Grant: $643,758 - Department of Health and Human Services - May. 8, 2009
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Award Description: Foundations will be laid in this proposal for use of both functional magnetic resonance imaging (fMRI) maps and resting state functional connectivity maps to study brain plasticity that occurs following surgery to repair peripheral nerves injured by trauma. A rat brain model of nerve injury of the forearm will be developed at 9.4T. There are three well focused aims. In Aim 1, two classes of novel radio frequency surface coils specifically tailored to the rat brain will be developed as follows: a one-turn with improved depth sensitivity and a 2 x 1 multichannel coil for whole rat brain imaging. Aim 1 is dedicated to achieving increased fMRI spatial resolution using cubic voxels through use of multichannel arrays of small coils. Aim 1 serves the other two aims, each of which acquires rat fMRI and functional connectivity MRI (fcMRI) data. In Aim 2, electrical stimulation electrodes will be implanted on the individual peripheral nerves of the rat upper extremity, including the use of multiple electrodes. Extensive preliminary data for the major nerves are reported. Extension to high spatial resolution fMRI of the major nerves and also to smaller branching nerves using the multichannel coils of Aim 1 is proposed. High resolution resting state functional connectivity maps also will be produced. This aim is directed to acquisition of normal high resolution fMRI maps of nerves of the forearm as well as corresponding high resolution resting-state functional connectivity maps. It provides a baseline for interpretation of the trauma and plasticity maps of Aim 3. In Aim 3, a rat model of nerve trauma is developed. A nerve is cut, and fMRI as well as functional connectivity maps are obtained at acute and sub-acute intervals after the injury. Functional MRI and functional connectivity maps will be acquired at high spatial resolution using the multichannel coils and signal processing methods of Aim 1, and the normative studies of Aim 2 will facilitate interpretation of observed brain plasticity. The overall significance of the project lies in the hypothesis that improved fMRI of the rat in a context of nerve injury will lead to improved models of human disease, and that the manipulations that are possible with a rat model will lead to improved human diagnosis and treatment. Specifically, a long-term goal is to address extremely debilitating injuries of the nerves of the forearm that occur in childbirth and also in adult trauma associated with motorcycle, snowmobile, and automobile accidents, and in military operations such as the Iraq and Afghanistan wars. In addition, the work proposed here is expected to contribute fundamentally to knowledge of brain plasticity following nerve injury.
Project Description: The theme of this proposal has three parts. (1) CNS remodeling begins shortly after PNS injury in an acute phase and continues for weeks/months in a chronic phase. Further remodeling occurs both acutely and chronically after nerve repair. This proposal will characterize the CNS plasticity that occurs in the setting of nerve injury and repair. (2) Surgical outcomes are poorer as the site of the injury progresses from the periphery toward the CNS. This proposal aims to characterize the CNS plasticity that occurs in response to nerve injury and repair. (3) Functional MRI and fcMRI allow noninvasive monitoring of the CNS remodeling that is linked to PNS injury, repair, and rehabilitation. (See Pawela et al. NeuroImage [in press 2009].) The overall significance of the project lies in the hypothesis that improved fMRI of the rat will lead to improved models of human disease, and that the manipulations possible with a rat model will lead to improved human diagnosis and treatment. In 2009 Pawela et al. (NeuroImage 46:1137) identified dexmedetomidine as an anesthetic that allows assessment of nerve recovery over time using fMRI. The same animal can be anesthetized at certain time points while fMRI images are obtained to assess cortical representation of nerves as they recover from injury. We have also focused on isolating and stimulating at the level of the nerve root. Our anatomic knowledge and surgical technique have allowed us to reproducibly isolate the brachial plexus to the level of the C7 nerve root. When stimulated we see a large motor cortex activation and a small S1 sensory cortex activation on BOLD imaging. Upon completion of our C7 cortical map, we will proceed with a survival study using a C7 nerve injury model. Additionally, we have successfully designed a series of electrodes that can be used in functional study of peripheral nerves, making longitudinal experiments on the same rat possible and allowing us to obtain refined sensory representation in the cortex.
Jobs Summary: Postdoctoral Fellow (Total jobs reported: 0)
Project Status: Less Than 50% Completed
This award's data was last updated on May. 8, 2009. Help expand these official descriptions using the wiki below.