Benjamin Marty1,2, Bertrand Coppa1,2, Pierre-Yves Baudin3, and Pierre G. Carlier1,2
1NMR Laboratory, Institute of Myology, Paris, France, 2NMR Laboratory, CEA, DRF, I²BM, MIRCen, Paris, France, 3Consultants for Research in Imaging and Spectroscopy, Tournai, Belgium
Synopsis
The development of quantitative NMR outcome
measures in order to monitor natural history of neuromuscular disorders or
therapeutic interventions is crucial. Global muscle T1 values is strongly
affected in chronic disease when healthy muscle is replaced by fat and this parameter
can be used for diagnostic purposes. Nevertheless, very little is known about
the effects of tissue water compartmentation and distribution on muscle T1
values. Here, we investigated the variations of skeletal muscle T1 values under
various physiological conditions using a fast T1 mapping sequence and evaluated
the potential of this biomarker in the context of disease monitoring.
PURPOSE
In
the field of neuromuscular diseases, recent years have seen tremendous progress
towards the development of quantitative NMR-based outcome measures in order to
monitor natural history of diseases or therapeutic interventions. The
outcome measures the most frequently integrated in clinical research protocols are
the muscle cross sectional volume, the percentage of intramuscular fat and the
muscle water T2 which are respectively used to monitor muscle trophicity,
chronic degenerative changes, and disease activity1. It is also well
known that global muscle T1 values can be strongly affected in chronic disease
when healthy muscle is replaced by fat. This is often used for diagnostic
purposes: T1 weighted images can be graded using the Mercury-Lamminen scale2
to qualitatively assess chronic degenerative changes. Nevertheless, very little
is known about the effects of inflammatory or lesional processes, and more
generally on tissue water compartmentation and distribution on muscle T1
values. With the development of fast T1 mapping sequences, it is now possible
to quantitatively monitor this parameter within acquisition times compatible
with clinical research protocols. The goal of this study was to investigate the
variations of skeletal muscle T1 values under various physiological conditions using
a fast T1 mapping sequence and evaluate the potential of this biomarker in the
context of disease monitoring.METHODS
NMR imaging
of the lower limbs was performed at 3T on 24 healthy volunteers and 43 patients
suffering from different neuromuscular pathologies (13 Becker and 12 Duchenne
dystrophy, 6 inclusion body myositis: IBM, 12 other myopathies). Five volunteers
were scanned on the lower legs before and after a 10’ plantar extension bout. The
T1 mapping sequence consisted in the acquisition of a 1000 radial spokes FLASH
echo train following magnetization inversion. A golden angle of 111.2° was
imposed between the acquisitions of 2 successive spokes for optimal k-space
coverage. The following parameters were used: TE/TR = 2.75/5.08 ms, FA = 8°, BW
= 1000 Hz/px, FOV = 350 mm2, resolution = 1.8x1.8 mm2, 5
slices, slice thickness = 10 mm, Tacq = 50s. For each slice, 141
images were reconstructed using view sharing and a compressed sensing algorithm
with total variation regularization3 (Figure 1). Bloch simulations combined
with a dictionary fitting approach allowed to adjust the signal evolution and derive
a T1 value (Figure 2). An MSME sequence was also acquired (TR=3000 ms, nominal
flip angles=90°/180°, a train of 17 echoes from 9.5 to 161ms, ES = 9.5ms, resolution
= 1.4x1.4mm2, same slice geometry, Tacq = 3min41s) to
estimate water T2 with a bi-component EPG fitting approach4. Finally,
a 3D GRE acquisition was performed (TE1/TE2/TE3/TR = 2.75/3.95/7.55/10ms,
spatial resolution = 1x1x5mm3, Tacq = 1min36s) to derive fat
fraction maps using the 3-pt Dixon approach5.RESULTS
Figure
3 represents T1 maps estimated at the thigh and leg levels on a healthy
volunteer, a Duchenne patient, an IBM patient, and at the leg level for a
volunteer before and after exercise. T1 variations within muscle groups are clearly
visible on the two patients, and in the recruited muscles of the volunteer
post-exercise. As expected, on the whole cohort of subjects, T1 values
negatively correlated with fat fractions (R = -0.76). T1 were also positively
correlated with water T2 values in regions of interest where fat fractions were
less than 6% (R = 0.65). Mean T1 and water T2 values in these regions were
summarized in table 1. They were both significantly higher in the legs than in
the thighs for the volunteer group (p<0.01) and both statistically higher in
the IBM and Duchene group than in the volunteers group (p<0.01).DISCUSSION
T1
maps were successfully acquired on a large cohort of subjects with acquisitions
time compatible with clinical research protocols. Indeed, this short scan time of
10 seconds per slice provides a valuable advantage to this approach if fast
imaging is mandatory (dynamic acquisitions, imaging of pediatric population).
The global T1 measured here integrated both water and fat contributions, and
was, as expected lowered when intramuscular fat was present. Nevertheless,
global T1 alone would have been pointless if fat fractions had not been
obtained from Dixon. Interestingly, in regions of low fat fractions, global T1
was systematically increased when water T2 was increased. The sensitivity of
the T1 and T2 approaches were equivalent to discriminate between the different muscle
conditions. The next step will be to develop a bi-compartment fitting approach
in order to simultaneously estimate water T1 and fat fractions from this T1
mapping sequence.CONCLUSION
Water
T1 represents a good candidate for fast, sensitive and quantitative monitoring
of neuromuscular diseases.Acknowledgements
No acknowledgement found.References
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Trials. Journal of Neuromuscular Diseases, vol. 3, no. 1, pp. 1-28, 2016 .
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Schneider E. Three-point Dixon technique for true water/fat decomposition with
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