Morphological, Compositional, and Fiber Architectural Changes in from Unilateral Limb Suspension Induced Acute Atrophy Model in the Medial Gastrocnemius Muscle.
Shantanu Sinha1, Vadim Malis2, Robert Csapo1, Jiang Du1, and Usha Sinha3

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


Acute muscle atrophy is characterized by a loss of muscle mass and muscle force. Changes are likely to occur in muscle composition, microenvironment, and fiber architecture which could impact muscle function. This study focuses on the changes in these parameters using MR based fat and connective tissue quantification and DTI in a model of acute atrophy induced by Unilateral limb suspension (ULLS). The % changes in fat and connective tissue were minimal while significant decreases were found in fiber diameter (decrease) and in the pennation angle. These changes could be primarily responsible for muscle force loss in acute atrophy.


Structural changes in the muscle are known to occur in both chronic and acute atrophy with these changes potentially linked to muscle function. Most such studies assess only muscle mass and volume changes with atrophy while other potential atrophy induced changes including adipose infiltration, increase in connective tissue, microarchitecture (fiber atrophy and endomysium volume changes), and muscle fiber architecture have not been investigated simultaneously. This study focuses on using MR imaging to determine the changes in these structural parameters by assessing them at baseline (pre-ULLS) and post-ULLS.


Six subjects were recruited for the acute atrophy study after IRB approval. Subjects were scanned prior to ULLS and just post-ULLS. The ULLS model included a 4 week unloading of the dominant leg using crutches and the non-dominant leg supported by a raised shoe. Identical scanning protocols were performed at two time points and in addition to high resolution morphological imaging included the following sequences (geometry parameters were identical for all three at FOV/slice thickness/ acquisition matrix: 200x200mm2, 5mm, 256x256 (DTI was 80x80 extrapolated to 256x256). Adipose Quantification: IDEAL (Iterative Decomposition of Water and Fat with Echo Asymmetry and Least-Squares Estimation) sequence: six TEs between 4.6 and 8.3 ms;1 IMCT Quantification: Fat suppressed 3D Ultra Short Echo Time (UTEs, 3D Cones) sequence: four TEs 0.03ms/2.7ms/5.4ms/7.2ms, TR 71ms.2 DTI: Fat suppressed single shot EPI. 32 gradient directions with a b-factor of 400s/mm2 was used. Imaging parameters were echo time (TE)/repetition time (TR): 49 ms/4000 ms with 4 signal averages. Diffusion data were pre-processed for eddy currents, field map corrections followed by B-spline registration to a volume with geometric fidelity for susceptibility induced artifacts, and denoised prior to computing the diffusion tensor. IMAT and IMCT were segmented from T2* images calculated by Least Means Squares Fit of UTEs images at 4 time points.


The average decrease in maximum voluntary contraction was 26%. An average whole muscle volume change of 15% (from baseline) was determined from the volume measurements of pre and post ULLS MR morphological images (Fig. 1). The absolute values of both connective and adipose tissue (whole muscle) decreased by ~13% which when normalized to muscle changes showed relatively small changes on acute atrophy. Figure 2 shows the segmented adipose and connective tissue from muscle images acquired pre- and post-ULLS. The post-ULLS DTI data showed significant changes from pre-ULLS values: l3 decreased by 22% while the FA values increased by 26%. Figure 3 shows the color coded FA maps from muscle images acquired pre- and post-ULLS on one of the subjects. Pennation angles measured from fibers tracked from the middle of the MG length decreased significantly (average of 8% decrease) with acute atrophy while fiber lengths did not change significantly.


Chronic atrophy (as in aging muscle) results in large increases in both adipose and connective tissue3 while acute atrophy appears to preserve the relative volumes of both types of tissue. This is not surprising in that acute atrophy is over a shorter time period and further, is not accompanied by other changes that may be initiated by the aging process. However, this does not rule out changes in the extracellular matrix such as an increase in the stiffness of connective tissue with acute atrophy. Our dynamic studies using eccentric contraction indicate an increased stiffness of the ECM post-ULLS. The DTI shows interesting results: in the DTI model of diffusion, λ3 is proportional to the fiber diameter and decreases in this parameter indicate that the muscle fiber diameter decreases post-ULLS. The FA value increases since the other two eigenvalues are not affected by the change in the fiber diameter. There were small increases in λ1 presumably arising from the relative increase in the endomysium in a given voxel, since the muscle fiber decreased in diameter. These findings in the acute atrophy are in contrast to the aging model of chronic atrophy where all the three eigenvalues increased with a small increase in FA when comparing a young and old cohort.4 This was explained on the basis of the relatively large increase in the extracellular tissue (e.g., endomysium) which resulted in an increase in all three eigenvalues despite a decrease in fiber diameter. On the other hand, DTI of post-ULLS is determined primarily by the decrease in fiber diameter as there is no significant increase in connective tissue in acute atrophy.


A comprehensive assessment of the structural changes in acute atrophy shows that muscle fiber diameter and pennation angles are significantly altered and these changes can potentially explain the loss of muscle force.


This work was supported by National Institute of Arthritis and Musculo- skeletal and Skin Diseases Grant 5RO1-AR-053343-08. We also acknowledge Michael Carl (GE Medical Systems) for the help with UTEs 3D Cones sequence.


1. Reeder SB, McKenzie CA, Pineda AR, et al. Water–fat separation with IDEAL gradient-echo imaging. J Magn Reson Imaging. 2007;25(3):644-652.

2. Carl M, Bydder GM, Du J. UTE imaging with simultaneous water and fat signal suppression using a time-efficient multispoke inversion recovery pulse sequence. Magn Reson Med. August 2015:n/a–n/a.

3. Csapo R, Malis V, Sinha U, Du J, Sinha S. Age-associated differences in triceps surae muscle composition and strength – an MRI-based cross-sectional comparison of contractile, adipose and connective tissue. BMC Musculoskeletal Disorders. 2014;15(1):209.

4. Sinha U, Csapo R, Malis V, Xue Y, Sinha S. Age-related differences in diffusion tensor indices and fiber architecture in the medial and lateral gastrocnemius. J Magn Reson Imaging. 2015;41(4):941-953.


Figure 1. Morphological images with the muscle mask overlaid on the images from one subject. Corresponding anatomical slices are displayed on the top row (pre-ULLS) and bottom row (post-ULLS). The decrease in muscle cross sectional areas at the three anatomical levels can be appreciated visually.

Figure 2. The top row shows the pre-ULLS and the lower row shows the post-ULLS images of one subject with the segmented tissue overlaid on one of the UTE images. The adipose voxels were determined from the corresponding slice in the IDEAL image. Voxels with both adipose and connective tissue are shown as well.

Figure 3. Eigenvector maps of the low leg for pre- and post-ULLS studies from DTI. The color code is (blue:SI, green: AP, red: LR).

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