Diffusion Tensor Imaging (DTI) of the myopathic and dystrophic skeletal muscle
Sarah Keller1, Jerry Zhiyue Wang2, Amir Golsari3, Adam Gerhard1, Hendrick Kooijman4, Mathias Gelderblom3, and Jin Yamamura1

1Diagnostic and Interventional Radiology, University Medical Center Hamburg Eppendorf (UKE), Hamburg, Germany, 2Radiology, University of Texas Soutwestern Medical Center, Dallas, TX, United States, 3Neurology, University Medical Center Hamburg Eppendorf (UKE), Hamburg, Germany, 4MRI, Philips GmbH, Hamburg, Germany

Synopsis

MRI-Diffusion tensor imaging (DTI) based fiber tracking is an emerging tool for the evaluation of alterations in the skeletal muscle architecture caused by trauma and various inflammatory or hereditary diseases. It remains still a matter of debate, whether dystrophic conditions of the skeletal muscle, which are frequently associated with fatty infiltration, can be reliable assessed by DTI, as previous studies showed the potential biasing effect of the fat fraction (%FF) and the concomitant decrease of the signal to noise ratio (SNR) [1, 2]. The goal of this study was to analyze the DTI based apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography data in various conditions of muscular disease, either with or without increase of the FF in comparison to healthy controls on a 3T system.

Purpose

To analyze the DTI based apparent diffusion coefficient (ADC), fractional anisotropy (FA) and tractography data in various conditions of muscular disease, either with or without increase of the MFF in comparison to controls on a 3T system.

Methods

NINE PATIENTS (age 43±19.9y, m:f 5:4) suffering of hereditary muscular dystrophies (Duchenne, Becker and Limb Girdle Muscular Dystrophy Type IIa (DMD, BMD, LGMD), Central Core Disease (CCD) and Spinal Muscular Atrophy Type III (SMA)) and chronic inflammatory myopathy (IMNM), with involvement of the limb girdle muscles and dystrophic changes upon histology and 10 controls were included (Table 1). DTI-based diffusion and tractography data were assessed in combination with the 2p-mDixon muscle fat fraction (MFF%) in the rectus femoris (RF), semitendinosus (ST), biceps femoris (BF) and gracilis (G) muscle in patients and controls.

MRI-scans were performed on a 3.0-Tesla (T) MRI (Ingenia, Software Release 5.1.7, Philips, Best, Netherlands). Subjects were examined in supine position, feet first using a 28-channel sensitivity encoding torso array coil. After a gradient echo localizer sequence (TR/TE 8.0/2.3ms; FOV: RL 450mm, AP 115mm, FH 450mm; slice thickness 15mm), an axial T2w turbo spin echo sequence with Dixon fat-water separation (T2w mDixon TSE), (TR 8111ms; TE 80 ms; FoV 270 x 221 x 300mm with a voxel of 0.65x0.65x3 mm3, TSE factor 13) with post processed images (in-phase- and water images) was performed. For the DTI sequence an axial fat-suppressed multislice spin-echo single-shot echo planar imaging sequence (EPI) (TR/TE 2479/43ms, NSA 8, gradient directions 15, b-values 0, 250 and 500s/mm2, slice thickness 6mm, 1.5mm in-plane resolution) was used. This was followed by an axial water-fat 3D FFE T1-weighted Dixon Sequence (T1w mDixon) with following parameters: TR/TE/ΔTE 4.4 ms/1.18ms/2.6ms, flip angle 3°, FoV 250x250x250mm with voxel 2.0x1.0x0.5 mm3. Post processing produced in- and opposed- phase water and fat images.

