1H NMRS of carnosine combined with 31P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy

In recent years, quantitative nuclear magnetic resonance imaging and spectroscopy (NMRI and NMRS) have been used more systematically as outcome measures in natural history and clinical trial studies for Duchenne muscular dystrophy (DMD). Whereas most of these studies have emphasized the evaluation of the fat fraction as an assessment for disease severity, less focus has been placed on metabolic indices measured by NMRS. 31P NMRS in DMD reveals an alkaline inorganic phosphate (Pi) pool, originating from either leaky dystrophic myocytes or an increased interstitial space. 1H NMRS, exploiting the pH‐sensitive proton resonances of carnosine, an intracellular dipeptide, was used to distinguish between these two hypotheses. NMR data were obtained in 23 patients with DMD and 14 healthy subjects on a 3‐T clinical NMR system. Both 31P and 1H NMRS data were acquired at the level of the gastrocnemius medialis muscle. A multi‐slice multi‐echo imaging acquisition was performed for the determination of water T2 and fat fraction in the same region of interest. Whereas nearly all patients with DMD showed an elevated pH compared with healthy controls when using 31P NMRS, 1H NMRS‐determined pH was not systematically increased. As expected, the carnosine‐based intracellular pH was never found to be alkaline in the absence of a concurrent Pi‐based pH elevation. In addition, abnormal intracellular pH, based on carnosine, was never associated with normal water T2 values. We conclude ...
Source: NMR in Biomedicine - Category: Radiology Authors: Tags: RESEARCH ARTICLE Source Type: research