Bart Bolsterlee1,2, Elizabeth A Bye3,4, Junya Eguchi1,5, Joanne Glinsky3, Jeanette Thom5, and Robert D Herbert1,5
1Neuroscience Research Australia, Randwick, Australia, 2Graduate School of Biomedical Engineering, University of New South Wales, Randwick, Australia, 3John Walsh Centre for Rehabilitation Research, Sydney University, Sydney, Australia, 4Spinal Injury Unit, Prince of Wales Hospital, Randwick, Australia, 5School of Medical Sciences, University of New South Wales, Randwick, Australia
Synopsis
Accurate quantification of fat content of human muscles could
help assess disease status and test effectiveness of interventions in people
with neurological conditions, whose muscles are frequently infiltrated with fat.
We compared two commonly used MRI methods based on T1-weighted and mDixon scans
to quantify intramuscular fat in 112 muscles from people with and without
spinal cord injury. Fat fraction measurements agreed well in muscles with high
proportions of fat, but the T1-weighted method could not be used in muscles
with small proportions of fat. We recommend against the use of T1-weighted
methods to quantify intramuscular fat.
Introduction
Healthy muscles are composed predominantly of water and
contractile proteins, but also contain small amounts of fat1. Muscles affected by various
neurological conditions, e.g. stroke, cerebral palsy or spinal cord injury,
frequently have an increased proportion of fat2, which may contribute to
weakness and increased stiffness of these muscles. Accurate quantification of
intramuscular fat content could help assess disease status and progression, and
test the effectiveness of interventions aimed at reducing intramuscular fat
content.
The primary aim of this study was to compare measurements of
whole-muscle fat fraction in human muscles using two commonly used MRI methods.
The first method uses T1-weighted scans to classify voxels as ‘fat’ or ‘muscle’
based on an intensity threshold2,3.
The second method uses mDixon scans in which differences in chemical shift
frequency between water and fat are used to quantify, for each voxel, a fat proportion4. We compare a total of 224
fat fraction measurements before and after strength training in individuals with
spinal cord injury and able-bodied individuals.Methods
We used previously published T1-weighted and mDixon MRI
scans of the left or right thigh of nine individuals with partially paralysed
muscles following spinal cord injury (group SCI; median (IQR) age 47 (37 to 66)
years; see ref 5 for details of participant
characteristics). Here we report further analyses of those data and of new
scans from 11 able-bodied young individuals (group AB; age 20 (19 to 22) years)
(Fig. 1).
Scans were obtained both before and after a six-week (SCI) or
eight-week (able-bodied) progressive resistance training program of the upper
leg5. Measurements of fat
fractions were made on a total of 112 muscles (68 from participants with SCI
and 44 from able-bodied participants), both before and after training.
The following scan parameters were used. mDixon: 2-point 3D multi-echo mDixon
fast field echo (FFE) sequence, TR/TE1/TE2=5.9/3.5/4.6ms, field of view
(FOV)=180 × 180mm, acquisition matrix=180 × 180 (reconstructed to 192 × 192),
slice=1 mm, number of slices=320 and scan time of 334 s. T1-weighted: TSE sequence, TR/TE=700/12 ms, FOV=180 × 180 mm,
acquisition matrix=256 × 188 (reconstructed to 864 × 864), slice=4 mm, number
of slices=80.
The four quadriceps muscles were manually segmented on the scans.
In the group with SCI, the four hamstring muscles were also segmented. Segmentations
were cropped by 2 mm to ensure exclusion of all extramuscular tissues.
T1-weighted scans were corrected for B0-inhomogeneities. For
each muscle and slice of the T1-weighted scan, voxels were classified as either
‘fat’ or ‘muscle’ using a fuzzy C-means clustering algorithm (exponent 2, max.
iterations 200, end tolerance 0.01)6.
Whole-muscle fat fraction was calculated (%fat T1) by dividing the number of
‘fat’ voxels by the total number of ‘fat and ‘muscle’ voxels, excluding slices
for which visual inspection revealed implausible classification. Muscles for
which more than 50% of slices were deemed implausible were excluded from
further analysis. From the mDixon scans, fat fractions per voxel were
calculated by dividing the intensity of the mDixon fat image by the sum of the
intensities of the mDixon water and fat image. Fat fractions per muscle (%fat
mDixon) were calculated as the average fat fraction of all voxels assigned to
that muscle.
Fat fraction measurements from T1 and mDixon scans were
compared using the mean signed difference, the mean absolute difference and the
absolute agreement intraclass correlation coefficient (ICC) adjusted for clustering
at the level of participant, muscle and time of measurement (pre/post
training).
The strength training intervention appeared to not affect
the structure5 and proportion of fat in
muscles, so we used the pre- and post-training data to determine minimal
detectable differences (MDD) for both methods.
Results
Fat fraction measurements were successfully obtained from
mDixon scans for all muscles. The %fat mDixon in the able-bodied group was 5.7 ±
1.6 % and in the group with SCI 22.3 ± 18.3 % (values are mean ±
SD).
In the group with SCI, 31/136 (23%) of measurements from
T1-weighted scans were excluded. The excluded muscles had a smaller proportion
of fat (7.4%, measured from mDixon) than the group average (22.3%). In the able-bodied
group, the algorithm could not find a distinctive threshold between fat and
muscle, so it was not possible to obtain plausible measurements of %fat from
T1-weighted scans. A plausible threshold could also not be identified manually.
There was high agreement (ICC = 0.76, 95% CI 0.67 to 0.84)
between %fat mDixon and %fat T1 in muscles of people with SCI (Fig. 2). The
mean absolute difference between the measures was 5.1 ± 6.2%. There was little
systematic difference between the methods: the mean signed difference was 1.1 ±
8.0%.
The minimal detectable difference in the group with SCI was
4.2% and 8.9% using the mDixon and T1-weighted measures, respectively.Conclusion
T1-weighted and mDixon measurements of intramuscular fat
fractions agreed well in muscles with high proportions of fat (group with SCI),
but we could not obtain plausible measurements of intramuscular fat using the
T1-weighted method in muscles with small proportions of fat. The T1-weighted
measures were also less reproducible than the mDixon measures. We recommend the
use of mDixon methods rather than T1-weighted methods for quantification of
intramuscular fat fraction.Acknowledgements
The authors acknowledge the facilities and scientific and technical assistance of NeuRA Imaging, a node of the National Imaging Facility, a National Collaborative Research Infrastructure Strategy (NCRIS) capability.References
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