{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T13:54:04Z","timestamp":1784555644813,"version":"3.55.0"},"reference-count":28,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T00:00:00Z","timestamp":1613606400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Microscopy"],"published-print":{"date-parts":[[2021,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In pathology protocols, a tissue block, such as one containing a mouse brain or a biopsy sample from a patient, can produce several hundred thin sections. Substantial time may be required to analyse all sections. In cases of uncertainty regarding which sections to focus on, noninvasive scout imaging of intact blocks can help in guiding the pathology procedure. The scouting step is ideally done in a time window of minutes without special sample preparation that may interfere with the pathology procedures. The challenge is to obtain some visibility of unstained tissue structures at sub\u201010 \u00b5m resolution.<\/jats:p><jats:p>We explored a novel x\u2010ray tomosynthesis method as a way to maximise contrast\u2010to\u2010noise ratio, a determinant of tissue visibility. It provided a <jats:italic>z<\/jats:italic>\u2010stack of thousands of images at 7.3 \u03bcm resolution (10% contrast, half\u2010period of 68.5 line pairs\/mm), in scans of 5\u201015 minutes. When compared with micro\u2010CT scans, the straight\u2010line tomosynthesis scan did not need to rotate the sample, which allowed flat samples, such as paraffin blocks, to be kept as close as possible to the x\u2010ray source. Thus, given the same hardware, scan time and resolution, this mode maximised the photon flux density through the sample, which helped in maximising the contrast\u2010to\u2010noise ratio. The tradeoff of tomosynthesis is incomplete 3D information.<\/jats:p><jats:p>The microtomosynthesis scanner has scanned 110 unstained human and animal tissue samples as part of their respective pathology protocols. In all cases, the <jats:italic>z<\/jats:italic>\u2010stack of images showed tissue structures that guided sectioning or provided correlative structural information. We describe six examples that presented different levels of visibility of soft tissue structures. Additionally, in a set of coronary artery samples from an HIV patient donor, microtomosynthesis made a new discovery of isolated focal calcification in the internal elastic lamina of coronary wall, which was the onset of medial calcific sclerosis in the arteries.<\/jats:p>","DOI":"10.1111\/jmi.13003","type":"journal-article","created":{"date-parts":[[2021,1,23]],"date-time":"2021-01-23T05:53:03Z","timestamp":1611381183000},"page":"9-20","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["X\u2010ray microtomosynthesis of unstained pathology tissue samples"],"prefix":"10.1111","volume":"283","author":[{"given":"David T.","family":"Nguyen","sequence":"first","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas C.","family":"Larsen","sequence":"additional","affiliation":[{"name":"College of Medicine University of Arizona  Tucson Arizona"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muyang","family":"Wang","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Russel H.","family":"Knutsen","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihong","family":"Yang","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric E.","family":"Bennett","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dumitru","family":"Mazilu","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zu\u2010Xi","family":"Yu","sequence":"additional","affiliation":[{"name":"National Heart, Lung and Blood Institute National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Tao","sequence":"additional","affiliation":[{"name":"School of Biomedical Engineering Southern Medical University  Guangzhou Guangdong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle R.","family":"Donahue","sequence":"additional","affiliation":[{"name":"Mouse Imaging Facility National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed M.","family":"Gharib","sequence":"additional","affiliation":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases National Institutes of Health  Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1029-3444","authenticated-orcid":false,"given":"Christopher K. 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