{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:22:33Z","timestamp":1762507353424,"version":"3.37.3"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"15","license":[{"start":{"date-parts":[[2018,3,14]],"date-time":"2018-03-14T00:00:00Z","timestamp":1520985600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000275","name":"Leverhulme Trust","doi-asserted-by":"publisher","award":["RPG-2014-019"],"award-info":[{"award-number":["RPG-2014-019"]}],"id":[{"id":"10.13039\/501100000275","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Royal College of Radiologists Small Project"},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"CRUK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Clinician Scientist","award":["C19221\/A22746"],"award-info":[{"award-number":["C19221\/A22746"]}]},{"DOI":"10.13039\/501100000289","name":"CRUK","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EPSRC Cancer Imaging Centre in Cambridge and Manchester"},{"DOI":"10.13039\/501100000770","name":"University of Manchester","doi-asserted-by":"publisher","award":["C8742\/A18097"],"award-info":[{"award-number":["C8742\/A18097"]}],"id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Imaging demonstrates that preclinical and human tumors are heterogeneous, i.e. a single tumor can exhibit multiple regions that behave differently during both development and also in response to treatment. The large variations observed in control group, tumors can obscure detection of significant therapeutic effects due to the ambiguity in attributing causes of change. This can hinder development of effective therapies due to limitations in experimental design rather than due to therapeutic failure. An improved method to model biological variation and heterogeneity in imaging signals is described. Specifically, linear Poisson modeling (LPM) evaluates changes in apparent diffusion co-efficient between baseline and 72\u2009h after radiotherapy, in two xenograft models of colorectal cancer. The statistical significance of measured changes is compared to those attainable using a conventional t-test analysis on basic apparent diffusion co-efficient distribution parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>When LPMs were applied to treated tumors, the LPMs detected highly significant changes. The analyses were significant for all tumors, equating to a gain in power of 4-fold (i.e. equivalent to having a sample size 16 times larger), compared with the conventional approach. In contrast, highly significant changes are only detected at a cohort level using t-tests, restricting their potential use within personalized medicine and increasing the number of animals required during testing. Furthermore, LPM enabled the relative volumes of responding and non-responding tissue to be estimated for each xenograft model. Leave-one-out analysis of the treated xenografts provided quality control and identified potential outliers, raising confidence in LPM data at clinically relevant sample sizes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>TINA Vision open source software is available from www.tina-vision.net.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/bty115","type":"journal-article","created":{"date-parts":[[2018,3,12]],"date-time":"2018-03-12T12:08:10Z","timestamp":1520856490000},"page":"2625-2633","source":"Crossref","is-referenced-by-count":4,"title":["A new method for the high-precision assessment of tumor changes in response to treatment"],"prefix":"10.1093","volume":"34","author":[{"given":"P D","family":"Tar","sequence":"first","affiliation":[{"name":"Division of Informatics, Imaging and Data Science, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N A","family":"Thacker","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Science, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Babur","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Y","family":"Watson","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Science, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S","family":"Cheung","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Science, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R A","family":"Little","sequence":"additional","affiliation":[{"name":"Division of Informatics, Imaging and Data Science, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R G","family":"Gieling","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, Manchester Pharmacy School, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K J","family":"Williams","sequence":"additional","affiliation":[{"name":"Division of Pharmacy and Optometry, Manchester Pharmacy School, Manchester, UK"},{"name":"Division of Cancer Sciences, University of Manchester"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J P B","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"Division of Cancer Sciences, University of Manchester"},{"name":"Department of Radiology, The Christie Hospital NHS Trust, Manchester, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2018,3,14]]},"reference":[{"key":"2023012713051658600_bty115-B1","doi-asserted-by":"crossref","first-page":"846","DOI":"10.1038\/nm.3915","article-title":"Toward understanding and exploiting tumor heterogeneity","volume":"21","author":"Alizadeh","year":"2015","journal-title":"Nat. Med"},{"key":"2023012713051658600_bty115-B2","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1093\/biomet\/35.3-4.246","article-title":"The transformation of poisson, binomial and negative-binomial data","volume":"35","author":"Anscombe","year":"1948","journal-title":"Biometrika"},{"key":"2023012713051658600_bty115-B3","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature12627","article-title":"Tumour heterogeneity in the clinic","volume":"501","author":"Bedard","year":"2013","journal-title":"Nature"},{"key":"2023012713051658600_bty115-B4","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s00259-014-2980-7","article-title":"Biomarkers in preclinical cancer imaging","volume":"42","author":"Bernsen","year":"2015","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"2023012713051658600_bty115-B5","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1038\/nrclinonc.2015.62","article-title":"Pandolfi pp. mouse hospital and co-clinical trial project\u2013from bench to bedside","volume":"12","author":"Clohessy","year":"2015","journal-title":"Nat. Rev. Clin. Oncol"},{"key":"2023012713051658600_bty115-B6","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/0165-1684(94)90029-9","article-title":"Independent component analysis\u2014a new concept?","volume":"36","author":"Comon","year":"1994","journal-title":"Sig. Processing"},{"key":"2023012713051658600_bty115-B7","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1038\/nrc3724","article-title":"Developments in preclinical cancer imaging: innovating the discovery of therapeutics","volume":"14","author":"Conway","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"2023012713051658600_bty115-B8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1038\/nrc3751","article-title":"Imaging