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藤井さんの論文がJ Anatomyに掲載

  • 比較解剖学的研究で哺乳類の気管支樹の基本モデルとして提案されている左右の気管支の対称性が、ヒトの胎児の気管支樹に当てはまるかどうかを検討
  • ヒト成人の気管支分岐構造の原型が胎児期に形成され、維持されることを実証
  • すべての肺葉気管支、B6、B8、B9、および B10 の亜分節気管支の形態および分岐位置は、遺伝的に決定される可能性がある
  • B10 の亜分節気管支以降の末梢枝では個々の胚間に共通の構造は見つからず、この領域での枝形成は遺伝的要因よりも環境的要因により影響されることが示唆された

Fujii S, Muranaka T, Matsubayashi J, Yamada S, Yoneyama A, Takakuwa T. Bronchial tree of the human embryo: Examination based on a mammalian model. J Anatomy 2024, 244, 159-169 http://doi.org/10.1111/joa.13946 .

The symmetry of right and left bronchi, proposed in a previous comparative anatomical study as the basic model of the mammalian bronchial tree, was examined to determine if it applied to the embryonic human bronchial tree. Imaging data of 41 human embryo specimens at Carnegie stage (CS) 16–23 (equivalent to 6–8 weeks after fertilization) belonging to the Kyoto collection were obtained using phase-contrast X-ray computed tomography. Three-dimensional bronchial trees were then reconstructed from these images. Bronchi branching from both main bronchi were labeled as dorsal, ventral, medial, or lateral systems based on the branching position with numbering starting cranially. The length from the tracheal bifurcation to the branching point of the labeled bronchus was measured, and the right-to-left ratio of the same labeled bronchus in both lungs was calculated. In both lungs, the human embryonic bronchial tree showed symmetry with an alternating pattern of dorsal and lateral systems up to segmental bronchus B9 as the basic shape, with a more peripheral variation. This pattern is similar to that described in adult human lungs. Bronchial length increased with the CS in all labeled bronchi, whereas the right-to-left ratio was constant at approximately 1.0. The data demonstrated that the prototype of the human adult bronchial branching structure is formed and maintained in the embryonic stage. The morphology and branching position of all lobar bronchi and B6, B8, B9, and the subsegmental bronchus of B10 may be genetically determined. On the other hand, no common structures between individual embryos were found in the peripheral branches after the subsegmental bronchus of B10, suggesting that branch formation in this region is influenced more by environmental factors than genetic factors.

福井さんの修士論文がJ Anatomyに掲載

福井さんの修士論文がJ Anatomyに受諾されました。ヒト胎児期初期の左房の形成を肺静脈のとりこみと左心耳の形成を中心に解析しました。

  • 23例の胚子期、19例の胎児期初期標本を選択した。
  • 高分解能イメージング(位相CTとMRI)から三次元心臓画像を再構成し、左心耳を含む肺静脈と左心房を形態学的および定量的に評価した。
  • 心臓の背側中膜結合が退縮したとき(CS18以降)、心膜折り返しの位置が2つの肺静脈(右肺静脈と左肺静脈)と4つの肺静脈でほぼ同時に決定された。
  • 左心房のひだが体部と静脈成分の接合部に存在することが確認された。
  • 左心房の肺静脈由来の静脈成分は成長に比例して増加することが示された。肺静脈成分と左心房体との接合部は徐々に目立たなくなったが、観察された初期胎児期の終わりにはまだ認識可能であった。

Fukui N, Toru KanahashiT, MatsubayashiJ, ImaiH, YoneyamaA, OtaniH, YamadaS, Takakuwa T. Morphogenesis of the pulmonary vein and left atrial appendage in human embryos and early fetuses. J Anatomy 2024, 244, 142-158, in press, https://doi.org/10.1111/joa.13941

