Joep van Oorschot¹, Hermien Kan², Andrew Webb², Klaas Nicolay¹, and Jeroen Jeneson^1
1Biomedical NMR, University of Technology Eindhoven, Eindhoven, Noord-Brabant, Netherlands, ²C.J. Gorter Center for High Field MRI, Dept. of Radiology, Leiden University Medical Center, Leiden, Netherlands

Non-invasive assessment of mitochondrial content in skeletal muscle, during rest, using 31P spectroscopy would be a major improvement over conventional methods, including kinetics of phosphocreatine (PCr) recovery from exercise. Previous research at 7T attributed a peak at 5.2 ppm to the Pi pool inside the mitochondrial matrix (Pi2). In this study we obtained further evidence for this hypothesis, by showing a correlation between Pi2 intensity assessed at 7T to the PCr recovery rate as assessed during in-magnet exercise at 1.5T. Studies were done in both endurance trained athletes and normally active subjects.

Dimitrios C Karampinos¹, Huanzhou Yu², Ann Shimakawa², Thomas M. Link¹, and Sharmila Majumdar^1
1Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States, ²Global Applied Science Laboratory, GE Healthcare, Menlo Park, CA, United States

Quantitative chemical shift-based water/fat separation approaches rely on a precalibrated multi-peak fat spectrum. However, water-fat susceptibility differences can induce fat spectrum resonance shifts depending on the shape and orientation of the fatty inclusions. The effect is of particular interest in the skeletal muscle due to the anisotropic arrangement of extracellular lipids. In the present work, the effect of susceptibility-induced resonance shift on quantitative chemical shift-based water/fat separation approaches is characterized and a novel algorithm is proposed in order to quantify the resonance shift. The technique is validated in a phantom and preliminaryin vivo results are shown in the calf muscle.

Alison Sleigh¹, Philippa Raymond-Barker², David Porter³, Kerrie Thackray⁴, Louise McGrath¹, Soren Brage⁴, Mensud Hatunic⁴, T. A. Carpenter¹, Kevin M Brindle^5,6, Graham J Kemp⁷, Steve O'Rahilly⁴, Rob K Semple⁴, and David B Savage^4
1Wolfson Brain Imaging Centre, University of Cambridge, Cambridge, United Kingdom, ²Wellcome Trust Clinical Research Facility, Addenbrooke's Hospital, Cambridge, United Kingdom, ³Siemens AG Healthcare Sector, Erlangen, Germany, ⁴Institute of Metabolic Science, University of Cambridge, Cambridge, United Kingdom, ⁵Dept. of Biochemistry, University of Cambridge, Cambridge, United Kingdom, ⁶Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom, ⁷Magnetic Resonance and Image Analysis Research Centre, University of Liverpool, Liverpool, United Kingdom

We use ³¹P-MRS at rest (saturation transfer technique), and post exercise (PCr recovery rate), in subjects with congenital severe insulin resistance due to loss-of-function mutations in the INSR gene. PCr recovery post exercise is significantly slowed in the INSR patients suggesting that primary congenital insulin resistance can precede mitochondrial dysfunction. Resting ATP synthesis rate (ST V_ATP) measured from the saturation transfer method did not differ significantly between groups. This is consistent with recent findings in rats, which support concerns over its validity in accurately measuring ATP synthesis rates. We found no significant correlation between ST V_ATP and PCr recovery rate.

Xing Chen¹, Anke Henning¹, and Peter Boesiger^1
1Institute for Biomedical Engineering, University and ETH Zurich, Zürich, Zürich, Switzerland

It has been shown that the altered fatty acid contents after supplementation are different according to the specific tissues. However, the low signal sensitivity of natural abundance 13C MRS which is so far the only way to detect unsaturated fatty acids noninvasively limits the measurement in specific positions. In this work, we apply the sequence which combines DEPT and PRESS localization on protons to in vivo detection of UFA. Theoretical calculation by the product operator formalism, phantom measurements and in vivo results from human thigh muscle at 7T showed that the sequence achieved sufficient SNR enhancement as well as precise localization. The UFA detected from posterior and medial thigh muscle on two healthy volunteers indicates that the sequence based on DEPT and PRESS is capable of assessing the fatty acids characterization in specific tissues non-invasively in vivo.

Vaclav Brandejsky¹, Roland Kreis², Christine Sandra Bolliger², and Chris Boesch^2
1Dept. of Clinical Research, University of Bern, Bern, Bern, Switzerland, ²Dept. of Clinical Research, University of Bern, Bern, Switzerland

Intra- (IMCL) and extramyocellular (EMCL) lipids have been studied by diffusion weighted MRS, which is optimized to avoid motion- and vibration-related artifacts at large b-values. Results show differences between the diffusion properties of the EMCL/IMCL lipid pools in human muscle. The low apparent diffusion coefficient of IMCL can only be explained by restricted diffusion while EMCL seems to diffuse freely. The results indicate that in vivo droplet size measurements of IMCL using MRS might be possible.

