Quantifying Lactate and Energy Metabolism in Working Muscle

What we are looking into When muscles are working, they are turning the energy stored in our food into force and motion by converting and burning nutrients. At low to moderate exercise intensity, this requires less or just as much oxygen as is available to the muscles via breathing and transport by blood. It is possible to quantify these processes as they happen directly in a persons the muscle, when lying in an MRI scanner. Because the energy-rich molecules (like ATP) contain phosphorus, one uses a technique for this, called phosphorus-31 magnetic resonance spectroscopy (or P MRS). But when more power is needed, for example to run very fast, the oxidative processes are insufficient, and would need more oxygen than can be delivered to the muscle. At such high exercise intensities, different processes contribute to energy turnover. Glycolysis can generate ATP independently of oxygen and results, among others, in lactate production. From blood samples, the gross amount of lactate accumulated in the entire body can be analysed. But for a better understanding of physiology, a method that can quantify lactate exactly where and when it is produced in the muscle is needed. How we are doing this Lactate can also be observed with an MRI scanner, by looking at the molecules hydrogen (H) atoms. Unfortunately, also fat contains 1H groups that are hard to distinguish from the ones in lactate. Moreover, the lactate signals appearance is different whether it is inside or outside a muscle cell, and even the angle of the muscle cells to the magnetic field of the MRI scanner makes a difference. In this project, we are going to use these difficulties to our advantage: Using MRI, we will determine muscle fibre directions at the position where we are going to collect the lactate signal. We will then use this knowledge to optimise the radiofrequency (RF) pulses and magnetic field gradients played out by the MRI scanner to excite the signal. Our goal is also to determine how long the produced lactate dwells inside the muscle cells before leaving the cells or being metabolised. This requires very high signal quality, which we are going to achieve by building an RF coil with a high number of 1H and 31P channels, carefully adapted for these measurements, and we will use an MRI scanner with very high magnetic field. We will finally receive the information on all biochemical processes at the same time, by combining H MRS and P MRS in one protocol. What are we going to learn from this Up to now, it is not exactly known how much and how fast lactate is produced in muscle and how long it remains in the cell under in-vivo conditions. The developed methods will enable us to study this quantitatively in human subjects, without invasive interventions. Such techniques probing muscle energy metabolism and lactate directly in the muscle will improve the understanding of physical activity and of chronic diseases, and thus ultimately have significant impact on public health.