Abstract

The ability to acquire 3D images of the heart and its vasculature at cellular resolution facilitates a more detailed study of many heart diseases. Here, we describe a novel technique to image in 3D the heart vasculature by combining the CUBIC clearing protocol combined with in vivo administration of fluorescent-labeled lectin. The use of these techniques in combination with Selective Plane Illumination Microscopy (SPIM) made it possible to obtain high resolution 3D images of the cardiac vascular tree. This methodological approach may enhance the visualization of 3D images of the cardiac vasculature remodeling associated with coronary disease.

© 2017 Optical Society of America

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References

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    [Crossref] [PubMed]
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    [Crossref] [PubMed]

2016 (5)

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

A. Feuchtinger, A. Walch, and M. Dobosz, “Deep tissue imaging: a review from a preclinical cancer research perspective,” Histochem. Cell Biol. 146(6), 781–806 (2016).
[Crossref] [PubMed]

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

2015 (4)

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

D. S. Richardson and J. W. Lichtman, “Clarifying tissue clearing,” Cell 162(2), 246–257 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

2014 (3)

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

A. J. Moy, P. C. Lo, and B. Choi, “High-resolution visualization of mouse cardiac microvasculature using optical histology,” Biomed. Opt. Express 5(1), 69–77 (2014).
[Crossref] [PubMed]

2012 (4)

J. B. Strait and E. G. Lakatta, “Aging-associated cardiovascular changes and their relationship to heart failure,” Heart Fail. Clin. 8(1), 143–164 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

2010 (1)

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

2009 (1)

N. Jährling, K. Becker, and H. U. Dodt, “3D-reconstruction of blood vessels by ultramicroscopy,” Organogenesis 5(4), 227–230 (2009).
[Crossref] [PubMed]

2007 (1)

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

2006 (1)

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

2005 (1)

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Abe, T.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Amores-Arriaga, B.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Arganda-Carreras, I.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Arranz, A.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Avants, B. B.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Aylward, S.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Bachoo, R. M.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Balaban, E.

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Bauer, C.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Becker, K.

N. Jährling, K. Becker, and H. U. Dodt, “3D-reconstruction of blood vessels by ultramicroscopy,” Organogenesis 5(4), 227–230 (2009).
[Crossref] [PubMed]

Beichel, R.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Bocancea, D.

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Buatti, J.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Capek, M.

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

Caplice, N. M.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Cardona, A.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Chade, A. R.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Choi, B.

Choi, K. H.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Cook, P. A.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Dallabrida, S. M.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Deloid, G. M.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Depinho, R. A.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Desco, M.

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Dickie, R.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Dobosz, M.

A. Feuchtinger, A. Walch, and M. Dobosz, “Deep tissue imaging: a review from a preclinical cancer research perspective,” Histochem. Cell Biol. 146(6), 781–806 (2016).
[Crossref] [PubMed]

Dodt, H. U.

N. Jährling, K. Becker, and H. U. Dodt, “3D-reconstruction of blood vessels by ultramicroscopy,” Organogenesis 5(4), 227–230 (2009).
[Crossref] [PubMed]

Dong, D.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Egan, A.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Eguchi, M.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Eliceiri, K.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Engelhardt, J.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Fedorov, A.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Fennessy, F.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Feuchtinger, A.

A. Feuchtinger, A. Walch, and M. Dobosz, “Deep tissue imaging: a review from a preclinical cancer research perspective,” Histochem. Cell Biol. 146(6), 781–806 (2016).
[Crossref] [PubMed]

Fillion-Robin, J. C.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Fillion-Robin, J.-C.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Finet, J.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Fried, G.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Frise, E.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Gee, J. C.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Giese, G.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Gómez-Gaviro, M. V.

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Greger, K.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Hartenstein, V.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Ivins, S.

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

Jährling, N.

N. Jährling, K. Becker, and H. U. Dodt, “3D-reconstruction of blood vessels by ultramicroscopy,” Organogenesis 5(4), 227–230 (2009).
[Crossref] [PubMed]

Janácek, J.

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

Jennings, D.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Kalpathy-Cramer, J.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Kaynig, V.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Kikinis, R.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Kishino, F.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Kiyonari, H.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Kolesová, H.

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

Kubota, S. I.

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

Kuno, A.

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

Lai, J.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Lakatta, E. G.

