{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:24:55Z","timestamp":1785414295165,"version":"3.56.0"},"reference-count":55,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,2,5]],"date-time":"2021-02-05T00:00:00Z","timestamp":1612483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000266","name":"Engineering and Physical Sciences Research Council","doi-asserted-by":"publisher","award":["EP\/N018702\u20101"],"award-info":[{"award-number":["EP\/N018702\u20101"]}],"id":[{"id":"10.13039\/501100000266","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["aapm.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Medical Physics"],"published-print":{"date-parts":[[2021,3]]},"abstract":"<jats:sec><jats:title>Purpose<\/jats:title><jats:p>Proton therapy could benefit from noninvasively gaining tumor microstructure information, at both planning and monitoring stages. The anatomical location of brain tumors, such as meningiomas, often hinders the recovery of such information from histopathology, and conventional noninvasive imaging biomarkers, like the apparent diffusion coefficient (ADC) from diffusion\u2010weighted MRI (DW\u2010MRI), are nonspecific. The aim of this study was to retrieve discriminative microstructural markers from conventional ADC for meningiomas treated with proton therapy. These markers were employed for tumor grading and tumor response assessment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>DW\u2010MRIs from patients affected by meningioma and enrolled in proton therapy were collected before (n\u00a0=\u00a035) and 3 months after (n\u00a0=\u00a025) treatment. For the latter group, the risk of an adverse outcome was inferred by their clinical history. Using Monte Carlo methods, DW\u2010MRI signals were simulated from packings of synthetic cells built with well\u2010defined geometrical and diffusion properties. Patients\u2019 ADC was modeled as a weighted sum of selected simulated signals. The weights that best described a patient\u2019s ADC were determined through an optimization procedure and used to estimate a set of markers of tumor microstructure: diffusion coefficient (D), volume fraction (vf), and radius (R). Apparent cellularity (\u03c1<jats:sub>app<\/jats:sub>) was estimated from vf and R for an easier clinical interpretability. Differences between meningothelial and atypical subtypes, and low\u2010 and high\u2010grade meningiomas were assessed with nonparametric statistical tests, whereas sensitivity and specificity with ROC analyses. Similar analyses were performed for patients showing low or high risk of an adverse outcome to preliminary evaluate response to treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) differences in median ADC, D, vf, R, and \u03c1<jats:sub>app<\/jats:sub> values were found when comparing meningiomas\u2019 subtypes and grades. ROC analyses showed that estimated microstructural parameters reached higher specificity than ADC for subtyping (0.93 for D and vf vs 0.80 for ADC) and grading (0.75 for R vs 0.67 for ADC). High\u2010 and low\u2010risk patients showed significant differences in ADC and microstructural parameters. The skewness of \u03c1<jats:sub>app<\/jats:sub> was the parameter with highest AUC (0.90) and sensitivity (0.75).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Matching measured with simulated ADC yielded a set of potential imaging markers for meningiomas grading and response monitoring in proton therapy, showing higher specificity than conventional ADC. These markers can provide discriminative information about spatial patterns of tumor microstructure implying important advantages for patient\u2010specific proton therapy workflows.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mp.14689","type":"journal-article","created":{"date-parts":[[2020,12,28]],"date-time":"2020-12-28T18:41:15Z","timestamp":1609180875000},"page":"1250-1261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Improving the characterization of meningioma microstructure in proton therapy from conventional apparent diffusion coefficient measurements using Monte Carlo simulations of diffusion MRI"],"prefix":"10.1002","volume":"48","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5504-1262","authenticated-orcid":false,"given":"Giulia","family":"Buizza","sequence":"first","affiliation":[{"name":"Department of Electronics, Information and Bioengineering (DEIB) Politecnico di Milano Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4787-8649","authenticated-orcid":false,"given":"Chiara","family":"Paganelli","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering (DEIB) Politecnico di Milano Milan 20133 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7560-8163","authenticated-orcid":false,"given":"Francesco","family":"Ballati","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology Residency School University of Pavia Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-3099","authenticated-orcid":false,"given":"Simone","family":"Sacco","sequence":"additional","affiliation":[{"name":"Diagnostic Radiology Residency School University of Pavia Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5479-2766","authenticated-orcid":false,"given":"Lorenzo","family":"Preda","sequence":"additional","affiliation":[{"name":"Department of Clinical Surgical, Diagnostic and Pediatric Sciences University of Pavia Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Iannalfi","sequence":"additional","affiliation":[{"name":"Clinical Department National Center of Oncological Hadrontherapy (CNAO) Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2439-350X","authenticated-orcid":false,"given":"Daniel C.","family":"Alexander","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing (CMIC) Department of Computer Science University College London (UCL) London WC1V6LJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5464-0164","authenticated-orcid":false,"given":"Guido","family":"Baroni","sequence":"additional","affiliation":[{"name":"Department of Electronics, Information and Bioengineering (DEIB) Politecnico di Milano Milan 20133 Italy"},{"name":"Bioengineering