In-magnet bicycling exercise : a novel 31P MRS window on the energetics of human locomotion

The clinical standard test of patient fitness is the upright bicycle exercise test. For a number of reasons, no proper equivalent human MR exercise test has been available. Past 31P MR studies employing single limb exercise regimens generally failed to put any significant demands on the cardiovascular system (1). As such, a comprehensive understanding of skeletal muscle performance during whole body activity has been lacking. Here, we report on 31P MRS studies employing a novel ergometer that for the first time offers true in-magnet human bicycling exercise testing. Heart rates directly following exercise were of 150 + 15 bpm. In addition to 31P MRS study of ATP metabolism over a 100-fold dynamic range of ATP turnover at near-constant pH, it allows for non-invasive 31P MRS study of glycogenolysis through the dynamics of hexose monophosphate (HMP) resonances. Here (but not previously (2)) we routinely observed HMP accumulations of up to 10 mM within 2 minutes after termination of exercise at high workloads indicating massive activation of glycogenolysis during the preceding exercise. Yet intramuscular pH typically did not fall below 6.8 during exercise confirming our previous observation of unique homeostatic robustness of quadriceps muscle involved in two-legged exercise (2)

Computational modelling identifies impact of subtle anatomical variation on skeletal muscle local calcium dynamics

Calcium is the main regulator of skeletal muscle metabolic activity. The question has been addressed whether the highly structured spatial organization of sites of Ca2+ release, uptake and action in skeletal muscle substantially impacts the dynamics of cytosolic Ca2+ handling and thereby the physiology of the cell. Hereto, the spatiotemporal dynamics of the free calcium distribution in a fast-twitch muscle sarcomere was studied using a reaction-diffusion computational model. The model was based on the model of Baylor and Hollingworth (J Gen Physiol. 1998 112:297–316), but was adapted to handle local calcium dynamics in mouse EDL fast twitch muscle at 35C. Furthermore, the Ca2+ mass balance was closed by adding a mathematical representation of the sarcoplasmic reticulum. Experimental calcium time courses (high time resolution, but spatially averaged) obtained under physiological conditions (35C, 125 Hz stimulation frequency) were used for model validation. The model showed that subtle changes in sarcomere microstructure influenced the local calcium concentration. Furthermore, local calcium concentration sensed by mitochondria was higher than average calcium concentration and also above the activation constant of the mitochondria, whereas the local concentration was not. Furthermore, the free Ca2+ concentration was higher at the positions with troponin C than without troponin C

MRI-based screening for metabolic insufficiency of leg muscle during aerobic exercise in Cystic Fibrosis

There is evidence for mitochondrial dysfunction in various tissues in Cystic Fibrosis (CF) including muscle. Among others, a slow rate of high-energy phosphate resynthesis following exercise involving single limb muscle activity was found in human CF using in vivo 31P magnetic resonance spectroscopy (MRS). This raises the question whether this outcome would be ameliorated versus exacerbated if instead an exercise regime is used that puts a significant cardiopulmonary load on the body as in running or bicycling. This is of interest because exercise therapy is commonly prescribed in CF. To investigate this matter, ten pediatric CF patients (age 12–16 years) and healthy peers performed two ramp exercise tests to volitional exhaustion using a bicycle ergometer fit for use inside a MR scanner. Endurance, VO2max and heart rate were determined in the exercise laboratory. Quadriceps muscle energy-and acid/base balance during exercise and recovery were measured on a separate day using MR imaging-based 31P MRS. This study brings together for the first time this powerful biomedical imaging platform and whole body exercise testing in the clinical setting of human CF

Quantification of myocardial creatine and triglyceride content in the human heart: precision and accuracy of in vivo proton magnetic resonance spectroscopy