J. B. Strait and E. G. Lakatta, “Aging-associated cardiovascular changes and their relationship to heart failure,” Heart Fail. Clin. 8(1), 143–164 (2012).
[Crossref] [PubMed]

Lerman, A.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Lerman, L. O.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Lichtman, J. W.

D. S. Richardson and J. W. Lichtman, “Clarifying tissue clearing,” Cell 162(2), 246–257 (2015).
[Crossref] [PubMed]

Lin, B.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Lo, P. C.

Longair, M.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Lorrio, M. T.

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Lu, X.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Marcello, M.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Miller, J. V.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Miyawaki, A.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Moy, A. J.

Murakami, T.

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

Nehrhoff, I.

Onoe, H.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Pampaloni, F.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Perrin, D.

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Pieper, S.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Pietzsch, T.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Pompeiano, M.

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Preibisch, S.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Pujol, S.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Radochová, B.

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

Richardson, D. S.

D. S. Richardson and J. W. Lichtman, “Clarifying tissue clearing,” Cell 162(2), 246–257 (2015).
[Crossref] [PubMed]

Ripoll, J.

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Ritman, E. L.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Roberts, C.

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

Rodriguez-Porcel, M.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Rogers, R. A.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Rueden, C.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Rupnick, M. A.

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Saalfeld, S.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Sadayappan, S.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Saif, M. T.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Scambler, P. J.

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

Scherbarth, A.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Schindelin, J.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Schmid, B.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Schwarz, M. K.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Sedmera, D.

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

Shen, C.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Shi, L.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Shimizu, Y.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Sivaguru, B. S.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Sivaguru, M.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Sivaguru, V. A.

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Sonka, M.

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Sprengel, R.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Stelzer, E. H. K.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Strait, J. B.

J. B. Strait and E. G. Lakatta, “Aging-associated cardiovascular changes and their relationship to heart failure,” Heart Fail. Clin. 8(1), 143–164 (2012).
[Crossref] [PubMed]

Susaki, E. A.

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Swoger, J.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Tainaka, K.

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Tawara, T.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Theer, P.

M. K. Schwarz, A. Scherbarth, R. Sprengel, J. Engelhardt, P. Theer, and G. Giese, “Fluorescent-protein stabilization and high-resolution imaging of cleared, intact mouse brains,” PLoS One 10(5), e0124650 (2015).
[Crossref] [PubMed]

Tian, J.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Tinevez, J.-Y.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Tomancak, P.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Tustison, N. J.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Ueda, H. R.

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Vaquero, J.

Vaquero, J. J.

I. Nehrhoff, D. Bocancea, J. Vaquero, J. J. Vaquero, J. Ripoll, M. Desco, and M. V. Gómez-Gaviro, “3D imaging in CUBIC-cleared mouse heart tissue: going deeper,” Biomed. Opt. Express 7(9), 3716–3720 (2016).
[Crossref] [PubMed]

M. V. Gómez-Gaviro, E. Balaban, D. Bocancea, M. T. Lorrio, M. Pompeiano, M. Desco, J. Ripoll, and J. J. Vaquero, “Optimized CUBIC protocol for 3D imaging of chicken embryos at single-cell resolution,” Developmentdev.145805 (2017).

Vernay, B.

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

Verveer, P. J.

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

Walch, A.

A. Feuchtinger, A. Walch, and M. Dobosz, “Deep tissue imaging: a review from a preclinical cancer research perspective,” Histochem. Cell Biol. 146(6), 781–806 (2016).
[Crossref] [PubMed]

Wang, J.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Watanabe, T. M.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

White, D. J.

J. Schindelin, I. Arganda-Carreras, E. Frise, V. Kaynig, M. Longair, T. Pietzsch, S. Preibisch, C. Rueden, S. Saalfeld, B. Schmid, J.-Y. Tinevez, D. J. White, V. Hartenstein, K. Eliceiri, P. Tomancak, and A. Cardona, “Fiji: an open-source platform for biological-image analysis,” Nat. Methods 9(7), 676–682 (2012).
[Crossref] [PubMed]

Yamaguchi, S.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Yang, Y.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Yokota, H.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Yokoyama, C.

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Yukinaga, H.

E. A. Susaki, K. Tainaka, D. Perrin, H. Yukinaga, A. Kuno, and H. R. Ueda, “Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging,” Nat. Protoc. 10(11), 1709–1727 (2015).
[Crossref] [PubMed]

Yushkevich, P. A.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Zheng, Y.

