{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:46:04Z","timestamp":1792788364347,"version":"4.5.0"},"reference-count":19,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T00:00:00Z","timestamp":1502236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Build in Canada Innovation Program","award":["EN579-172270\/001\/SC"],"award-info":[{"award-number":["EN579-172270\/001\/SC"]}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Accurate digital image analysis of abnormal microscopic structures relies on high quality images and on minimizing the rates of false positive (FP) and negative objects in images. Cytogenetic biodosimetry detects dicentric chromosomes (DCs) that arise from exposure to ionizing radiation, and determines radiation dose received based on DC frequency. Improvements in automated DC recognition increase the accuracy of dose estimates by reclassifying FP DCs as monocentric chromosomes or chromosome fragments. We also present image segmentation methods to rank high quality digital metaphase images and eliminate suboptimal metaphase cells. A set of chromosome morphology segmentation methods selectively filtered out FP DCs arising primarily from sister chromatid separation, chromosome fragmentation, and cellular debris. This reduced FPs by an average of 55% and was highly specific to these abnormal structures (\u226597.7%) in three samples. Additional filters selectively removed images with incomplete, highly overlapped, or missing metaphase cells, or with poor overall chromosome morphologies that increased FP rates. Image selection is optimized and FP DCs are minimized by combining multiple feature based segmentation filters and a novel image sorting procedure based on the known distribution of chromosome lengths. Applying the same image segmentation filtering procedures to both calibration and test samples reduced the average dose estimation error from 0.4 Gy to &lt;0.2 Gy, obviating the need to first manually review these images. This reliable and scalable solution enables batch processing for multiple samples of unknown dose, and meets current requirements for triage radiation biodosimetry of high quality metaphase cell preparations.<\/ns3:p>","DOI":"10.12688\/f1000research.12226.1","type":"journal-article","created":{"date-parts":[[2017,8,9]],"date-time":"2017-08-09T06:00:15Z","timestamp":1502258415000},"page":"1396","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":34,"title":["Accurate cytogenetic biodosimetry through automated dicentric chromosome curation and metaphase cell selection"],"prefix":"10.12688","volume":"6","author":[{"given":"Jin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanxin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Wilkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farrah","family":"Flegal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan H.M.","family":"Knoll","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2070-5254","authenticated-orcid":false,"given":"Peter K.","family":"Rogan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2017,8,9]]},"reference":[{"key":"ref-1","doi-asserted-by":"publisher","first-page":"494-504","DOI":"10.1097\/01.HP.0000175913.36594.a4","article-title":"Early-response biological dosimetry--recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism.","volume":"89","author":"W Blakely","year":"2005","journal-title":"Health Phys."},{"key":"ref-2","doi-asserted-by":"publisher","first-page":"551-560","DOI":"10.1667\/RR1272.1","article-title":"Interlaboratory comparison of the dicentric chromosome assay for radiation biodosimetry in mass casualty events.","volume":"169","author":"R Wilkins","year":"2008","journal-title":"Radiat Res."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"600-612","DOI":"10.1109\/TIP.2003.819861","article-title":"Image quality assessment: from error visibility to structural similarity.","volume":"13","author":"W Zhou","year":"2004","journal-title":"IEEE Trans Image Process."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"813-825","DOI":"10.1117\/12.56114","article-title":"Objective image quality measure derived from digital image power spectra.","volume":"31","author":"N Nill","year":"1992","journal-title":"Opt Eng."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"515-519","DOI":"10.1109\/TNN.2010.2040192","article-title":"Objective image quality assessment based on support vector regression.","volume":"21","author":"M Narwaria","year":"2010","journal-title":"IEEE Trans Neural Netw."},{"key":"ref-6","doi-asserted-by":"publisher","first-page":"393-402","DOI":"10.1002\/jemt.22642","article-title":"Automated discrimination of dicentric and monocentric chromosomes by machine learning-based image processing.","volume":"79","author":"Y Li","year":"2016","journal-title":"Microsc Res Tech."},{"key":"ref-7","doi-asserted-by":"publisher","first-page":"3613-3616","DOI":"10.1109\/ICIP.2010.5652017","article-title":"An image processing algorithm for accurate extraction of the centerline from human metaphase chromosomes","author":"A Arachchige","year":"2010"},{"key":"ref-8","doi-asserted-by":"publisher","first-page":"1-4","DOI":"10.1109\/CCECE.2012.6334866","article-title":"Intensity integrated Laplacian algorithm for human metaphase chromosome centromere detection","author":"A Arachchige","year":"2012"},{"key":"ref-9","doi-asserted-by":"publisher","first-page":"2005-2013","DOI":"10.1109\/TBME.2013.2248008","article-title":"Intensity integrated Laplacian-based thickness measurement for detecting human metaphase chromosome centromere location.","volume":"60","author":"A Arachchige","year":"2013","journal-title":"IEEE Trans Biomed Eng."