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
Synopsis
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.Purpose
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.
Methods
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: 200x200mm
2, 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/mm
2 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.
Results
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.
Discussion
Chronic
atrophy (as in aging muscle) results in large increases in both adipose and
connective tissue
3 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, λ
3 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 λ
1
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.
Conclusions
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.
Acknowledgements
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.References
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