Abstract

The left atrium wall has several origins, including the body, appendage, septum, atrial–ventricular canal, posterior wall, and venous component. Here, we describe the morphogenesis of left atrium based on high-resolution imaging (phase-contrast X-ray computed tomography and magnetic resonance imaging). Twenty-three human embryos and 19 fetuses were selected for this study. Three-dimensional cardiac images were reconstructed, and the pulmonary veins and left atrium, including the left atrial appendage, were evaluated morphologically and quantitatively. The positions of the pericardial reflections were used as landmarks for the border of the pericardial cavity. The common pulmonary vein was observed in three specimens at Carnegie stage 17–18. The pericardium was detected at the four pulmonary veins (left superior, left inferior, right superior, and right inferior pulmonary veins) at one specimen at Carnegie stage 18 and all larger specimens, except the four samples. Our results suggest that the position of the pericardial reflections was determined at two pulmonary veins (right and left pulmonary vein) and four pulmonary veins almost simultaneously when the dorsal mesocardial connection between the embryo and heart regressed. The magnetic resonance images and reconstructed heart cavity images confirmed that the left atrium folds were present at the junction between the body and venous component. Three-dimensional reconstruction showed that the four pulmonary veins entered the dorsal left atrium tangentially from the lateral to the medial direction. More specifically, the right pulmonary veins entered at a greater angle than the left pulmonary veins. The distance between the superior and inferior pulmonary veins was shorter than that between the left and right pulmonary veins. Three-dimensional reconstruction showed that the venous component increased proportionally with growth. No noticeable differences to discriminate between the right and left parts of the venous component emerged, while the junction between the venous component and body gradually became inconspicuous but was still recognizable by the end of the observed early fetal period. The left superior pulmonary vein had the smallest cross-sectional area and most flattened shape, whereas the other three were similar in area and shape. The left atrial appendage had a large volume in the center and extended to the periphery as a lobe-like structure. The left atrial appendage orifice increased in the area and tended to become flatter with growth. The whole left atrium volume^(1/3) increased almost proportionally with growth, parallel to the whole heart volume. This study provided a three-dimensional and quantitative description of the developmental process of left atrium, comprising the venous component and left atrial appendage formation, from the late embryonic to the early fetal stages.

胚子期の股関節の肢位についての論文がPLoS Oneに掲載

胚子期の股関節の肢位についての論文がPLoS Oneに掲載されました。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, 18(5): e0285190. https://doi.org/10.1371/journal.pone.0285190.

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.

松成さんの卒業研究がAnat Recに掲載

中脳が大脳に覆われていない時期の硬膜

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.

金橋先生の論文がJ Anatに掲載されました

CRL71 mm胎児右側面像

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

表紙に採用されました

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.

野原さんの修士論文がJ Anatに掲載

野原さんの修論がJ Anatomyに掲載されました。

胚子期末の2次口蓋形成時の舌、口蓋だな、下顎(メッケル軟骨)、鼻腔の動きを主成分分析等を用いて解析し、口蓋だな上昇、融合前の数日間の下顎(メッケル軟骨)、舌が極度に前後に圧縮される時期を”approach period”として見出しました。

  • 口蓋棚の上昇・癒合はCS23中におきる。
  • 「アプローチ期間」の間、下顎骨 (メッケル軟骨と舌) と上顎骨 (口蓋と鼻腔) の構造は位置を変えなかったが、構造の両方のグループが前後に圧縮されていた。
  • 口蓋棚上昇前後では、上顎と下顎の構造、特に舌の上の棚の配置、および舌と下顎骨の突出の間に有意な変化を示した。
  • これらの結果は、メッケル軟骨の成長が舌を再配置して棚の上昇を促進する上で積極的な役割を果たしていることを示唆している。

ヒトの二次口蓋閉鎖の 3 つの異なるPhaseを表す現在のデータは、口蓋棚の水平配置の前後に発生する形態学的成長変化と、ヒトの二次口蓋をうまく閉じるためのそれらの融合の理解を進めることができます。

 Nohara A, Owaki N, Matsubayashi J, Katsube M, Imai H, Yoneyama A, Yamada S, Kanahashi T, Takakuwa T. Morphometric analysis of secondary palate development in human embryos. J Anatomy, 2022, 241(6), 1287-1302, 2022, DOI:10.1111/joa.13745

Abstract

Rapid shelf elevation and contact of the secondary palate and fusion reportedly occur due to a growth-related equilibrium change in the structures within the oro-nasal cavity. This study aimed to quantitatively evaluate complex three-dimensional morphological changes and their effects on rapid movements, such as shelf elevation and contact, and fusion. Morphological changes during secondary palate formation were analyzed using high-resolution digitalized imaging data (phase-contrast X-ray computed tomography and magnetic resonance images) obtained from 22 human embryonic and fetal samples. The three-dimensional images of the oro-nasal structures, including the maxilla, palate, pterygoid hamulus, tongue, Meckel’s cartilage, nasal cavity, pharyngeal cavity, and nasal septum, were reconstructed manually.

