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大坂さんの修論が Anat Recに掲載

大坂さんの修論の前半部がAnatomical Recordに掲載されました。

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頭部・顔面形成にともなう眼の位置変化を胚子期から胎児期初期にかけて解析しました。

  • CS16の正面像ではで眼球は、外側に位置し、発生がすすむとに内側に位置を変更
  • CS17まで神経頭蓋内、CS18以降に内臓頭蓋の内側および尾側に位置を変更
  • 眼球の位置変化が顕著な胚子期 (Phase1)と変化が少ない胎児期初期(Phase2)に大別され
  • それらは Differential Growthの結果として説明できる

より詳しく>>

Osaka M, Ishikawa A, Yamada S, Uwabe C, Imai H, Matsuda T, Yoneyama A, Takeda T, Takakuwa T, Positional changes of the ocular organs during craniofacial development, Anatomical Record, 300(12), 2107–2114, 2017 DOI: 10.1002/ar.23588

ABSTRACT

The present study aimed to describe the positional changes of the ocular organs during craniofacial development; moreover, we examined the relationships among the ocular organs and other internal structures. To do this, we traced the positions of the ocular organs in 56 human early fetal samples at different stages of development using high-resolution magnetic resonance imaging and phase-contrast X-ray computed tomography. The eyes were located on the lateral side in the ventral view at Carnegie stage (CS) 16, and then changed their positions medially during development. The eyes remained in the neurocranium until CS17. However, the eyes changed their positions medially and caudally in the viscerocranium after CS18. The positional relationship between the eyes and pituitary gland changed in the lateral view as development progressed. Specifically, they were close to each other at CS17, but moved apart during the later stages of development. These positional changes were also demonstrated quantitatively with morphometric analyses. Based on the present data, the positional changes of the eyes can be categorized into phases, as follows: Phase 1, dramatic positional changes (early fetal period until CS23); and Phase 2, mild positional changes (stabilized; early fetal period after CS23). Notably, all absolute lengths measured in the present study linearly increased as the crown-rump length increased irrespective of the phase, while features of the measured angles and ratios differentially changed in Phases 1 and 2. The present data may help improve our understanding of both the normal and abnormal development of the ocular organs and craniofacial area.

勝部先生の論文の図がprenatal Diagの表紙に採用

共同研究者の勝部先生の論文の図がprenatal Diagの表紙に採用されました。

  • 出生前初期の成長に伴う鼻中隔、 anterior nasal spine(ANS) の発達を評価
  • 正中矢状画像を用いて鼻中隔の発達について幾何学的形態計測学を使用して分析
  • ANS および鼻中隔の形状の成熟期間は、それぞれ12 週および 14 週前後
  • 鼻中隔の前後方向の発達は、妊娠 14 週まで特異的であり、鼻の突出と ANS の発達に重要
  • この時期の発達の障害は、バインダー表現型等の低鼻変形を誘発する可能性

⑭ Katsube M, Yamada S, Miyazaki R, Yamaguchi Y, Makishima H, Takakuwa T, Yamamoto A, Fujii Y, Morimoto N, Ito T, Imai H, Suzuki S, Quantitation of nasal development in the early prenatal period using geometric morphometrics and MRI: A new insight into the critical period of Binder phenotype. Prenatal Diag 37: 907–915, 2017, DOI: 10.1002/pd.5106.2017

Abstract

Objectives

Disturbance of the development of the nasal septum in the early prenatal period causes congenital facial anomalies characterized by a flat nose and defects of the anterior nasal spine (ANS), such as Binder phenotype. The present research aimed to assess the development of the nasal septum and the ANS with growth in the early prenatal period.

Methods

Magnetic resonance images were obtained from 56 specimens. Mid-sagittal images were analyzed by using geometric morphometrics for the development of the nasal septum, and angle analysis was performed for the development of the ANS. Additionally, we calculated and visualized the ontogenetic allometry of the nasal septum.

Results

Our results showed that the nasal septum changed shape in the anteroposterior direction in smaller specimens, while it maintained an almost isometric shape in larger specimens. Furthermore, mathematical evidence revealed that the maturation periods of the shapes of the ANS and the nasal septum were around 12 and 14 weeks of gestation, respectively.

Conclusion

The anteroposterior development of the nasal septum is specific until 14 weeks of gestation, and it is important for nasal protrusion and the development of the ANS. Therefore, the disturbance of such development could induce low nasal deformity, including Binder phenotype.

