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Quantitative assessment of follicular density in cryopreserved cortical tissue is critical for evaluating tissue quality and estimating its reproductive potential. Conventional analysis, based on manual follicle counts in serial histological sections, is time-consuming, labor-intensive, and prone to variability from uneven follicle distribution and inconsistent tissue orientation. To address these limitations, we developed a high-throughput, automated method combining micro-CT, machine learning, and morphological analysis to quantify oocyte density and other morphological features throughout entire ovarian cortical tissue samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three-dimensional segmentation analysis enabled quantification of oocyte density in the samples within the cortical region 1\u00a0mm below the surface epithelium. Oocytes in pediatric samples were located significantly closer to the surface compared to those in adult tissue, with median distances of 139.4\u00a0\u03bcm and 370.2\u00a0\u03bcm, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001) and exhibited markedly higher local oocyte neighbor counts, with median values of 6 and 2 in pediatric and adult tissues, respectively (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.0001), consistent with higher oocyte density and clustered spatial organization in younger individuals. Simulated histology using every 10th virtual sections \u2014corresponding to 40\u00a0\u03bcm separated histology slices\u2014 closely approximated full-volume micro-CT estimates of oocyte density. Analysis based on only five virtual sections aligned with micro-CT data exclusively in pediatric samples with high oocyte density, whereas in adult samples it led to substantial inaccuracies in oocyte density estimation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Micro-CT scanning combined with machine learning analysis represents a novel high-throughput and automated approach for estimating oocyte count in cryopreserved ovarian cortical samples. In addition, three-dimensional analysis offers valuable insights into oocyte localization and spatial distribution within the ovarian cortex, presenting a promising alternative to conventional histology for future clinical and research applications.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13048-025-01897-8","type":"journal-article","created":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T00:46:47Z","timestamp":1766450807000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Micro-CT and machine learning: a high-throughput alternative to histology for follicle reserve assessment in cryopreserved ovarian tissue"],"prefix":"10.1186","volume":"19","author":[{"given":"Katri","family":"Knuus","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mai","family":"Nguyen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Hannula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasmin","family":"Hassan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marjut","family":"Otala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Tuuri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karolina","family":"Lundin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atte","family":"Lahtinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauliina","family":"Damdimopoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jari","family":"Hyttinen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsi","family":"Jahnukainen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,23]]},"reference":[{"issue":"4","key":"1897_CR1","doi-asserted-by":"publisher","first-page":"hoaa052","DOI":"10.1093\/hropen\/hoaa052","volume":"2020","author":"RA Anderson","year":"2020","unstructured":"Anderson RA, Amant F, Braat D, D\u2019Angelo A, Chuva de Sousa Lopes SM, Demeestere I, et al. 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Nat Commun. 2024;15(1):6989.","journal-title":"Nat Commun"}],"container-title":["Journal of Ovarian Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13048-025-01897-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13048-025-01897-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13048-025-01897-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T10:44:37Z","timestamp":1768473877000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s13048-025-01897-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,23]]},"references-count":46,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["1897"],"URL":"https:\/\/doi.org\/10.1186\/s13048-025-01897-8","relation":{},"ISSN":["1757-2215"],"issn-type":[{"value":"1757-2215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,23]]},"assertion":[{"value":"17 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"7 November 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The use of adult samples for research was approved by the Ethics Committee of Helsinki University Hospital (HUS\/3319\/2017 and HUS\/614\/2023). The patients were informed of the study by the hospital personnel and patients could voluntarily donate their tissue to the research by writing a consent.Child patients and their guardians were informed by the hospital personnel and written consent was obtained from all age-appropriate patients or their guardians. This study was approved by the Ethics Committee of Helsinki University Hospital (Dnr:340\/13\/03\/03\/2015) and the Swedish Ethical Review Authority (Dnr:2019\u201303802).To ensure privacy, all samples were pseudonymized with random codes. This study was conducted in accordance with the Declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15"}}