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Erschienen in: Brain Tumor Pathology 1/2023

12.11.2022 | Original Article

Three-dimensional visualization of human brain tumors using the CUBIC technique

verfasst von: Yangyang Xu, Qi He, Mengqi Wang, Yang Wu, Yifeng Shi, Wei Wang, Jie Zhang

Erschienen in: Brain Tumor Pathology | Ausgabe 1/2023

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Abstract

Application of tissue clearing techniques on human brain tumors is still limited. This study was to investigate the application of CUBIC on 3D pathological studies of human brain tumors. Brain tumor specimens derived from 21 patients were cleared with CUBIC. Immunostaining was conducted on cleared specimens to label astrocytes, microglia and microvessels, respectively. All tumor specimens achieved transparency after clearing. Immunostaining and CUBIC are well compatible in a variety of human brain tumors. Spatial morphologies of microvessels, astrocytes and microglia of tumors were clearly visualized in 3D, and their 3D morphological parameters were easily quantified. By comparing the quantitative morphological parameters of microvessels among brain tumors of different malignancy, we found that mean vascular diameter was positively correlated with tumor malignancy. Our study demonstrates that CUBIC can be successfully applied to 3D pathological studies of various human brain tumors, and 3D studies of human brain tumors hold great promise in helping us better understand brain tumor pathology in the future.
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Literatur
1.
Zurück zum Zitat Louis DN, Perry A, Reifenberger G et al (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRef Louis DN, Perry A, Reifenberger G et al (2016) The 2016 world health organization classification of tumors of the central nervous system: a summary. Acta Neuropathol 131:803–820CrossRef
2.
Zurück zum Zitat Sun L, Wang D, Zubovits JT et al (2009) An improved processing method for breast whole-mount serial sections for three-dimensional histopathology imaging. Am J Clin Pathol 131:383–392CrossRef Sun L, Wang D, Zubovits JT et al (2009) An improved processing method for breast whole-mount serial sections for three-dimensional histopathology imaging. Am J Clin Pathol 131:383–392CrossRef
3.
Zurück zum Zitat Booth ME, Treanor D, Roberts N et al (2015) Three-dimensional reconstruction of ductal carcinoma in situ with virtual slides. Histopathology 66:966–973CrossRef Booth ME, Treanor D, Roberts N et al (2015) Three-dimensional reconstruction of ductal carcinoma in situ with virtual slides. Histopathology 66:966–973CrossRef
4.
Zurück zum Zitat Richardson DS, Lichtman JW (2015) Clarifying Tissue Clearing. Cell 162:246–257CrossRef Richardson DS, Lichtman JW (2015) Clarifying Tissue Clearing. Cell 162:246–257CrossRef
5.
Zurück zum Zitat Ueda HR, Erturk A, Chung K et al (2020) Tissue clearing and its applications in neuroscience. Nat Rev Neurosci 21:61–79CrossRef Ueda HR, Erturk A, Chung K et al (2020) Tissue clearing and its applications in neuroscience. Nat Rev Neurosci 21:61–79CrossRef
6.
Zurück zum Zitat Erturk A, Becker K, Jahrling N et al (2012) Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc 7:1983–1995CrossRef Erturk A, Becker K, Jahrling N et al (2012) Three-dimensional imaging of solvent-cleared organs using 3DISCO. Nat Protoc 7:1983–1995CrossRef
7.