奥村さんの卒研がPLoS Oneに掲載

奥村さんの卒業研究がPLoS Oneに受諾されました。

ヒトの骨格形成は、保存しやすく、レントゲンでの解析が可能な骨化中、骨化後の解析がほとんどで、軟骨形成期の解析はほとんどされていません。今回、骨盤の軟骨形成期に着目し解析を進めました。

  • CRL 12 -75 mm) の骨盤骨格における軟骨形成を検討し以下のTimeTableをえる
    • 腸骨、坐骨、および恥骨の軟骨化中心は、寛骨臼の周囲にCS18 で同時に出現し、後のステージで放射状に成長
    • 腸骨稜は CS20 で形成
    • 腸骨体は CS22 で円盤状
    • 仙腸関節は CS21で形成
    • 恥骨結合の関節接合、仙骨の関節柱の接続、寛骨臼への寛骨の 3 つの部分の Y 字型の接続はCS23 で形成
    • 坐骨と恥骨枝の接続は、胎児の初期に形成
    • 仙骨の中心での接続の程度は、標本間で異なる
  • 成長率は腸骨が恥骨、坐骨に比べて大きい
  • 小骨盤の骨盤入口の横方向および前後方向の長さ, 恥骨下の角度はCRLと相関しない。
  • 軟骨構造は、骨構造の形態に影響を与えることを示唆

28. Okumura M, Ishikawa A, Aoyama T, Yamada S, Uwabe C, Imai H, Matsuda T, Yoneyama A, Takeda T, Takakuwa T, Cartilage Formation in the Pelvic Skeleton during the Embryonic and Early-Fetal Period, PLoS One 12(4): e0173852. https://doi.org/10.1371/journal. pone.0173852 [Open Access]

Abstract

骨盤(胎児期初期)

The pelvic skeleton is formed via endochondral ossification. However, it is not known how the normal cartilage is formed before ossification occurs. Furthermore, the overall timeline of cartilage formation and the morphology of the cartilage in the pelvis are unclear. In this study, cartilage formation in the pelvic skeletons of 25 human fetuses (crown-rump length [CRL] = 11.9–75.0 mm) was observed using phase-contrast computed tomography and 7T magnetic resonance imaging. The chondrification center of the ilium, ischium, and pubis first appeared simultaneously at Carnegie stage (CS) 18, was located around the acetabulum, and grew radially in the later stage. The iliac crest formed at CS20 while the iliac body’s central part remained chondrified. The iliac body formed a discoid at CS22. The growth rate was greater in the ilium than in the sacrum-coccyx, pubis, and ischium. Connection and articulation formed in a limited period, while the sacroiliac joint formed at CS21. The articulation of the pubic symphysis, connection of the articular column in the sacrum, and Y-shape connection of the three parts of the hip bones to the acetabulum were observed at CS23; the connection of the ischium and pubic ramus was observed at the early-fetal stage. Furthermore, the degree of connection at the center of the sacrum varied among samples. Most of the pelvimetry data showed a high correlation with CRL. The transverse and antero-posterior lengths of the pelvic inlet of the lesser pelvis varied among samples (R2 = 0.11). The subpubic angle also varied (65–90°) and was not correlated with CRL (R2 = 0.22). Moreover, cartilaginous structure formation appeared to influence bone structure. This study provides valuable information regarding the morphogenesis of the pelvic structure.

吉田さんの卒論がCongenit Anomに掲載

スクリーンショット 2016-08-03 12.56.41

吉田さんの卒論がCongenit Anomに掲載されました。胎児の脳溝形成の様子をGyrification Indexを用いて解析しました。また、同号の表紙に、論文のFigureが採用されました。

  • 16 -40 週の大脳の脳溝形成について、GI値を用いて検討
  •  GI 値は、体重500g(CRL 200 mm )まで約 1.0(脳溝なし)
  • その後、GI値は体重と CRL に相関して増加(脳溝形成あり)
  • 妊娠21週で一次脳溝とGIのピークが対応
  • 31-40週数で前頭側頭領域よりも頭頂後頭領域でGI値は増加
1409g の胎児の脳の左側面図とGI値。

Gyrification index (GI) of brain slices in a left lateral view of the brain in a 1409g fetus. The line graph above the brain shows the GI of each slice below it. The GI of the whole hemisphere changed in the rostro-caudal dimension. Several maxima of the GI curve appeared in relation to gross landmarks. Further details can be seen in the article by Yoshida et al. in this issue.