Unit National Center of Oncological Hadrontherapy (CNAO) Pavia 27100 Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4892-7967","authenticated-orcid":false,"given":"Marco","family":"Palombo","sequence":"additional","affiliation":[{"name":"Centre for Medical Image Computing (CMIC) Department of Computer Science University College London (UCL) London WC1V6LJ UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2017.30"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrclinonc.2012.194"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-020-01524-4"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-016-1545-1"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2481-1"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2018.06.018"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2011.08.027"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.wneu.2019.08.149"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminoncol.2019.07.005"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.23801"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.21037\/cco.2017.05.02"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tranon.2018.06.010"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.08.061"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-010-0343-1"},{"key":"e_1_2_8_16_1","first-page":"69","article-title":"Perfusion and diffusion in meningioma tumors: a preliminary multiparametric analysis with dynamic susceptibility contrast and intravoxel incoherent motion MRI","volume":"2020","author":"Zampini MA","year":"2019","journal-title":"Magn Reson Imaging"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0501532102"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5662"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2016.07.038"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20180088"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11307-018-1166-2"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2018.04.075"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.25664"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1593\/neo.81328"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.27101"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmri.26293"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-13-2511"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.12.062"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphy.2017.00058"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.21037\/tcr.2017.06.03"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.radonc.2019.04.018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2012.04.010"},{"key":"e_1_2_8_33_1","unstructured":"ShacklefordJ ShusharinaN VerbergJ.Plastimatch 1.6: current capabilities and future directions. Proc MICCAI;2012."},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers8070067"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-65956-4"},{"key":"e_1_2_8_36_1","first-page":"765","article-title":"Neighbor list collision\u2010driven molecular dynamics simulation for nonspherical hard particles.II. Applications to ellipses and ellipsoids","volume":"202","author":"Donev A","year":"2005","journal-title":"J Comput Phys"},{"key":"e_1_2_8_37_1","unstructured":"Blender Online Community.Blender \u2010 a 3D modelling and rendering package.2017;http:\/\/www.blender.org"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1109\/TMI.2009.2015756"},{"key":"e_1_2_8_39_1","unstructured":"CookPA BaiY SeunarineKK HallMG ParkerGJ AlexanderDC.Camino Open\u2010Source Diffusion\u2010MRI Reconstruction and Processing. 14th Sci Meet Int Soc Magn Reson Med2006;14:2759."},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/RLI.0000000000000115"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(1950)3:1<32::AID-CNCR2820030106>3.0.CO;2-3"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mri.2014.03.010"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0962280214537333"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2012.06.002"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A0996"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.17752"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/mrm.28196"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13014-015-0384-x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmp.2016.11.106"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2014.05.1314"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.14338\/IJPT-18-00018.1"},{"key":"e_1_2_8_52_1","first-page":"6841","article-title":"Correlation between different ADC fractions, cell count, Ki\u201067, total nucleic areas and average nucleic areas in meningothelial meningiomas","volume":"35","author":"Surov A","year":"2015","journal-title":"Anticancer Res"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027442"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.3171\/FOC-07\/10\/E3"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroimage.2017.02.013"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1259\/bjr.20170912"}],"container-title":["Medical Physics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.14689","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mp.14689","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mp.14689","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,2]],"date-time":"2023-09-02T03:48:12Z","timestamp":1693626492000},"score":1,"resource":{"primary":{"URL":"https:\/\/aapm.onlinelibrary.wiley.com\/doi\/10.1002\/mp.14689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,5]]},"references-count":55,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2021,3]]}},"alternative-id":["10.1002\/mp.14689"],"URL":"https:\/\/doi.org\/10.1002\/mp.14689","archive":["Portico"],"relation":{},"ISSN":["0094-2405","2473-4209"],"issn-type":[{"value":"0094-2405","type":"print"},{"value":"2473-4209","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,5]]},"assertion":[{"value":"2020-07-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-12-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-02-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}