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Single-shot Trace Diffusion Weighted Radial Spectroscopic Imaging of Human Calf Muscle: Intra-/Extra-myocellular Lipids and Metabolites

Michael Albert Thomas¹, Ajin Joy¹, Andres Saucedo¹, Uzay Emir², and Christine Darwin³
¹Radiological Sciences, UCLA Geffen School of Medicine, Los Angeles, CA, United States, ²College of Health and Human Sciences, Purdue University, West Lafayette, IN, United States, ³Medicine, UCLA Geffen School of Medicine, Los Angeles, CA, United States

Synopsis

Keywords: Muscle, Diffusion/other diffusion imaging techniques, Magnetic Resonance Spectroscopic Imaging, Radial trajectories

Motivation: To investigate the diffusion of calf muscle intra-myocellular droplets in diabetes and obesity.

Goal(s): To validate diffusion-weighted radial echo-planar spectroscopic imaging (DW-REPSI) in calf muscle.

Approach: We acquired DW-REPSI spectra using 2 different b-values in 3 young healthy subjects and one type2 diabetic patient; regional variations of intra- and extra- myocellular lipids (IMCL and EMCL), creatine and trimethylamines (TMA) and their diffusivities were quantified.

Results: Decreased TMA was recorded in the tibialis anterior muscle compared to that of soleus and gastronomic muscles. ADCs of IMCL and EMCL and metabolites were quantified. Lower ADCs of IMCL indicated restricted motion. Shifts in EMCL was observed.

Impact: A diffusion-weighted spectroscopic imaging sequence was evaluated to investigate the diffusion characteristics and regional variations of IMCL, EMCL and metabolites in calf muscle. The outcome may provide new biophysical insights in the investigation of lipid metabolism in diabetes.

Introduction

In skeletal muscle tissues, two pools of lipids are found: intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL)^1-3. In sedentary and diabetic subjects, an inverse correlation was found between the IMCL and insulin sensitivity^4-6. In addition to IMCL and EMCL in leg muscles, metabolite resonances of creatine/phosphocreatine (Cr/PCr), choline or trimethylamines (TMA) and carnosine (Car) have also been detected in calf muscle earlier⁷. Varying IMCL and EMCL levels in different muscle regions using MR spectroscopic Imaging (MRSI) have also been reported^7-10. It has been known previously that the magnetic field deviations experienced by EMCL compartments were between 0.6 to -0.2 ppm with respect to the resonance of IMCL in the soleus muscle^11-12. High resolution MRSI of calf muscle was demonstrated by Weis et al. using echo-planar spectroscopic imaging¹². Radial k-space sampling techniques have gained widespread use in MRI due to their relatively decreased sensitivity to motion-related artifacts, inherent SNR advantage, and great potential for high acceleration^13-14. Feasibility of radial echo-planar spectroscopic imaging (REPSI) to record metabolites in multiple-regions of brain was demonstrated recently¹⁵. The goals of the present study were 1) to evaluate a recently implemented single-shot trace DW-REPSI using radial trajectories in human calf muscles and 2) to quantify apparent diffusion coefficients of lipids and metabolites in different calf muscle regions.

