京都大学 大学院医学研究科 人間健康科学系専攻 病理学研究室（形態形成医療科学）

掛谷さんの修士論文がJ Anatomyに掲載されました。

発生途中、消化管は臍帯腔内に脱出し、CRL40mmころに短時間で還納されます。還納の仕方は、これまで消化管の動きを中心に研究されており、slide-stack model（消化管はループを形成したまま還納するというモデル）が優勢でした。本論文では、下記の２つの定説を覆す内容です。

• 消化管の臍帯内脱出の還納はCRL30mmころから時間をかけて行われること
• 消化管は臍帯輪通過時にはループが解除されていること

複雑な小腸の走行を追跡しても限界があることを認識し、この論文では消化管を栄養する上腸間膜動脈とその小腸枝の走行を正確に追うことで、還納経過中の小腸の位置や形状、走行をしめすとともに、血管系の分布、形状変化も示すことができました。還納は腸管の動きとして認識される時期に先行する血管系の位置の変化により開始され、これまでのコンセンサスよりも早く始まることを示しました。臍帯輪通過時には、消化管とそれを栄養する動脈の走行は形状を変えます。消化管はループがほどけ、臍帯輪を２本以上の消化管が通過することはありません。また、臍帯輪において消化管、腸間膜、動脈は整然とならび、どの個体でもほぼ一定です。

この組織だった配置は腸管への血行が安全に確保されるために必要とかんがえられます。

KakeyaM, Matsubayashi J, Kanahashi T, Männer J, Yamada S, Takakuwa T. The return process of physiological umbilical herniation in human fetuses: the possible role of the vascular tree and umbilical ring. J Anatomy 2022, 241(3), 846-859. https://doi.org/10.1111/joa.13720

Abstract

The human intestine elongates during the early fetal period, herniates into the extraembryonic coelom (EC), and subsequently returns to the abdominal cavity (AC). The process by which the intestinal loop returns to the abdomen remains unclear. This study aimed to document positional changes in the intestinal tract with the superior mesenteric artery (SMA) and branches in 3D to elucidate the intestinal loop return process (transition phase). Serial histological cross-sections from human fetuses (crown–rump length [CRL] range: 30–50 mm) in the herniation (n = 1), transition (n = 7), and return (n = 2) phases were selected from the Blechschmidt Collection. The distribution of the SMA trunk and all intestinal and sister branches entering the intestines was visualized so that positional changes in branches were continuous from the herniation to return phases. Positional changes in SMA branches proceeded in an orderly and structured manner; this is essential for continuous blood supply via the SMA to the intestine during transition and for safe intestinal return. Changes in the SMA distribution proceeded prior to the detection of initiation of intestinal tract return, which might start earlier and last much longer than our consensus (i.e., that the return of the herniated intestine begins when the CRL is approximately 40 mm and ends within a short time). In the cross-section of the umbilical ring in the herniation and transition phases, one proximal limb and one distal limb were observed with SMA intestinal branches, which were fully packed in the umbilical ring. The SMA branches were aligned from inferior to superior along the SMA main trunk. In the herniation phase, the distribution of 3rd–13th branches aligned from proximal inferior medial to distal superior left with a slight spiral in the EC, the tips of which suggested an orderly running course of the small intestine. In the transition phase, SMA branches running across the umbilical ring that fed the small intestine were observed, suggesting that the intestine was uncoiled and ran across the umbilical ring almost vertically. The estimated curvature value supported the phenomenon of uncoiling at the umbilical ring; the value at the umbilical ring was lesser than that in the AC and EC. During the transition phase, the proximal and distal limbs transversely ran side by side in the AC, umbilical ring, limbs on the cranial side, and mesentery on the caudal side. The SMA trunk and its branches ran in parallel, cranially to caudally aligned in the mesentery. This layout of the umbilical ring was maintained during the transition phase. In the return phase, the SMA trunk was gently curved from the upper left to the lower right of the AC; around 12 branches spread with a winding staircase appearance. The intestinal tract reached its definitive position immediately after all tissues crossed the umbilical ring and released any restriction. Each SMA branch and the corresponding region of the intestinal tract form a unit and change their position, though the conformation may change within each unit when running across the umbilical ring. We suggest that the slide–stack model requires revision.

