{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T13:49:53Z","timestamp":1789480193555,"version":"build-2803163510"},"reference-count":55,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Stereotactic MR\u2010guided Adaptive Radiation Therapy (SMART) dose painting for hypoxia has potential to improve treatment outcomes, but clinical implementation on low\u2010field MR\u2010Linac faces substantial challenges due to dramatically lower signal\u2010to\u2010noise ratio (SNR) characteristics. While quantitative MRI and T<jats:sub>1<\/jats:sub> mapping of hypoxia biomarkers show promise, T<jats:sub>1<\/jats:sub>\u2010to\u2010noise ratio (T<jats:sub>1<\/jats:sub>NR) optimization at low fields is paramount, particularly for the clinical implementation of oxygen\u2010enhanced (OE)\u2010MRI. The 3D Magnetization Prepared (2) Rapid Gradient Echo (MP2RAGE) sequence stands out for its ability to acquire homogeneous T<jats:sub>1<\/jats:sub>\u2010weighted contrast images with simultaneous T<jats:sub>1<\/jats:sub> mapping.<\/jats:p><\/jats:sec><jats:sec><jats:title>Purpose<\/jats:title><jats:p>To optimize MP2RAGE for low\u2010field T<jats:sub>1<\/jats:sub> mapping; conduct experimental validation in a ground\u2010truth phantom; establish feasibility and reproducibility of low\u2010field MP2RAGE acquisition and T<jats:sub>1<\/jats:sub> mapping in healthy volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The MP2RAGE optimization was performed to maximize the contrast\u2010to\u2010noise ratio (CNR) of T<jats:sub>1<\/jats:sub> values in white matter (WM) and gray matter (GM) brain tissues at 0.35T. Low\u2010field MP2RAGE images were acquired on a 0.35T MR\u2010Linac (ViewRay MRIdian) using a multi\u2010channel head coil. Validation of T<jats:sub>1<\/jats:sub> mapping was performed with a ground\u2010truth Eurospin phantom, containing inserts of known T<jats:sub>1<\/jats:sub> values (400\u2013850\u00a0ms), with one and two average (1A and 2A) MP2RAGE scans across four acquisition sessions, resulting in eight T<jats:sub>1<\/jats:sub> maps. Mean (\u00b1\u00a0SD) T<jats:sub>1<\/jats:sub> relative error, T<jats:sub>1<\/jats:sub>NR, and intersession coefficient of variation (CV) were determined. Whole\u2010brain MP2RAGE scans were acquired in 5 healthy volunteers across two sessions (A and B) and T<jats:sub>1<\/jats:sub> maps were generated. Mean (\u00b1\u00a0SD) T<jats:sub>1<\/jats:sub> values for WM and GM were determined. Whole\u2010brain T<jats:sub>1<\/jats:sub> histogram analysis was performed, and reproducibility was determined with the CV between sessions. Voxel\u2010by\u2010voxel T<jats:sub>1<\/jats:sub> difference maps were generated to evaluate 3D spatial variation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Low\u2010field MP2RAGE optimization resulted in parameters: MP2RAGE<jats:sub>TR<\/jats:sub> of 3250\u00a0ms, inversion times (TI<jats:sub>1<\/jats:sub>\/TI<jats:sub>2<\/jats:sub>) of 500\/1200\u00a0ms, and flip angles (<jats:italic>\u03b1<\/jats:italic><jats:sub>1<\/jats:sub>\/<jats:italic>\u03b1<\/jats:italic><jats:sub>2<\/jats:sub>) of 7\/5\u00b0. Eurospin T<jats:sub>1<\/jats:sub> maps exhibited a mean (\u00b1\u00a0SD) relative error of 3.45%\u00a0\u00b1\u00a01.30%, T<jats:sub>1<\/jats:sub>NR of 20.13\u00a0\u00b1\u00a05.31, and CV of 2.22%\u00a0\u00b1\u00a00.67% across all inserts. Whole\u2010brain MP2RAGE images showed high anatomical quality with clear tissue differentiation, resulting in mean (\u00b1\u00a0SD) T<jats:sub>1<\/jats:sub> values: 435.36\u00a0\u00b1\u00a010.01\u00a0ms for WM and 623.29\u00a0\u00b1\u00a014.64\u00a0ms for GM across subjects, showing excellent concordance with literature. Whole\u2010brain T<jats:sub>1<\/jats:sub> histograms showed high intrapatient and intersession reproducibility with characteristic intensity peaks consistent with voxel\u2010level WM and GM T<jats:sub>1<\/jats:sub> values. Reproducibility analysis revealed a CV of 0.46%\u00a0\u00b1\u00a00.31% and 0.35%\u00a0\u00b1\u00a00.18% for WM and GM, respectively. Voxel\u2010by\u2010voxel T<jats:sub>1<\/jats:sub> difference maps show a normal 3D spatial distribution of noise in WM and GM.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Low\u2010field MP2RAGE proved effective in generating accurate, reliable, and reproducible T<jats:sub>1<\/jats:sub> maps with high T<jats:sub>1<\/jats:sub>NR in phantom studies and in vivo feasibility established in healthy volunteers. While current work is focused on refining the MP2RAGE protocol to enable clinically efficient OE\u2010MRI, this study establishes a foundation for TOLD T<jats:sub>1<\/jats:sub> mapping for hypoxia biomarkers. This advancement holds the potential to facilitate a paradigm shift toward MR\u2010guided biological adaptation and dose painting by leveraging 3D hypoxic spatial distributions and improving outcomes in conventionally challenging\u2010to\u2010treat cancers.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.17353","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T13:29:35Z","timestamp":1723642175000},"page":"8124-8140","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Optimization and validation of low\u2010field MP2RAGE T<sub>1<\/sub> mapping on 0.35T MR\u2010Linac: Toward adaptive dose painting with hypoxia biomarkers"],"prefix":"10.1002","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7603-0340","authenticated-orcid":false,"given":"Claire Keun Sun","family":"Park","sequence":"first","affiliation":[{"name":"Division of Physics and Biophysics Department of Radiation 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