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However, entropy is often perceived as statistical data lacking clinical significance. We aimed to generate a voxel-by-voxel visual map of local tumor entropy, thus allowing to (1) make entropy explainable and accessible to clinicians; (2) disclose and quantitively characterize any intra-tumoral entropy heterogeneity; (3) evaluate associations between entropy and pathology data. We analyzed the portal phase of preoperative CT of 20 patients undergoing liver surgery for colorectal metastases. A three-dimensional core kernel (5\u2009\u00d7\u20095\u2009\u00d7\u20095 voxels) was created and used to compute the local entropy value for each voxel of the tumor. The map was encoded with a color palette. We performed two analyses: (a) qualitative assessment of tumors\u2019 detectability and pattern of entropy distribution; (b) quantitative analysis of the entropy values distribution. The latter data were compared with standard Hounsfield data as predictors of post-chemotherapy tumor regression grade (TRG). Entropy maps were successfully built for all tumors. Metastases were qualitatively hyper-entropic compared to surrounding parenchyma. In four cases hyper-entropic areas exceeded the tumor margin visible at CT. We identified four \u201centropic\u201d patterns: homogeneous, inhomogeneous, peripheral rim, and mixed. At quantitative analysis, entropy-derived data (percentiles\/mean\/median\/root mean square) predicted TRG (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) better than Hounsfield-derived ones (<jats:italic>p<\/jats:italic>\u2009=\u2009n.s.). We present a standardized imaging technique to visualize tumor heterogeneity built on a voxel-by-voxel entropy assessment. The association of local entropy with pathology data supports its role as a biomarker.<\/jats:p>\n                <jats:p><jats:bold>Graphical Abstract<\/jats:bold><\/jats:p>","DOI":"10.1007\/s10278-023-00799-9","type":"journal-article","created":{"date-parts":[[2023,2,27]],"date-time":"2023-02-27T22:02:46Z","timestamp":1677535366000},"page":"1038-1048","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Mapping Tumor Heterogeneity via Local Entropy Assessment: Making Biomarkers Visible"],"prefix":"10.1007","volume":"36","author":[{"given":"Guido","family":"Costa","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lara","family":"Cavinato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Fiz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Sollini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arturo","family":"Chiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guido","family":"Torzilli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Ieva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4108-4832","authenticated-orcid":false,"given":"Luca","family":"Vigan\u00f2","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2023,2,27]]},"reference":[{"issue":"4","key":"799_CR1","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1016\/j.ejca.2011.11.036","volume":"48","author":"P Lambin","year":"2012","unstructured":"Lambin P, Rios-Velazquez E, Leijenaar R et al. 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Approval was granted by the Ethics Committee of the Humanitas Research Hospital (protocol #83\/20).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics Approval"}},{"value":"Because of the retrospective design of the study, specific written informed consent was waived by the Institutional Review Board.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Participate"}},{"value":"No individual details, images or videos are included in the present manuscript. Accordingly, no informed consent for publication of the images was needed.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to Publish"}},{"value":"We state that there are no personal conflicts of interest of any of the authors pertinent to the present manuscript. Considering the conflicts of interest in general, we state that: Luca Vigan\u00f2 received speaker\u2019s honoraria from Johnson & Johnson. Arturo Chiti received speaker\u2019s honoraria from the following companies: Advanced Accelerator Applications, General Electric Healthcare, Sirtex Medical Europe, AmGen Europe, travel grants form General Electric Healthcare and Sirtex Medical Europe; he is a member of Blue Earth Diagnostics\u2019 and Advanced Accelerator Applications\u2019 advisory boards and received scientific support, in terms of a three-year Ph.D. fellowship, from the Sanofi Genzyme. Francesco Fiz acts as a consultant for the MSD Sharp & Dohme GmbH (LLC).","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}]}}