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With the emergence of hyperpolarized MRI, rapid noninvasive and tomographic pH imaging within minutes has become a realistic and highly appealing option for clinical diagnosis and treatment. In this study, we uncover that the pH\u2010responsive behavior of the MRI\u2010based pH probe 2\u2010oxo\u20104\u2010methyl\u20103\u2010pentene\u20101,5\u2010dioic acid (OMPD), particularly its pronounced pH\u2010dependent\n                    <jats:sup>13<\/jats:sup>\n                    C chemical shift changes, originates from a reversible cyclization process. We demonstrate that the cyclic lactol form of OMPD explains its favorable p\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>a<\/jats:sub>\n                    (ca. 6.5) and its pronounced pH\u2010dependent NMR chemical shift changes. Guided by this mechanistic insight, we developed an optimized synthesis of the lactol and achieved over 50,000\u2010fold\n                    <jats:sup>13<\/jats:sup>\n                    C NMR signal enhancement (at 1 T) of OMPD using hyperpolarization via reversible exchange with parahydrogen. By elucidating the molecular basis of OMPD's sensing behavior and establishing an efficient parahydrogen\u2010based method for its hyperpolarization, this work represents a significant step toward broader preclinical and clinical implementation.\n                  <\/jats:p>","DOI":"10.1002\/anie.8891303","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T09:01:07Z","timestamp":1788512467000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of the Cyclic Form of MRI pH\u2010Sensor\n                    <i>Z<\/i>\n                    \u2010OMPD Enables &gt;5%\n                    <sup>13<\/sup>\n                    C Hyperpolarization by SABRE"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6972-2165","authenticated-orcid":false,"given":"Juanita","family":"Ferreira","sequence":"first","affiliation":[{"name":"Institute of Organic Chemistry and Center 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