palatal shelves were not elevated in all the samples at Carnegie stage (CS)21 and CS22 and in three samples at CS23. In contrast, the palatal shelves were elevated but not in contact in one sample at CS23. Further, the palatal shelves were elevated and fused in the remaining four samples at CS23 and all three samples from the early fetal period. For each sample, 70 landmarks were subjected to Procrustes and principal component (PC) analysis. PC-1 accounted for 67.4% of the extracted gross changes before and after shelf elevations. Notably, the PC-1 values of the negative and positive value groups differed significantly. The PC-2 value changed during the phases in which the change in the PC-1 value was unnaturally slow and stopped at CS22 and the first half of CS23. This period, defined as the “approach period”, corresponds to the time before dynamic changes occur as the palatal shelves elevate, the tongue and mandibular tip change their position and shape, and secondary palatal shelves contact and fuse. During the “approach period”, measurements of PC-2 changes showed that structures on the mandible (Meckel’s cartilage and tongue) and maxilla (palate and nasal cavity) did not change positions, albeit both groups of structures appeared to be compressed anterior-posteriorly. However, during and after shelf elevation, measurements of PC-1 changes showed significant changes between maxillary and mandibular structures, particularly positioning of the shelves above the tongue and protrusion of the tongue and mandible. These results suggest an active role for Meckel’s cartilage growth in repositioning the tongue to facilitate shelf elevation. The present data representing three distinct phases of secondary palate closure in humans can advance the understanding of morphological growth changes occurring before and after the horizontal positioning of palatal shelves and their fusion to close the secondary palate in humans successfully.

掛谷さんの修士論文がJ Anatに掲載

生理的臍帯ヘルニア還納途中のSMA分岐の分布

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.

熊野くんの卒業研究がAnat Recに掲載

腹側からみた上肢(肩甲骨・上腕骨)の肢位

熊野くんの卒業研究のうち上肢の解析分がAnatomical Recに掲載されました。

胚子期後期から胎児期初期、中期についての上肢の肢位について、上腕骨と体幹、体幹と肩甲骨、肩甲骨と上腕と解剖学的にわけて検討しています。

  • 上腕の外転と屈曲ともに、CS20 で極大値を示し、外転は中期胎児期まで徐々に減少した。
  • 肩甲骨は、関節腔が頭側および腹側を向いた独特の位置を示した。
  • この独特な肩甲骨の位置は、肩甲骨_上腕関節の角度の鏡像的な変化により上腕の姿勢にほとんど影響を与えない。

Kumano Y, Tanaka S, Sakamoto R, Kanahashi T, Imai H, Yoneyama A, Yamada S, Takakuwa T. Upper arm posture during human embryonic and fetal development. Anatomical Rec 2022, 305 1682-1691, https://doi.org/10.1002/ar.24796

Abstract

The upper extremity posture is characteristic of each Carnegie stage (CS), particularly between CS18 and CS23. Morphogenesis of the shoulder joint complex largely contributes to posture, although the exact position of the shoulder joints has not been described. In the present study, the position of the upper arm was first quantitatively measured, and the contribution of the position of the shoulder girdle, including the scapula and glenohumeral (GH) joint, was then evaluated. Twenty-nine human fetal specimens from the Kyoto Collection were used in this study. The morphogenesis and three-dimensional position of the shoulder girdle and humerus were analyzed using phase-contrast X-ray computed tomography and magnetic resonance imaging. Both abduction and flexion of the upper arm displayed a local maximum at CS20. Abduction gradually decreased until the middle fetal period, which was a prominent feature. Flexion was less than 90° at the local maximum, which was discrepant between appearance and measurement value in our study. The scapular body exhibited a unique position, being oriented internally and in the upward direction, with the glenoid cavity oriented cranially and ventrally. However, this unique scapular position had little effect on the upper arm posture because the angle of the scapula on the thorax was canceled as the angle of the GH joint had changed to a mirror image of that angle. Our present study suggested that measuring the angle of the scapula on the thorax and that of the GH joint using sonography leads to improved staging of the human embryo.