Grants Funded

Abstract

Project Summary: Peripheral nerve injuries (PNI) affect 1-3% of limb trauma cases in the United States and often leave patients with significant long-term disabilities. Outcomes after peripheral nerve injury could be significantly improved by early and accurate diagnosis. However, precise assessment of nerve injuries remains a challenge. Current diagnostic modalities are often unable to distinguish between nerve injuries that can spontaneously recover and those that cannot. This leads to delays in surgical repair, during which muscle denervation from PNI leads to irreversible loss of function over time. The study outlined in this proposal aims to assess the feasibility of using 18F-DCFPyL radiolabeled PET imaging, which targets the biomarker Glutamate Carboxypeptidase II (GCPII), to accurately identify denervated muscles. This innovation could transform care by differentiating between patients who need surgery and those who can undergo observation for spontaneous recovery. It addresses a significant gap in diagnosis, potentially preventing irreversible muscle loss and improving outcomes for patients. The proposed study includes two tasks: (1) Correlate GCPII expression with EMG results for PNI: This task aims to establish that PET imaging can be used to identify muscle denervation as compared to electromyography (EMG), the current gold-standard. To accomplish this, 15 adult patients with upper extremity nerve injuries will undergo PET scans as well as EMG assessments. GCPII expression will then be correlated with EMG grades to assess the feasibility of this method. (2) Evaluate the safety and tolerance of 18F-DCFPyL PET scans in patients with PNI: Although the radiotracer has previously been demonstrated as safe for use in cancer imaging, assessing its safety specifically for use in PNI patients is crucial. To accomplish this, we will monitor patients for immediate side effects and follow up with a questionnaire a month later to assess any delayed side effects. Overall, this research will introduce a new imaging tool that could change the way peripheral nerve injuries are diagnosed and managed, potentially improving patient outcomes and quality of life.

Impact Statement: We propose muscle glutamate carboxypeptidase II (GCPII) expression as a novel biomarker for peripheral nerve injury, detectable through positron emission tomography (PET). This research addresses key questions about GCPII as related to peripheral nerve injury (PNI): can its expression be used to accurately identify muscle denervation and is GCPII-based PET imaging safe and tolerable? GCPII-based PET shows promise in precisely diagnosing PNI, enabling timely surgeries for muscle salvage and distinguishing salvageable muscles from those lost to denervation-induced atrophy. Improved diagnosis of PNI using GCPII-based PET will inform clinical decision making to maximize post-injury functional recovery and quality of life for patients.

Biography
Dr. Sami Tuffaha is an Assistant Professor in the Department of Plastic and Reconstructive Surgery at Johns Hopkins University School of Medicine. Serving as Co-Director of the Multidisciplinary Peripheral Nerve Center at Johns Hopkins, his clinical focus centers on restoring function post-peripheral nerve injury. Along with his clinical role, he also leads a basic and translational research laboratory, pioneering strategies for functional recovery and neuropathic pain prevention following nerve injury. His lab’s multidisciplinary collaborations drive advancements in peripheral nerve injury research in multiple areas including: (1) pioneering imaging devices and tracer dyes for visualizing injured and regenerating nerves, aiding in precise diagnostics and treatment planning, (2) targeted delivery of key protein therapeutics, like IGF-1 and agrin, crucial for nerve regeneration, (3) engineered devices and novel surgical methods to prevent painful neuroma formation post-injury and (4) developing implantable wireless devices that capture signals from severed nerves, enabling intuitive prosthetic control via muscle interface. Dr. Tuffaha's dedication to collaboration and scientific exploration highlights his strong commitment to enhancing patient care and improving outcomes in the field of peripheral nerve injury and rehabilitation.