MRI changes in the spinal cord and brain as markers in SCI rehabilitation
Funded in: 2014, 2015, 2016
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Problem: The neuronal mechanisms underpinning functional recovery are not well understood.
Target: Visualization of training associated changes in the structure and function of the brain using magnetic resonance imaging (MRI) for the development of novel MRI biomarkers.
Goal: Biomarkers which can be used as surrogate endpoints in clinical trials and to personalize the care of patients with SCI.
Introduction: Functional recovery following human spinal cord injury (SCI) remains limited and the majority of patients are left with severe impairments. While rehabilitative training has been shown to improve functional recovery following SCI and has a major effect on patients' quality of life, the neuronal mechanisms underpinning functional recovery are not well understood. Until recently, degenerative changes in the brain and spinal cord above the level of the primary injury at the spinal level were thought to occur slowly (over years) with unclear relationship to the degree of disability. Using longitudinal magnetic resonance imaging protocols the applicant has shown that these structural changes in fact occur early and progress both at the cord and brain level according to a specific spatial and temporal pattern (Freund et al 2013, Lancet Neurology).
Aims: The aim is to develop a training paradigm that is both applicable in chronic SCI patients and controls in order to investigate training associated changes in the structure and function of the brain using magnetic resonance imaging of the brain and spinal cord. The team also aims to show whether increased, targeted training intensity over and above conventional rehabilitation regimes can reduce the rate of progressive atrophy of the sensorimotor system, and thus further improve recovery in SCI patients.
Methods: In a three-year project, the project team will apply longitudinal analysis to estimate the rate (acceleration, deceleration) of structural and functional brain and spinal cord changes in a group of healthy subjects and SCI patients as they undergo specific and intensive motor learning. Following the identification of the brain areas that are susceptible to change in healthy controls, the same protocol in tetraplegic and paraplegic SCI patients will be assessed. The relationship between anatomical and microstructural MRI changes and objective measures of the quantity (intensity, dosing, and frequency) and quality (improving performance) of activity will be determined.
Conclusion: Novel neuroimaging measures of dynamic structural CNS changes in response to training hold significant potential to elucidate neuronal changes associated with functional recovery. The so developed sensitive and accurate MRI biomarkers can be applied as surrogate endpoints in clinical trials and to personalize the care of patients with SCI.