Imaging Strategies to Evaluate Bone Health After Nerve Injury Repair and Rehabilitation

NIH RePORTER · VA · I01 · · view on reporter.nih.gov ↗

Abstract

Peripheral nerve damage is a debilitating consequence of traumatic or iatrogenic injury to the extremities of soldiers, and a secondary outcome following spinal cord injury (SCI). Functional recovery from nerve damage is often poor, especially for chronically injured nerves, resulting in impaired motor function, sensory loss, and pain. Beyond the direct impacts of nerve injury, systemic effects related to nerve damage are additionally devastating. One particularly insidious and unsolved clinical challenge resulting from nerve injury is a reduction in the structural integrity and strength of bone. This is in part due to reduced bone loading due to motor dysfunction. However, increasing evidence highlights strong coupling among bone innervation (sensory and sympathetic), vascularity, and regulation of bone turnover. Beyond increased risk of fracture, bone degeneration can also impact whole-body homeostasis, including hematopoiesis and downstream immune dysfunction. Given such long-term sequelae of chronic nerve injury, Veterans bear a tremendous burden on their quality of life, and the VA healthcare system bears a corresponding financial challenge. Imaging is an important strategy for evaluating bone health after nerve injury, nerve repair, and rehabilitative intervention. Unfortunately, existing techniques are limited. Dual energy X-ray absorptiometry (DEXA), which quantifies bone mineral density (BMD), is considered the standard of care in clinical practice. However, the majority of bone components, including the organic matrix and water, which together occupy approximately 60% of bone by volume, is inaccessible using current approaches. These “invisible” tissue components make important contributions to the mechanical properties of bone, partially explaining why BMD alone poorly predicts fractures or other bone-related complications. Further, there is no opportunity to non-invasively measure biological correlates of bone health such as vascularity. These shortcomings contribute strongly to the lack of current interventional approaches to preserve or restore bone health. In this study, we propose to apply innovative magnetic resonance imaging (MRI) to interrogate several structural and physiological properties of bone following nerve injury and rehabilitative intervention. In particular, we will develop and apply quantitative ultrashort echo time (UTE) MRI techniques to measure multi-scale features of bone, including macro- and micro-scale structure and micro-scale vascularity. Our specific aims are: 1) To evaluate changes in bone morphology and neurovascular supply during the progression of chronic nerve injury; 2) To evaluate changes in bone morphology and neurovascular supply following repair of acute and chronic nerve injury; 3) To evaluate changes in bone morphology and neurovascular supply following treadmill- based rehabilitation following chronic nerve injury and repair. The primary outcome of our proposed study is to validate the util...

Key facts

NIH application ID
10747836
Project number
1I01RX004518-01A1
Recipient
VA SAN DIEGO HEALTHCARE SYSTEM
Principal Investigator
Sameer B. Shah
Activity code
I01
Funding institute
VA
Fiscal year
2024
Award amount
Award type
1
Project period
2024-01-01 → 2027-12-31