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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.

松成さんの卒業研究がAnat Recに受諾

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に受諾されました。

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) 2022, in press

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.

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.

金橋先生の論文がJ Anatに受諾

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.

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.

山崎さんの修士論文がCells Tissues Organsに掲載

山崎さんの修士論文がCells Tissues Organsに受諾されました。

気管軟骨、喉頭軟骨の形態形成について軟骨の発生段階を立体的に細かく示しました。頭尾方向の分化の同調性については、これまでの報告と異なっています。

  • Phase 2の最初の分化 は正中面ではなく、舌骨、甲状軟骨、輪状軟骨、気管軟骨ともに両外側に 一つずつあり、それぞれのタイムラインに従って分化し正中面で融合した。
  • 気管軟骨のPhase2 の分化は頭側で始まり、体軸に沿って短期間で伝播し、Phase 3 の分化が始まる前に同調する。
  • Phase 3 分化は正中で始まり、側方に伝播する。頭尾方向については、同調して分化し、差はない。
  • 気管気管支軟骨の数と分布は成人と同様である。
CS20 気管の縦断面;気管軟骨は頭尾方向でPhase 2の分化を示しており、同調している。

54. Yamazaki Y, Kanahashi T, Yamada S, Männer J, Takakuwa T. Three-dimensional analysis of human laryngeal and tracheobronchial cartilages during the late embryonic and early fetal period. Cells Tissues Organs, 2021 in press

Abstract

Laryngeal and tracheobronchial cartilages are present as unique U-shaped forms around the respiratory tract and contribute to the formation of rigid structures required for the airway. Certain discrepancies still exist concerning cartilage formation in humans. To visualize the accurate timeline of cartilage formation, tracheobronchial and laryngeal cartilages were 3D reconstructed based on serial tissue sections during the embryonic period (Carnegie stage [CS] 18–23) and early fetal period (crown rump length [CRL] = 35–45 mm). The developmental phases of the cartilage were estimated by histological studies, which were performed on the reconstructed tissue sections. The hyoid greater horns were recognizable at CS18 (phase 2). Fusion of 2 chondrification centers in the mid-sagittal region was observed at CS19 in the hyoid bone, at CS20 in the cricoid cartilage, and in the specimen with CRL 39 mm in the thyroid cartilage. Phase 3 differentiation was observed at the median part of the hyoid body at CS19, which was the earliest among all other laryngeal and tracheobronchial cartilages. Most of the laryngeal cartilages were in phase 3 differentiation at CS22 and in phase 4 differentiation at CS23. The U-shaped tracheobronchial cartilages with phase 2 differentiation covered the entire extrapulmonary region at CS20. Phase 3 differentiation started on the median section and propagates laterally at CS21. The tracheobronchial cartilages may form simultaneously during the embryonic period at CS22-23 and early fetal periods, similar to adults in number and distribution. The spatial propagation of the tracheal cartilage differentiation provided in the present study indicates that cartilage differentiation may have propagated differently on phase 2 and phase 3. This study demonstrates a comprehensible timeline of cartilage formation. Such detailed information of the timeline of cartilage formation would be useful to improve our understanding of the development and pathophysiology of congenital airway anomalies.

寺島さんの修士論文がJ Anatに掲載

胚子期末大脳におけるプレサブプレートの3次元分布

寺島さんの修士論文がJ Anatomyに受諾されました。おめでとうございます。

  • 胎児期のみに出現し、大脳皮質の形成、自発活動の開始に関わる可能性のあるプレサブプレート(pSP)の形成について、連続組織画像を用いて立体的に視覚化し、定量化した。
  • PSPはCS21で大脳壁の中外側領域に存在し、この領域を中心とした拡大が観察され、胎児期の初期(CRL 39 mm)に大脳半球全体で観察した。
  • pSP-IZ の厚さは 3D で表示され、中外側領域で大きかった。CRL 64 mm)に、厚い領域は、島の原基の周りの外側、上部、および後部領域に拡大しました。
  • 層構造は、発達初期に厚くなるのではなく、薄く成長して広がった。

Terashima, M., Ishikawa A., Männer J., Yamada S.&Takakuwa T. (2021) Early development of the cortical layers in the human brain. Journal of Anatomy, 239, 1039–1049. https://doi.org/10.1111/joa.13488

