{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:03:04Z","timestamp":1791918184033,"version":"4.3.4"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T00:00:00Z","timestamp":1663891200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002341","name":"Academy of Finland","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002341","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004212","name":"P\u00e4ivikki ja Sakari Sohlbergin S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004212","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006306","name":"Sigrid Jus\u00e9liuksen S\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006306","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003406","name":"Tekes","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003406","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005744","name":"Lastentautien Tutkimuss\u00e4\u00e4ti\u00f6","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005744","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009960","name":"Pirkanmaan Sairaanhoitopiiri","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009960","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Duodenal histology remains the diagnostic reference standard in celiac disease. However, traditional methods have suboptimal sensitivity and reproducibility for early mucosal changes and research purposes. We validated a recently introduced micro-CT imaging method for an accurate digital evaluation of duodenal histomorphometry and mucosal surface areas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Endoscopic biopsies from 58 individuals were utilized for the micro-CT imaging, selecting histological changes ranging from normal to severely damaged mucosa. The imaging protocol was optimized for practicability and resolution. The Bland\u2013Altman method was applied to test intra- and interobserver variations in the blinded measurements.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The 3D micro-CT reconstructions enabled easy and precise digital cutting with optimal orientation and computer-assisted measurement of the surface area. Intraobserver analysis of morphological measurements showed a mean difference of 0.011 with limits of agreement (LA) from -0.397 to 0.375 and a standard deviation (SD) of 0.197. The corresponding figures for interobserver analysis were 0.080, from -0.719 to 0.537 and 0.320, respectively. The intraclass correlation coefficients (ICC) for the intraobserver and interobserver variations were 0.981 and 0.954, respectively. Intraobserver surface area analysis yielded a mean difference of 0.010, LA from -0.764 to 0.785 and an SD of 0.395, and an interobserver analysis mean difference of 0.028, LA from -0.642 to 0.698 and SD of 0.342. The respective ICCs for the intra- and interobserver variations were 0.963 and 0.972.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Micro-CT showed excellent accuracy and reproducibility in the evaluation of mucosal morphometry and surface areas. The improved sensitivity for histological changes is a powerful tool for the diagnosis of celiac disease and for clinical and pharmacological studies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2022.945197","type":"journal-article","created":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T13:08:01Z","timestamp":1663938481000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Validation of the X-ray microtomography in the assessment of duodenal morphometry and surface area in celiac disease"],"prefix":"10.3389","volume":"13","author":[{"given":"Johannes","family":"Virta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hannula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Lindfors","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilmari","family":"Tamminen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juha","family":"Taavela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heini","family":"Huhtala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katri","family":"Kaukinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P\u00e4ivi","family":"Saavalainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Hyttinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalle","family":"Kurppa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-018-0054-z","article-title":"Coeliac disease","volume":"5","author":"Lindfors","year":"2019","journal-title":"Nat Rev Dis Prim"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/2916024","article-title":"Diagnosing celiac disease: Towards wide-scale screening and serology-based criteria","volume":"2019","author":"Popp","year":"2019","journal-title":"Gastroenterol Res Pract"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/MPG.0000000000002497","article-title":"European Society paediatric gastroenterology, hepatology and nutrition guidelines for diagnosing coeliac disease 2020","volume":"70","author":"Husby","year":"2020","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314853","article-title":"Outcome measures in coeliac disease trials: The Tampere recommendations","volume":"67","author":"Ludvigsson","year":"2018","journal-title":"Gut"},{"key":"B5","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1056\/NEJMoa2032441","article-title":"A randomized trial of a transglutaminase 2 inhibitor for celiac disease","volume":"385","author":"Schuppan","year":"2021","journal-title":"N Engl J Med"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2010.153","article-title":"How patchy is patchy villous atrophy? Distribution pattern of histological lesions in the duodenum of children with celiac disease","volume":"105","author":"Ravelli","year":"2010","journal-title":"Am J Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1097\/MCG.0000000000001349","article-title":"Nonbiopsy approach for celiac disease is accurate when using exact duodenal histomorphometry: Prospective study in 2 countries","volume":"55","author":"Popp","year":"2020","journal-title":"J Clin Gastroenterol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2017.06.002","article-title":"Accuracy in diagnosis of celiac disease without biopsies in clinical practice","volume":"153","author":"Werkstetter","year":"2017","journal-title":"Gastroenterology"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0076163","article-title":"Validation of morphometric analyses of small-intestinal biopsy readouts in celiac disease","volume":"8","author":"Taavela","year":"2018","journal-title":"PLoS One"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-320913","article-title":"Accuracy of a no-biopsy approach for the diagnosis of coeliac disease across different adult