Muscle physiology

How can muscle metabolism be measured?

But why is mitochondrial function so important?
Oxidative phosphorylation and glycolysis are the most important sources of cellular energy. Mitochondria account for ATP production through oxidative phosphorylation. Consequently, mitochondrial performance is crucial for organ function, whereas mitochondrial dysfunction plays a major role in the onset of a number of degenerative diseases including type 2 diabetes, dyslipidaemia and sarcopenia.

Which processes can be measured?
As the muscles start to work, energy demand within the myofibrils of the muscle is increased. To provide energy for the muscular contraction, the high-energy molecule adenosine triphosphate (ATP) is split into adenosine diphosphate (ADP) and inorganic phosphate as well as H+ ions by the ATPase enzyme.

In order to rephosphorylate ADP to ATP, a phosphate group of the phosphocreatine (PCr) is transferred to ADP by the creatine kinase reaction. Creatine itself is rephosphorylated in the mitochondria to PCr. PCr acts as an intermediate energy buffer and ‘shuttles’ energy-rich phosphates from the mitochondria to the myofibrils, connecting sites of energy production with sites of energy utilization.

PCr + MgADP- + H+ –> Creatine Kinase –> MgATP2- + creatine

At the onset of muscular work, mitochondrial ATP production is too low to completely rephosphorylate creatine to PCr. This triggers a progressive PCr decline in the cytosol. The muscle cell tries to partially cover ATP demand by anaerobic glycolysis – this phase is termed the anaerobic phase. More ATP for the oxidative rephosphorylation of creatine can be provided by enzymatic activation and increased oxygen supply by means of an increased blood flow, finally leading to PCr hydrolysis equilibrium/steady-state und rephosphorylation. This equilibrium normally follows a mono-exponential course. The time constants which express the transition phase of progressive PCr decline to reach a steady state ranging from 30 to 60 seconds in healthy subjects, and correlate with the increased perfusion of the supply arteries.

In order to calculate appropriate time constants a temporal resolution of 5 to 15 seconds as well as an MR-compatible ergometer with adjustable load-intervals is required during the measurement. However, most conventional systems cannot adjust the power output during the measurement because the power output is not indicated online in an appropriate manner. The time constants allow evaluation of mitochondrial oxygen turnover within the muscle. 31P MRS spectroscopy is thereby a unique method for measuring the achievements of the so-called power stations of the cell. Via this approach, the recovery of PCr from exercise in skeletal muscle is a reliable and accepted measure of oxidative capacity.

Why is 31P MRS important in the field of sports medicine?
In muscle physiology, mitochondrial function determined by the time constant of PCr recovery after a tiring load, is of particular interest. Endurance athletes show faster regeneration of PCr compared to sprint-trained athletes (Pesta 2010). Endurance exercise leads to mitochondrial biogenesis and hence to an increased mitochondrial density in the muscle.

• Phase 1: 5 minutes of resting measurements (baseline)
• Phase 2: 15 minutes of dynamic load with a gradual increase in resistance every 3 minutes
• Phase 3: 5 minutes of recovery measurements in the muscle at rest

Functional Specification:

• calf muscles, muscles of the planta pedis, tendons of the extensor muscles, Achilles tendon, ankle for loaded MRI

• macrovascular disease, e.g. peripheral arterial disease (PAD), microvascular disease, e.g. diabetes mellitus (DM),
• disorders of muscle metabolism (myopathies, lipid metabolism),
• changes in lactate metabolism (cancer, diabetes mellitus(DM)),
• assessment of muscle fiber type composition (MFTC) of athletes (non-invasive discrimination between endurance and strength athletes),
• determination of the intramuscular recruitment pattern for the evaluation of the risk of calf muscle injuries in athletes and amateur sportsmen (e.g.: soccer players),
• tumour perfusion before, during and after chemotherapy,
• tissue perfusion after transplantations, replantation, frostbite or drug application,
• assessment of training progress in patients (e.g. peripheral arterial disease (PAD)),
• exercise responses of athletes, amateur sportsmen and patients,
• exercise responses to gravity-independent training

• 31P MRS, 13C MRS: determination of mitochondrial function, anaerobic and aerobic capacity and glycogen metabolism
• 1H-MRS: lipid metabolism and deoxymyoglobin: tracking of intra- and extra-myocellular lipids and myoglobin
• LATEST: lactate chemical exchange saturation transfer (CEST) to image lactate in vivo
• blood oxygen level dependency (BOLD): monitoring of the oxygen supply within the tissue (e.g. diabetes mellitus (DM))
• perfusion MRI: microcirculation within the exercising muscle
• phase-contrast MRI: assessment of blood flow or changes in tissue elasticity (calf muscles)
• CINE MRI: real-time imaging of calf muscles during exercise testing
• relaxometry: determination of oedema or water content of the calf muscles during exercise testing
• elastography: elasticity testing and evaluation of re-ruptures after surgical fixation
• mfMRI: T2-imaging of the flexor muscles to determine intramuscular water content changes under strain
• conventional loaded MRI: investigation of anatomical structures under isometric strain

• angiologists, gerontologists, interventional radiologists, neurologists, orthopaedists, paediatricians, physiologists, plastic surgeons, radiologists, sports physicians, training facilities for astronauts and athletes, traumatologists, vascular physicians/surgeons

Functional Specification:

• extensor muscles of the lower leg, tendons of the flexor muscles, Achilles tendon, ankle for loaded MRI

• disorders of muscle metabolism (myopathies, lipid metabolism),
• changes in lactate metabolism (e.g. cancer, diabetes mellitus (DM)),
• assessment of muscle fiber type composition (MFTC) of athletes (non-invasive discrimination between endurance and strength athletes),
• tumour perfusion before, during and after chemotherapy,
• tissue perfusion after transplantations, replantation, frostbite or drug application,
• exercise responses of athletes, amateur sportsmen and patients,
• exercise responses to gravity-independent training

• 31P MRS, 13C MRS: determination of mitochondrial function, anaerobic and aerobic capacity and glycogen metabolism
• 1H-MRS: lipid metabolism and deoxymyoglobin: tracking of intra- and extra-myocellular lipids and myoglobin
• LATEST: lactate chemical exchange saturation transfer (CEST) to image lactate in vivo
• perfusion MRI: microcirculation within the exercising muscle
• phase-contrast MRI: assessment of blood flow or changes in tissue elasticity
• CINE MRI: real-time imaging of the extensor muscles of the lower leg during exercise testing
• relaxometry: determination of oedema or water content within the extensor muscles under stress
• elastography: elasticity testing and evaluation of re-ruptures after surgical fixation
• conventional loaded MRI: investigation of anatomical structures under isometric strain

• neurologists, gerontologists, orthopaedists, paediatricians, physiologists, plastic surgeons, radiologists, sports physicians, training facilities for astronauts and athletes, traumatologists

Functional Specification:

• extensor muscles of the thigh, quadriceps and patellar tendon, internal knee structures for loaded MRI

• disorders of muscle metabolism (myopathies, lipid metabolism),
• changes in lactate metabolism (cancer, diabetes mellitus (DM)),
• assessment of muscle fiber type composition (MFTC) of athletes (non-invasive discrimination between endurance and strength athletes),
• determination of the intramuscular recruitment pattern for the evaluation of the risk of muscular injuries in athletes and amateur sportsmen (e.g.: soccer players),
• tumour perfusion before, during and after chemotherapy,
• tissue perfusion after transplantations, replantation or drug application,
• exercise responses of athletes, amateur sportsmen and patients,
• exercise responses to gravity-independent training

• 31P MRS, 13C MRS: determination of mitochondrial function, anaerobic and aerobic capacity and glycogen metabolism
• 1H-MRS: lipid metabolism and deoxymyoglobin: tracking of intra- and extra-myocellular lipids and myoglobin
• LATEST: lactate chemical exchange saturation transfer (CEST) to image lactate in vivo
• Perfusion MRI: microcirculation within the exercising muscle
• Phase-contrast MRI: assessment of blood flow or changes in tissue elasticity (thigh muscles)
• CINE MRI: real-time imaging of the extensor muscles of the thigh during exercise testing
• relaxometry: determination of oedema or water content under stress (thigh muscles)
• elastography: evaluation of re-ruptures after surgical fixation
• mfMRI: T2-imaging of the flexor muscles to determine intramuscular water content changes under strain
• Conventional loaded MRI: investigation of anatomical structures under isometric strain

• gerontologists, neurologists, orthopaedists, paediatricians, physiologists, plastic surgeons, radiologists, sports physicians, training facilities for astronauts and athletes, traumatologists

• flexor muscles of the thigh, internal structures of hip and knee for loaded MRI

• disorders of muscle metabolism (myopathies, lipid metabolism),
• changes in lactate metabolism (cancer, diabetes mellitus (DM)),
• assessment of muscle fiber type composition (MFTC) of athletes (non-invasive discrimination between endurance and strength athletes),
• assessment of the intramuscular recruitment pattern for the evaluation of the risk of hamstring injuries in athletes and amateur sportsmen (e.g.: soccer players),
• tumour perfusion before, during and after chemotherapy,
• tissue perfusion after transplantations, replantation and drug application,
• exercise responses of athletes, amateur sportsmen and patients,
• exercise responses to gravity-independent training

• 31P MRS, 13C MRS: determination of mitochondrial function, anaerobic and aerobic capacity and glycogen metabolism
• 1H-MRS: lipid metabolism and deoxymyoglobin: tracking of intra- and extra-myocellular lipids and myoglobin
• LATEST: lactate chemical exchange saturation transfer (CEST) to image lactate in vivo
• perfusion MRI: microcirculation within the exercising muscle
• phase-contrast MRI: assessment of blood flow or changes in tissue elasticity (flexor muscles)
• CINE MRI: real-time imaging of the flexor muscles of the thigh during exercise testing
• relaxometry: determination of oedema or water content under stress (flexor muscles)
• elastography: elasticity testing and evaluation of re-ruptures after surgical fixation
• mfMRI: T2-imaging of the flexor muscles to determine intramuscular water content changes under strain
• Conventional loaded MRI: investigation of anatomical structures under isometric strain

• gerontologists, neurologists, orthopaedists, paediatricians, physiologists, plastic surgeons, radiologists, sports physicians, training facilities for astronauts and athletes, traumatologists