RESUMEN
(31)P magnetic resonance spectroscopy (MRS) is widely used for non-invasive investigation of muscle metabolism dynamics. This study aims to extend knowledge on parameters derived from these measurements in detail and comprehensiveness: proton (H(+)) efflux, buffer capacity and the contributions of glycolytic (L) and oxidative (Q) rates to ATP synthesis were calculated from the evolutions of phosphocreatine (PCr) and pH. Data are reported for two muscles in the human calf, for each subject and over a wide range of exercise intensities. 22 subjects performed plantar flexions in a 7T MR-scanner, leading to PCr changes ranging from barely noticeable to almost complete depletion, depending on exercise protocol and muscle studied by localized MRS. Cytosolic buffer capacity was quantified for the first time non-invasively and individually, as was proton efflux evolution in early recovery. Acidification started once PCr depletion reached 60-75%. Initial and end-exercise L correlated with end-exercise levels of PCr and approximately linear with pH. Q calculated directly from PCr and pH derivatives was plausible, requiring fewer assumptions than the commonly used ADP-model. In conclusion, the evolution of parameters describing cellular energy metabolism was measured over a wide range of exercise intensities, revealing a relatively complete picture of muscle metabolism.
Asunto(s)
Adenosina Trifosfato/metabolismo , Ejercicio Físico/fisiología , Espectroscopía de Resonancia Magnética/métodos , Músculo Esquelético/metabolismo , Protones , Femenino , Humanos , MasculinoRESUMEN
OBJECTIVES: This study demonstrates the applicability of semi-LASER localized dynamic (31)P MRS to deeper lying areas of the exercising human soleus muscle (SOL). The effect of accurate localization and high temporal resolution on data specificity is investigated. MATERIALS AND METHODS: To achieve high signal-to-noise ratio (SNR) at a temporal resolution of 6 s, a custom-built human calf coil array was used at 7T. The kinetics of phosphocreatine (PCr) and intracellular pH were quantified separately in SOL and gastrocnemius medialis (GM) muscle of nine volunteers, during rest, plantar flexion exercise, and recovery. RESULTS: The average SNR of PCr at rest was [Formula: see text] in SOL ([Formula: see text] in GM). End exercise PCr depletion in SOL ([Formula: see text] %) was far lower than in GM ([Formula: see text] %). The pH in SOL increased rapidly and, in contrast to GM, remained elevated until the end of exercise. CONCLUSION: (31)P MRS in single-shots every 6 s localized in the deeper-lying SOL enabled quantification of PCr recovery times at low depletions and of fast pH changes, like the initial rise. Both high temporal resolution and accurate spatial localization improve specificity of Pi and, thus, pH quantification by avoiding multiple, and potentially indistinguishable sources for changing the Pi peak shape.
Asunto(s)
Ejercicio Físico/fisiología , Rayos Láser , Espectroscopía de Resonancia Magnética/instrumentación , Músculo Esquelético/fisiología , Fosfocreatina/metabolismo , Diseño de Equipo , Análisis de Falla de Equipo , Femenino , Humanos , Masculino , Isótopos de Fósforo/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Adulto JovenRESUMEN
PURPOSE: The aim of this study was to develop a measurement protocol for noninvasive simultaneous perfusion quantification and T2 *-weighted MRI acquisition in the exercising calf muscle at 7 Tesla. METHODS: Using a nonmagnetic ergometer and a dedicated in-house built calf coil array, dynamic pulsed arterial spin labeling (PASL) measurements with a temporal resolution of 12 s were performed before, during, and after plantar flexion exercise in 16 healthy volunteers. RESULTS: Postexercise peak perfusion in gastrocnemius muscle (GAS) was 27 ± 16 ml/100g/min, whereas in soleus (SOL) and tibialis anterior (TA) muscles it remained at baseline levels. T2 *-weighted and ASL time courses in GAS showed comparable times to peak of 161 ± 72 s and 167 ± 115 s, respectively. The T2 *-weighted signal in the GAS showed a minimum during exercise (88 ± 6 % of the baseline signal) and a peak during the recovery (122 ± 9%), whereas in all other muscles only a signal decrease was observed (minimum 91 ± 6% in SOL; 87 ± 8% in TA). CONCLUSION: We demonstrate the feasibility of dynamic perfusion quantification in skeletal muscle at 7 Tesla using PASL. This may help to better investigate the physiological processes in the skeletal muscle and also in diseases such as diabetes mellitus and peripheral arterial disease.
