Dynamic 31P MRSI with spiral readout for quantification of mitochondrial capacity in muscles of the calf during plantar flexion exercise at 7T
Ladislav Valkovič1,2,3,4, Marek Chmelík1,2, Martin Meyerspeer1,5, Borjan Gagoski6, Martin Krššák1,2,7, Christopher T Rodgers4, Ivan Frollo3, Ovidiu C Andronesi8, Siegfried Trattnig1,2,9, and Wolfgang Bogner1,2

1High-field MR Centre, Medical University of Vienna, Vienna, Austria, 2Department of Biomedical Imaging and Image-guided Therapy, Medical University of Vienna, Vienna, Austria, 3Department of Imaging Methods, Institute of Measurement Science, Slovak Academy of Sciences, Bratislava, Slovakia, 4Oxford Centre for Clinical Magnetic Resonance Research, University of Oxford, Oxford, United Kingdom, 5Center for Medical Physics and Biomedical Engineering, Medical University of Vienna, Vienna, Austria, 6Fetal Neonatal Neuroimaging and Developmental Science Center, Boston Children's Hospital, Boston, MA, United States, 7Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria, 8Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, United States, 9Christian Doppler Laboratory for Clinical Molecular MR Imaging, Vienna, Austria

Synopsis

Typically, only rough localization by the sensitive volume of the surface coil is used for dynamic 31P-MRS. However, such localization often mixes signals from several muscle groups. Available single-muscle localization techniques (e.g., semi-LASER or DRESS) provide only limited coverage and current 31P-MRSI techniques suffer from slow acquisition. To overcome the low temporal resolution of the standard 31P-MRSI, caused by slow Cartesian readout, we have developed, and tested in healthy subjects at 7T, a 31P-MRSI sequence using spiral readout trajectory. This sequence enables spatially resolved quantification of mitochondrial capacity in several investigated muscles (e.g., GM, GL and SOL) simultaneously at 7T.

Introduction

Dynamic phosphorus MR spectroscopy (31P-MRS), allows direct estimation of mitochondrial capacity. Typically, only rough localization by the sensitive volume of the surface coil is used, due to high SNR, methodological simplicity and robustness. However, such localization often mixes signals from several muscle groups that are involved differently in the exercise performed (e.g., soleus and gastrocnemius during plantar flexion)1. To overcome this issue, single-muscle localization techniques (e.g., semi-LASER1 or DRESS2) can be used. Moreover, in order to measure mitochondrial metabolism in several muscles simultaneously, 31P-MRS imaging, using lengthy exercise protocols (i.e., gated 31P-MRSI3), or frequency-selective 31P-MRI4-6, providing only limited amount of information in comparison to MRSI, have been proposed.

To overcome the low spatial and temporal resolution of the standard 31P-MRSI, caused by slow Cartesian readout, we aimed to develop a 31P-MRSI sequence using rapid readout, for spatially resolved quantification of mitochondrial capacity in the human calf muscles during plantar flexion at 7T.

Materials & Methods

To accelerate the acquisition and, hence, increase the temporal resolution of dynamic 31P-MRSI scans, we have implemented a constant-density spiral spectroscopic readout7,8 (Fig.1). To compensate for the increased dwelltime with increasing matrix size, temporal interleaving was employed. The number of temporal interleaves was adjusted to the targeted matrix size (i.e., n=5 for 14x14 matrix), making sure that the readout bandwidth remained >1.45 kHz (i.e., 12 ppm). The readout bandwidth/dwelltime was set to minimize the deadtime between adjacent spirals as this optimizes SNR. Spiral samples were two-dimensionally gridded with a Kaiser-Bessel kernel and the entire spiral-trajectory calculation, gradient-delay correction and data reconstruction was implemented on our 7T MR system (Siemens Healthcare, Erlangen, Germany), equipped with an SC72CD gradient system featuring 70 mT/m nominal gradient strength and 200 mT/m/s maximum slew rate.

Ten healthy individuals (7M/3F, age: 28.3±4.1 years, BMI: 22.7±2.6 kg.m-2) participated in the study. Subjects were positioned supine on a plantar-flexion ergometer (Ergospect, Innsbruck, Austria) with a 1H/31P surface RF-coil (10 cm diameter, Rapid Biomedical, Rimpar, Germany) fixed to the right calf. The proposed 2D-MRSI sequence was used for the dynamic protocol (rest/exercise/recovery – 2/6/6 minutes) and its parameters were set as follows: TE*=1 ms; TR=2 s; temporal resolution=10 s; acquisition bandwidth (BW)=1450 Hz; matrix size=14x14; FOV=200x200 mm; slice thickness=30 mm, and the nominal voxel size was 14.3x14.3x30 mm3 (i.e., 6.1 mL). During the exercise phase volunteers performed plantar flexions at a workload of ~35% of maximal voluntary contraction, once every TR.