},{"key":"ref-10","doi-asserted-by":"publisher","first-page":"1565","DOI":"10.12688\/f1000research.9075.1","article-title":"Centromere detection of human metaphase chromosome\u00a0images using a candidate based method [version 1; 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<i>Posted: 10 Oct 2017<\/i>; Regarding the use of fluorescent probes to highlight centromeres:PNA-FISH or any type of FISH can achieve higher intensities and contrast at centromeres than Giemsa staining, and would presumably require fewer morphological segmentation features to distinguish these structures. In our early publications (Figure 5 of Subasinghe et al. 2010; Figure 7 of Subasinghe et al. 2013 [compare panels a and b with panels c \u2013 f]), we stained chromosomes with DAPI to digitally locate centromeres &nbsp;by epifluorescence. This type of staining also results in significant contrast between centromeric regions and non-centromeric regions. In contrast with FISH or PNA probes, DAPI is inexpensive, abundant, and available from many sources. It would be feasible to develop epifluorescent staining approaches that could be integrated into the software described in this study, were the market and the investment to justify&nbsp; it.&nbsp;&nbsp;There are additional steps in FISH laboratory procedures that are not required for Giemsa staining, which means that more time is required to obtain chromosome imaging data. This and the associated FISH reagent costs would have a substantial impact on the throughput of diagnoses for any type of radiation mass casualty.&nbsp; We shifted our algorithm development several years ago to Giemsa staining, because the published IAEA protocol was established with this approach. Besides, it has been standardized, it is inexpensive, and uses less complex, bright field microscopy systems. It is also a bedrock method in just about every cytogenetics laboratory.&nbsp;&nbsp; <u>Subasinghe A<\/u>, J Samarabandu, Knoll J, <u>Khan W<\/u>, Rogan PK. An Accurate Image Processing Algorithm for Detecting FISH Probe Locations Relative to Chromosome Landmarks&nbsp;on DAPI Stained Metaphase Chromosome Images. IEEE 2010 Canadian Conference on Computer and Robot Vision. 2010. Pp 223-230. DOI: 10.1109\/CRV.2010.36. <u>Subasinghe AA<\/u>, J Samarabandu, J Knoll, PK Rogan. Intensity Integrated Laplacian Based Thickness Measurement for Detecting Human Metaphase Chromosome Centromere Location. IEEE Trans. Biomedical Engineering, 60:2005-13, 2013.","URL":"https:\/\/f1000research.com\/articles\/6-1396\/v1#referee-comment-3091","order":1,"name":"referee-comment-3091","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.13236.r25106, Eric Gregoire, Biological Dosimetry Laboratory (LDB), Institute for Radiological Protection and Nuclear Safety (IRSN), Fontenay-aux-Roses, France, 31 Aug 2017, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/6-1396\/v1#referee-response-25106","order":2,"name":"referee-response-25106","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Peter Rogan<\/b>; <i>Posted: 10 Oct 2017<\/i>; We agree that a direct comparison of ADCI with DCScore might be worthwhile in the future, but it was not possible to carry this out in the present study.&nbsp; In our previous study (Rogan et al. 2016), we did point out a number of differences between our respective approaches.&nbsp;ADCI can accurately process bent chromosomes, those with indistinct or fuzzy boundaries, and ones with some separation of sister chromatids. &nbsp;It can separate and segment touching chromosomes.&nbsp; For these reasons, most manual pre- and post-processing steps in DCScore are unnecessary with ADCI. Nevertheless, users have the ability to curate individual images in ADCI should they desire.&nbsp; Unlike DCScore, ADCI is intentionally restricted from processing highly overlapped chromosomes, so objects with two centromeres that are not single chromosomes called DCs. &nbsp;The single interface of ADCI for processing metaphases is integrated with calibration curve generation and dose estimation. DCScore does not generate or store calibration curves or estimate dose of test samples. &nbsp;The software allows reuse of previously processed biodosimetry curves and can estimate doses across a range of sensitivies and specificities for DC detection, set by the user.&nbsp;Rogan PK,&nbsp; Li Y, Wilkins R, Flegal FN, and Knoll JHM. Radiation Dose Estimation by Automated Cytogenetic Biodosimetry. Rad. Prot. Biodosimetry, 172(1-3):207-217, 2016.","URL":"https:\/\/f1000research.com\/articles\/6-1396\/v1#referee-comment-3092","order":3,"name":"referee-comment-3092","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Peter Rogan<\/b>; <i>Posted: 01 Mar 2021<\/i>; The work described in this paper is the subject of United States Patent Number&nbsp;&nbsp;10,929,641.","URL":"https:\/\/f1000research.com\/articles\/6-1396\/v1#article-response-6401","order":4,"name":"article-response-6401","label":"Article Comment","group":{"name":"article-comments","label":"Article Comments"}},{"value":"This study was supported by the Build in Canada Innovation Program (Contract No. EN579-172270\/001\/SC) and CytoGnomix Inc. Previous software versions and associated algorithms were supported by the Western Innovation Fund; the Natural Sciences and Engineering Research Council of Canada (NSERC Discovery Grant 371758-2009); US Public Health Service (DART-DOSE CMCR, 5U01AI091173-0); the Canadian Foundation for Innovation; Canada Research Chairs, and CytoGnomix Inc. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":5,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}