{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T11:44:19Z","timestamp":1783338259616,"version":"3.54.6"},"reference-count":60,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T00:00:00Z","timestamp":1510444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>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. <jats:sup>31<\/jats:sup>P NMRS in DMD reveals an alkaline inorganic phosphate (P<jats:sub>i<\/jats:sub>) pool, originating from either leaky dystrophic myocytes or an increased interstitial space. <jats:sup>1<\/jats:sup>H NMRS, exploiting the pH\u2010sensitive 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\u2010T clinical NMR system. Both <jats:sup>31<\/jats:sup>P and <jats:sup>1<\/jats:sup>H NMRS data were acquired at the level of the gastrocnemius medialis muscle. A multi\u2010slice multi\u2010echo imaging acquisition was performed for the determination of water <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> 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 <jats:sup>31<\/jats:sup>P NMRS, <jats:sup>1<\/jats:sup>H NMRS\u2010determined pH was not systematically increased. As expected, the carnosine\u2010based intracellular pH was never found to be alkaline in the absence of a concurrent P<jats:sub>i<\/jats:sub>\u2010based pH elevation. In addition, abnormal intracellular pH, based on carnosine, was never associated with normal water <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> values. We conclude that, in one group of patients, both <jats:sup>1<\/jats:sup>H and <jats:sup>31<\/jats:sup>P NMRS showed an alkaline pH, originating from the intracellular compartment and reflecting ionic dysregulation in dystrophic myocytes. In the other patients with DMD, intracellular pH was normal, but an alkaline P<jats:sub>i<\/jats:sub> pool was still present, suggesting an extracellular origin, probably revealing an expanded interstitial volume fraction, often associated with fibrotic changes. The data demonstrate that <jats:sup>1<\/jats:sup>H NMRS could serve as a biomarker to assess the normalization of intramyocytic pH and sarcolemmal permeability following therapy inducing dystrophin expression in patients with DMD.<\/jats:p>","DOI":"10.1002\/nbm.3839","type":"journal-article","created":{"date-parts":[[2017,11,12]],"date-time":"2017-11-12T20:16:35Z","timestamp":1510517795000},"source":"Crossref","is-referenced-by-count":21,"title":["<sup>1<\/sup>H NMRS of carnosine combined with <sup>31<\/sup>P NMRS to better characterize skeletal muscle pH dysregulation in Duchenne muscular dystrophy"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0777-2711","authenticated-orcid":false,"given":"Harmen","family":"Reyngoudt","sequence":"first","affiliation":[{"name":"NMR Laboratory Institute of Myology  Paris France"},{"name":"CEA, DRF, IBFJ, MIRCen  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suna","family":"Turk","sequence":"additional","affiliation":[{"name":"NMR Laboratory Institute of Myology  Paris France"},{"name":"CEA, DRF, IBFJ, MIRCen  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre G.","family":"Carlier","sequence":"additional","affiliation":[{"name":"NMR Laboratory Institute of Myology  Paris France"},{"name":"CEA, DRF, IBFJ, MIRCen  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(87)90579-4"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/21675511.2015.1010966"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2010.11.005"},{"issue":"12","key":"e_1_2_8_5_1","first-page":"9734","article-title":"Metabogenic and nutriceutical approaches to address energy dysregulation and skeletal muscle wasting in Duchenne muscular dystrophy","volume":"7","author":"Rybalka E","year":"2015","journal-title":"Forum Nutr"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aaa7322"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6733-x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2015.05.006"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3352"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2016.07.013"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2016.09.013"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(82)92635-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.284.6322.1072"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.23.6.494"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.37.1.165"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(93)90326-T"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.3199"},{"issue":"1","key":"e_1_2_8_18_1","doi-asserted-by":"crossref","DOI":"10.1002\/nbm.3667","article-title":"Elevated phosphodiester and T2 levels can be measured in the absence of fat infiltration in Duchenne muscular dystrophy patients","volume":"30","author":"Hooijmans MT","year":"2016","journal-title":"NMR Biomed"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1139\/o91-124"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00256-011-1240-1"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.2785"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2000.279.3.R899"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(19)43389-9"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00039.2012"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1938.sp003605"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.85.21.7836"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/0010-406X(70)90049-6"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02265166"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00084.2012"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.01218.2013"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2012.06.005"},{"key":"e_1_2_8_32_1","first-page":"3358","article-title":"Validation of a very fast B1\u2010mapping sequence for parallel transmission on a human brain at 7T","volume":"20","author":"Amadon A","year":"2012","journal-title":"Proc Int Soc Mag Reson Med"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.24613"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02668096"},{"issue":"1","key":"e_1_2_8_35_1","first-page":"35","article-title":"Improved method for accurate and efficient quantification of MRS data with use of prior knowledge","volume":"129","author":"Vanhamme L","year":"1997","journal-title":"Magn Reson Imaging"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2006.04393.x"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(93)90052-Z"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e31823b9c78"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-012-6512-8"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.1.51"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1098\/rspb.1993.0030"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.070452"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13760-016-0607-4"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.151"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2001.00993.x"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00510.2003"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep31727"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12968-015-0150-0"},{"issue":"3","key":"e_1_2_8_49_1","first-page":"184","article-title":"The role of fibrosis in Duchenne muscular dystrophy","volume":"31","author":"Klingler W","year":"2012","journal-title":"Acta Myol"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/965631"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1517"},{"issue":"9","key":"e_1_2_8_52_1","first-page":"1","article-title":"31P MR spectroscopy and computational modeling identify a direct relation between Pi content of an alkaline compartment in resting muscle and phosphocreatine resynthesis kinetics in active muscle in humans","volume":"8","author":"Oorschot JWM","year":"2013","journal-title":"PLoS One"},{"issue":"7","key":"e_1_2_8_53_1","first-page":"71","article-title":"Mechanisms for exercise training\u2010induced increases in skeletal muscle blood flow capacity: differences with interval sprint training versus aerobic endurance training","volume":"59","author":"Laughlin MH","year":"2008","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.90872.2008"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00343295"},{"issue":"1","key":"e_1_2_8_56_1","first-page":"77","article-title":"Bioenergetics of intact human muscle. A 31P nuclear magnetic resonance study","volume":"1","author":"Taylor DJ","year":"1983","journal-title":"Mol Biol Med"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1148\/radiol.13121948"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2014.01.015"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.24917"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24599"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000000775"}],"container-title":["NMR in Biomedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fnbm.3839","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/nbm.3839","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T11:21:31Z","timestamp":1760959291000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/nbm.3839"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,12]]},"references-count":60,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2018,1]]}},"alternative-id":["10.1002\/nbm.3839"],"URL":"https:\/\/doi.org\/10.1002\/nbm.3839","archive":["Portico"],"relation":{},"ISSN":["0952-3480","1099-1492"],"issn-type":[{"value":"0952-3480","type":"print"},{"value":"1099-1492","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,12]]},"article-number":"e3839"}}