TY - JOUR
T1 - An analysis modality for vascular structures combining tissue-clearing technology and topological data analysis
AU - Takahashi, Kei
AU - Abe, Ko
AU - Kubota, Shimpei I.
AU - Fukatsu, Noriaki
AU - Morishita, Yasuyuki
AU - Yoshimatsu, Yasuhiro
AU - Hirakawa, Satoshi
AU - Kubota, Yoshiaki
AU - Watabe, Tetsuro
AU - Ehata, Shogo
AU - Ueda, Hiroki R.
AU - Shimamura, Teppei
AU - Miyazono, Kohei
N1 - Funding Information:
The authors thank Dr. Hiroyuki Miyoshi (deceased, formerly RIKEN) for providing plasmids, Dr. Tomoyuki Mano (Okinawa Institute of Science and Technology Graduate University) for technical assistance of machine learning, Dr. Etsuo A. Susaki (Juntendo University) for his expertise on the tissue-clearing method, Dr. Seiji Yamamoto (Toyama University) for his expertise on vascular biology, and all the members at Miyazono and Shimamura laboratories, especially Dr. Ryo Tanabe and Ms. Keiko Yuki for their supports. We also thank Bitplane for instruction in operating the Imaris software. This work was supported by grants from KAKENHI grants-in-aid for scientific research on Innovative Area on Integrated Analysis and Regulation of Cellular Diversity (K.M. and S.E., grant number 17H06326), KAKENHI grants-in-aid for scientific research (S) (K.M., grant number 15H05774; H.R.U., grant number JP25221004), KAKENHI grants-in-aid for scientific research (A) (K.M., grant number 20H00513), KAKENHI grants-in aid for scientific research (B) (T.S., grant number 20H04281), KAKENHI grants-in-aid for scientific research on Innovative Areas on Constructive Understanding of Multi-Scale Dynamism of Neuropsychiatric Disorders (T.S., grant number 19H05210), KAKENHI grants-in-aid for scientific research on Innovative Area on Transomics Analysis of Metabolic Adaptation (T.S., grant number 20H04841), KAKENHI grants-in-aid for Challenging Exploratory Research (T.S., grant number 20K21832), and KAKENHI grants-in-aid for early-career scientists (K.T., grant number 19K16604; S.I.K., grant number 20K16212; K.A., grant number 20K19921) from the Japan Society for the Promotion of Science (JSPS), RADDAR-J (T.S., grant number JP20ek0109488), Brain/MINDS Health and Diseases (T.S., grant number JP21wm0425007), Brain/MINDS (H.R.U., grant number JP21dm0207049), Science and Technology Platform Program for Advanced Biological Medicine (H.R.U., grant number JP21am0401011) from Japan Agency for Medical Research and Development (AMED), HFSP Research Grant Program (H.R.U., grant number HFSP RGP0019/2018) from Human Frontier Science Program (HFSP), grant-in-aid from Takeda Science Foundation (H.R.U.), Moonshot R&D (T.S., grant number JPMJMS2025), and ERATO (H.R.U., grant number JPMJER2001) from Japan Science and Technology Agency (JST).
Funding Information:
The authors thank Dr. Hiroyuki Miyoshi (deceased, formerly RIKEN) for providing plasmids, Dr. Tomoyuki Mano (Okinawa Institute of Science and Technology Graduate University) for technical assistance of machine learning, Dr. Etsuo A. Susaki (Juntendo University) for his expertise on the tissue-clearing method, Dr. Seiji Yamamoto (Toyama University) for his expertise on vascular biology, and all the members at Miyazono and Shimamura laboratories, especially Dr. Ryo Tanabe and Ms. Keiko Yuki for their supports. We also thank Bitplane for instruction in operating the Imaris software. This work was supported by grants from KAKENHI grants-in-aid for scientific research on Innovative Area on Integrated Analysis and Regulation of Cellular Diversity (K.M. and S.E., grant number 17H06326), KAKENHI grants-in-aid for scientific research (S) (K.M., grant number 15H05774; H.R.U., grant number JP25221004), KAKENHI grants-in-aid for scientific research (A) (K.M., grant number 20H00513), KAKENHI grants-in aid for scientific research (B) (T.S., grant number 20H04281), KAKENHI grants-in-aid for scientific research on Innovative Areas on Constructive Understanding of Multi-Scale Dynamism of Neuropsychiatric Disorders (T.S., grant number 19H05210), KAKENHI grants-in-aid for scientific research on Innovative Area on Transomics Analysis of Metabolic Adaptation (T.S., grant number 20H04841), KAKENHI grants-in-aid for Challenging Exploratory Research (T.S., grant number 20K21832), and KAKENHI grants-in-aid for early-career scientists (K.T., grant number 19K16604; S.I.K., grant number 20K16212; K.A., grant number 20K19921) from the Japan Society for the Promotion of Science (JSPS), RADDAR-J (T.S., grant number JP20ek0109488), Brain/MINDS Health and Diseases (T.S., grant number JP21wm0425007), Brain/MINDS (H.R.U., grant number JP21dm0207049), Science and Technology Platform Program for Advanced Biological Medicine (H.R.U., grant number JP21am0401011) from Japan Agency for Medical Research and Development (AMED), HFSP Research Grant Program (H.R.U., grant number HFSP RGP0019/2018) from Human Frontier Science Program (HFSP), grant-in-aid from Takeda Science Foundation (H.R.U.), Moonshot R&D (T.S., grant number JPMJMS2025), and ERATO (H.R.U., grant number JPMJER2001) from Japan Science and Technology Agency (JST).
Funding Information:
The authors (K.M., S.E., and H.R.U.) declare the following competing interests. K.M. and S.E. were partly supported by Eisai, Co., Ltd. H.R.U. is a co-inventor on patent applications covering the CUBIC reagents (PCT/JP2014/070618 (pending), patent applicant: RIKEN, PCT/JP2017/016410 (pending), patent applicant: RIKEN) and CUBIC-HV reagents (PCT/JP2020/ 31840 (pending), patent applicant: CUBICStars) and a co-founder of CUBICStars. All other authors declare no competing interests. This work was partly done by technical support of Olympus Corporation.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/12
Y1 - 2022/12
N2 - The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.
AB - The blood and lymphatic vasculature networks are not yet fully understood even in mouse because of the inherent limitations of imaging systems and quantification methods. This study aims to evaluate the usefulness of the tissue-clearing technology for visualizing blood and lymphatic vessels in adult mouse. Clear, unobstructed brain/body imaging cocktails and computational analysis (CUBIC) enables us to capture the high-resolution 3D images of organ- or area-specific vascular structures. To evaluate these 3D structural images, signals are first classified from the original captured images by machine learning at pixel base. Then, these classified target signals are subjected to topological data analysis and non-homogeneous Poisson process model to extract geometric features. Consequently, the structural difference of vasculatures is successfully evaluated in mouse disease models. In conclusion, this study demonstrates the utility of CUBIC for analysis of vascular structures and presents its feasibility as an analysis modality in combination with 3D images and mathematical frameworks.
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UR - http://www.scopus.com/inward/citedby.url?scp=85137698027&partnerID=8YFLogxK
U2 - 10.1038/s41467-022-32848-2
DO - 10.1038/s41467-022-32848-2
M3 - Article
C2 - 36097010
AN - SCOPUS:85137698027
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 5239
ER -