Zurück zum Zitat Susaki EA, Tainaka K, Perrin D et al (2015) Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Nat Protoc 10:1709–1727CrossRef Susaki EA, Tainaka K, Perrin D et al (2015) Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Nat Protoc 10:1709–1727CrossRef
8.
Zurück zum Zitat Chung K, Wallace J, Kim SY et al (2013) Structural and molecular interrogation of intact biological systems. Nature 497:332–337CrossRef Chung K, Wallace J, Kim SY et al (2013) Structural and molecular interrogation of intact biological systems. Nature 497:332–337CrossRef
9.
Zurück zum Zitat Wan P, Zhu J, Xu J et al (2018) Evaluation of seven optical clearing methods in mouse brain. Neurophotonics 5:035007CrossRef Wan P, Zhu J, Xu J et al (2018) Evaluation of seven optical clearing methods in mouse brain. Neurophotonics 5:035007CrossRef
10.
Zurück zum Zitat Lloyd-Lewis B, Davis FM, Harris OB et al (2016) Imaging the mammary gland and mammary tumours in 3D: optical tissue clearing and immunofluorescence methods. Breast Cancer Res 18:127CrossRef Lloyd-Lewis B, Davis FM, Harris OB et al (2016) Imaging the mammary gland and mammary tumours in 3D: optical tissue clearing and immunofluorescence methods. Breast Cancer Res 18:127CrossRef
11.
Zurück zum Zitat Tainaka K, Kubota SI, Suyama TQ et al (2014) Whole-body imaging with single-cell resolution by tissue decolorization. Cell 159:911–924CrossRef Tainaka K, Kubota SI, Suyama TQ et al (2014) Whole-body imaging with single-cell resolution by tissue decolorization. Cell 159:911–924CrossRef
12.
Zurück zum Zitat Xu Y, Li P, Wang M et al (2019) Imaging the brain in 3D using a combination of CUBIC and immunofluorescence staining. Biomed Opt Express 10:2141–2149CrossRef Xu Y, Li P, Wang M et al (2019) Imaging the brain in 3D using a combination of CUBIC and immunofluorescence staining. Biomed Opt Express 10:2141–2149CrossRef
13.
Zurück zum Zitat Liang H, Wang H, Wang S et al (2018) 3D imaging of PSD-95 in the mouse brain using the advanced CUBIC method. Mol Brain 11:50CrossRef Liang H, Wang H, Wang S et al (2018) 3D imaging of PSD-95 in the mouse brain using the advanced CUBIC method. Mol Brain 11:50CrossRef
14.
Zurück zum Zitat Louis D, Perry A, Wesseling P et al (2021) The 2021 who classification of tumors of the central nervous system: a summary. Neuro Oncol 23:1231–1251CrossRef Louis D, Perry A, Wesseling P et al (2021) The 2021 who classification of tumors of the central nervous system: a summary. Neuro Oncol 23:1231–1251CrossRef
15.
Zurück zum Zitat Boulagnon-Rombi C, Fleury C, Fichel C et al (2017) Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics. J Neuropathol Exp Neurol 76:289–298CrossRef Boulagnon-Rombi C, Fleury C, Fichel C et al (2017) Immunohistochemical Approach to the Differential Diagnosis of Meningiomas and Their Mimics. J Neuropathol Exp Neurol 76:289–298CrossRef
16.
Zurück zum Zitat Deb P, Boruah D, Dutta V (2012) Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade. Microvasc Res 84:34–43CrossRef Deb P, Boruah D, Dutta V (2012) Morphometric study of microvessels in primary CNS tumors and its correlation with tumor types and grade. Microvasc Res 84:34–43CrossRef
17.
Zurück zum Zitat Karperien A, Ahammer H, Jelinek HF (2013) Quantitating the subtleties of microglial morphology with fractal analysis. Front Cell Neurosci 7:3CrossRef Karperien A, Ahammer H, Jelinek HF (2013) Quantitating the subtleties of microglial morphology with fractal analysis. Front Cell Neurosci 7:3CrossRef
18.
Zurück zum Zitat Baslan T, Hicks J (2017) Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat Rev Cancer 17:557–569CrossRef Baslan T, Hicks J (2017) Unravelling biology and shifting paradigms in cancer with single-cell sequencing. Nat Rev Cancer 17:557–569CrossRef