Background Proton magnetic resonance spectroscopy (H-1-MRS) of the human heart is deemed to be a quantitative method to investigate myocardial metabolite content, but thorough validations of in vivo measurements against invasive techniques are lacking.Purpose To determine measurement precision and accuracy for quantifications of myocardial total creatine and triglyceride content with localized H-1-MRS.Study type Test-retest repeatability and measurement validation study.Subjects Sixteen volunteers and 22 patients scheduled for open-heart aortic valve replacement or septal myectomy.Field Strength/Sequence Prospectively ECG-triggered respiratory-gated free-breathing single-voxel point-resolved spectroscopy (PRESS) sequence at 3 T.Assessment Myocardial total creatine and triglyceride content were quantified relative to the total water content by fitting the H-1-MR spectra. Precision was assessed with measurement repeatability. Accuracy was assessed by validating in vivo H-1-MRS measurements against biochemical assays in myocardial tissue from the same subjects.Statistical Tests Intrasession and intersession repeatability was assessed using Bland-Altman analyses. Agreement between H-1-MRS measurements and biochemical assay was tested with regression analyses.Results The intersession repeatability coefficient for myocardial total creatine content was 41.8% with a mean value of 0.083% +/- 0.020% of the total water signal, and 36.7% for myocardial triglyceride content with a mean value of 0.35% +/- 0.13% of the total water signal. Ex vivo myocardial total creatine concentrations in tissue samples correlated with the in vivo myocardial total creatine content measured with H-1-MRS: n = 22, r = 0.44; P < 0.05. Likewise, ex vivo myocardial triglyceride concentrations correlated with the in vivo myocardial triglyceride content: n = 20, r = 0.50; P < 0.05.Data Conclusion We validated the use of localized H-1-MRS of the human heart at 3 T for quantitative assessments of in vivo myocardial tissue metabolite content by estimating the measurement precision and accuracy.Level of Evidence 2Technical Efficacy Stage 2Cardiovascular Aspects of Radiolog

In-magnet bicycling exercise : a novel 31P MRS window on the energetics of human locomotion

The clinical standard test of patient fitness is the upright bicycle exercise test. For a number of reasons, no proper equivalent human MR exercise test has been available. Past 31P MR studies employing single limb exercise regimens generally failed to put any significant demands on the cardiovascular system (1). As such, a comprehensive understanding of skeletal muscle performance during whole body activity has been lacking. Here, we report on 31P MRS studies employing a novel ergometer that for the first time offers true in-magnet human bicycling exercise testing. Heart rates directly following exercise were of 150 + 15 bpm. In addition to 31P MRS study of ATP metabolism over a 100-fold dynamic range of ATP turnover at near-constant pH, it allows for non-invasive 31P MRS study of glycogenolysis through the dynamics of hexose monophosphate (HMP) resonances. Here (but not previously (2)) we routinely observed HMP accumulations of up to 10 mM within 2 minutes after termination of exercise at high workloads indicating massive activation of glycogenolysis during the preceding exercise. Yet intramuscular pH typically did not fall below 6.8 during exercise confirming our previous observation of unique homeostatic robustness of quadriceps muscle involved in two-legged exercise (2)

A metabolic control analysis of kinetic controls in ATP free energy metabolism in contracting skeletal muscle.

free energy metabolism in contracting skeletal muscl

An MR-compatible bicycle ergometer for in-magnet whole-body human exercise testing

An MR-compatible ergometer was developed for in-magnet whole-body human exercise testing. Designed on the basis of conventional mechanically braked bicycle ergometers and constructed from nonferrous materials, the ergometer was implemented on a 1.5-T whole-body MR scanner. A spectrometer interface was constructed using standard scanner hardware, complemented with custom-built parts and software to enable gated data acquisition during exercise. High-quality 31P NMR spectra were reproducibly obtained from the medial head of the quadriceps muscle of the right leg of eight healthy subjects during two-legged high-frequency pedaling (80 revolutions per minute) at three incremental workloads, including maximal. Muscle phosphocreatine content dropped 82%, from 32.2 ± 1.0 mM at rest to 5.7 ± 1.1 mM at maximal workload (mean ± standard error; n = 8), indicating that the majority of quadriceps motor units were recruited. The cardiovascular load of the exercise was likewise significant, as evidenced by heart rates of 150 (±10%) beats per minute, measured immediately afterward. As such, the newly developed MR bicycling exercise equipment offers a powerful new tool for clinical musculoskeletal and cardiovascular MR investigation. The basic design of the ergometer is highly generic and adaptable for application on a wide selection of whole-body MR scanners