Max Kaplan1,2, Alice Hatt1, Bezahd Babaei1,3, Lauriane Jugé1,2, and Lynne Bilston1,2
1Neuroscience Research Australia, Randwick, Australia, 2University of New South Wales, Kensington, Australia, 3University of Melbourne, Parkville, Australia
Synopsis
Intramuscular
fat (IMF) increases with BMI and age, but it is unknown how it affects skeletal
muscle viscoelastic properties, despite the key role skeletal muscle mechanical
properties play in our capacity to move. We studied the effects of IMF on
the anisotropic mechanical properties under large deformation of the calf
muscles in healthy and obese participants, using an advanced approach
incorporating diffusion tensor imaging data into magnetic resonance
elastography reconstructions. Results show that intramuscular fat had no
significant effect on muscle shear moduli, but stretching or shortening muscle altered
the parallel and/or perpendicular stiffness and viscosity of some muscles.
Introduction
Intramuscular fat (IMF) is a form of ectopic adipose tissue
which has been shown to increase with BMI1 and age2. With
an increasingly overweight and ageing population, it is important to understand
the effects that this under-researched tissue is having on our bodies. A number
of studies have investigated the metabolic properties of IMF3, but
no experimental studies have investigated the effect of IMF on the mechanics of
skeletal muscles. This is significant as the mechanical properties of skeletal
muscle govern our capacity to ambulate, interact with the world and move,
affecting all aspects of our daily lives.
Most previous studies investigating the mechanical
properties of soft tissues have only captured small deformation effects, and
assume mechanical isotropy, where skeletal muscle is distinctly anisotropic and
regularly undergoes very large deformations. Recent studies have developed
methods for reconstructing the anisotropic mechanical properties of soft
tissues4 and for the determination of large deformation effects on
soft tissue5, but no studies have sought to combine these methods.
The aim of this study is to determine the effect of
intramuscular fat and of large deformations on the anisotropic viscoelastic
properties of skeletal muscle in vivo
using newly developed methods to combine magnetic resonance elastography (MRE)
and diffusion tensor imaging (DTI). The hypothesis of the study is that large
deformation muscle anisotropic properties will vary with muscle fat content.Methods
Ten obese participants ( BMI >30kg/m2,
5 women) with a sedentary lifestyle, and 10 control subjects matched
individually for age and gender with a normal BMI (<25kg/m2) and
active lifestyle were scanned on a 3T MRI (Philips Achieva 3TX). Images were
collected in a plane obliquely through the right calf in three ankle positions
(neutral, maximally dorsiflexed, maximally plantarflexed) and in the neutral
position during an isometric plantarflexion contraction of 10% of maximum, to
investigate the large deformation mechanical behaviour of the the Medial Gastrocnemius (MG), Soleus (Sol)
and Tibialis Anterior (TA) (Figures 1 and 2). In each condition, oblique-sagittal Magnetic
Resonance Elastography (MRE), Diffusion
Tensor Imaging (DTI) and two-point gradient echo mDixon were collected. Imaging
parameters used were:
MRE : 50Hz
excitation applied to the Tibia, TR/TE = 182.5/9.21ms, voxel size 3x3x3mm, FOV
192x192mm2, nine slices, flip angle 30°. DTI: Single-shot EPI sequence, 33 gradient direction, b
factor = 500s/mm2 and TR/TE = 360ms/51.48ms with matching field of
view (FOV) and voxel size as the MRE scans. mDixon: TR/TE = 4.152/2.37 ms, flip
angle = 5°, resolution = 128x128mm and 3mm slice thickness.
An axial
mDixon scan of the whole calf was collected to determine the fat fraction of each muscle (MG, Sol, TA) (Figure 3). Out-of-phase mDixon images were used to define
regions of interest for the MG, Sol and TA stiffness maps (Figure 4A). The
first eigenvector of the diffusion tensor from DTI scans was combined with
isotropic viscoelastic properties derived from MRE in a previously described process4 to
determine the transversely isotropic stiffness (G'∥,G’⊥) and the
isotropic viscosity of each voxel (G"). Repeated
measured two-way ANOVAs were used to investigate change in mechanical
properties with strain for each muscle.Results
Muscle shear
moduli varied significantly with deformation. Specifically, muscle stretch resulted
in significant increases in storage and loss moduli both parallel and
perpendicular to the muscle fibre direction, although the effects varied
between muscles (Figures 4 and 5) (MG G'∥ & G" p<0.005; Sol G'∥ p<0.005, G" p=0.046; TA G’⊥ p=0.018). No
statistically significant interaction was found between the effects of IMF
group (normal mean ~6%, high mean ~9%) and muscle strain (slack, neutral or
stretched) or contraction (neutral or 10% plantarflexion) on muscle shear
moduli.Conclusion
Muscle
deformation, especially stretch, has a substantial effect on the apparent
stiffness of the muscle as measured by anisotropic MRE, while intramuscular fat
appears to have minimal effect on stiffness. Specifically, when under tension,
whether from flexion or passive stretching, skeletal muscles become
significantly more stiff parallel to the muscle fibre’s axis, and this increase
is greater than that observed in the direction perpendicular to the muscle
fibres. This suggests that skeletal muscle becomes more anisotropic under tension.Acknowledgements
The authors of this study would like to thank the staff at
the i-Med Imaging facility at NeuRA, in particular radiographers Mardi
Salvestrin and Adrian Hudson. We would also like to thank Dave Menardo and Artemij
Iberzanov in the NeuRA workshop for their assistance with building the
equipment used in this study, and Bart Bolsterlee for his input into the
analysis of DTI data.References
1. T. N. Hilton, L. J. Tuttle, K. L. Bohnert, et al. Excessive
Adipose Tissue Infiltration in Skeletal Muscle in Individuals With Obesity,
Diabetes Mellitus, and Peripheral Neuropathy: Association With Performance and
Function. Physical Therapy, vol. 88, no. 11, pp. 1336-1344, 2008.
2. R. L. Marcus, O. Addison, J. P. Kidde, et al. Skeletal
Muscle Fat Infiltration: Impact of Age, Inactivity, and Exercise. The Journal
of Nutrition, Health & Aging, vol. 14, no. 5, pp. 362-366, 2010.
3. O. Addison, R. L. Marcus, P. C. LaStayo, et al. Intermuscular
Fat: A Review of the Consequences and Causes. International Journal of
Endocrinology, vol. 2014, p. 11, 2014, Art. no. 309570.
4. E. C. Qin, et al. Combining MR elastography and diffusion
tensor imaging for the assessment of anisotropic mechanical properties: A
phantom study. Journal of Magnetic Resonance Imaging, vol. 37, no. 1, pp.
217-226, 2013.
5. K. Tan, L. Jugé, A. Hatt, et al. Measurement of large
strain properties in calf muscles in vivo using magnetic resonance elastography
and spatial modulation of magnetization. NMR in Biomedicine, 31:e3925, 2018.