19.
Zurück zum Zitat P B, M P, I F et al. (2003) Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: evidence for distinct angiogenic subtypes. Brain pathology (Zurich, Switzerland) 13: 133–143 P B, M P, I F et al. (2003) Vascular patterns in glioblastoma influence clinical outcome and associate with variable expression of angiogenic proteins: evidence for distinct angiogenic subtypes. Brain pathology (Zurich, Switzerland) 13: 133–143
20.
Zurück zum Zitat Komori T (2022) Grading of adult diffuse gliomas according to the 2021 WHO classification of tumors of the central nervous system. Lab Invest 102:126–133CrossRef Komori T (2022) Grading of adult diffuse gliomas according to the 2021 WHO classification of tumors of the central nervous system. Lab Invest 102:126–133CrossRef
21.
Zurück zum Zitat Gomez-Gaviro MV, Sanderson D, Ripoll J, Desco M. (2020) Biomedical applications of tissue clearing and three-dimensional imaging in health and disease. iScience; 23: 101432. Gomez-Gaviro MV, Sanderson D, Ripoll J, Desco M. (2020) Biomedical applications of tissue clearing and three-dimensional imaging in health and disease. iScience; 23: 101432.
22.
Zurück zum Zitat Almagro J, Messal HA, Zaw Thin M et al (2021) Tissue clearing to examine tumour complexity in three dimensions. Nature Rev Cancer 21:718–730CrossRef Almagro J, Messal HA, Zaw Thin M et al (2021) Tissue clearing to examine tumour complexity in three dimensions. Nature Rev Cancer 21:718–730CrossRef
23.
Zurück zum Zitat Tian T, Yang Z, Li X (2020) Tissue clearing technique: recent progress and biomedical applications. J Anat 238:489–507CrossRef Tian T, Yang Z, Li X (2020) Tissue clearing technique: recent progress and biomedical applications. J Anat 238:489–507CrossRef
24.
Zurück zum Zitat Ando K, Laborde Q, Lazar A et al (2014) Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D. Acta Neuropathol 128:457–459CrossRef Ando K, Laborde Q, Lazar A et al (2014) Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D. Acta Neuropathol 128:457–459CrossRef
25.
Zurück zum Zitat Liu AK, Hurry ME, Ng OT et al (2016) Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions. Neuropathol Appl Neurobiol 42:573–587CrossRef Liu AK, Hurry ME, Ng OT et al (2016) Bringing CLARITY to the human brain: visualization of Lewy pathology in three dimensions. Neuropathol Appl Neurobiol 42:573–587CrossRef
26.
Zurück zum Zitat Lagerweij T, Dusoswa SA, Negrean A et al (2017) Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment. Angiogenesis 20:533–546CrossRef Lagerweij T, Dusoswa SA, Negrean A et al (2017) Optical clearing and fluorescence deep-tissue imaging for 3D quantitative analysis of the brain tumor microenvironment. Angiogenesis 20:533–546CrossRef
27.
Zurück zum Zitat Zhu X, Huang L, Zheng Y et al (2019) Ultrafast optical clearing method for three-dimensional imaging with cellular resolution. Proc Nati Acad Sci US Am 116:11480–11489CrossRef Zhu X, Huang L, Zheng Y et al (2019) Ultrafast optical clearing method for three-dimensional imaging with cellular resolution. Proc Nati Acad Sci US Am 116:11480–11489CrossRef
28.
Zurück zum Zitat Susaki EA, Shimizu C, Kuno A et al (2020) Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues. Nat Commun 11:1982CrossRef Susaki EA, Shimizu C, Kuno A et al (2020) Versatile whole-organ/body staining and imaging based on electrolyte-gel properties of biological tissues. Nat Commun 11:1982CrossRef
29.
