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However, current chemical exchange saturation transfer (CEST)\u2013based PCr imaging (PCrCEST) remains limited by pH\u2010dependent contrast. Here, we present a pH\u2010insensitive PCrCEST strategy that minimizes pH\u2010related signal variability, enabling more reliable in\u00a0vivo quantification during exercise, when tissue pH may change. Theoretical derivation, simulations, and phantom studies confirmed that PCrCEST signals varied by less than 20% across the physiological pH range when the saturation radial frequency (\u03b3\n                    <jats:italic>B<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    ) matches the guanidinium proton exchange rate. Under this optimized\n                    <jats:italic>B<\/jats:italic>\n                    <jats:sub>1<\/jats:sub>\n                    condition, kinetic simulations further show that the PCrCEST\u2010derived recovery time constant (\n                    <jats:italic>\u03c4<\/jats:italic>\n                    <jats:sub>PCr<\/jats:sub>\n                    ) closely follows expected behavior even during dynamic pH changes. The pH\u2010insensitive strategy was implemented at both 3 and 5\u2009T and assessed in human calf muscle during plantar flexion exercise. These results demonstrate that pH\u2010insensitive PCrCEST enabled robust mapping of muscle CK metabolism. The availability of pH\u2010insensitive CEST mapping improves the potential of CEST not only for exercise measurements but also for broader clinical translation.\n                  <\/jats:p>","DOI":"10.1002\/nbm.70280","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T08:40:39Z","timestamp":1775637639000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Noninvasive Mapping of Creatine Kinase Metabolism in Human Muscle Using pH\u2010Insensitive PCrCEST MRI at 3 and 5\u2009T"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6748-2778","authenticated-orcid":false,"given":"Xinran","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Electronic Science Xiamen University  Xiamen Fujian China"},{"name":"Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"Key Laboratory of Biomedical Imaging Science and System Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"State Key Laboratory of Biomedical Imaging Science and System  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8726-5834","authenticated-orcid":false,"given":"Xi","family":"Xu","sequence":"additional","affiliation":[{"name":"Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"Key Laboratory of Biomedical Imaging Science and System Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"State Key Laboratory of Biomedical Imaging Science and System  Shenzhen Guangdong China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-1983","authenticated-orcid":false,"given":"Chongxue","family":"Bie","sequence":"additional","affiliation":[{"name":"Key Laboratory for Magnetic Resonance and Multimodality Imaging of Guangdong Province Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"Key Laboratory of Biomedical Imaging Science and System Chinese Academy of Sciences  Shenzhen Guangdong China"},{"name":"State Key Laboratory of Biomedical Imaging Science and System  Shenzhen Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9706-1066","authenticated-orcid":false,"given":"Peter","family":"van Zijl","sequence":"additional","affiliation":[{"name":"F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute  Baltimore MD USA"},{"name":"The Russell H. Morgan Department of Radiology The Johns Hopkins University, School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nirbhay","family":"Yadav","sequence":"additional","affiliation":[{"name":"F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute  Baltimore MD USA"},{"name":"The Russell H. Morgan Department of Radiology The Johns Hopkins University, School of Medicine  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiadi","family":"Xu","sequence":"additional","affiliation":[{"name":"F.M. Kirby Research Center for Functional Brain Imaging Kennedy Krieger Institute  Baltimore MD USA"},{"name":"The Russell H. 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