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Markus Klarhöfer¹, Sebastian Kos², Markus Aschwanden², Augustinus Ludwig Jacob², Klaus Scheffler¹, Deniz Bilecen²

¹University of Basel, Basel, Switzerland; ²University Hospital Basel, Basel, Switzerland

Purpose was to evaluate the feasibility of interleaved MR BOLD imaging in calf and foot muscles for the examination of blood supply of most peripheral tissues. 15 healthy volunteers underwent a short term ischemia / reactive hyperemia experiment. Simultaneous T2* mapping was possible with a temporal resolution of 1 second. Reactive hyperemia led to higher and faster T2* changes in m. soleus of the calf than in m. adductor hallucis of the foot. However, further studies have to clarify, if disorders in the vascular periphery cause significant changes of the T2* evolution in foot muscles during a cuff compression paradigm.

Wen-Chau Wu¹, ², Jiongjiong Wang¹, John A. Detre¹, Felix W. Wehrli¹, Emile Mohler¹, Sarah Ratcliffe¹, Thomas F. Floyd¹

¹University of Pennsylvania, Philadelphia, USA; ²National Taiwan University, Taipei, Taiwan

We report the results of the application of continuous ASL (CASL) to systematically study perfusion differences between all major muscle groups in the calf. Results show that the hyperemic response to a 5-min ischemia is significantly larger in the deep flexor and soleus muscle than more superficial muscles. The finding correlates with the fiber composition of muscles. CASL proves to be able to detect the flow heterogeneity between muscle groups in human extremities. The ability to reliably measure heterogeneity may help understanding the vascular/metabolic mechanisms in skeletal muscle and possibly provide diagnostic information for the assessment of peripheral vascular disease.

Kun Lu¹, Eric C. Wong¹, Lawrence R. Frank¹, ²

¹University of California San Diego, La Jolla, USA; ²VA, La Jolla, USA

The ability to non-invasively measure tissue perfusion is critical for assessing the physiological functions of human skeletal muscle in both healthy and disease states. The traditional techniques to measure tissue perfusion in human muscle are invasive and measure only bulk properties which do not render information on either spatial or temporal heterogeneity. Velocity selective arterial spin labeling (VSASL) MRI has been shown previously to be sensitive to muscle perfusion in humans [1], but does not allow a full exploration of important properties associated with the muscle perfusion, such as perfusion anisotropy and perfusion directions. Perfusion Tensor Imaging (PTI) was proposed in 2004 by Frank and Wong [2] in a study of perfusion anisotropy in the human brain, where VSASL was applied with a spherical velocity encoding scheme similar to that used in diffusion tensor imaging (DTI). The perfusion measurements can then be characterized by a perfusion tensor (P), analogous to the diffusion tensor in DTI, from which the estimates of the mean perfusion, fractional perfusion anisotropy and principle perfusion direction can be derived. This study demonstrates that PTI can also be used to measure perfusion properties of human skeletal muscle.

Martin Meyerspeer¹, ², Thomas Mandl¹, Martin Reichel¹, Winfried Mayr¹, Christian Hofer², Helmut Kern³, Ewald Moser¹

¹Vienna Medical University, Vienna, Austria; ²Wilhelminenspital Vienna,, Vienna, Austria; ³Wilhelminenspital Vienna, Vienna, Austria

Functional electrical stimulation (FES) for paraplegic patients, with the long-term goal of restoring muscle function, has several positive therapeutic effects. In denervated muscle, FES induced activation follows the electrical field which can be modelled in simulations.For verifying these models, maps of relative T2 change induced by FES were calculated: T2 parameter images were acquired using multi-slice multi-spin-echo MRI before and after FES in 9 denervated paraplegic patients and 3 healthy subjects. Images acquired pre and post exercise were realigned and normalised.Results show that the training effect f FES of denervated muscles can be visualised by T2 parameter images.

Douglas E. Befroy¹, Roberto Codella¹, Gerald I. Shulman¹, ², Douglas L. Rothman¹

¹Yale University School of Medicine, New Haven, Connecticut, USA; ²Howard Hughes Medical Institute, New Haven, Connecticut, USA

The emergence of many transgenic mouse models with modulated muscle gene expression offers vast potential for the investigation of muscle metabolism. However, the application of the conventional saturation-transfer (CST) technique to assess metabolic reaction rates in mouse has been restricted by the small amount of muscle tissue available for MRS, necessitating very long experimental durations for a full CST experiment. We demonstrate that implementation of the Four-Angle Saturation Transfer (FAST) technique in mouse offers a rapid and practical alternative to CST for measuring muscle ATP synthesis in-vivo.

