Ericky Caldas de Almeida Araujo1,2, Harmen Reyngoudt1,2, and Pierre G. Carlier1,2
1NMR Laboratory, Neuromuscular Investigation Center, Institute of Myology, Paris, France, 2NMR Laboratory, CEA/DRF/IBFJ/MIRCen, Paris, France
Synopsis
Although
sensitive to disease activity, the mono-exponential muscle water T2
is non-specific to the underlying dominant pathophysiological processes taking
place in the different neuromuscular disorders. In this work we performed
multi-exponential analysis of muscle water T2-relaxation data acquired in healthy
subjects, Duchenne Muscular Dystrophy and Inclusion Body Myositis patients. T2-decay curves were obtained using 1H NMR spectra acquired at
different echo times. The results put in evidence a distinct water T2-relaxation
behavior between inflammatory and dystrophic myopathies, supporting the
hypothesis that a multi-exponential analysis of T2-relaxation data can reveal
specific pathophysiological information that is missing from mono-exponential
analysis.
Introduction
NMR is a largely exploited tool in clinical
studies in the field of neuromuscular disorders. Increased mono-exponential water
T2 (T2w) in
skeletal muscle is a marker of different pathophysiological processes such as
inflammation, edema, cellular membrane disruption or alterations of
histological water compartmentation1,2. However, the T2-relaxation
of water signals in skeletal muscle is known to be characterized by a
multi-exponential behavior which probably reflects the histological
compartmentation of water in the tissue3. We hypothesize that a multi-exponential
analysis of the water T2-relaxation could provide disease activity markers that
are specific to the underlying pathophysiological process2. In the present work we investigate the
multi-exponential behavior of the muscle water T2-relaxation in inflammatory
and dystrophic myopathies, obtained from 1H NMRS data.Methodology
NMR
examinations were performed on 3T (Trio and Prisma, Siemens) clinical scanners. Data were acquired in the leg (Gastrocnemius
Med. or Tibialis Ant. or Soleus) using a 15-channel volume transceiver knee
coil or in the thigh (Vastus Lat. or Vastus Med. or Rectus femoris or
Sartorius) using the body coil transmitter and an 18-channel surface coil receiver.
The cohort included 114
Inclusion Body Myositis (IBM) patients, 30 Duchenne Muscular Dystrophy (DMD) patients and 55 control subjects. Single
voxel (STEAM) 1H NMR spectra were obtained at 14 echo times
(TE=20/27/36/45/54/63/81/90/108/135/162/198/243/288 ms) with the frequency
centered to the water resonance (4.7 ppm). Other relevant parameters were: TR=6500ms,
TM=10ms and 4 averages. VOI’s sizes ranged between 15x15x15 mm3 and
20x20x20 mm3 and care was taken to avoid the inclusion of visible
blood vessels. Automatic three-dimensional map shim and further interactive "manual" shimming were performed. 1H NMR spectra were processed in jMRUI.
All spectra were aligned with the water frequency at 4.7 ppm, followed by
Lorentzian apodization and zero order phasing if necessary. Using the AMARES
algorithm, the water and up to six lipid resonances were fitted, adding prior
knowledge for frequencies, phases, linewidths and lineshapes (Lorentzian). The
T2-relaxation curves were obtained by plotting the water peak area at each TE.
Mono- and bi-exponential models were fitted to the data using non-negative
least squares (Matlab, Mathworks). For each decay curve, the best adapted model
was determined by comparing the adjusted R2 of both fits. This
process allowed to separate the data into two sets: the monoexp set which regroups the data presenting a mono-exponential
behavior; and a biexp set which regroups
data presenting a bi-exponential behavior. Kruskal-Wallis
tests were performed for comparing the extracted mono- and
bi-exponential parameters between the three groups of subjects. First, the comparisons included all data for
both models. Then the comparisons of the mono- and bi-exponential parameters
were performed within the corresponding monoexp
and biexp sets, respectively.Results
The percentages of data that are better
represented by mono- and bi-exponential models in IBM patients were
significantly different from those observed in the DMD and control groups
(p<0.001, Chi-square test). In the
control and DMD groups, 84% (46 out of 55) and 90% (27 out of 30) of the data,
respectively, were better represented by a mono-exponential model, while 79% (90
out of 114) of the data from the IBM group were better represented by a
bi-exponential model. Significant differences (p<0.001) of T2w
obtained from mono-exponential fitting were observed between controls and patients in both comparisons (including all
subjects or within the monoexp set) (Fig.
1). Concerning the bi-exponential results, for the data in the monoexp set, the results were
meaningless, either presenting two identic T2 values or negligible
long-T2 relative fractions (<1%) with extremely large confidence
intervals for the long-T2 value (>1000ms). For this reason the
comparisons were restricted to subjects in the biexp set. IBM patients were characterized with an abnormally high relative
fraction of the long-T2 component (13±1% against 4±4% in controls,
p<0.01) (Fig. 2-a). No significant differences were observed on the
extracted T2 values between the IBM and controls (Figs. 2-b and 2-c). The DMD
group was excluded from the statistical analysis of the bi-exponential parameters due to low statistical power
(only 3 subjects in the biexp set).Discussion and Conclusion
Although
mono-exponential T2w has been once again confirmed as a marker of
disease activity, it was unable to separate between DMD and IBM patients. On
the other hand, the multi-exponential analysis put in evidence a distinct
behavior of the T2-decays between the DMD and IBM groups, which probably
reflects the distinct pathophysiological processes taking place in
dystrophic (DMD) and inflammatory (IBM) myopathies. This result supports the
hypothesis that a multi-exponential analysis of T2-relaxation data might reveal
specific pathophysiological information that are missing from mono-exponential
analysis and from standard T2-mapping methods, which usually assume a
mono-exponential behavior for muscle water T2-relaxation4,5.Acknowledgements
No acknowledgement found.References
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