{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:17:58Z","timestamp":1787318278228,"version":"build-2736575974"},"reference-count":84,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,1,23]],"date-time":"2024-01-23T00:00:00Z","timestamp":1705968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    A unique feature of the tumor microenvironment is extracellular acidosis in relation to intracellular milieu. Metabolic reprogramming in tumors results in overproduction of H\n                    <jats:sup>+<\/jats:sup>\n                    ions (and lactate), which are extruded from the cells to support tumor survival and progression. As a result, the transmembrane pH gradient (\u0394pH), representing the difference between intracellular pH (pH\n                    <jats:sub>i<\/jats:sub>\n                    ) and extracellular pH (pH\n                    <jats:sub>e<\/jats:sub>\n                    ), is posited to be larger in tumors compared with normal tissue. Controlling the transmembrane pH difference has promise as a potential therapeutic target in cancer as it plays an important role in regulating drug delivery into cells. The current study shows successful development of an MRI\/MRSI\u2010based technique that provides \u0394pH imaging at submillimeter resolution. We applied this technique to image \u0394pH in rat brains with RG2 and U87 gliomas, as well as in mouse brains with GL261 gliomas. pH\n                    <jats:sub>i<\/jats:sub>\n                    was measured with Amine and Amide Concentration\u2010Independent Detection (AACID), while pH\n                    <jats:sub>e<\/jats:sub>\n                    was measured with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS). The results indicate that pH\n                    <jats:sub>i<\/jats:sub>\n                    was slightly higher in tumors (7.40\u20137.43 in rats, 7.39\u20137.47 in mice) compared with normal brain (7.30\u20137.38 in rats, 7.32\u20137.36 in mice), while pH\n                    <jats:sub>e<\/jats:sub>\n                    was significantly lower in tumors (6.62\u20136.76 in rats, 6.74\u20136.84 in mice) compared with normal tissue (7.17\u20137.22 in rats, 7.20\u20137.21 in mice). As a result, \u0394pH was higher in tumors (0.64\u20130.81 in rats, 0.62\u20130.65 in mice) compared with normal brain (0.13\u20130.16 in rats, 0.13\u20130.16 in mice). This work establishes an MRI\/MRSI\u2010based platform for \u0394pH imaging at submillimeter resolution in gliomas.\n                  <\/jats:p>","DOI":"10.1002\/nbm.5102","type":"journal-article","created":{"date-parts":[[2024,1,24]],"date-time":"2024-01-24T01:07:20Z","timestamp":1706058440000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Transmembrane pH gradient imaging in rodent glioma models"],"prefix":"10.1002","volume":"37","author":[{"given":"Sandeep Kumar","family":"Mishra","sequence":"first","affiliation":[{"name":"Department of Radiology &amp; Biomedical Imaging Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Gois","family":"Santana","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Mihailovic","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Biomedical Imaging Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahmeed","family":"Hyder","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Biomedical Imaging Yale University  New Haven Connecticut USA"},{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6289-0817","authenticated-orcid":false,"given":"Daniel","family":"Coman","sequence":"additional","affiliation":[{"name":"Department of Radiology &amp; Biomedical Imaging Yale University  New Haven Connecticut USA"},{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut 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