S. Sendhil Velan¹, Kartik Narasimhan¹, Rolf F. Schulte², Ali Bahu¹, Richard G. Spencer³, Raymond R. Raylman¹, Michael Albert Thomas⁴, Stephen E. Alway¹

¹West Virginia University, Morgantown, USA; ²GE Global Research, Munich, Germany; ³NIH/National Institute on Aging, Baltimore, USA; ⁴University of California, Los Angeles, Los Angeles, USA

In this study we employed localized 2D MRS approaches for detecting both J and residual dipolar couplings in skeletal muscle. The cross peaks in L COSY and J PRESS spectra can be generated by either J couplings usually observed in isotropic liquids, but normally not varying in size, or direct dipole-dipole interaction, only observable in oriented media. The residual dipolar couplings vanished in L COSY and collapsed in J PRESS spectra when the angle between the internuclear vector and the external magnetic field is 54 .  Our results agree with the hypothesis that the elongated spaces between the actin and myosin chains hinder the creatine molecule from isotropic tumbling.

Nicole M.A. van den Broek¹, Henk MML De Feyter¹, Klaas Nicolay¹, Jeanine J. Prompers¹

¹Eindhoven University of Technology, Eindhoven, Netherlands

Literature suggests decreased mitochondrial oxidative capacity and intramyocellular lipid (IMCL) accumulation might be a major risk factor to develop insulin resistance. Skeletal muscle oxidative capacity and IMCL content in a rat model of early, lifestyle-induced insulin resistance was investigated using in vivo ¹H and ³¹P MRS. After 2 weeks high-fat diet, Wistar rats were insulin resistant and had elevated IMCL levels compared to controls. Remarkably, t_PCr is decreased in the insulin resistant rats. This means mitochondrial dysfunction does not play a role in the early stage of insulin resistance in a validated animal model of lifestyle-induced insulin resistance.

Jeanine J. Prompers¹, Nicole M.A. van den Broek¹, Klaas Nicolay¹, Jeroen A.L. Jeneson¹

¹Eindhoven University of Technology, Eindhoven, Netherlands

The recent discovery of extensive and dynamic protein phosphorylation in the mitochondrial matrix has rekindled the debate on the mechanistic underpinnings of energy balance in the active mammalian cell. We have previously reported evidence that the mitochondrial sensitivity to ADP may well be central to cellular energy balance. Here, we report new evidence in the form of rich ³¹P NMR spectroscopy data sets of ATP metabolism in human skeletal muscle and quantitative analysis of the post-exercise recovery state confirming our hypothesis that  mitochondria are ultrasensitive to variations in the cytosolic concentration of the ATP hydrolysis product ADP.

Kieren Grant Hollingsworth¹, Julia L. Newton¹, Roy Taylor¹, David E. Jones¹, Andrew M. Blamire¹

¹Newcastle University, Newcastle Upon Tyne, UK

Primary Biliary Cirrhosis is an autoimmune liver disease with 50% of patients suffering profound, debilitating fatigue. This study uses phosphorus spectroscopy to non-invasively probe the concentrations of high-energy phosphates during a plantar flexion exercise. 8 healthy control subjects, 8 PBC patients without fatigue and 7 PBC patients with significant fatigue were put through two 3 minute periods of exercise, with loads of 25% and 35% of maximum voluntary contraction. Several significant abnormalities in pH and mitochondrial handling were found amongst the PBC patients, some of which affected all PBC patients and others which were restricted to the fatigued PBC patients.

Hermien E. Kan¹, Dennis W.J. Klomp¹, Marielle Wohlgemuth¹, Tom W.J. Scheenen¹, George W. Padberg¹, Arend Heerschap¹

¹Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

Facioscapulohumeral muscular dystrophy (FSHD) is characterized by asymmetric dysfunctioning of individual muscles. We used a combined approach of MRI and ³¹P MRSI to characterize anatomic and metabolic differences between affected and apparently non-affected muscles. We show, for the first time, dedicated application of ³¹P MRSI in affected and non-affected muscles in FSHD showing increased tissue pH and decreased PCr/ATP in affected muscles. Interestingly, non-affected muscles show no abnormalities, indicative of normal metabolism. It is unknown if this is also the case in other muscular dystrophies, as these are commonly studied by unlocalized ³¹P MRS