IMAGE ANALYSIS The ROI localization was chosen for the maximal transverse crosssectional area of each muscle and ROIs were drawn circumferentially around the muscle using a freehand technique in the RF, ST, BF and G muscle. DTI datasets were analysed using the manufacturers software (FiberTrak; Philips Healthcare). For the fiber tracking analysis, a single ROI line propagation technique with the following parameters was used: FA threshold 0.15, direction threshold 6.75°. Quantitative ADC and FA-values were generated. Muscle fat fraction% (FF) was obtained using two-point Dixon-based MRI (2pt-MRIDIXON) with chemical shift selective reconstruction of fat- and watersignal [3, 4]. Three ROIs, covering the whole muscle were drawn in the (SIFAT) and water-only (SIWATER) image of the proximal, middle and distal part of the RF, ST, BF and G muscle using Osirix (version 6.5). The Muscle Fat Fraction (MFF) was calculated using the algorithm:

MFF% = meanSIFAT/ (meanSIFAT+ meanSIWATER) x 100

STATISTICAL ANALYSIS was performed using GraphPad Prism 6.0f (GraphPad Software Inc., La Jolla, California, USA). Correlation and significance of DTI values from controls and patients was tested by the Student’s T-test and parametric Pearson correlation analyses. The dif-ference was considered statistically significant if the significance level α = 0.05 was reached.

Results

Fiber tractography of affected muscles groups resulted in a significant shortened fiber track lengths, which was predominantly evident in the RF and ST muscle (RF: 28.5±3.3 mm vs. 76.5±7.1 mm; p=0.002; ST: 34.4±5.9 mm vs. 81.8±10.2 mm; p=0.004). The mean ADC was significantly reduced in patient muscle and accompanied by a concomitant increase of the FA (ST: ADC 1.055±0.479 mm2/s*10-3, FA 0.498±0.145; G: ADC 1.056±0.357 mm2/s*10-3, FA 0.532±0.126) (Figure 2). MFF resulted to be elevated in patient muscles (median 11.6%; range 2.9-91.8%) versus control (median 4.8%; range 1.5-9.6%). Using Pearson analysis there was an inverse correlation of the RF, ST, BF and G muscle ADC and FA (rs= -0.91; p<0.0001), and a good correlation of the ADC and fiber length (rs= 0.4551; p=0.005). FA and ADC data of controls and patients correlated significantly to the MFF (FA r= 0.5335; 95%CI 0.248-0.7335; p=0.0008; ADC r=-0.589; 95%CI -0.749-0.2822; p=0.0004) (Figure 3). Automatic calculation of the fiber count revealed a higher variability in fiber count and a tendency of fiber reduction in affected muscles, despite not significant.

Discussion/Conclusion

Our data confirm previous studies, presuming a biasing effect of the MFF% and low SNR on DTI parameters, reflected by an overestimation of the FA and an underestimation of the ADC in highly dystrophic muscles. These confounding factors are not of major concern in muscle disease without concomitant increase of the fatty infiltration and could be circumvented by a ROI selective analysis of muscle tissue without overt fatty infiltration and a high SNR cut-off value.

Acknowledgements

Many thanks to the Department of Neurology for the clinical support and patients contact.

There is no actual or potential conflict of interest in relation to this abstract.

References

1. Froeling, M., et al., DTI of human skeletal muscle: the effects of diffusion encoding parameters, signal-to-noise ratio and T2 on tensor indices and fiber tracts. NMR Biomed, 2013. 26(11): p. 1339-52.

2. Hooijmans, M.T., et al., Evaluation of skeletal muscle DTI in patients with duchenne muscular dystrophy. NMR Biomed, 2015.

3. Dixon, W.T., Simple proton spectroscopic imaging. Radiology, 1984. 153(1): p. 189-94.

4. Ma, J., Dixon techniques for water and fat imaging. J Magn Reson Imaging, 2008. 28(3): p. 543-58.

Figures

Fig.1: DTI tractography (with anatomical T1w fusion) of the RF and ST muscle of a healthy control, moderate and severely affected patient.

Fig. 2.: ADC and FA values obtained in the RF, ST, BF and G muscle in patients and controls. Control black, patients white dots. a) ADC b) FA

Fig. 3.: Pearson Correlation of DTI data and MFF in RF, ST, BF and G muscle in patients and controls. a) Significant inverse correlation of ADC and MFF% (r=-0.589; 95%CI (dashed line) -0.749-0.2822; p=0.0004) b) Significant correlation of FA and MFF% (r= 0.5335; 95%CI (dashed line) 0.248-0.7335; p=0.0008).



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
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