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We aim to validate a previously-trained machine learning algorithm that generates cellularity prediction maps (CPM) from multiparametric MRI data to an independent, retrospective external cohort of gliomas undergoing image-guided biopsies, and to compare the performance of CPM and diffusion MRI apparent diffusion coefficient (ADC) in predicting cellularity.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>A cohort of patients with treatment-na\u00efve or recurrent gliomas were prospectively studied. All patients underwent pre-surgical MRI according to the standardized brain tumor imaging protocol. The surgical sampling site was planned based on image-guided biopsy targets and tissue was stained with hematoxylin\u2013eosin for cell density count. The correlation between MRI-derived CPM values and histological cellularity, and between ADC and histological cellularity, was evaluated both assuming independent observations and accounting for non-independent observations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>Sixty-six samples from twenty-seven patients were collected. Thirteen patients had treatment-na\u00efve tumors and fourteen had recurrent lesions. CPM value accurately predicted histological cellularity in treatment-na\u00efve patients (b\u2009=\u20091.4, R<jats:sup>2<\/jats:sup>\u2009=\u20090.2, <jats:italic>p<\/jats:italic>\u2009=\u20090.009, rho\u2009=\u20090.41, <jats:italic>p<\/jats:italic>\u2009=\u20090.016, RMSE\u2009=\u20091503 cell\/mm<jats:sup>2<\/jats:sup>), but not in the recurrent sub-cohort. Similarly, ADC values showed a significant association with histological cellularity only in treatment-naive patients (b\u2009=\u20091.3, R<jats:sup>2<\/jats:sup>\u2009=\u20090.22, <jats:italic>p<\/jats:italic>\u2009=\u20090.007; rho\u2009=\u2009-0.37, <jats:italic>p<\/jats:italic>\u2009=\u20090.03), not statistically different from the CPM correlation. These findings were confirmed with statistical tests accounting for non-independent observations.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>MRI-derived machine learning generated cellularity prediction maps (CPM) enabled a non-invasive evaluation of tumor cellularity in treatment-na\u00efve glioma patients, although CPM did not clearly outperform ADC alone in this cohort.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s11060-025-05105-x","type":"journal-article","created":{"date-parts":[[2025,6,21]],"date-time":"2025-06-21T04:09:59Z","timestamp":1750478999000},"page":"111-122","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Independent histological validation of MR-derived radio-pathomic maps of tumor cell density using image-guided biopsies in human brain tumors"],"prefix":"10.1007","volume":"175","author":[{"given":"Gianluca","family":"Nocera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Sanvito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonoko","family":"Oshima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel A.","family":"Bobholz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley","family":"Teraishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina","family":"Raymond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard G.","family":"Everson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda M.","family":"Liau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Connelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Castellano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Mortini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriko","family":"Salamon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy F.","family":"Cloughesy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter S.","family":"LaViolette","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin M.","family":"Ellingson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,6,21]]},"reference":[{"issue":"12 Suppl 2","key":"5105_CR1","doi-asserted-by":"publisher","first-page":"iv1","DOI":"10.1093\/neuonc\/noad149","volume":"25","author":"QT Ostrom","year":"2023","unstructured":"Ostrom QT et al (2023) CBTRUS statistical report: primary brain and other central nervous system tumors diagnosed in the United States in 2016\u20132020. 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TFC is cofounder, major stock holder, consultant and board member of Katmai Pharmaceuticals, holds stock for Erasca, member of the board and paid consultant for the 501c3 Global Coalition for Adaptive Research, holds stock in Chimerix and receives milestone payments and possible future royalties, member of the scientific advisory board for Break Through Cancer, member of the scientific advisory board for Cure Brain Cancer Foundation, has provided paid consulting services to Blue Rock, Vida Ventures, Lista Therapeutics, Stemline, Novartis, Roche, Sonalasense, Sagimet, Clinical Care Options, Ideology Health, Servier, Jubilant, Immvira, Gan & Lee, BrainStorm, Katmai, Sapience, Inovio, Vigeo Therapeutics, DNATrix, Tyme, SDP, Kintara, Bayer, Merck, Boehinger Ingelheim, VBL, Amgen, Kiyatec, Odonate Thera- peutics QED, Medefield, Pascal Biosciences, Bayer, Tocagen, Karyo- pharm, GW Pharma, Abbvie, VBI, Deciphera, VBL, Agios, Genocea, Celgene, Puma, Lilly, BMS, Cortice, Novocure, Novogen, Boston Biomedical, Sunovion, Insys, Pfizer, Notable labs, Medqia, Trizel, Medscape and has contracts with UCLA for the Brain Tumor Program with Roche, VBI, Merck, Novartis, BMS, AstraZeneca, Servier. The Regents of the University of California (T.F.C. employer) has licensed intellectual property co-invented by TFC to Katmai Pharmaceuticals. PSL Holds US Patent 12171542 that protects portions of the intellectual property of the radio-pathomic mapping methods used in this study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"The collection and analysis of clinical and imaging data for this research was approved by the institutional review board under the identification number IRB#14-001261.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All patients gave written informed consent for their datasets and clinical information to be included in a database used for research.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}