preclinical tumour models: improving translational power","volume":"14","author":"de Jong","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"2023012713051658600_bty115-B9","article-title":"Quantifying biological samples using linear poisson independent component analysis for MALDI-TOF mass spectra","author":"Deepaisarn","year":"2017","journal-title":"Bioinformatics"},{"key":"2023012713051658600_bty115-B10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.2517-6161.1977.tb01600.x","article-title":"Maximum likelihood from incomplete data via the em algorithm","volume":"39","author":"Dempster","year":"1977","journal-title":"J. R. Stat. Soc. Ser. B"},{"key":"2023012713051658600_bty115-B11","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1002\/jmri.24955","article-title":"Apparent diffusion coefficient is highly reproducible on preclinical imaging systems: evidence from a seven-center multivendor study","volume":"42","author":"Doblas","year":"2015","journal-title":"J. Magn. Reson. Imaging"},{"key":"2023012713051658600_bty115-B12","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1056\/NEJMoa1113205","article-title":"Intratumor heterogeneity and branched evolution revealed by multiregion sequencing","volume":"366","author":"Gerlinger","year":"2012","journal-title":"N. Engl. J. Med"},{"key":"2023012713051658600_bty115-B13","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1126\/science.287.5460.1969","article-title":"Mechanism-based target identification and drug discovery in cancer research","volume":"287","author":"Gibbs","year":"2000","journal-title":"Science"},{"key":"2023012713051658600_bty115-B14","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1109\/RBME.2009.2034865","article-title":"Histopathological image analysis: a review","volume":"2","author":"Gurcan","year":"2009","journal-title":"IEEE Rev. Biomed. Eng"},{"key":"2023012713051658600_bty115-B15","first-page":"2259","article-title":"Tumor heterogeneity","volume":"44","author":"Heppner","year":"1984","journal-title":"Cancer Res"},{"key":"2023012713051658600_bty115-B16","doi-asserted-by":"crossref","first-page":"2205","DOI":"10.1038\/bjc.2014.512","article-title":"Improving tumour heterogeneity MRI assessment with histograms","volume":"111","author":"Just","year":"2014","journal-title":"Br. J. Cancer"},{"key":"2023012713051658600_bty115-B17","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1093\/bioinformatics\/2.3.151","article-title":"Spreadsheet statistics","volume":"2","author":"Kibby","year":"1986","journal-title":"Bioinformatics"},{"key":"2023012713051658600_bty115-B18","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.canlet.2013.10.010","article-title":"One mouse, one patient paradigm: new avatars of personalized cancer therapy","volume":"344","author":"Malaney","year":"2014","journal-title":"Cancer Lett"},{"key":"2023012713051658600_bty115-B19","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.semcdb.2016.10.001","article-title":"Cancer heterogeneity and imaging","volume":"64","author":"O\u2019Connor","year":"2017","journal-title":"Semin. Cell Dev. Biol"},{"key":"2023012713051658600_bty115-B20","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1158\/1078-0432.CCR-14-0990","article-title":"Imaging intratumor heterogeneity: role in therapy response, resistance, and clinical outcome","volume":"21","author":"O\u2019Connor","year":"2015","journal-title":"Clin. Cancer Res"},{"key":"2023012713051658600_bty115-B21","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1593\/neo.81328","article-title":"Diffusion-weighted magnetic resonance imaging as a cancer biomarker: consensus and recommendations","volume":"11","author":"Padhani","year":"2009","journal-title":"Neoplasia"},{"key":"2023012713051658600_bty115-B22","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1038\/nrd2110","article-title":"The mighty mouse: genetically engineered mouse models in cancer drug development","volume":"5","author":"Sharpless","year":"2006","journal-title":"Nat. Rev. Drug Discov"},{"key":"2023012713051658600_bty115-B23","first-page":"1","article-title":"Linear poisson models: a pattern recognition solution to the histogram composition problem","volume":"2014","author":"Tar","year":"2014","journal-title":"Ann. BMVA"},{"key":"2023012713051658600_bty115-B24","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.asr.2015.03.043","article-title":"Automated quantitative measurements and associated error covariances for planetary image analysis","volume":"56","author":"Tar","year":"2015","journal-title":"Adv. Space Res"},{"key":"2023012713051658600_bty115-B25","doi-asserted-by":"crossref","first-page":"580","DOI":"10.1093\/jnci\/djj162","article-title":"Minimally invasive pharmacokinetic and pharmacodynamic technologies in hypothesis-testing clinical trials of innovative therapies","volume":"98","author":"Workman","year":"2006","journal-title":"J. Natl. Cancer Inst"},{"key":"2023012713051658600_bty115-B26","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1038\/sj.bjc.6605642","article-title":"Guidelines for the welfare and use of animals in cancer research","volume":"102","author":"Workman","year":"2010","journal-title":"Br. J. Cancer"},{"key":"2023012713051658600_bty115-B27","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1093\/bioinformatics\/btw768","article-title":"An ensemble approach to protein fold classification by integration of template-based assignment and support vector machine classifier","volume":"33","author":"Xia","year":"2017","journal-title":"Bioinformatics"},{"key":"2023012713051658600_bty115-B28","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1093\/bioinformatics\/btx188","article-title":"Deepem3d: approaching human-level performance on 3d anisotropic em image segmentation","volume":"33","author":"Zeng","year":"2017","journal-title":"Bioinformatics"},{"key":"2023012713051658600_bty115-B29","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1093\/bioinformatics\/btx160","article-title":"Deep mining heterogeneous networks of biomedical linked data to predict novel drug-target associations","volume":"33","author":"Zong","year":"2017","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/15\/2625\/48935430\/bioinformatics_34_15_2625.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/34\/15\/2625\/48935430\/bioinformatics_34_15_2625.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:54:14Z","timestamp":1720140854000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/34\/15\/2625\/4934935"}},"subtitle":[],"editor":[{"given":"Jonathan","family":"Wren","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2018,3,14]]},"references-count":29,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2018,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/bty115","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2018,8,1]]},"published":{"date-parts":[[2018,3,14]]}}}