Functional Changes in Medial Gastrocnemius from Unilateral Limb Suspension Induced Acute Atrophy: a 2D Strain Rate Study during Isometric Contraction
Vadim Malis1, Usha Sinha2, Robert Csapo3, and Shantanu Sinha3

1Physics, University of California at San Diego, San Diego, CA, United States, 2Physics, San Diego State University, San Diego, CA, United States, 3Radiology, University of California at San Diego, San Diego, CA, United States


Unilateral limb suspension is a controlled method to generate acute atrophy. The loss of muscle force with acute atrophy may be due to changes in contractile elements and extracellular matrix (ECM); a study of the strain rate (SR) patterns could provide information on these changes. Subjects were assessed at baseline (pre-ULLS) and post-ULLS using dynamic velocity encoded phase contrast MR imaging. The indices extracted from the SR tensor show at post-ULLS (i) a decrease in the asymmetry of deformation in the fiber cross-section and (ii) larger SR-muscle fiber angles. These findings may reflect a loss of integrity in the ECM.


Acute atrophy induced by unilateral limb suspension (ULLS) results in muscle force loss disproportionate to the loss of muscle mass.1 Spatially localized strain rate tensors can be computed from velocity encoded phase contrast images that have the potential to identify changes in tissue deformation along and perpendicular to the muscle fiber. This study maps the muscle strain rate (SR) tensor from a series of velocity encoded phase contrast (VE-PC) images acquired under isometric contraction at baseline (pre-ULLS) and after ULLS for 4 weeks (post-ULLS) to explore the changes induced by acute atrophy.


Six subjects were recruited after IRB approval and scanned at baseline, post-ULLS, and after rehabilitation for 4 weeks. Muscle atrophy was induced using the ULLS model for 4 weeks, in which the subjects used a pair of crutches and a 5-cm raised heel shoe on the non-dominant foot. The dominant leg was thus unloaded for that period inducing acute atrophy of the leg. Dynamic images of the lower leg were acquired during isometric contraction using a gated VE-PC sequence on a 1.5-T GE scanner with a specially designed 8-Ch phased array coil, and the leg in a plaster cast.2 Images were velocity encoded in all three directions, and collected in 22 phases, 7 oblique-sagittal contiguous slices, 5mm thick and 1.7x1.7 mm in-plane resolution. Subjects were provided visual feedback within the scanner to maintain consistent contractions at ~40% MVC. Muscle fascicles were manually delineated on water-suppressed images to obtain fiber orientation during the dynamic cycle and tracked using VE-PC. The symmetric part, D, of the strain rate tensor SR tensor was calculated from the spatial gradient tensor, L and diagonalized; eigenvectors corresponding to the positive and negative values were analyzed separately. The out-of-plane strain rate was calculated from sum of the in-plane eigenvalues at each voxel. The angle made by -ve eigenvectors with the positive X-axis was defined as the SR angle and SR-muscle fiber angles were calculated. Statistical analysis compared pre- to post-ULLS cohorts based on (i) SR indices at peak –ve eigenvalue and (ii) at the same force level (corresponding to the post-ULLS force for each subject) during contraction.


Fig. 1 shows the eigenvalue images from pre-and post-ULLS imaging studies for one subject at the peak of the contraction cycle. Figure 2 shows the dynamic plots of the three eigenvalues and SR-fiber angle; the values are averaged over 3 ROIs (proximal, middle and distal), slices and subjects. The differences between the pre- and post ULLS subjects is most evident in the SR in the fiber cross-section (Fig. 1, middle and last columns) as well as in the SR-fiber angle (Fig. 2, last column). As muscle is incompressible, the sum of the two eigenvalues (out-plane component) should be close to zero if the SR is completely in-plane; this component increases significantly in the post-ULLS study. Statistical significant differences were found in the SR-fiber angle (Fig. 3) and in the positive eigenvalues comparing pre and post ULLS cohorts (SR-fiber angle larger and positive eigenvalue smaller post-ULLS); regional differences were seen in the SR along the fiber with proximal values significantly smaller than middle and distal regions.