All spectra were analyzed using AMARES in jMRUI. The γ-ATP peak was used as a concentration reference (8.2 mM). The parameters of oxidative metabolism (e.g., time-constant of PCr recovery [τPCr], initial PCr recovery rate [VPCr] and mitochondrial capacity [Qmax]) were calculated and compared between three muscle groups (gastrocnemius medialis [GM], gastrocnemius lateralis [GL] and soleus [SOL]) by a one-way ANOVA and a Bonferroni post-hoc test.

Results & Discussion

Representative spectra acquired at rest and at the end of exercise from each muscle group are given in Fig.2. To demonstrate the importance of localization, a voxel combining GM and SOL tissue is also visualized (green). The mixture of signals arising from differently active muscles causes a splitting of the Pi signal, representing two different pH values. Voxels directly between adjacent muscles have been, therefore, avoided in our analysis. The temporal and spatial resolution of our spiral-MRSI sequence enabled mapping of the time evolution of 31P metabolites in all visible muscles simultaneously. Sample time courses of the PCr and Pi signals for GL, GM and SOL are depicted in Fig.3. Readily visible lower PCr depletion in the SOL muscle in comparison to GM and GL has been also found statistically significant (p<0.001). Similarly, lower VPCr and Qmax values have been calculated for SOL muscle, however this can be explained by minimal participation of SOL in the performed exercise and, hence, low activation of its mitochondria. All measured parameters of oxidative metabolism are given in Table 1.

In comparison to our approach, gated 31P-MRSI for dynamic experiments3 suffered from slow Cartesian readout, which significantly limited the spatial resolution and even required a prolonged exercise protocol. Due to recent development, spectrally-selective 31P-MRI allows slightly higher spatial (1.6-3.0 ml)5,6 and similar temporal resolution (~10 s) at 7T, and even enables quantification of pH6. However, 31P-MRI still provides only limited amount of information in comparison to MRSI techniques, e.g., no ATP signal for concentration quantification.

Conclusion

In our study, we have successfully implemented spiral trajectory readout into a 31P-MRSI sequence and demonstrated its potential for highly resolved measurements of oxidative metabolism in the muscles of the human calf during plantar flexion exercise at 7T.

Acknowledgements

This study was supported by the ÖNB Jubiläumsfond (grant #15455, #16133 and #15363), by Christian Doppler Society – Clinical Molecular MR Imaging (MOLIMA) and as well by a grant from the Agency of the Slovak Academy of Science, VEGA 2/0013/14.

References

1. Fiedler GB, et al. Magn Reson Mater Phy 2015;28(5):493-501

2. Valkovic L, et al. NMR Biomed 2014;27(11):1346-52

3. Forbes SC, et al. NMR Biomed 2009;22(10):1063-71

4. Greenman RL, et al. Acad Radiol 2011;18(7):917-23

5. Parasoglou P, et al. NMR Biomed 2013;26(3):348-56

6. Schmid AI, et al. Magn Reson Med 2015; doi:10.1002/mrm.25822

7. Adalsteinsson E, et al. Magn Reson Med 1998;39(6):889-98

8. Andronesi OC, et al. Radiology 2012;262(2):647-61

Figures

Figure 1: Schematic pulse sequence diagram of the 31P 2D-MRSI sequence with the implemented spiral trajectory readout.

Figure 2: Representative 31P MR spectra acquired at rest (dotted) and at the end of exercise (solid line) in voxels representing single muscle i.e., gastrocnemius lateralis (GL), gastrocnemius medialis (GM), and soleus (SOL), or a mixture of GM and SOL tissue. Note the Pi splitting in the mix (green) voxel.

Figure 3: Time courses of the PCr (full) and Pi (dotted) signal intensities measured in the investigated muscles (2-4 voxels), normalized to the resting PCr signal intensity. Higher PCr depletion in GL and GM shows prevailing involvement of these muscles in plantar-flexion exercise. The exercise period is indicated in grey.

Table 1: Comparison of the metabolic parameters measured in the different muscle groups. Significantly lower (p<0.01) PCr drop, VPCr and Qmax were found in SOL muscle in comparison to GL (*) and GM (§).



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