50 patients enrolled between 2006 and mid-2014) and MRI-COMA-Test (140 patients followed up in clinical routine from 2014) sub-cohorts. These latter patients were pooled with 56 ICU patients (enrolled from 2014 to 2020) from CENTER-TBI cohort (NCT02210221). Patients were dichotomised depending on their 1-year Glasgow outcome scale extended (GOSE) score: GOSE 1-3, unfavorable outcome (UFO); GOSE 4-8, favorable outcome (FO). A support vector classifier incorporating fractional anisotropy and mean diffusivity measured in deep white matter, and age at the time of injury was developed to predict whether the patients would be either UFO or FO. RESULTS: The model achieved an area under the ROC curve of 0.93 on MRI-COMA-Train training dataset, and 49% sensitivity for 96.8% specificity in predicting UFO and 58.5% sensitivity for 97.1% specificity in predicting FO on the pooled MRI-COMA-Test and CENTER-TBI validation datasets. CONCLUSION: The model successfully identified, with a specificity compatible with a personalized decision-making process in ICU, one in two patients who had an unfavorable outcome at 1 year after the injury, and two-thirds of the patients who experienced a favorable outcome.

Long-term cognitive disability after traumatic brain injury: Contribution of the DEX relative questionnaires.

Executive functions are high-level cognitive processes commonly impaired after severe traumatic brain injury (sTBI), which may be associated with persistent anosognosia. The dysexecutive questionnaire (DEX) was designed to assess different domains of executive functioning in daily life. Two versions of the DEX exist (DEX-S completed by the patient, DEX-O completed by a relative) to compare cognitive complaints and patient's awareness. This work was aimed at studying the relevance of DEX-O for assessing daily-life limitations, the persistence of anosognosia and its association with global disability (GOSE) and magnetic resonance imaging (MRI) markers of brain alterations. Sixty-three patients (and relatives) were included within 63.4 months (±20.7) after sTBI. DEX-S and DEX-O scores were significantly positively correlated. We obtained significant correlations between DEX-S and episodic memory and phasic alert but not with executive assessment, GOSE and diffusion MRI markers. DEX-O was significantly correlated with executive function, episodic memory, attention (phasic alert sustained and divided attention), with the GOSE and the volume of the body of the corpus callosum (MRI marker). Anosognosia score (DEX-O minus DEX-S) correlated with mean diffusivity measure. These results highlight the clinical interest of DEX-O in assessing long-term disability.

Use of brain diffusion tensor imaging for the prediction of long-term neurological outcomes in patients after cardiac arrest: a multicentre, international, prospective, observational, cohort study.

BACKGROUND: Prediction of neurological outcome after cardiac arrest is a major challenge. The aim of this study was to assess whether quantitative whole-brain white matter fractional anisotropy (WWM-FA) measured by diffusion tensor imaging between day 7 and day 28 after cardiac arrest can predict long-term neurological outcome. METHODS: This prospective, observational, cohort study (part of the MRI-COMA study) was done in 14 centres in France, Italy, and Belgium. We enrolled patients aged 18 years or older who had been unconscious for at least 7 days after cardiac arrest into the derivation cohort. The following year, we recruited the validation cohort on the same basis. We also recruited a minimum of five healthy volunteers at each centre for the normalisation procedure. WWM-FA values were compared with standard criteria for unfavourable outcome, conventional MRI sequences (fluid-attenuated inversion recovery and diffusion-weighted imaging), and proton magnetic resonance spectroscopy. The primary outcome was the best achieved Glasgow-Pittsburgh Cerebral Performance Categories (CPC) at 6 months, dichotomised as favourable (CPC 1-2) and unfavourable outcome (CPC 3-5). Prognostication performance was assessed by the area under the receiver operating characteristic (ROC) curves and compared between groups. This study was registered with ClinicalTrials.gov, number NCT00577954. FINDINGS: Between Oct 1, 2006, and June 30, 2014, 185 patients were enrolled in the derivation cohort, of whom 150 had an interpretable multimodal MRI and were included in the analysis. 33 (22%) patients had a favourable neurological outcome at 6 months. Prognostic accuracy, as quantified by the area under the ROC curve, was significantly higher with the normalised WWM-FA value (area under the ROC curve 0·95, 95% CI 0·91-0·98) than with the standard criteria for unfavourable outcome or other MRI sequences. In a subsequent validation cohort of 50 patients (enrolled between April 1, 2015, and March 31, 2016), a normalised WWM-FA value lower than 0·91, set from the derivation cohort, had a negative predictive value of 71·4% (95% CI 41·9-91·6) and a positive predictive value of 100% (90·0-100), with 89·7% sensitivity (75·8-97·1) and 100% specificity (69·1-100) for the prediction of unfavourable outcome. INTERPRETATION: In patients who are unconscious 7 days after cardiac arrest, the normalised WWM-FA value, measured by diffusion tensor imaging, could be used to accurately predict neurological outcome at 6 months. This evidence requires confirmation from future large-scale trials with a strict protocol of withdrawal or limitation-of-care decisions and time window for MRI. FUNDING: French Ministry of Health, French National Agency for Research, Italian Ministry of Health, and Regione Lombardia.