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

Zhu, S.

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

Zhu, X. Y.

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Am. J. Physiol. Heart Circ. Physiol. (1)

M. Rodriguez-Porcel, X. Y. Zhu, A. R. Chade, B. Amores-Arriaga, N. M. Caplice, E. L. Ritman, A. Lerman, and L. O. Lerman, “Functional and structural remodeling of the myocardial microvasculature in early experimental hypertension,” Am. J. Physiol. Heart Circ. Physiol. 290(3), 978–984 (2005).
[Crossref] [PubMed]

Annu. Rev. Cell Dev. Biol. (1)

K. Tainaka, A. Kuno, S. I. Kubota, T. Murakami, and H. R. Ueda, “Chemical principles in tissue clearing and staining protocols for whole-body cell profiling,” Annu. Rev. Cell Dev. Biol. 32(1), 713–741 (2016).
[Crossref] [PubMed]

Biomed. Opt. Express (2)

Biotechniques (1)

M. Sivaguru, G. Fried, B. S. Sivaguru, V. A. Sivaguru, X. Lu, K. H. Choi, M. T. Saif, B. Lin, and S. Sadayappan, “Cardiac muscle organization revealed in 3-D by imaging whole-mount mouse hearts using two-photon fluorescence and confocal microscopy,” Biotechniques 59(5), 295–308 (2015).
[Crossref] [PubMed]

Cell (2)

D. S. Richardson and J. W. Lichtman, “Clarifying tissue clearing,” Cell 162(2), 246–257 (2015).
[Crossref] [PubMed]

E. A. Susaki, K. Tainaka, D. Perrin, F. Kishino, T. Tawara, T. M. Watanabe, C. Yokoyama, H. Onoe, M. Eguchi, S. Yamaguchi, T. Abe, H. Kiyonari, Y. Shimizu, A. Miyawaki, H. Yokota, and H. R. Ueda, “Whole-brain imaging with single-cell resolution using chemical cocktails and computational analysis,” Cell 157(3), 726–739 (2014).
[Crossref] [PubMed]

Heart Fail. Clin. (1)

J. B. Strait and E. G. Lakatta, “Aging-associated cardiovascular changes and their relationship to heart failure,” Heart Fail. Clin. 8(1), 143–164 (2012).
[Crossref] [PubMed]

Histochem. Cell Biol. (2)

H. Kolesová, M. Čapek, B. Radochová, J. Janáček, and D. Sedmera, “Comparison of different tissue clearing methods and 3D imaging techniques for visualization of GFP-expressing mouse embryos and embryonic hearts,” Histochem. Cell Biol. 146(2), 141–152 (2016).
[Crossref] [PubMed]

A. Feuchtinger, A. Walch, and M. Dobosz, “Deep tissue imaging: a review from a preclinical cancer research perspective,” Histochem. Cell Biol. 146(6), 781–806 (2016).
[Crossref] [PubMed]

IEEE Trans. Med. Imaging (1)

N. J. Tustison, B. B. Avants, P. A. Cook, Y. Zheng, A. Egan, P. A. Yushkevich, and J. C. Gee, “N4ITK: improved N3 bias correction,” IEEE Trans. Med. Imaging 29(6), 1310–1320 (2010).
[Crossref] [PubMed]

J. Biomed. Opt. (1)

D. Dong, A. Arranz, S. Zhu, Y. Yang, L. Shi, J. Wang, C. Shen, J. Tian, and J. Ripoll, “Vertically scanned laser sheet microscopy,” J. Biomed. Opt. 19(10), 106001 (2014).
[Crossref] [PubMed]

J. Vis. Exp., (1)

S. Ivins, C. Roberts, B. Vernay, and P. J. Scambler, “Analysis of coronary vessels in cleared embryonic hearts,” J. Vis. Exp., 118, 54800 (2016).
[PubMed]

Magn. Reson. Imaging (2)

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J.-C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

A. Fedorov, R. Beichel, J. Kalpathy-Cramer, J. Finet, J. C. Fillion-Robin, S. Pujol, C. Bauer, D. Jennings, F. Fennessy, M. Sonka, J. Buatti, S. Aylward, J. V. Miller, S. Pieper, and R. