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TRAUMATISM

investigation du TRAUmatisme Médullaire et de ses Altérations sensorimotrices par Tests fonctionnels et Imagerie/Spectroscopie par résonance Magnétique (IRM/SRM)
Funder: French National Research Agency (ANR)Project code: ANR-09-BLAN-0295

TRAUMATISM

Description

BACKGROUND Spinal cord injury (SCI) is not a common condition, but it has a major effect on the injured person's functional, medical, financial, and psychosocial well-being. Spinal cord injury is an insult to the spinal cord that can occur through different mechanisms, including contusion, compression and ischemia. SCI causes either temporary or permanent damage to white myelinated fiber tracts that carry sensation and motor signals to and from the brain; it also damages vasculature, as well as gray matter in the central part, causing segmental losses of inter and motor neurons. The traumatic insult leads to functional disruptions below the site of injury such as loss of voluntary movements and muscle atrophy, as well as functional deficits such as cardiovascular system, breathing or pain control. Within weeks or months, endogenous repair (by neuronal recovery and neovasculature) as well as functional recovery may occur and gradually returns to control levels. The last decade has seen many advances in understanding, visualizing and treating spinal cord injuries, however a better description and characterization of the pathology is still necessary. OBJECTIVE The general objective of this project is to develop a non invasive in vivo spinal cord (SC) multimodal MR imaging strategy, which will provide a better characterization of the tissue alterations and repairs that occur after the injury. By taken advantage of the non-invasiveness and the multi-parametric investigation properties of MRI, the proposed project would present, in case of successfulness, an alternative approach to the techniques usually used for the investigation of SCI animal models. Despite their high sensitivity and being well-adapted to inherent SC challenges (size, complex structure...), most of the used techniques (histopathology, optical imaging') suffered from main limitations including invasiveness properties and limitative field of investigation. Therefore, the ability of performing longitudinal studies, although crucial in SCI investigation, is limited, so is the variety of physiological investigated parameters. The proposed project and the associated MRI technique might give some solutions to the previously described limitations. This project appears then very novel and ambitious. Important fundamental advances are expected, in particular on animal models, but also on clinical studies, MRI protocols offering the advantage of being directly adapted for human studies. DESCRIPTION OF THE PROJECT The proposed project will be conducted according to three main axes. The first step will concern the development of a multimodal MRI approach for the pathological mouse SC exploration. Based on classical high-resolution MRI techniques (anatomy, relaxometry and diffusion imaging), the project will also integrate 2 ambitious techniques: perfusion imaging and NMR spectroscopy. The overall applied MR techniques will provide non-invasively and in vivo, morphological, structural, metabolic and hemodynamic parameters relative to the physiological state of the spinal cord. The second step will focus on the establishment of correlations between the evolution of MR parameters, with functional evolution and histopathology studies, in the case of SCI compression model. The sensitivity of the MR techniques will be a key point for the success of this part since characterization of mild lesions, detection of early changes and fine discrimination between 3 groups of mice are expected: non-treated mice, naturally trained mice placed in an enriched environment and pharmacologically treated mice. The correlations that should be observed between the SC lesion deficit/repair (identified by MR SC investigations), the motor, muscular and sensory alteration/recovery (observed by functional test) and the histological evaluation will furthermore permit to point out on the most relevant MR parameters involved in the regeneration processes. Finally, the third step will be the transfer and development of similar multimodal MR methods on the clinical MR scanners for investigation of human spinal cord injury.

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