Magnetic Resonance Spectroscopy for Dynamic Measurement of Skeletal Muscle Energetics During Exercise

Principal Investigator: Alexander Lin

Authors: Sai Merugumala, Vicky Liao, Wufan Zhao, Sanjay Divakaran, Tom Storer, Shalender Bhasin, Alexander Lin
Lay Abstract

Measuring metabolism at the biochemical level has been a challenge in human subjects and patients. Classically, invasive procedures such as biopsies have been needed to provide measurements of the underlying biochemistry of an organ or tissue. With Magnetic Resonance Spectroscopy (MRS), a tissue’s metabolite concentrations can be measured, which may non-invasively ascertain the same information as a biopsy, acting as a type of virtual biopsy. With Phosphorus (31P) MRS, it is possible to go even further than a traditional biopsy and measure metabolism in near real time in living tissue, like an exercising leg muscle. 31P allows the measurement of the energy storage molecules within muscle cells. Metabolite levels can change rapidly, and our method allows us to capture data in real time that could not be obtained from measuring after exercise. An exercise device was developed that could fit inside an MRI machine. These measurements are taken during a 3-phase protocol of resting, exercising, and recovery. We have successfully applied this method in one study aimed at looking at changes in energy metabolites caused by a therapeutic drug, and in another on Peripheral Artery Disease.

Scientific Abstract

Introduction: Deficiency in oxidative metabolism is associated with the pathophysiology of many diseases. 31P MRS provides a noninvasive method of measuring metabolic markers such as Phosphocreatine (PCr), etc. At 7T, more metabolites such as NAD+NADH can be measured. This allows 31P MRS to reveal insights about oxidative metabolism at the biochemical level in human subjects non- invasively. In an exercising skeletal muscle, dynamic 31P MRS can be used to obtain nearly real time measurements of phosphate containing metabolites.

Methods: A supine leg extension ergometer was designed to function within the bore of a Siemens 7 T Terra MRI system to perform a dynamic 31P MRS acquisition with simultaneous exercise. The protocol consisted of resting, exercise and recovery phases performed during the 31P MRS acquisition.

Results: The ergometer apparatus proved effective at allowing a wide range of subjects to perform the exercise within the bore of the MRI system. In a study of a therapeutic targeting NAD levels, 55 scans with 34 subjects were completed. In another studying Peripheral Artery Disease, a total of 10 scans with 5 subjects were completed.

Conclusion: Dynamic 31P MRS at 7 T provides a noninvasive method to assess skeletal muscle biochemistry.

Clinical Implications
Phosphorous-31 Magnetic Resonance Spectroscopy (31P MRS) can measure markers of oxidative metabolism at the biochemical level in human subjects non-invasively. Dynamic measurements during exercise can reveal nearly real time changes in skeletal muscle energetics.

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