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Quantitative assessment of the inter- and intra-muscle fat fraction variability in Duchenne muscular dystrophy patients
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B. Wokke1, J. van den Bergen1, A. Aartsma-Rus2, A. Webb3, J. Verschuuren1, and H. Kan3
Neurology, Leiden University Medical Centre, Leiden, Netherlands, 2Human genetics, Leiden University Medical Centre, 3Radiology, Leiden University Medical
Centre
Introduction: Duchenne muscular dystrophy (DMD) is an X-linked recessive disease characterized by progressive muscle weakness. In young
patients the weakness predominates in the pelvic girdle and upper leg and eventually becomes more generalized leading to wheelchair dependence in
patients’ early teens and death in their late twenties. Regular T1-weighted MR imaging of the muscles shows increased fatty infiltration with age,
with some muscles being earlier and more severely affected at an earlier stages of the disease1.
With the recent development of potential therapies for the disease2.3, interest in non-invasive methods for longitudinal follow up has increased. A
promising method is the 3-point Dixon technique4 which can be used for quantitative evaluation of the fat fraction in the muscle5. For this technique
to be used in therapy evaluation, a quantitative and detailed overview of the natural history and variability of the disease is very important. In this
study, we aimed to quantitatively assess the variation in fat fraction between and within muscles in DMD patients from 8–13 years of age.
Methods: Ten DMD patients (age 10.5 ± 2.5 years) and eight healthy age-matched controls were scanned on a 3T Philips Achieva Scanner (Best,
NL). The scanning protocol consisted of a T1-weighted (twenty five 5 mm slices, 0.5mm gap, TR 600, TE 16) and a 3-point Dixon scan with
multipeak reconstruction6 (twenty five 5 mm slices, 0.5mm gap, TR 400, TE 4.41, FA 8°) for both the upper- and the lower leg. Regions of interest
(ROIs) were manually drawn on the co-registered T1 images in the muscles in the 12 central slices in the upper- and the 10 central slices in the lower
leg using MIPAV7. Fat fraction was obtained as SIfat /(SIfat+cSIwater), where the factor c corrects for the differences in proton density and T2
relaxation effects8. Seven muscles were analyzed in the lower leg (medial gastrocnemius, lateral gastrocnemius, soleus, anterior tibialis, extensor
digitorum longus, peroneus and the posterior tibialis) and eleven muscles in the upper leg (rectus femoris, vastus lateralis, vastus intermedius, vastus
medialis, biceps femoris short en long head, semitendinosus, semimembranosus, adductor magnus, gracilis and sartorius muscle). For each muscle,
fat fractions were correlated with age and approximated with linear regression to obtain
an overview of the rate of fatty infiltration per muscle. Additionally, the variation
between the fat fraction in the two most proximal and two most distal slices were
compared with a paired t-test.
a.
b.
Fig.1 Fatty infiltration in the upper leg of an eight
year old (a) and 13 year old (b) DMD patient
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Posterior tibialis
tibialis muscles the fat fraction was higher in the proximal than in the distal slices.
In healthy controls there was a significant difference in the medial and lateral
gastrocnemic muscle as well. However, this difference was in opposite direction
with a higher fat fraction in the proximal slices.
Peroneus
Fat fraction %
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Fat fraction %
Results: All controls and nine patients completed the protocol successfully, in one
patient only the lower leg was scanned because the patient could not be positioned
comfortably. In the upper leg all muscles in all patients were clearly affected (fig.1) with
fat fractions ranging from 5.5% to 92.5%. Interestingly, the semitendinosus, gracilis and
sartorius muscles were relatively spared in the younger patients. In the lower leg fat
fractions ranged from 3.7% to 76.5% and were lowest in the posterior tibialis and highest
in the peroneus muscle (fig.2). Linear regression of the data showed that
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the peroneus muscle increased with 14% per year (R2=0.87) while the
posterior tibialis muscle only increased with 5.6% per year (R2=0.74).
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In addition to differences between muscles, variation in fatty infiltration
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within muscles was also present. In the medial and lateral
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gastrocnemius differences up to 30%, and in the anterior and posterior
20
tibialis muscle differences up to 18 % were observed between the most
distal and most proximal slices. In the gastrocnemii the fat fraction was
0
0
2
higher in the distal slices than in the proximal ones, however in the
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40
20
4
6
8
Age (yrs)
10
12
14
0
0
2
4
6
8
10
12
14
Age (yrs)
Fig. 2 Increase of fat fraction with age in the posterior tibialis and
peroneus muscle in a DMD patient. The rate of increase in fatty
infiltration is higher in the peroneus muscle compared to the
posterior tibialis muscle
Conclusion: In this study we carried out a detailed and quantitative overview of fatty infiltration in 18 different muscles in the legs of DMD patients.
In agreement with previous qualitative methods1,9, a large variation is present in the amount of fatty infiltration between the various muscles in DMD
patients, especially in the early stages of the disease. Our quantitative analysis shows differences in the rate of fatty infiltration between different
muscles. We approximated the increase in fatty infiltration with linear regression due to the relatively low number subjects in our study, however the
increase is likely to be sigmoidal. We also observed differences in the fat fraction between the distal and proximal regions of the same muscles which,
to our knowledge, has not been reported before.
If the amount of fatty infiltration is used as a method for quantitative therapy follow-up in DMD patients, it is not feasible to analyze all muscles. Our
study suggests that analyzing only the most affected, such as the peroneus muscle and the least affected muscle, the posterior tibialis, might provide
sufficient information to evaluate the disease process. Nevertheless the variation between the distal and proximal slices, as observed in several
muscles, underlines the importance of analyzing multiple slices.
References
[1] Liu et al, Radiology 186 475-480 (1993) [2] Van Deutekom et al. N Engl J Med, 357(26), 2677-2686 (2007) [3] Kinali et al. Lancet Neurology 8, 918-928 (2009) [4]
Dixon WT Radiology 153, 189-194 (1984) [5] Wren et al AJR J Roentgenol., 190, W8-W12 (2008) [6] Yu et al. Magn. Reson. Med, 60, 1122-1134 (2008) [7]
http://mipav.cit.nih.gov [8] Reeder SB, et al. Proc. Intl. Soc. Mag. Reson. Med. 17, 211 (2009) [9] Mercuri et al. J.Magn.Reson.Imaging 25, 433-440 (2007)
Proc. Intl. Soc. Mag. Reson. Med. 19 (2011)
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