Materials and Methods

A Siemens 3T Prisma-Fit MRI Scanner with a 15-channel phased-array receive/transmit knee coil was used. The study participants consisted of three young healthy volunteers (mean age 27.7 years), and one 69 years-old type 2 diabetes mellitus (T2DM) subject. A PRESS localization was used for volumetric excitation with an initial 90° RF excitation pulse along the slice (z) direction followed by two Mao 180° RF pulses along the x and y directions to acquire an axial in-plane orientation. Outer volume suppression bands were placed to suppress signals from lipid-dominant outer regions and water suppression was done using a three-pulse WET sequence¹⁶. The 20mm slab thickness of the volume-of-interest (VOI) with the matrix size of 32×32 and FOV of 320×320 mm2 resulted in a voxel volume of 2.0 mL. A symmetric bi-polar trapezoidal gradient echo train was used for the spatial-spectral readout with a spectral bandwidth of 1190 Hz (100 kHz ADC bandwidth, ramp durations of 50 μs, and 32×32 k-space points (kx-ky) sampled during the gradient plateaus. To achieve diffusion-trace weighting in only one measurement, we used 12 pairs of bipolar diffusion-sensitizing gradient (DSG) lobes interleaved within the PRESS localization which resulted in: (a) cancellation of signal weighted by off-diagonal terms in the diffusion tensor, and (b) elimination of any cross-terms originating between any static background gradients and the diffusion-sensitizing gradients¹⁷. In contrast to a single spin-echo slice selection, the second refocusing pulse in the PRESS sequence is crucial for eliminating cross-term due to static background gradients.

Results

Fig.2 and Fig.3 show spectra from DW-REPSI acquired in 2 young healthy subjects. Regional variations of IMCL, EMCL, TMA, Cr/PCr were evident in different muscle regions: soleus, tibialis anterior (TA) and gastrocnemius (GAS) muscles. Lipid spectra from the tibial marrow and fibula showed resonances due to polymethylene, methyl, methylene and olefinic protons. Table 1 shows the ADC values of lipids and metabolites in the soleus, TA and GAS calculated from the spectra acquired using low and high b-values. The decreased ADC values of IMCL and EMCL in one diabetic calf muscle was observed in different muscles.Two EMCL peaks due to bulk magnetic susceptibility (BMS) shifts were detected as reported earlier¹².

Discussion

Compared to MRSI using phase-encoding gradients, shorter acquisition was possible using DW-REPSI. Also, the sequence enabled motion robustness due to multiple crossings of k-space origin. Multi-voxel MR spectra using low and high b-values were of excellent quality as evident in Fig.2 and Fig.3. Significant reduction of TMA in the TA muscle was observed compared to that in the soleus and GAS muscles. In agreement with earlier reports, the ADC values of IMCL were smaller than those of EMCL in soleus, with TA and GAS muscles reflecting restricted diffusion of IMCLs compared to EMCL. The high b-value of 1600 s/mm2 is a limitation of the current study and DW acquisition using higher b-values and longer diffusion times needs further investigation¹⁸.

Conclusions

Regional variations of IMCL and EMCL were detected in different calf muscle regions. The diffusion trace-weighted sequence could provide the trace ADC of the lipid and metabolites in a much shorter scan time compared to conventional diffusion-weighted spectroscopic imaging techniques.

Acknowledgements

This research was supported by grants from NIH/NIMH: (1R21MH125349-02) and NIH/NIBIB: (1R21EB02088302).

References

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Figures

Fig.1. Sagittal (left), axial (middle) and coronal (right) slices represent T1-weighted localizer MRI recorded in a 27-year-old young healthy subject; ROIs represent the selected VOI for the DW-REPSI acquisition in 3 different planes.

Fig.2. DW-REPSI extracted spectra from tibialis anterior (A), tibia (B), soleus (C), fibula (D) and gastrocnemius (E). Each spectrum was acquired from a 2ml voxel in a 23 years-old healthy subject. Two spectra in each location were acquired using b values of 51s/mm2 and 1601 s/mm2.

Fig.3. DW-REPSI extracted spectra from tibia (A), tibialis anterior (B), soleus (C), fibula (D) and gastrocnemius (E). Each spectrum was acquired from a 2ml voxel in a 23 years-old healthy subject. Two spectra in each location were acquired using b values of 51s/mm² and 1601 s/mm².

Table 1. (A) ADCs of IMCL,EMCL,Cr/PCr and TMA in different muscle regions and (B) lipids in the tibial and fibula marrow.

Proc. Intl. Soc. Mag. Reson. Med. 32 (2024)

1702

DOI: https://doi.org/10.58530/2024/1702