Abstract

The cortical plate (CP) first appears at seven postconceptional weeks (pcw), when it splits the preexisting preplate into two layers, the marginal zone and the presubplate (pSP). Although three-dimensional (3D) analysis using fetal magnetic resonance imaging and two-dimensional tissue observations have been reported, there have been no studies analyzing the early development of the layer structure corresponding to the pSP stage in 3D. Here, we reconstructed 3-D models of the brain with a focus on the cortical layers in pSP stage. To achieve this, we digitized serial tissue sections of embryos between CS20 and CS23 from the Kyoto Collection (n = 7, approximately 7–8.5 pcw), and specimens at early fetal phase from the Blechschmidt Collection (n = 2, approximately 9.5–12 pcw, crown rump length [CRL] 39 and 64 mm). We observed tissue sections and 3D images and performed quantitative analysis of the thickness, surface area, and volume. Because the boundary between pSP and the intermediate zone (IZ) could not be distinguished in hematoxylin and eosin-stained sections, the two layers were analyzed together as a single layer in this study. The histology of the layers was observed from CS21 and became distinct at CS22. Subsequently, we observed the 3-D models; pSP-IZ was present in a midlateral region of the cerebral wall at CS21, and an expansion centered around this region was observed after CS22. We observed it over the entire cerebral hemisphere at early fetal phase (CRL 39 mm). The thickness of pSP-IZ was visible in 3D and was greater in the midlateral region. At the end of the pSP stage (CRL 64 mm), the thick region expanded to lateral, superior, and posterior regions around the primordium of the insula. While, the region near the basal ganglia was not included in the thickest 10% of the pSP-IZ area. Middle cerebral artery was found in the midlateral region of the cerebral wall, near the area where pSP-IZ was observed. Feature of layer structure growth was revealed by quantitative assessment as thickness, surface area, and volume. The maximum thickness value of pSP-IZ and CP increased significantly according to CRL, whereas the median value increased slightly. The layer structure appeared to grow and spread thin, rather than thickening during early development, which is characteristic during pSP stages. The surface area of the cerebral total tissue, CP, and pSP-IZ increased in proportion to the square of CRL. The surface area of CP and pSP-IZ approached that of the total tissue at the end of the pSP stage. Volume of each layer increased in proportion to the cube of CRL. pSP-IZ and CP constituted over 50% of the total tissue in volume at the end of the pSP stages. We could visualize the growth of pSP-IZ in 3D and quantify it during pSP stage. Our approach allowed us to observe the process of rapid expansion of pSP-IZ from the midlateral regions of the cerebral wall, which subsequently becomes the insula.

ヒト胎児期初期の脳の形態形成についての論文がJ Anatに掲載されました

ヒト胎児期初期の脳の形態形成についての論文がJ Anatomyに掲載されました。5年以上かけて、ようやくまとめることができました。

  • 高解像度MRIを用いて胎児期初期の(受胎後 9 ~ 13 週) の脳の形態計測学的分析を行った。
  • 脳梁の出現(CRL62mm), 皮質内側の脳溝の出現(CRL114mm),
  • 小脳半球、後外側裂溝、小脳半分の結合、虫部の形成(CRL43.5mm), 一次裂溝の出(CRL56mm), 錐体前裂(CRL75mm), 
  • 大脳側面における大脳の比率 (長さ/高さ) と基準線に対する大脳の角度は、大脳の成長と C 字型の形成を反映している可能性がある。
  • これらの所見は、胎児期初期を細分化するための候補となる可能性がある。

52. Takakuwa T, Shiraishi N, Terashima M,Yamanaka M, Okamoto I, Imai H, Ishizu K, Yamada S, Ishikawa A, Kanahashi T. Morphology and morphometry of the human early fetal brain: A three-dimensional analysis. J Anatomy; 239 (2) 498-516, 2021, doi.org/10.1111/joa.13433

Abstract

Morphometric analyses in the early foetal phase (9-13 postconceptional week) are critical for evaluating normal brain growth. In this study, we assessed sequential morphological and morphometric changes in the foetal brain during this period using high-resolution T1-weighted magnetic resonance imaging (MRI) scans from 21 samples preserved at Kyoto University. MRI sectional views (coronal, mid-sagittal, and horizontal sections) and 3D reconstructions of the whole brain revealed sequential changes in its external morphology and internal structures. The cerebrum’s gross external view, lateral ventricle and choroid plexus, cerebral wall, basal ganglia and thalamus, and corpus callosum were assessed. The development of the cerebral cortex, white matter microstructure, and basal ganglia can be well-characterized using MRI scans. The insula became apparent and deeply impressed as brain growth progressed. A thick, densely packed cellular ventricular/subventricular zone and ganglionic eminence became apparent at high signal intensity. We detected the emergence of important landmarks which may be candidates in the subdivision processes during the early foetal period; the corpus callosum was first detected in the sample with crown-rump length (CRL) 62 mm. A primary sulcus on the medial part of the cortex (cingulate sulcus) was observed in the sample with CRL 114 mm. In the cerebellum, the hemispheres, posterolateral fissure, union of the cerebellar halves, and definition of the vermis were observed in the sample with CRL 43.5 mm, alongside the appearance of a primary fissure in the sample with CRL 56 mm and the prepyramidal fissure in the sample with CRL 75 mm. The volumetric, linear, and angle measurements revealed the comprehensive and regional development, growth, and differentiation of brain structures during the early foetal phase. The early foetal period was neither morphologically nor morphometrically uniform. The cerebral proportion (length/height) and the angle of cerebrum to the standard line at the lateral view of the cerebrum, which may reflect the growth and C-shape formation of the cerebrum, may be a candidate for subdividing the early foetal period. Future precise analyses must establish a staging system for the brain during the early foetal period. This study provides insights into brain structure, allowing for a correlation with functional maturation and facilitating the early detection of brain damage and abnormal development.