{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T05:51:35Z","timestamp":1775973095915,"version":"3.50.1"},"posted":{"date-parts":[[2025,5,11]]},"group-title":"Bioengineering","reference-count":36,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,5,11]],"date-time":"2025-05-11T00:00:00Z","timestamp":1746921600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"name":"National Institute on Aging of the National Institutes of Health","award":["RF1AG087306"],"award-info":[{"award-number":["RF1AG087306"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["R01AG063869"],"award-info":[{"award-number":["R01AG063869"]}]},{"name":"National Institute on Aging of the National Institutes of Health","award":["R01AG091760"],"award-info":[{"award-number":["R01AG091760"]}]},{"name":"National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health","award":["P41EB029460"],"award-info":[{"award-number":["P41EB029460"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,5,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Precise demarcation of brain tumor boundaries is critical for optimizing treatment strategies and improving patient outcomes.\n                  <jats:italic>In vivo<\/jats:italic>\n                  characterization of tumor using PET\/CT and MRI is clinical standard. PET\/CT highlights the metabolic aspects of the tumor, while MRI provides information on functional, metabolic and structural changes. Even with technological advancements in both PET\/CT and MRI, a method that can precisely delineate infiltrative tumor boundaries from normal-appearing brain regions (NABR)\n                  <jats:italic>in vivo<\/jats:italic>\n                  is still lacking. To address this limitation, we explored a relatively new MR imaging method, the Nuclear Overhauser Effect Magnetization Transfer Ratio (NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  ), in conjunction with a gadolinium-based contrast agent (Gd-DOTA), to precisely delineate the tumor boundaries in a rat model of infiltrative gliosarcoma. NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  imaging was performed in the rat model (n=5) before and after Gd-DOTA administration. The post-Gd-DOTA NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  map was subtracted from the pre-Gd-DOTA map and compared with contrast-enhanced T\n                  <jats:sub>1<\/jats:sub>\n                  -weighted images and immuno-histological findings. The resulting NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  difference map clearly highlighted both the tumor core and infiltrative boundaries, which was not discernible on the post-contrast T\n                  <jats:sub>1<\/jats:sub>\n                  -weighted images. The extended tumor boundaries observed on the NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  difference map corroborated with the IHC image, which confirmed the presence of infiltrative tumor cells and macrophages in these regions. Guided by the NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  difference map, regions of interest (ROI) were drawn to quantify NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  signal changes in the tumor core, tumor boundaries, and NABR post-Gd-DOTA. Tumor core showed a significant \u223c43% reduction in NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  signal (plJ=lJ0.003), while the tumor periphery exhibited a moderate reduction of \u223c10%, (plJ=lJ0.045). No appreciable change in was observed in the NABR (plJ=lJ0.371). In contrast, the post contrast T\n                  <jats:sub>1<\/jats:sub>\n                  -weighted signal changes in tumor core, tumor periphery and NABR were, 33.32% (p = 0.092), 3.8% (p = 0.478), and 8.7% (p = 0.464) respectively. These findings suggest that NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  imaging provides enhanced tumor contrast, particularly at the infiltrative tumor margins, where conventional contrast enhanced T\n                  <jats:sub>1<\/jats:sub>\n                  -weighted MRI may underestimate tumor extent. Histological validation confirmed the presence of infiltrative tumor cells and macrophages in the tumor periphery, as highlighted by the NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  difference map. Overall, NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  imaging, in combination with Gd-DOTA administration, demonstrates superior delineation of brain tumor boundaries compared to conventional MRI. As NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  imaging is a fast acquisition scan (under 10 minutes) and performed on standard 3 Tesla, it can be easily integrated into clinical protocols. By improving visualization of tumor infiltration and distinguishing tumor regions from NABR, NOE\n                  <jats:sub>MTR<\/jats:sub>\n                  imaging holds promise for advancing neuro-oncological diagnostics and treatment planning.\n                <\/jats:p>","DOI":"10.1101\/2025.05.06.652446","type":"posted-content","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T02:45:11Z","timestamp":1747017911000},"source":"Crossref","is-referenced-by-count":1,"title":["Magnetic Resonance Imaging for Improved Brain Tumor Detection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2480-4164","authenticated-orcid":false,"given":"Blake","family":"Benyard","sequence":"first","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6436-7299","authenticated-orcid":false,"given":"Narayan Datt","family":"Soni","sequence":"additional","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-8610","authenticated-orcid":false,"given":"Anshuman","family":"Swain","sequence":"additional","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nishi","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6270-5001","authenticated-orcid":false,"given":"Sunil Kumar","family":"Khokar","sequence":"additional","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2996-217X","authenticated-orcid":false,"given":"Nadir","family":"Yehya","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology and Critical Care Medicine, Children\u2019s Hospital of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dushyant","family":"Kumar","sequence":"additional","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ravi Prakash Reddy","family":"Nanga","sequence":"additional","affiliation":[{"name":"Center for Metabolic Imaging in Precision Medicine (CAMIPM), Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5055-8024","authenticated-orcid":false,"given":"Michael P.","family":"Frenneaux","sequence":"additional","affiliation":[{"name":"Hamad Medical Corporation, Doha, 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