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To our knowledge, no previous study has attempted a three\u2010dimensional (<jats:styled-content style=\"fixed-case\">3\u2010D<\/jats:styled-content>) analysis and evaluation of diaphragmatic morphogenesis and development from the embryonic to the early fetal period. This study aimed to evaluate the morphogenesis and fibrous architecture of the developing human diaphragm during the late embryonic and early fetal periods. Fifty\u2010seven human embryos and fetuses (crown\u2010rump length [<jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content>]\u00a0=\u00a08\u201388\u2009mm) preserved at the Congenital Anomaly Research Center of Kyoto University and Shimane University were analyzed. <jats:styled-content style=\"fixed-case\">3\u2010D<\/jats:styled-content> morphogenesis and fiber orientation of the diaphragm were assessed using phase\u2010contrast X\u2010ray computed tomography, <jats:styled-content style=\"fixed-case\">T1<\/jats:styled-content>\u2010weighted magnetic resonance imaging (<jats:styled-content style=\"fixed-case\">T1W MRI<\/jats:styled-content>), and diffusion tensor imaging (<jats:styled-content style=\"fixed-case\">DTI<\/jats:styled-content>). <jats:styled-content style=\"fixed-case\">T1W MR<\/jats:styled-content> images and <jats:styled-content style=\"fixed-case\">DTI<\/jats:styled-content> scans were obtained using a <jats:styled-content style=\"fixed-case\">7\u2010T MR<\/jats:styled-content> system. The diaphragm was completely closed at Carnegie stage (<jats:styled-content style=\"fixed-case\">CS<\/jats:styled-content>) 20 and gradually developed a dome\u2010like shape. The diaphragm was already in contact with the heart and liver ventrally in the earliest <jats:styled-content style=\"fixed-case\">CS16<\/jats:styled-content> specimen observed, and the adrenal glands dorsally at <jats:styled-content style=\"fixed-case\">CS19<\/jats:styled-content> or later. In the fetal period, the diaphragm contacted the gastric fundus in samples with a <jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content> \u226541\u2009mm, and the spleen in samples with a <jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content> \u226570\u2009mm. The relative position of the diaphragm with reference to the vertebrae changed rapidly from <jats:styled-content style=\"fixed-case\">CS16<\/jats:styled-content> to <jats:styled-content style=\"fixed-case\">CS19<\/jats:styled-content>. The most cranial point of the diaphragm was located between the 4th and 8th thoracic vertebrae, regardless of fetal growth, in samples with a <jats:styled-content style=\"fixed-case\">CRL of<\/jats:styled-content> \u226516\u2009mm. Diaphragmatic thickness was nearly uniform (0.15\u20130.2\u2009mm) across samples with a <jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content> of 8\u201341\u2009mm. The sternal, costal, lumbar parts, and the area surrounding the esophageal hiatus thickened with growth in samples with a <jats:styled-content style=\"fixed-case\">CRL of<\/jats:styled-content> \u226546\u2009mm. The thickness at the center of the diaphragm and the left and right hemidiaphragmatic domes did not increase with growth. Tractography showed that the fiber orientation of the sternal, costal, and lumbar parts became more distinct as growth progressed in <jats:styled-content style=\"fixed-case\">CS19<\/jats:styled-content> or later. All fibers in the costal and lumbar regions ran toward the left and right hemidiaphragmatic domes, except for those running to the caval opening and esophageal hiatus. The fiber orientation patterns from the right and left crura surrounding the esophageal hiatus were classified into three types. Distinct fiber directions between the costal and sternal and between the costal and lumbar diaphragmatic parts were observable in samples with a <jats:styled-content style=\"fixed-case\">CRL<\/jats:styled-content> of \u226546\u2009mm. Anterior costal and sternal fibers ran toward the center. Fiber tracts around the center and the left and right hemidiaphragmatic domes; between the costal and lumbar orientations; and between the costal and sternal orientations showed a tendency for decreasing fractional anisotropy values with fetal growth and showed less density than other areas. In conclusion, we used <jats:styled-content style=\"fixed-case\">3\u2010D<\/jats:styled-content> thickness assessment and <jats:styled-content style=\"fixed-case\">DTI<\/jats:styled-content> tractography to identify qualitative changes in the muscular and tendonous regions of the diaphragm during the embryonic and early fetal periods. This study provides information on normal human diaphragm development for the progression of fetal medicine and furthering the understanding of congenital anomalies.<\/jats:p>","DOI":"10.1111\/joa.13760","type":"journal-article","created":{"date-parts":[[2022,9,2]],"date-time":"2022-09-02T15:31:36Z","timestamp":1662132696000},"page":"174-190","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Three\u2010dimensional morphogenesis of the human diaphragm during the late embryonic and early fetal period: Analysis using <scp>T1<\/scp>\u2010weighted and diffusion tensor imaging"],"prefix":"10.1111","volume":"242","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9895-0500","authenticated-orcid":false,"given":"Toru","family":"Kanahashi","sequence":"first","affiliation":[{"name":"Human Health Science, Graduate School of Medicine Kyoto University  Kyoto 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