Nerve Trauma and Repair
An increased incidence of nerve trauma has been noted in the military due to modern body armor, which allows combatants to survive wounds that would formerly have been lethal. Nerve damage following trauma can result in catastrophic loss of function if not detected and treated in a timely manner. Surgery is often required to regain function, but outcomes are variable and options for post-surgical monitoring are painful and limited. Because regeneration is slow, physicians must “wait and watch” for months to years and rely on measures from patient history/exam to determine success. During this time, muscles atrophy, the critical window for surgical revision passes, and the prospect for recovery diminishes.
Given these limitations, this project seeks to develop and validate new MRI-based biomarkers (e.g., diffusion tensor imaging, multi-dimensional diffusion, magnetization transfer, perfusion) that monitor nerve regeneration before muscle reinnervation, which would enable earlier detection of failed repairs, earlier re-operations, and improved restoration of sensorimotor function. This involves both translational studies in humans and validation studies in animal models of nerve trauma.
Nerve Transfers in Spinal Cord Injury
Spinal cord injuries have devastating, life-changing consequences for nearly all aspects of the affected individual’s life. In the military, war-related spinal cord injuries are generally more severe, with a greater likelihood of complete injuries, than the civilian population. In these patients, restoration of hand and arm function is one of the highest priorities. Recent advances in nerve transfer procedures, where a non-critical nerve from above the level of injury is transferred to critical nerve below the level of injury, have allowed surgeons to restore these critical limb functions in many patients. Unfortunately, these nerve transfer methods are prone to failure because we do not have objective methods to:
- Select the best donor nerves prior to surgery
- Detect failed nerve transfers after surgery in a timely fashion
In this project, we seek to develop, evaluate, and validate new MRI methods to address these limitations. In the short-term, these imaging methods would improve the surgeon’s ability to restore upper extremity function (i.e., reverse paralysis and reanimate the arm) by identifying optimal donor nerves for transfers, detecting failed transfers earlier than is currently possible, and guiding secondary surgeries when necessary. Longer-term, these imaging methods would allow researchers to objectively evaluate next-generation surgical methods that may further improve our ability to reverse paralysis.
Myelin Damage and Repair in Multiple Sclerosis
Neurodegeneration, featured by myelin loss, is a key pathological feature and outcome determinant in patients with multiple sclerosis. Currently, there are no treatments that promote myelin repair and the development of these therapies is hindered by a lack of reproducible myelin-specific biomarkers.
This project proposes to overcome this limitation by developing and optimizing a myelin-specific MRI method known as selective inversion recovery, which uses conventional sequences and a user-friendly analysis. Our goal is to move this “turnkey” myelin MRI method toward clinical trial readiness by
- Reducing scan times
- Demonstrating consistency across MRI vendors and sites
- Providing clinical validation via longitudinal studies in patients with multiple sclerosis.
Barrow Neurological Institute and the Dortch Laboratory are members of the North American Imaging in MS Cooperative (NAIMS).
Disease Progression in Inherited Neuropathies
The overarching goal of this project is to advance the clinical trial readiness of candidate MRI biomarkers of disease progression in Charcot-Marie-Tooth (CMT) diseases. Although promising treatments for certain CMT subtypes are on the horizon, the evaluation of therapies in human trails is hindered by a lack of responsive biomarkers, which is critical due to the slowly progressive nature of many CMT subtypes.
To overcome this challenge, this project proposes to develop novel MRI methods to assay the pathology of interest (e.g., demyelination via magnetization transfer methods) within nerves. Current work focuses on 1) determining the responsiveness of these candidate MRI biomarkers and 2) determining their inter-site and inter-vendor reproducibility and repeatability. More recently projects focus on evaluating the relevance of these methods as biomarkers in inflammatory neuropathies (e.g., Guillain-Barré syndrome).