In vivo measurement of membrane permeability and myofiber size in human muscle using time‐dependent diffusion tensor imaging and the random permeable barrier model

Abstract

The time dependence of the diffusion coefficient is a hallmark of tissue complexity at the micrometer level. Here we demonstrate how biophysical modeling, combined with a specifically tailored diffusion MRI acquisition performing diffusion tensor imaging (DTI) for varying diffusion times, can be used to determine fiber size and membrane permeability of muscle fibers in vivo. We describe the random permeable barrier model (RPBM) and its assumptions, as well as the details of stimulated echo DTI acquisition, signal processing steps, and potential pitfalls. We illustrate the RPBM method on a few pilot examples involving human subjects (previously published as well as new), such as revealing myofiber size derived from RPBM increase after training in a calf muscle, and size decrease with atrophy in shoulder rotator cuff muscle. Finally, we comment on the potential clinical relevance of our results. Copyright © 2016 John Wiley & Sons, Ltd.

Quantifying myofiber integrity using diffusion MRI and random permeable barrier modeling in skeletal muscle growth and Duchenne muscular dystrophy model in mice

“…Myofiber diameters from other histologic studies were about 30 to 50 μm for human tongue muscles and 30 to 60 μm for beef chuck . More recently, Fieremans et al used the RPBM method to track human calf diameters following an exercise regimen and noted an increase in size in the gastrocnemius medialis . Microstructural changes in the rotator cuff muscles, supraspinatus and infraspinatus, were also examined pre‐operatively and postoperatively and showed a decrease in myofiber size and atrophy secondary to mobility and activity following surgical repair.…”

“…Subsequently, the eigenvalues and eigenvectors of each tensor were calculated. The average of the second and third eigenvalues at each diffusion time t was assumed as the measure of diffusion coefficient D ( t ) perpendicular to the muscle fibers, to which the DTI‐RPBM was fitted . The RPBM mimics the essential geometry of tight fiber packing in which muscle tissue is modeled with infinite planes, representing permeable membranes, randomly placed and oriented, so that they divide the sample into pores with random shapes.…”

“…Recently, Novikov et al developed a model to quantify both cell diameter and membrane permeability based on time‐dependent DTI. The random permeable barrier model (RPBM) provides estimates of average muscle fiber surface‐to‐volume ratio (and thereby fiber diameter), membrane permeability, and water diffusivity in sarcoplasm . This model has been validated using Monte Carlo simulations .…”

Fundamentals of diffusion MRI physics

“…The diffusion coefficient has been found for all times and for a broad range of membrane parameters. It turns out that muscle fibers can be described by the two‐dimensional version of this model, since the fiber membranes are flat and tend to align along common planes over length scales exceeding the typical fiber diameter; see also the article by Fieremans et al in this issue . This model has been applied to accurate diffusion measurements in excised muscles, and has allowed the estimation of intrinsic biophysical parameters such as membrane permeability and the diameter of muscle fibers.…”

Time-Dependent Diffusion MRI in Cancer: Tissue Modeling and Applications

“…Although never applied in tumors, the RBPM geometry is well suited for muscle studies [56], and tissue permeability and cell size were recently estimated in vivo and on clinical scanners [68]. This approach could provide an interesting approach to characterizing sarcomas using TDD in the near future.…”