Image-Based Modeling of Pediatric Charcot-Marie-Tooth Disease Relative to Neuromuscular Development and Treatment - PROJECT SUMMARY Charcot Marie Tooth disease (CMT) is a progressive neurologic disease that causes a characteristic cavovarus foot deformity associated with pain, decreased ambulation, and escalating disability. CMT primarily presents in children and adolescents, but lack of objective treatment algorithms limits the ability of adolescents with CMT to maintain independence and preserve mobility during their development and transition to adulthood. Variability in treatment planning is caused in part by the wide variability in presentation and poor characterization of foot structure and function across the spectrum of genetic subtypes that prevents objective decision-making about physical therapy, orthotic design, and surgical intervention to maximally protect mobility. While the deformity of CMT is believed to be caused by alignment change, recent research suggests that differences in bony morphology additionally contribute. Further, muscle strength is known to be decreased but muscle morphology has not been studied in CMT and the variability of foot symptoms in CMT is not currently linked to specific genetic subtypes or foot shape. The main objective of this study is to characterize bone morphology across genetic subtype and treatment conditions and to investigate the relationships between bone morphology, muscle morphology, and functional outcomes in adolescents with CMT. In Aim 1, I will utilize statistical shape modeling (SSM) from retrospectively collected weight-bearing computed tomography (WBCT) datasets to evaluate differences in bony morphology and foot alignment between genetic subtypes of CMT. I will further analyze differences in foot structure with use of ankle-foot orthoses or following surgical correction of cavovarus deformity. In Aim 2, I will expand this modeling technique to image data from WBCT and magnetic resonance imaging (MRI) to create combined SSMs of bone and muscle morphology. I will then use these models to analyze differences in morphology relative to genetic subtype and age and to correlate morphology with muscle strength and functional ability. Together, these aims will contribute to a better understanding of CMT-associated foot and ankle deformity to ultimately improve treatment planning for this complex population. My interdisciplinary team of mentors will provide training in medical imaging, computational modeling, and pediatric human-subjects research, complemented by clinical mentorship and shadowing in orthopaedics, neurology, and rheumatology. The training plan was developed in collaboration with my Sponsors to address my primary goals of conducting independent, collaborative human-subjects research; advancing communication and grant-writing skills; learning mentoring and leadership; and honing clinical skills. This training is ideal for a future physician-scientist with the goal of improving patient care in pediatric neuromusculoskeletal medicine.