27. Yoshida R, Koichi Ishizu K, Yamada S, Chigako Uwabe C, Okada T, Togashi K, Takakuwa T, The dynamics of gyrification in the human cerebral cortex during development, Congenit Anom, 57 (1) 8-14, 2017, DOI: 10.1111/cga.12179, 10.1111/cga.12181

Abstract

This study quantitatively characterized cortical gyrus folding over human neocortical development by calculating the gyrification index (GI) in 22 human fetal specimens from 16 to 40 weeks with magnetic resonance imaging data. GI values remained constant at approximately 1.0 until the fetal specimens reached 500 g body weight and 200 mm crown-rump length (CRL), respectively, and then increased in correlation with the body weight and CRL. The rostrocaudal GI distribution in the cerebral cortex revealed a correspondence of GI peaks with indentations of early-generated primary sulci at 21 weeks of gestation and more frequently increased GI values in the parieto-occipital region than in the fronto-temporal region at 31 and 40 weeks of gestation. These results provide a quantitative reference set for gyrification in normal human cortical development, which may help reveal the mechanism of neurodevelopmental disorders.

Anat Recに総説を掲載

本研究室で行われているヒト胚子・胎児研究についてまとめた総説がAnatomical Recに掲載されました。

幅広い発達期間をカバーする大規模で高解像度なデジタルデータセットの確立し、そのメリットを活かした研究展開を示しました。デジタルデータのメリット、それを活かした展開として

  • 形態計測分析に適した平面の抽出、
  • 形態学的観察の効率化。
  • 発生の特徴を定量的に評価、実証、異常なサンプルのスクリーニング
  • 超音波検査データを比較
  • 解剖学的ランドマークの 3D 座標は
  • 位置変化とそれらの関係を分析するために有用
  • 3D 座標を使用した微分成長の説明
  • 統計分析、数学的分析に応用

器官形成時の動的で複雑なプロセスの解析、正確な形態学的データの提供への寄与が期待されます。

30. Takakuwa T, 3D analysis of human embryos and fetuses using digitized datasets from the Kyoto Collection, Anat Rec 2018, 301,960-969 doi: 10.1002/ar.23784 (英文で読む)

ABSTRACT

Three-dimensional (3D) analysis of the human embryonic and early-fetal period has been performed using digitized datasets obtained from the Kyoto Collection, in which the digital datasets play a primary role in research. Datasets include magnetic resonance imaging (MRI) acquired with 1.5 T, 2.35 T, and 7 T magnet systems, phase-contrast X-ray computed tomography (CT), and digitized histological serial sections. Large, high-resolution datasets covering a broad range of developmental periods obtained with various methods of acquisition are key elements for the studies. The digital data have gross merits that enabled us to develop various analysis. Digital data analysis accelerated the speed of morphological observations using precise and improved methods by providing a suitable plane for a morphometric analysis from staged human embryos. Morphometric data are useful for quantitatively evaluating and demonstrating the features of development and for screening abnormal samples, which may be suggestive in the pathogenesis of congenital malformations. Morphometric data are also valuable for comparing sonographic data in a process known as “sonoembryology.” The 3D coordinates of anatomical landmarks may be useful tools for analyzing the positional change of interesting landmarks and their relationships during development. Several dynamic events could be explained by differential growth using 3D coordinates. Moreover, 3D coordinates can be utilized in mathematical analysis as well as statistical analysis. The 3D analysis in our study may serve to provide accurate morphologic data, including the dynamics of embryonic structures related to developmental stages, which is required for insights into the dynamic and complex processes occurring during organogenesis. Anat Rec, 301:960–969, 2018.

尾関さんの修論がAnat Recに掲載

CS22聴覚器

尾関さんの修士論文のうち、中耳耳小骨の形成と外耳、内耳との立体的位置関係についてAnat Recに掲載されました。

MEO の形成と外耳と内耳の接続のタイムラインを決定しました。

  • 軟骨頭蓋は、CS18 までに認識可能
  • 軟骨形成開始は耳小骨(MEO)間で若干の相違。
  • CS19;槌骨、キヌタ骨、アブミ骨の順序で、前後方向に配置 CS22以降;MEO同士が関節を介し接続。
  • CS21以降にすべてのMEOの軟骨形成を確認
  • CS23;アブミ骨基底部分はfoot plate状ではない
  • ツチ骨のハンドルは 外耳道からは離れている
  • 耳介軟骨と耳嚢の軟骨膜境界は明確

26. Ozeki-Satoh M, Ishikawa A, Yamada S, Uwabe C, Takakuwa T. Morphogenesis of the Middle Ear Ossicles and Spatial Relationships with the External and Inner Ears during the Embryonic Period, Anat Rec 299:1325–1337, 2016, DOI 10.1002/ar.23457