金橋先生の横隔膜形成についての論文がJ. Anat.に受諾されました。

この研究は、胚子期後期から胎児期初期のヒト横隔膜の形態形成および線維構造の質的評価をすることを目的とし、従来使用しているT1強調像に加えて、DTIを用いた高解像度MRI画像を導入して解析しました。

• 横隔膜はCS20で完全に閉鎖した
• CRLが46mm以上のサンプルでは、​​胸骨、肋骨、腰部、および食道裂孔を囲む領域が肥厚したが、横隔膜の中心や左右の横隔膜ドーム頂部の厚さは変化しない。
• 肋骨と腰部のすべての線維は、大静脈開口部と食道裂孔周囲を除いて、左右の半横隔膜ドームに向かって走行した

Kanahashi T, Imai H, Otani H, Yamada S, Yoneyama A, Takakuwa T. Three-dimensional morphogenesis of the human diaphragm during the late embryonic and early fetal period: Analysis using T1-weighted and diffusion tensor imaging. J Anat. 2022, in press, DOI: 10.1111/joa.13760

Abstract

A precise understanding of human diaphragm development is essential in fetal medicine. To our knowledge, no previous study has attempted a three-dimensional (3-D) 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-seven human embryos and fetuses (crown-rump length [CRL] = 8–88 mm) preserved at the Congenital Anomaly Research Center of Kyoto University and Shimane University were analyzed. 3-D morphogenesis and fiber orientation of the diaphragm were assessed using phase-contrast X-ray computed tomography, T1-weighted magnetic resonance imaging (T1W MRI), and diffusion tensor imaging (DTI). T1W MR images and DTI scans were obtained using a 7-T MR system. The diaphragm was completely closed at Carnegie stage (CS) 20 and gradually developed a dome-like shape. The diaphragm was already in contact with the heart and liver ventrally in the earliest CS16 specimen observed, and the adrenal glands dorsally at CS19 or later. In the fetal period, the diaphragm contacted the gastric fundus in samples with a CRL ≥41 mm, and the spleen in samples with a CRL ≥70 mm. The relative position of the diaphragm with reference to the vertebrae changed rapidly from CS16 to CS19. The most cranial point of the diaphragm was located between the 4th and 8th thoracic vertebrae, regardless of fetal growth, in samples with a CRL ≥16 mm. Diaphragmatic thickness was nearly uniform (0.15–0.2 mm) across samples with a CRL of 8 mm to 41 mm. The sternal, costal, lumbar parts, and the area surrounding the esophageal hiatus thickened with growth in samples with a CRL ≥46 mm. 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 CS19 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 CRL ≥46 mm. 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 3-D thickness assessment and DTI 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.

The 20th Congress of International Federation of Associations of Anatomists (IFAA2022) 2022,8/5-7, Istanbul,Turkey/Onlineで発表しました。

Ishikawa A, Nagai-Tanima M, Ishida K, Imai H, Aoyama T, Takakuwa T. Three-dimensional analysis of knee joint development during the human fetal period.

第62回日本先天異常学会で発表しました(‘22,7/29-31, 金沢）

酷暑の中、対面、遠隔のハイブリッドで開催されました。

シンポジウム（正常と異常を顕かにするイメージング技術）

高桑徹也；三次元デジタル情報を活用したヒト胚子・胎児の解析
Analysis of human embryos and fetuses using three-dimensional digitalized images

＠座長もさせていただきました。現地に出席の方も結構おられ、かなり盛況でした。

一般演題

藤井 瀬菜、村中 太河、松林 潤、米山 明男、兵藤 一行、山田 重人、高桑徹也; ヒト胚子期における気管支樹の三次元的変化の定量的検討
The quantitative analysis of morphological change of the human embrionic bronchial tree

金橋　徹、今井宏彦、大谷　浩、山田重人、米山明男、高桑徹也; 拡散テンソルイメージングを応用したヒト胎児横隔膜形成の三次元的解析
Three-dimensional morphogenesis of the human diaphragm during the late embryonic and early fetal period: Analysis using diffusion tensor imaging