The muscle fiber is fairly simple when it comes to diffusion. Water molecules can either diffuse along the fiber, encountering some organelles and proteins on the way, or they can diffuse across the fiber, where they encounter the sarcolemma membrane. Diffusion MRI is sensitive to the invisible architecture that restricts water molecules. Our group expands on this sensitivity through biologicial modeling of the time-dependent diffusion coefficient. We use our proprietary Random Permeable Barrier Model (RPBM) to extract two parameters: myofiber diameter and sarcolemma membrane permeability.
The only other way to quantify myofiber diameter is through invasive procedures such as biopsy/histopathology. A non-invasive approach can have tremendous impact on the diagnostic ability on various traumatic injuries and myopathies.
One potential application is in assessing outcome within torn rotator cuff. The textbook definition of predicting rotator cuff outcome is to assess the degree of atrophy within major muscles of the rotator cuff. However, prior to our work, rotator cuff musculature was assessed by fatty infiltration as a proxy for muscular atrophy. This is typically done through qualitative assessments of fat content on T1-weighted images. Additionally these qualitative assessments have poor interobserver agreement [Spencer et al. Am J Sports Med. 2008]. Our work in modeling with time-dependent diffusion allows us to assess musculature directly in a user independent fashion, thereby eliminating concerns of reproducibility.
In regards to membrane permeability, there is no competing method to measure this quantity. Despite this, it has been shown to be a clinically relevant marker in a study involving the RPBM and chronic exertional compartment syndrome (CECS).
The RPBM was utilized to investigate changes in the calf muscle of normal and CECS volunteers. A time-dependent diffusion protocol was applied before and after exercise. Most of the resulting parameters remained unchanged. However, CECS volunteers experienced a large increase (~1.5 times) in membrane permeability following exercise, whereas normal volunteers experienced none.
We are currently looking into comprehensive validation of RPBM, while simultaneously looking for clinical applications.