Improving Prognostication for Traumatic Brain Injury

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PROJECT SUMMARY/ABSTRACT Despite more than 5 million people living in the U.S. with the long-term effects of traumatic brain injury (TBI), it remains unknown at what point the TBI functional recovery trajectory is fixed. Existing TBI prognostic models are imperfect and static, relying on data from admission and the first 6 hours only. Current models explain only one-third of the variability in outcomes. Despite the multiple CT and MRI scans obtained in TBI clinical care, neuroimaging remains underutilized for TBI prognostics. Image-based biomarkers and radiomics can extract predictive signals from neuroimaging already being obtained. Prognostication matters: better prognostics translate to better patient-centered clinical decision making and better prognostic stratification for clinical trials. Multiple TBI therapies have failed in clinical translation due to basic challenges in patient selection and predicting TBI recovery. At many hospitals across the U.S., trauma surgeons are the primary providers responsible for patients with hospitalized TBI. We can and should do better by developing a mature quantitative approach to prognostication that incorporates time-varying clinical data, advanced statistical modeling, TBI-specific biomarkers, and image-based biomarkers from clinical imaging already being obtained. This career development plan (PI: Amelia W. Maiga, Trauma Surgeon) helps sustain a minimum of 75% protected effort to hone her research expertise and eventual independence in advanced statistical modeling, clinical trials, and neuroimaging analysis for TBI prognostication. The research specific aims are to: AIM 1) build and validate a TBI prognostic model for 12-month functional outcomes with rich time-varying clinical data, radiomics imaging analysis, and biomarkers using two NIH cohorts (R01GM120484 and U01NS086090); and AIM 2) conduct a trajectory analysis of long-term functional and neurocognitive outcomes after TBI. This career development plan for Dr. Maiga integrates a) advanced didactics in clinical trials and neurocognitive follow-up in the critically injured, sophisticated statistical modeling, imaging analysis, and scientific communication and leadership; b) participation in local, regional, and national conferences to advance expertise in the above areas; c) a multidisciplinary mentored research experience; and d) an outstanding environment to propel towards independence. Her mentorship team consists of Drs. Mayur B. Patel (Primary Mentor, trauma, critical illness and TBI); Pratik P. Pandharipande (cognitive impairment); Rameela Raman (prognostic modeling, trajectory analysis); James C. Jackson (long-term outcomes); and Bennett A. Landman (neuroimaging, radiomics), supported by a Research Advisory Council of Drs. E. Wesley Ely (Director of Critical Illness and Brain Dysfunction Center); Robert S. Dittus (Director of Vanderbilt’s Institute of Medicine and Public Health); Geoff T. Manley (PI TRACK-TBI; Transforming Research and Clinical Knowledge in TBI). This research award will position Dr. Maiga to become a leader in TBI prognostics.