{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T05:39:42Z","timestamp":1761975582565,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2016,9,30]],"date-time":"2016-09-30T00:00:00Z","timestamp":1475193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"crossref","award":["C5255\/A15935"],"award-info":[{"award-number":["C5255\/A15935"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["NMR in Biomedicine"],"published-print":{"date-parts":[[2016,11]]},"abstract":"<jats:p>The purpose of this study was to develop realistic phantom models of the intracellular environment of metastatic breast tumour and na\u00efve brain, and using these models determine an analysis metric for quantification of CEST MRI data that is sensitive to only labile proton exchange rate and concentration. The ability of the optimal metric to quantify pH differences in the phantoms was also evaluated.<\/jats:p><jats:p>Novel phantom models were produced, by adding perchloric acid extracts of either metastatic mouse breast carcinoma cells or healthy mouse brain to bovine serum albumin. The phantom model was validated using <jats:sup>1<\/jats:sup>H NMR spectroscopy, then utilized to determine the sensitivity of CEST MRI to changes in pH, labile proton concentration, <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> time and <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> time; six different CEST MRI analysis metrics (MTR<jats:sub>asym<\/jats:sub>, APT*, MTR<jats:sub>Rex<\/jats:sub>, AREX and CESTR* with and without <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>\/<jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> compensation) were compared.<\/jats:p><jats:p>The new phantom models were highly representative of the <jats:italic>in vivo<\/jats:italic> intracellular environment of both tumour and brain tissue. Of the analysis methods compared, CESTR* with <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> and <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> time compensation was optimally specific to changes in the CEST effect (i.e. minimal contamination from <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> or <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> variation). In phantoms with identical protein concentrations, pH differences between phantoms could be quantified with a mean accuracy of 0.6 pH units.<\/jats:p><jats:p>We propose that CESTR* with <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub> and <jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> time compensation is the optimal analysis method for these phantoms. Analysis of CEST MRI data with <jats:italic>T<\/jats:italic><jats:sub>1<\/jats:sub>\/<jats:italic>T<\/jats:italic><jats:sub>2<\/jats:sub> time compensated CESTR* is reproducible between phantoms, and its application <jats:italic>in vivo<\/jats:italic> may resolve the intracellular alkalosis associated with breast cancer brain metastases without the need for exogenous contrast agents.<\/jats:p>","DOI":"10.1002\/nbm.3614","type":"journal-article","created":{"date-parts":[[2016,10,1]],"date-time":"2016-10-01T20:14:59Z","timestamp":1475352899000},"page":"1624-1633","source":"Crossref","is-referenced-by-count":12,"title":["Determination of an optimally sensitive and specific chemical exchange saturation transfer MRI quantification metric in relevant biological phantoms"],"prefix":"10.1002","volume":"29","author":[{"given":"Kevin J.","family":"Ray","sequence":"first","affiliation":[{"name":"Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology University of Oxford  Oxford OX3 7LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James R.","family":"Larkin","sequence":"additional","affiliation":[{"name":"Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology University of Oxford  Oxford OX3 7LE UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yee K.","family":"Tee","sequence":"additional","affiliation":[{"name":"Department of Mechatronics and Biomedical Engineering, Lee Kong Chian Faculty of Engineering and Science Universiti Tunku Abdul Rahman  Malaysia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandre A.","family":"Khrapitchev","sequence":"additional","affiliation":[{"name":"Cancer Research UK and Medical Research Council Oxford Institute for Radiation Oncology, Department of Oncology University of Oxford  Oxford OX3 7LE 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