Asunto(s)
Velocidad del Flujo Sanguíneo/fisiología , Imagen de Difusión por Resonancia Magnética/métodos , Ejercicio Físico/fisiología , Angiografía por Resonancia Magnética/métodos , Músculo Esquelético/fisiología , Esfuerzo Físico/fisiología , Adulto , Estudios de Factibilidad , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Pierna , Masculino , Músculo Esquelético/irrigación sanguínea , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
Skeletal muscle metabolism is impaired in disorders like diabetes mellitus or peripheral vascular disease. The skeletal muscle echo planar imaging (EPI) signal (S(EPI) ) and its relation to energy metabolism are still debated. Localised ³¹P MRS and S(EPI) data from gastrocnemius medialis of 19 healthy subjects were combined in one scanning session to study direct relationships between phosphocreatine (PCr), pH kinetics and parameters of T2∗ time courses. Dynamic spectroscopy (semi-LASER) and EPI were performed immediately before, during and after 5 min of plantar flexions. Data were acquired in a 7 T MR scanner equipped with a custom-built ergometer and a dedicated ³¹P/¹H radio frequency (RF) coil array. Using a form-fitted multi-channel ³¹P/¹H coil array resulted in high signal-to-noise ratio (SNR). PCr and pH in the gastrocnemius medialis muscle were quantified from each ³¹P spectrum, acquired every 6 s. During exercise, SEPI (t) was found to be a linear function of tissue pH(t) (cross-correlation r = -0.85 ± 0.07). Strong Pearson's correlations were observed between post exercise time-to-peak (TTP) of SEPI and (a) the time constant of PCr recovery τPCr recovery (r = 0.89, p < 10â»6), (b) maximum oxidative phosphorylation using the linear model, Q(max, lin) (r = 0.65, p = 0.002), the adenosine-diphosphate-driven model, Q(max,ADP) (r = 0.73, p = 0.0002) and (c) end exercise pH (r = 0.60, p = 0.005). Based on combined accurately localised ³¹P MRS and T2∗ weighted MRI, both with high temporal resolution, strong correlations of the skeletal muscle SEPI during exercise and tissue pH time courses and of post exercise SEPI and parameters of energy metabolism were observed. In conclusion, a tight coupling between skeletal muscle metabolic activity and tissue T2∗ signal weighting, probably induced by osmotically driven water shift, exists and can be measured non-invasively, using NMR at 7 T.
Asunto(s)
Ejercicio Físico/fisiología , Pierna/fisiología , Imagen por Resonancia Magnética , Músculo Esquelético/fisiología , Fosforilación Oxidativa , Fosfocreatina/metabolismo , Adulto , Demografía , Imagen Eco-Planar , Femenino , Humanos , Concentración de Iones de Hidrógeno , Masculino , Fosfocreatina/análogos & derivados , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: To propose a quantitative model for a reliable and operator independent estimation of parameters describing blood oxygen-level dependent (BOLD) MRI time course in calf muscles during reactive hyperemia. MATERIALS AND METHODS: Echo planar imaging-based BOLD-MRI of the human calf were acquired during and after cuff-induced ischemia of the leg. Regions of interest were drawn in soleus, gastrocnemius and tibialis anterior muscles. A gamma-variate plus a sigmoidal function were fitted to the reactive hyperemia time courses and parameters including time to peak (TTP), hyperemic peak value (HPV), peak area, and peak width were calculated. In addition, the TTP and HPV parameters were estimated manually by two operators to validate the reliability of the fitting procedure. RESULTS: The model function was fitted successfully to all data with a minimum reduced R(2) around 0.9. The in vivo results were in agreement with manually determined values (r ≥ 0.69), although significant inter-operator differences were observed. CONCLUSION: The proposed method allows for rapid, operator independent and robust quantification of muscle BOLD signal during reactive hyperemia. The model worked equally well over a wide range of imaging parameters and data quality. This approach should contribute significantly to the standardization of skeletal muscle BOLD-MRI, an important step toward its clinical application.
Asunto(s)
Hiperemia/patología , Procesamiento de Imagen Asistido por Computador , Isquemia/patología , Imagen por Resonancia Magnética , Músculo Esquelético/patología , Adulto , Imagen Eco-Planar , Humanos , Hiperemia/diagnóstico , Pierna/patología , Espectroscopía de Resonancia Magnética , Masculino , Modelos Teóricos , Reproducibilidad de los Resultados , Adulto JovenRESUMEN
BACKGROUND: Heme arginate can induce heme oxygenase-1 to protect tissue against ischemia-reperfusion injury. Blood oxygen level dependent (BOLD) functional magnetic resonance imaging measures changes in tissue oxygenation with a high spatial and temporal resolution. BOLD imaging was applied to test the effect of heme arginate on experimental ischemia reperfusion injury in the calf muscles. METHODS: A two period, controlled, observer blinded, crossover trial was performed in 12 healthy male subjects. Heme arginate (1 mg/kg body weight) or placebo were infused 24 h prior to a 20 min leg ischemia induced by a thigh cuff. 3 Tesla BOLD-imaging of the calf was performed and signal time courses from soleus, gastrocnemius and tibialis anterior muscle were available from 11 participants for technical reasons. RESULTS: Peak reactive hyperemia signal of the musculature was significantly increased and occurred earlier after heme arginate compared to placebo (106.2 ± 0.6% at 175 ± 16s vs. 104.5 ± 0.6% at 221 ± 19s; p = 0.025 for peak reperfusion and p = 0.012 for time to peak). CONCLUSIONS: A single high dose of heme arginate improves reperfusion patterns during ischemia reperfusion injury in humans. BOLD sensitive, functional MRI is applicable for the assessment of experimental ischemia reperfusion injury in skeletal muscle.