Zurück zum Zitat Jing D, Zhang S, Luo W et al (2018) Tissue clearing of both hard and soft tissue organs with the PEGASOS method. Cell Res 28:803–818CrossRef Jing D, Zhang S, Luo W et al (2018) Tissue clearing of both hard and soft tissue organs with the PEGASOS method. Cell Res 28:803–818CrossRef
30.
Zurück zum Zitat Pan C, Cai R, Quacquarelli FP et al (2016) Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Nat Methods 13:859–867CrossRef Pan C, Cai R, Quacquarelli FP et al (2016) Shrinkage-mediated imaging of entire organs and organisms using uDISCO. Nat Methods 13:859–867CrossRef
31.
Zurück zum Zitat Gleave JA, Lerch JP, Henkelman RM, Nieman BJ (2013) A method for 3D immunostaining and optical imaging of the mouse brain demonstrated in neural progenitor cells. PLoS ONE 8:e72039CrossRef Gleave JA, Lerch JP, Henkelman RM, Nieman BJ (2013) A method for 3D immunostaining and optical imaging of the mouse brain demonstrated in neural progenitor cells. PLoS ONE 8:e72039CrossRef
32.
Zurück zum Zitat Li J, Czajkowsky DM, Li X, Shao Z (2015) Fast immuno-labeling by electrophoretically driven infiltration for intact tissue imaging. Sci Rep 5:10640CrossRef Li J, Czajkowsky DM, Li X, Shao Z (2015) Fast immuno-labeling by electrophoretically driven infiltration for intact tissue imaging. Sci Rep 5:10640CrossRef
33.
Zurück zum Zitat Ku T, Guan W, Evans NB et al (2020) Elasticizing tissues for reversible shape transformation and accelerated molecular labeling. Nat Methods 17:609–613CrossRef Ku T, Guan W, Evans NB et al (2020) Elasticizing tissues for reversible shape transformation and accelerated molecular labeling. Nat Methods 17:609–613CrossRef
34.
Zurück zum Zitat Boruah D, Deb P, Srinivas V, Mani NS (2014) Morphometric study of nuclei and microvessels in gliomas and its correlation with grades. Microvasc Res 93:52–61CrossRef Boruah D, Deb P, Srinivas V, Mani NS (2014) Morphometric study of nuclei and microvessels in gliomas and its correlation with grades. Microvasc Res 93:52–61CrossRef
35.
Zurück zum Zitat Fortin D, Cairncross G, Hammond RJN (1999) Oligodendroglioma: an appraisal of recent data pertaining to diagnosis and treatment. Neurosurgery 45:1279–1291CrossRef Fortin D, Cairncross G, Hammond RJN (1999) Oligodendroglioma: an appraisal of recent data pertaining to diagnosis and treatment. Neurosurgery 45:1279–1291CrossRef
36.
Zurück zum Zitat Andersen B, Faust Akl C, Wheeler M et al (2021) Glial and myeloid heterogeneity in the brain tumour microenvironment. Nat Rev Cancer 21:786–802CrossRef Andersen B, Faust Akl C, Wheeler M et al (2021) Glial and myeloid heterogeneity in the brain tumour microenvironment. Nat Rev Cancer 21:786–802CrossRef
37.
Zurück zum Zitat Guo H, Kang H, Tong H et al (2019) Microvascular characteristics of lower-grade diffuse gliomas: investigating vessel size imaging for differentiating grades and subtypes. Eur Radiol 29:1893–1902CrossRef Guo H, Kang H, Tong H et al (2019) Microvascular characteristics of lower-grade diffuse gliomas: investigating vessel size imaging for differentiating grades and subtypes. Eur Radiol 29:1893–1902CrossRef
Metadaten
Titel
Three-dimensional visualization of human brain tumors using the CUBIC technique
verfasst von
Yangyang Xu
Qi He
Mengqi Wang
Yang Wu
Yifeng Shi
Wei Wang
Jie Zhang
Publikationsdatum
12.11.2022
Verlag
Springer Nature Singapore
Erschienen in
Brain Tumor Pathology / Ausgabe 1/2023
Print ISSN: 1433-7398
Elektronische ISSN: 1861-387X
DOI
https://doi.org/10.1007/s10014-022-00445-2

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