Abstract

We describe the three-dimensional morphogenesis of the middle ear ossicles (MEOs) according to Carnegie stage (CS) in human embryos. Seventeen samples including 33 MEOs from CS18 to 23 were selected from the Kyoto Collection. The primordia of the MEOs and related structures were histologically observed and three-dimensionally reconstructed from digital images. The timing of chondrogenesis was variable among structures. The stapes was recognizable as a vague condensation of the mesenchymal cells in all samples from CS18, whereas the malleus and incus were recognizable at CS19. Chondrogenesis of all MEOs was evident in all samples after CS21. The chondrocranium was recognizable in all samples by CS18, and the perichondrium border of the auricular cartilage and otic capsule was distinct in all samples at CS23. At CS19, the MEOs were positioned in the anterior to posterior direction, following the order malleus, incus, stapes, which adjusted gradually during development. The MEOs connected in all samples after CS22. The stapes was located close to the vestibular part of the inner ear, although the basal part was not differentiated into the “footplate” form, even at CS23. The handles of the malleus were close to the tubotympanic recess at CS23, but were distant from the external auditory meatus. Determining the timeline of the formation of MEOs and connection of the external and inner ears can be informative for understanding hearing loss caused by failure of this connection. These data may provide a useful standard for morphogenesis, and will contribute to distinguishing between normal and abnormal MEO development. 

Willis輪の形成についての論文Congenit Anomに掲載

Willis輪の発生(CS21); variationが多くみられる
Willis輪の発生(CS21); variationが多くみられる

ヒトのWillis輪の形成についての論文がCongenitAnomに掲載されました。
Willis輪は脳を養う血流が脳底部で輪状にあつまる部位で、成人ではvariationが多いことが知られています。
本論文では、20例の胚子期後期標本について検討し、以下の知見をえました。

  • Willis輪がCS22ころ完成すること
  • 胚子期後期でもvariationが多くみられること
  • Willis輪が未完成の標本が、成長に伴い完成したかはあきらかでないこと

25. Takakuwa T, Koike T, Muranaka T, Yamada S, Uwabe C. 2016. Formation of the circle of Willis during human embryonic development. Congenit Anom (Kyoto) 2016; 56, 233–236, DOI: 10.1111/cga.12165

Abstract

The circle of Willis (CW) is a circulatory anastomosis that supplies blood to the brain and adjacent structures. We examined the timing of formation of CW in 20 Japanese human embryo samples by using 3-dimensional reconstruction of serial histological sections. The CW was closed in 1 (n = 6), 2 (n = 8), 2 (n = 3) and 2 (n = 3) samples at Carnegie stages 20, 21, 22, and 23, respectively. The CW was unclosed in 13 samples (unclosed at ACOM alone, 6 samples; ACOM and bilateral P1, 4; left PCOM and right P1, 1; right PCOM and right P1, 1; ACOM and left PCOM, 1). It was difficult to predict whether the circle would close during further development, as such variations frequently exist in adults.

小林さんの卒論がPrenatal Diagnosisに掲載&表紙に採用

pd4818-toc-0001

小林さんの卒論がPrenatal Diagnosisに掲載されました。ヒト胚子期の標本を用いて脳の発生に伴う計測値の変化、特徴を論じたものです。

  • 胚子期の標本の脳の7直線、3領域の面積、体積を検討
  • すべての直線計測値はCRLと相関
  • bitemporal lengthと全脳、大脳体積は高い相関

得られた結果は、超音波データの修正と比較、出生前診断の改善に貢献することが期待されます。

また、同号の表紙にも採用されました。

23. Kobayashi A, Ishizu K, Yamada S, Uwabe C, Kose K, Takakuwa T, Morphometric human embryonic brain features according to developmental stage, Prenatal Diagnosis, 36:338–345, 2016, DOI: 10.1002/pd.4786. DOI: 10.1002/pd.4818

Abstract

Objectives

The present study investigated linear, area, and volume measurements of human brain samples according to Carnegie stages (CS) in an attempt to select suitable morphometric features that reflect embryonic development.

Methods

Using magnetic resonance imaging, we measured seven linear segments, three separate areas, and three regional volumes in 101 samples between CS13 and 23. Brain volume was determined via manual segmentation of the magnetic resonance image, whereby a formula was generated to estimate the volume of each linear measurement.

Results

All parameters correlated with crown-rump length. Bitemporal length and mesencephalic height increased linearly according to the CS, and a high correlation between bitemporal length and both whole-brain (r = 0.98) and prosencephalon (r = 0.99) volumes was found when brain cavity volume was excluded.

Conclusion

Morphometric data related to human embryonic stages are valuable for correcting and comparing sonographic data. The present approach may contribute to improvements in prenatal diagnostics by enabling the selection of more suitable measurements during early embryonic stages.