cohorts","volume":"70","author":"Penny","year":"2020","journal-title":"Gut"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/nu12092736","article-title":"Non-biopsy serology-based diagnosis of celiac disease in adults is accurate with different commercial kits and pre-test probabilities","volume":"12","author":"Yl\u00f6nen","year":"2020","journal-title":"Nutrients"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314461","article-title":"HLA-DQ: Gluten tetramer test in blood gives better detection of coeliac patients than biopsy after 14-day gluten challenge","volume":"67","author":"Sarna","year":"2018","journal-title":"Gut"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/ajg.2017.480","article-title":"Measuring change in small intestinal histology in patients with celiac disease","volume":"113","author":"Adelman","year":"2018","journal-title":"Am J Gastroenterol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.110.977884","article-title":"Non-destructive, high-resolution 3-dimensional visualization of a cardiac defect in the chick embryo resembling complex heart defect in humans using micro-computed tomography: Double outlet right ventricle with left juxtaposition of atrial appendages","volume":"122","author":"Happel","year":"2010","journal-title":"Circulation"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2011","article-title":"X-Ray microtomography in biology","volume":"42","author":"Mizutani","year":"2012","journal-title":"Micron"},{"key":"B16","doi-asserted-by":"publisher","first-page":"13164","DOI":"10.1038\/s41598-020-69487-w","article-title":"X-Ray microtomography is a novel method for accurate evaluation of small-bowel mucosal morphology and surface area","volume":"10","author":"Virta","year":"2020","journal-title":"Sci Rep"},{"key":"B17","doi-asserted-by":"publisher","first-page":"610","DOI":"10.1053\/j.gastro.2014.05.003","article-title":"Benefits of a gluten-free diet for asymptomatic patients with serologic markers of celiac disease","volume":"147","author":"Kurppa","year":"2014","journal-title":"Gastroenterology"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002270","article-title":"Effective detection of human leukocyte antigen risk alleles in celiac disease using tag single nucleotide polymorphisms","volume":"3","author":"Monsuur","year":"2009","journal-title":"PLoS One"},{"key":"B19","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1136\/gutjnl-2011-301346","article-title":"The Oslo definitions for coeliac disease and related terms","volume":"62","author":"Ludvigsson","year":"2013","journal-title":"Gut"},{"key":"B20","doi-asserted-by":"publisher","first-page":"3","DOI":"10.2466\/pr0.1966.19.1.3","article-title":"The intraclass correlation coefficient as a measure of reliability","volume":"1","author":"Bartko","year":"1966","journal-title":"Psychol Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(86)90837-8","article-title":"Statistical methods for assessing agreement between two methods of clinical measurement","volume":"1","author":"Bland","year":"1986","journal-title":"Lancet"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/jclinpath-2011-200372","article-title":"Variability in small bowel histopathology reporting between different pathology practice settings: Impact on the diagnosis of coeliac disease","volume":"65","author":"Arguelles-Grande","year":"2012","journal-title":"J Clin Pathol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2007.03.019","article-title":"Comparison of the interobserver reproducibility with different histologic criteria used in celiac disease","volume":"5","author":"Corazza","year":"2007","journal-title":"Clin Gastroenterol Hepatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.3109\/00365521.2011.589471","article-title":"Reproducibility of the histological diagnosis of celiac disease","volume":"46","author":"Mubarak","year":"2011","journal-title":"Scand J Gastroenterol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3732\/apps.1400033","article-title":"Easy leaf area: Automated digital image analysis for rapid and accurate measurement of leaf area","volume":"2","author":"Easlon","year":"2014","journal-title":"Appl Plant Sci"},{"key":"B26","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1136\/jcp.28.2.85","article-title":"Computer card morphometry of jejunal biopsies in childhood coeliac disease","volume":"28","author":"Meinhard","year":"1975","journal-title":"J Clin Pathol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-198212000-00012","article-title":"Morphometric study of the jejunal mucosa in various childhood enteropathies with special reference to intraepithelial lymphocytes","volume":"1","author":"Kuitunen","year":"1982","journal-title":"J Pediatr Gastroenterol Nutr"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2007.03311.x","article-title":"Persistent small bowel mucosal villous atrophy without symptoms in coeliac disease","volume":"25","author":"Kaukinen","year":"2007","journal-title":"Aliment Pharmacol Ther"},{"key":"B29","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1002\/ygh2.380","article-title":"Baseline quantitative histology in therapeutics trials reveals villus atrophy in most patients with coeliac disease who appear well controlled on gluten-free diet","volume":"2","author":"Daveson","year":"2020","journal-title":"GastroHep"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2015.00256","article-title":"In vivo small animal micro-CT using nanoparticle contrast agents","volume":"6","author":"Ashton","year":"2015","journal-title":"Front Pharmacol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-020-00378-1","article-title":"Current and emerging therapies for coeliac disease","volume":"18","author":"Kivel\u00e4","year":"2020","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2016-312271","article-title":"The clinical and phenotypical assessment of seronegative villous atrophy; a prospective UK centre experience evaluating 200 adult cases over a 15-year period (2000-2015)","volume":"66","author":"Aziz","year":"2017","journal-title":"Gut"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2004.023978","article-title":"Coeliac disease","volume":"58","author":"Corazza","year":"2005","journal-title":"J Clin Pathol"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.945197\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,23]],"date-time":"2022-09-23T13:08:05Z","timestamp":1663938485000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2022.945197\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,23]]},"references-count":33,"alternative-id":["10.3389\/fimmu.2022.945197"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2022.945197","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,23]]},"article-number":"945197"}}