{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T06:25:18Z","timestamp":1787207118935,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R21 CA274152"],"award-info":[{"award-number":["R21 CA274152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 CA280871"],"award-info":[{"award-number":["R01 CA280871"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Extracellular acidosis is a biologically important feature of the tumor microenvironment in the liver, promoting immune evasion, angiogenesis, and resistance to therapy, and representing a mechanistically important and potentially targetable axis in liver cancer. Imaging extracellular pH (pH\n                    <jats:sub>e<\/jats:sub>\n                    ) at high resolution is needed to better understand the immuno\u2010metabolic interplay, especially at the transition regions between the tumor core, tumor margin, and background liver, which is critical for any pharmacological or image\u2010guided intervention. Yet, there is a paucity of imaging techniques capable of providing pH\n                    <jats:sub>e<\/jats:sub>\n                    mapping at high resolution. Here, we demonstrate high\u2010resolution pH\n                    <jats:sub>e<\/jats:sub>\n                    imaging in a mouse Hepa1\u20136 liver tumor model using\n                    <jats:sup>1<\/jats:sup>\n                    H Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) with REduced Spherical Encoding with GAussian Weighting (RESEGAW). Eight tumor\u2010bearing C57BL\/6J mice were used to demonstrate pH\n                    <jats:sub>e<\/jats:sub>\n                    imaging with RESEGAW using the macrocyclic agent TmDOTP\n                    <jats:sup>5\u2212<\/jats:sup>\n                    at 0.6\u2009mm isotropic resolution on a 9.4\u2009T scanner, which was validated using\n                    <jats:sup>31<\/jats:sup>\n                    P\u2010MRSI with 3\u2010aminopropylphosphonate (3\u2010APP). pH\n                    <jats:sub>e<\/jats:sub>\n                    imaging with\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010BIRDS\u2010RESEGAW consistently showed acidic tumor regions (pH\n                    <jats:sub>e<\/jats:sub>\n                    \u2009=\u20096.77\u2009\u00b1\u20090.14) relative to adjacent normal liver (pH\n                    <jats:sub>e<\/jats:sub>\n                    \u2009=\u20097.14\u2009\u00b1\u20090.07). Mean pH\n                    <jats:sub>e<\/jats:sub>\n                    values measured by\n                    <jats:sup>31<\/jats:sup>\n                    P\u2010MRSI with 3\u2010APP and\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010BIRDS\u2010RESEGAW with TmDOTP\n                    <jats:sup>5\u2212<\/jats:sup>\n                    show no significant differences in tumors (pH\n                    <jats:sub>e<\/jats:sub>\n                    \u2009=\u20096.81\u2009\u00b1\u20090.13) and normal liver (pH\n                    <jats:sub>e<\/jats:sub>\n                    \u2009=\u20097.14\u2009\u00b1\u20090.06). Voxelwise comparison after co\u2010registration of\n                    <jats:sup>31<\/jats:sup>\n                    P\u2010MRSI with 3\u2010APP to\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010BIRDS\u2010RESEGAW using Bland\u2013Altman analysis demonstrated excellent agreement between the two methods, with minimal mean bias (\u22120.005 pH units) and variance of less than 0.1 pH units. These results demonstrate the feasibility and quantitative reliability of\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010BIRDS\u2010RESEGAW for imaging extracellular acidosis in liver tumors at submillimeter resolution, establishing a technical foundation for studying the immuno\u2010metabolic interplay in liver cancer and its response to therapy.\n                  <\/jats:p>","DOI":"10.1002\/nbm.70375","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T05:17:41Z","timestamp":1787203061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["High\u2010Resolution Imaging of Extracellular pH in Mouse Liver Tumor"],"prefix":"10.1002","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4370-5823","authenticated-orcid":false,"given":"Jessica Gois","family":"Santana","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-4336","authenticated-orcid":false,"given":"Sara","family":"Kurdi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-8862-5016","authenticated-orcid":false,"given":"Lisa Marie Helene","family":"Peschke","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Radiology Charit\u00e9\u2010Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin, Humboldt\u2010Universit\u00e4t, and Berlin Institute of Health  Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1016-0206","authenticated-orcid":false,"given":"Sandeep Kumar","family":"Mishra","sequence":"additional","affiliation":[{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine  New Haven Connecticut USA"},{"name":"Yale Biomedical Imaging Institute Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7822-4002","authenticated-orcid":false,"given":"Fahmeed","family":"Hyder","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"},{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine  New Haven Connecticut USA"},{"name":"Yale Biomedical Imaging Institute Yale School of Medicine  New Haven Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julius","family":"Chapiro","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Yale University  New Haven Connecticut USA"},{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine  New Haven Connecticut USA"},{"name":"Yale Biomedical Imaging Institute Yale School of Medicine  New Haven Connecticut USA"},{"name":"Department of Medicine, Department of Surgical Pathology  New Haven Connecticut USA"},{"name":"Section of Digestive Diseases, Department of Internal Medicine Yale University School of Medicine  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 Biomedical Engineering Yale University  New Haven Connecticut USA"},{"name":"Department of Radiology and Biomedical Imaging Yale School of Medicine  New Haven Connecticut USA"},{"name":"Yale Biomedical Imaging Institute Yale School of Medicine  New Haven Connecticut 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