Significant differences were seen only in the in-plane fiber cross-section SR, where the value decreased post-ULLS. It can be inferred that the in-plane deformation is more symmetric in the post-ULLS cohort (Fig. 4); this is also seen as an increase in the out-of-plane SR component in the post-ULLS cohort (Fig. 2, 3rd column). One of reasons hypothesized for the deformation asymmetry is the incorporation of tensile materials (such as costameres) oriented along the through-plane axis of the fiber to limit relaxation in that direction.3 The finding that post-ULLS SR results in lower asymmetry of deformation may potentially indicate a compromise in the tensile materials and/or the extracellular matrix. Earlier studies have hypothesized that the SR-fiber angle potentially reflects the effect of lateral transmission (of force generated distally since it is higher) mediated by the extracellular matrix (in the absence of any lateral force transmission, the principal axis of contraction (SR) should be along the fiber). Larger SR-fiber angles in the post-ULLS cohort may reflect the larger regional variation in that cohort (distal and middle larger than proximal).


Reduction in deformation asymmetry in the fiber cross-section and increase in SR-fiber angle may potentially be indices of extracellular remodeling with atrophy that could provide physiological insight into loss of muscle force disproportionate to loss of muscle volume in atrophy as well as disease conditions such as muscular dystrophy where architectural disruption decreases lateral force transmission.4


This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant 5RO1-AR-053343-08.


1. Shin D, Finni T, Ahn S, et al. Effect of chronic unloading and rehabilitation on human Achilles tendon properties: a velocity-encoded phase-contrast MRI study. J Appl Physiol. 2008;105(4):1179–1186.

2. Sinha S, Hodgson JA, Finni T, et al. Muscle kinematics during isometric contraction: Development of phase contrast and spin tag techniques to study healthy and atrophied muscles. J Magn Reson Imaging. 2004;20(6):1008–1019.

3. Kinugasa R, Hodgson JA, Edgerton VR, Sinha S. Asymmetric deformation of contracting human gastrocnemius muscle. J Appl Physiol. 2012;112(3):463–470.

4.Englund E, Christopher E, Qing X, et al. Combined Diffusion and Strain Tensor MRI Reveals a Heterogeneous, Planar Pattern of Strain Development During Isometric Muscle Contraction..” Am J Physiol Regul Integr Comp Physiol. 2011;300(5):R1079-9.


Figure 1. 2D SR indices extracted from pre- and post-ULLS imaging on one subject. The top row is pre-ULLS and lower row is that of post-ULLS. Values are color coded and SRfiber is the strain rate along a direction close to the muscle fiber direction; SRin-plane is the strain perpendicular to SRfiber in the plane of the image; SRout-plane is derived from the other two and is orthogonal to both. Changes are see in the MG in SRin-plane and SRout-plane post-ULLS.

Figure 2. SR indices (negative eigenvalue (1st column), positive eigenvalue (2nd column), sum-eigenvalues (3rd column), SR-fiber angle (4th column) averaged over ROIs, slices and subjects (pre- top row, and post- bottom row ULLS) over the dynamic cycle. Negative (positive) eigenvalues differ in the latter (first) half of the dynamic cycle confirming that changes occur in the in-plane deformations. Out-of-plane SR and SR-fiber angles are increased post-ULLS.

Figure 3. Streamlines are generated from the negative SR eigenvector at contraction peak. The SR lines are color coded by the –ve eigenvalue. Muscle fibers identified from the fascicles are shown in black. The inset shows the angle between the SR and fiber (SR-fiber angle) that is larger in the post-ULLS images.

Figure 4. Schematic of muscle fiber orientation and the definition of the SR eigenvalues: Figures b-e show the potential ways of deformation in the fiber cross-section (from symmetric (b), moderately asymmetric (c), severely asymmetric (d and e). The SRin-plane (light circle), is calculated form the VE-PC images while SRout-plane (dark circle) is derived from the other two eigenvalues. The pre-ULLS case is between (c) and (d) while the post-ULLS case is closer to (a).

Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)