Detection and Alterations of Acetylcarnitine in Human Skeletal Muscles by 1H MRS at 7 T

Abstract

ObjectivesThe aims of this study were to detect the acetylcarnitine resonance line at 2.13 ppm in the human vastus lateralis and soleus muscles, assess T1 and T2 relaxation times, and investigate the diurnal and exercise-related changes in absolute concentration noninvasively, using proton magnetic resonance spectroscopy at 7 T.Materials and MethodsAll measurements were performed on a 7 T whole-body Magnetom MR system with a 28-channel knee coil. Five healthy, moderately trained volunteers participated in the assessment of the detectability, repeatability, and relaxation times of acetylcarnitine. For the evaluation of the effect of training status, another 5 healthy, normally active volunteers were examined. In addition, normally active volunteers underwent a day-long protocol to estimate diurnal changes and response to the exercise.ResultsUsing a long echo time of 350 milliseconds, we were able to detect the acetylcarnitine resonance line at 2.13 ppm in both muscle groups without significant lipid contamination. The T1 of acetylcarnitine in the vastus lateralis muscle was found to be 1807.2 ± 513.1 milliseconds and T2 was found to be 129.9 ± 44.9 milliseconds. Concentrations of acetylcarnitine from the vastus lateralis muscle in moderately trained volunteers were higher than concentrations from normally active volunteers. Acetylcarnitine concentrations changed during the day, tending to be higher in the morning after an overnight fast than after lunch. After 10 minutes of high-intensity exercise, the concentration significantly increased, and 15 minutes after cessation of exercise, a decrease could be observed.ConclusionsOur results demonstrate an effective detection of acetylcarnitine using a long TE of 350 milliseconds at 7 T in the vastus lateralis and soleus muscles with high repeatability and reliability on a 7 T scanner. Our data emphasize the need for strict standardization, physical activity, and dietary conditions for the measurement of the acetylcarnitine.

Multinuclear Magnetic Resonance Spectroscopy of Human Skeletal Muscle Metabolism in Training and Disease

“…Recently, high-intensity exercise challenge to the vastus lateralis muscle by performing squats continuously for 10 min also showed an increase in the AcC level and approximately 15 min after the cessation of exercise, AcC depletion or washout was observed [33]. Similar effect of increasing AcC levels was observed in trained and untrained subject after 30 min of cycle ergometer exercise.…”

“…Among other typical uses of 1 H MRS belong: (a) detection of lactate (Lac) formation during exercise [8,[19][20][21]; (b) measurement of total creatine (Cr) content [22][23][24]; (c) assessment of muscle fiber orientation using dipolar coupling [25]; (d) measurement of intramyocellular metabolite diffusion [26]; and (e) the dynamic measurement of tissue (de)oxygenation using the signal of deoxymyoglobin (DMb) [27][28][29]. Furthermore, detection of resting muscle carnosine [30,31] and acetylcarnitine (AcC) [32,33] has been recently promoted as a promising use of 1 H MRS. An example of high resolved in vivo acquired 1 H MR spectrum of skeletal muscle is given in Figure 1.…”

“…The straight forward detection and quantification of AcC is challenging, due to the strong overlap of the 2.13 ppm line with lipid resonances, and the fact that the line at 3.20 ppm represents a combination of the trimethylammonium (TMA) groups of carnitine, AcC, and choline. Fortunately, the differences in T 2 relaxation times of AcC and lipids allow the detection of the 2.13 ppm line at rest, using long-TE 1 H MRS [32,33].…”

“…No significant difference has been reported in acetylcarnitine (AcC) concentration between endurance-trained and untrained lean sedentary or obese sedentary volunteers [32,121]. A recent study performed in trained and normally active subjects showed significant differences between AcC concentrations measured after overnight fast or after lunch [33]. This makes the comparison difficult and emphasizes the need for strict standardization of measurement time, dietary conditions, and physical activity (explained below) for the measurement of AcC/carnitine.…”

“…Muscle acetylcarnitine (AcC) levels measured at rest could be potentially used to tip the scales in the right direction, as it has been shown that while T2DM subjects have low muscle AcC concentration, endurance-trained subjects have high stores of muscle AcC [32]. Unfortunately, as the AcC levels are dependent on dietary status and physical activity [33], more studies accounting for these dependencies are required to support these initial findings. Multinuclear MRS studies have also revealed a link between IMCL accumulation measured by 1 H MRS and skeletal muscle glucose metabolism [17,118,154] assessed by 13 C and/or 31 P MRS, which has also been studied in different states of insulin resistance and physical fitness [155].…”