CORP: quantification of human skeletal muscle carnosine concentration by proton magnetic resonance spectroscopy

Abstract

Non-invasive techniques to quantify metabolites in skeletal muscle provide unique insight into human physiology and enable the translation of research into practice. Proton magnetic resonance spectroscopy (1H-MRS) permits the assessment of several abundant muscle metabolites in vivo, including carnosine, a dipeptide composed of the amino acids histidine and beta-alanine. Muscle carnosine loading - accomplished by chronic oral beta-alanine supplementation - improves muscle function, exercise capacity and has pathophysiological relevance in multiple diseases. Moreover, the marked difference in carnosine content between fast-twitch and slow-twitch muscle fibers has rendered carnosine an attractive candidate to estimate human muscle fiber type composition. However, the quantification of carnosine using 1H-MRS requires technical expertise in order to obtain accurate and reproducible data. In this review, we describe the technical and physiological factors that impact the detection, analysis and quantification of carnosine in muscle using 1H-MRS. We discuss potential sources of error during the acquisition and pre-processing of the 1H-MRS spectra, and present best practices to enable the accurate, reliable and reproducible application of this technique.

Under the Hood: Skeletal Muscle Determinants of Endurance Performance

“…Given the fact that high proportions of type-I fibers are suggested to display greater mechanical efficiency at common movement frequencies (i.e., 1-2Hz, e.g., cycling between 60 and 120 rpm) that are close to the type-I fiber's peak efficiency velocity (He et al, 2000;Joyner and Coyle, 2008), a higher percentage of type-I fibers would relate to a higher gross efficiency (Coyle et al, 1992;Horowitz et al, 1994), and therefore contributes to a higher endurance performance (Horowitz et al, 1994). Nowadays, non-invasive techniques such as 1 H-MRS measurements of muscle carnosine content are also used to estimate type-I and II muscle typology, thereby confirming prior muscle biopsy-based findings across athletes (Baguet et al, 2011;Bex et al, 2017;Lievens et al, 2020Lievens et al, , 2021.…”

Comment on “Cores of Reproducibility in Physiology (CORP): quantification of human skeletal muscle carnosine concentration by proton magnetic resonance spectroscopy”

“…Other practices, such as reporting individual data and spectrum, SNR, and carnosine peak width will help to promote transparency. We maintain, like Lievens et al (1), that the 1 H-MRS determination of muscle carnosine concentrations is important in the field of human physiology, but only if it is shown to be valid and reliable.…”

“…We quantified muscle carnosine with 1 H-MRS (5) using the same procedures as previously described (7) and showed poor agreement between 1 H-MRS and a reference method. Lievens et al (1) suggested that this could be explained by the small voxel size used in our study, leading to a lower signal-to-noise ratio (SNR). Noteworthy, all our 41 measurements displayed an SNR above their proposed (7) cut-off of SNR > 3 (SNR: 7.1 ± 2.4, min = 3.5, max = 14.2), meaning that voxel size does not account for the poor validity of 1 H-MRS shown in our study.…”

“…Large variation in 1 H-MRS carnosine results has been reported by several groups (6), including studies conducted by the same research group (8) as Lievens et al (1). Chung et al (8) reported discrepantly large mean and individual increases in gastrocnemius and soleus muscle carnosine (143 ± 147% and 161 ± 60%, respectively) in response to b-alanine supplementation.…”

“…According to the authors (1), 1 H-MRS can be validated in two ways: 1) by supplementation of b-alanine and 2) by comparing with high-performance liquid chromatography (HPLC) of a muscle tissue biopsy. However, any test must meet other criteria to be valid, including adequate reproducibility (i.e., low test-retest variation), accuracy (i.e., similarity with an external gold-standard reference), and an ability to discriminate knowingly different groups or conditions.…”