Beatrijs Wokke¹, Janneke van den Bergen¹, Annemieke Aartsma-Rus², Andrew Webb³, Jan Verschuuren¹, and Hermien Kan^3
1Neurology, Leiden University Medical Centre, Leiden, Netherlands, ²Human genetics, Leiden University Medical Centre, ³Radiology, Leiden University Medical Centre

Quantitative assessment of fatty infiltration in 18 muscles in the upper and lower leg of Duchenne Muscular Dystrophy (DMD) patients showed large variation in fat fractions between the analyzed muscles as well as variation between distal and proximal regions in several muscles in the lower leg. In a potential longitudinal study of DMD patients, analyzing only the most and least affected muscle could provide adequate information for monitoring. However, for the analysis of some muscles multiple slices should be acquired to prevent an under- or overestimation of the fat fraction.

Patricia M Nunes¹, Andor Veltien¹, Henk Arnts², Tineke van de Weijer³, Patrick Shrauwen³, Cees J Tack⁴, and Arend Heerschap^1
1Radiology, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ²Central Animal Laboratory, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands, ³Human Biology, NUTRIM, School of Nutrition, Toxicology and Metabolism, Maastricht University Medical Centre, Maastricht, Netherlands, ⁴Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands

Absence of adipose-triglyceride-lipase(ATGL), mainly expressed in muscle and adipose tissue, leads to triglyceride accumulation and decreased free-fatty-acid availability, boosting glucose metabolism. Here, we tested muscle mitochondrial oxidative capacity of ATGL-KO mice, in vivo, with dynamic 31PMRS, simultaneously with force measurements. ATGL-KO electro-stimulated muscles presented lower force and fast relaxation compared to WT. 31PMRS showed that resting muscles of WT and ATGL-KO did not differ in phosphor-metabolites or in pH. After contraction ATGL-KO and WT muscles had comparable PCr depletions and Pi formations, as well as pH. The mono-exponential-curve-fitting of PCr recovery showed similar recovery times, suggesting analogous mitochondrial oxidative capacities.

Danchin Daniel Chen¹, Diego Hernando², Curtis Laurence Johnson¹, Armen Alex Gharibans¹, Dolores D Guest³, Christie Ward⁴, Bhibha Das³, Ellen M Evans⁴, and John G Georgiadis^1
1Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Department of Radiology, University of Wisconsin, Madison, WI, United States, ³Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ⁴Department of Kinesiology, University of Georgia, Athens, GA, United States

A two-point Dixon MRI technique was used to quantify the adipose tissue depots in the thigh of elderly women. Women were divided into obese (n=24) and lean (n=17) groups based on BMI, and the lean group was further divided into active (n=9) and sedentary (n=8) based on physical activity level. Thigh composition in lean, sedentary women was found to be similar to that of obese women, while relative adipose tissue depots were elevated relative to active women.

Li Xiao^1,2, and Ed X Wu^1,2
1Laboratory of Biomedical Imaging and Signal Processing, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, People's Republic of, ²Department of Electrical and Electronic Engineering, The University of Hong Kong, Hong Kong, Hong Kong SAR, China, People's Republic of

Recognizing the correlation between insulin sensitivity and intramyocellular lipid (IMCL) level, non-invasive 1H MRS assessment of IMCLs has been extensively pursued. One major technical challenge in such IMCL quantitation is the spectral overlap and contamination by the large, broad and muscle orientation dependent extramyocellular lipid (EMCL) spectrum. Motivated by their difference in microscopic diffusion environment, we characterized the diffusion properties of IMCLs and EMCLs both ex vivo and in vivo. Our results demonstrated that EMCLs have significantly higher diffusivity, and they can be reliably suppressed via diffusion weighting while IMCLs remain visible. The proposed approach can be readily employed in study of human skeletal muscles in vivo, providing more reliable IMCL quantitation in MRS/MRI investigation of obesity and diabetes.

Armen Alex Gharibans¹, Danchin Daniel Chen¹, Curtis Laurence Johnson¹, Dolores D Guest², Christie Ward³, Bhibha Das², Ellen M Evans³, and John G Georgiadis^1
1Mechanical Science and Engineering, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ²Department of Kinesiology and Community Health, University of Illinois at Urbana-Champaign, Urbana, IL, United States, ³Department of Kinesiology, University of Georgia, Athens, GA, United States

Seeking to assess skeletal muscle quality, the primary and secondary eigenvector tracts were reconstructed from DTI in the vastus medialis of elderly women (n=41) blocked on adiposity (obese vs. lean), with the lean group (n = 17) further blocked on physical fitness (sedentary vs. physically active). Three parameters related to the asymmetry of the diffusion tensor in the direction perpendicular to the muscle fiber are used as structural metrics of muscle quality. Statistical analysis of the cross-sectional study outcome shows that physical activity and obesity influence muscle quality such that: slender/active group > slender/sedentary group > obese group.