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
Synopsis
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.Purpose
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.
Methods
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.
Results
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.
Discussion
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).
Conclusions
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 Acknowledgements
This work was supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases Grant 5RO1-AR-053343-08.References
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.