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Determining the three-dimensional (3D) structure of the necrotic granuloma, a characteristic feature of TB, will more accurately inform preventive TB strategies.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To ascertain the 3D shape of the human tuberculous granuloma and its spatial relationship with airways and vasculature within large lung tissues.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We characterized the 3D microanatomical environment of human tuberculous lungs by using micro computed tomography, histopathology, and immunohistochemistry. By using 3D segmentation software, we accurately reconstructed TB granulomas, vasculature, and airways in three dimensions and confirmed our findings by using histopathology and immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>We observed marked heterogeneity in the morphology, volume, and number of TB granulomas in human lung sections. Unlike depictions of granulomas as simple spherical structures, human necrotic granulomas exhibit complex, cylindrical, branched morphologies that are connected to the airways and shaped by the bronchi. The use of 3D imaging of human TB lung sections provides unanticipated insight into the spatial organization of TB granulomas in relation to the airways and vasculature.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings highlight the likelihood that a single, structurally complex lesion could be mistakenly viewed as multiple independent lesions when evaluated in two dimensions. In addition, the lack of vascularization within obstructed bronchi establishes a paradigm for antimycobacterial drug tolerance. Lastly, our results suggest that bronchogenic spread of Mycobacterium tuberculosis reseeds the lung.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.202101-0032oc","type":"journal-article","created":{"date-parts":[[2021,5,20]],"date-time":"2021-05-20T19:09:37Z","timestamp":1621537777000},"page":"583-595","update-policy":"https:\/\/doi.org\/10.1164\/crossmarkpolicies","source":"Crossref","is-referenced-by-count":59,"title":["Micro\u2013Computed Tomography Analysis of the Human Tuberculous Lung Reveals Remarkable Heterogeneity in Three-dimensional Granuloma Morphology"],"prefix":"10.1093","volume":"204","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2328-5208","authenticated-orcid":false,"given":"Gordon","family":"Wells","sequence":"first","affiliation":[{"name":"Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel N.","family":"Glasgow","sequence":"additional","affiliation":[{"name":"Department of Microbiology and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kievershen","family":"Nargan","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kapongo","family":"Lumamba","sequence":"additional","affiliation":[{"name":"Africa Health Research Institute, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajhmun","family":"Madansein","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kameel","family":"Maharaj","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Nelson Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert L.","family":"Hunter","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Texas Health Sciences Center at Houston, Houston, Texas"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Threnesan","family":"Naidoo","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, National Health Laboratory Service, Inkosi Albert Luthuli Central Hospital, Durban, South Africa; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Llelani","family":"Coetzer","sequence":"additional","affiliation":[{"name":"Computed Tomography Scanner Facility, Central Analytical Facilities, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"le Roux","sequence":"additional","affiliation":[{"name":"Computed Tomography Scanner Facility, Central Analytical Facilities, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anton","family":"du Plessis","sequence":"additional","affiliation":[{"name":"Computed Tomography Scanner Facility, Central Analytical Facilities, Stellenbosch University, Stellenbosch, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9177-8827","authenticated-orcid":false,"given":"Adrie J. 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