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）

胚子期の股関節の肢位についての論文がPLoS Oneに受諾されました。熊野くんが卒業研究で行ったデータに、胚子期の標本のデータを追加し解析しました。大腿骨（股関節）の肢位を正確に測定し、下肢の発達の時間軸を確立することを目的とした論文です。

• CS19-23の胚子期157体と胎児（CRL：37.2-225mm）18体のMRI画像を対象とした。
• 下肢と骨盤の選択された8つのランドマークの3次元座標を用いて大腿骨の肢位を計測。
• 胚子期には、股関節の屈曲、外転、側転の3つの姿勢パラメータが互いに線形相関を示し、各段階の大腿骨姿勢は3次元的に一定で、成長に応じて緩やかで滑らかな変化を示すことが示唆された。

60. Takakuwa T, Saizonou MA, Fujii S, Kumano Y, Ishikawa A, Aoyama T, Imai H, Yamada S, Kanahashi T. Femoral posture during embryonic and early fetal development: An analysis using landmarks on the cartilaginous skeletons of ex vivo human specimens. PLOS one, 2023, in press.

Abstract

The pre-axial border medially moves between the fetal and early postnatal periods, and the foot sole can be placed on the ground. Nonetheless, the precise timeline when this posture is achieved remains poorly understood. The hip joint is the most freely movable joint in the lower limbs and largely determines the lower-limb posture. The present study aimed to establish a timeline of lower-limb development using a precise measurement of femoral posture. Magnetic resonance images of 157 human embryonic samples (Carnegie stages [CS] 19–23) and 18 fetal samples (crown rump length: 37.2–225 mm) from the Kyoto Collection were obtained. Three-dimensional coordinates of eight selected landmarks in the lower limbs and pelvis were used to calculate the femoral posture. Hip flexion was approximately 14° at CS19 and gradually increased to approximately 65° at CS23; the flexion angle ranged from 90° to 120° during the fetal period. Hip joint abduction was approximately 78° at CS19 and gradually decreased to approximately 27° at CS23; the average angle was approximately 13° during the fetal period. Lateral rotation was greater than 90° at CS19 and CS21 and decreased to approximately 65° at CS23; the average angle was approximately 43° during the fetal period. During the embryonic period, three posture parameters (namely, flexion, abduction, and lateral rotation of the hip) were linearly correlated with each other, suggesting that the femoral posture at each stage was three-dimensionally constant and exhibited gradual and smooth change according to growth. During the fetal period, these parameters varied among individuals, with no obvious trend. Our study has merits in that lengths and angles were measured on anatomical landmarks of the skeletal system. Our obtained data may contribute to understanding development from anatomical aspects and provide valuable insights for clinical application.

第128回解剖学会で発表します (2023.3.18-20, 仙台, 現地開催)。

金橋先生の演題が、2022年度 第16回肉眼解剖トラベルアワード（献体協会賞）受賞しました!!
この賞は、肉眼解剖学の若手研究者の育成・奨励を目的として設立されたものです。

石田さんの演題が、学部学生優秀発表賞を受賞しました。!! 昨年度の岩佐さんに続いて2年連続の受賞です。

松成さんの卒業研究がAnat Recに掲載されました。

硬膜のような袋状の構造物は、組織形態学的手法では立体的な形状がとらえにくかったのですが、MRI等の立体情報の活用により可能になりました。

• 胚子期から胎児期の64個体の小脳テントの形成について、脳の形態との相互関係から立体的に解析
• 小脳テントの特徴により、胚子期、胎児期初期、中期にわけられる
• 大脳の後方への成長、中脳屈曲の解消等の脳形成時の変化がテントの形状や位置に影響をあたえる

59. Matsunari C, Kanahashi T, Otani H, Imai H, Yamada S, Okada T, Takakuwa T. Tentorium cerebelli formation during human embryonic and early fetal development. Anat Rec (Hoboken) 2023, 306(3), 515-526

Abstract

The morphologies of the fetal tentorium cerebelli (TC) and brain influence each other during development. This study aimed to analyze and more comprehensively understand the three-dimensional morphogenesis of the TC and fetal brain. We examined magnetic resonance imaging from 64 embryonic and fetal specimens (crown-rump length range, 9.2–225 mm). During the embryonic period, the lateral folds of the TC elongated to traverse the middle part of the midbrain. The TC and falx cerebri appeared separated, and no invaginations at the parieto-occipital region were observed. In the early fetal period, the cerebrum covered approximately half of the midbrain. The separation of the dural limiting layer at the parieto-occipital region widened from the posterior cerebrum to the cranial cerebellum. The lateral folds of the TC were spread between its tip, continuous with the falx cerebri, and its base plane, located between the midbrain and rostral hindbrain. Differences in the TC components’ growth directions gradually diminished as the cerebrum covered the midbrain. We observed rotation of the TC at its median section according to its growth, which ceased in the middle fetal period. The brainstem and cerebellum extended inferiorly via differential growth, with the cerebrum covering them superiorly. The morphology of the TC curved to conform to the cerebellar and cerebral surfaces. Our present study suggests that factors affecting TC morphology differ between the early and middle fetal periods. Present data provided a more comprehensive view of TC formation according to developmental stage.

金橋先生の横隔膜形成についての論文がJ. Anat.に掲載されました。また雑誌表紙に採用されました。

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. 2023, 242, 174-190, 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.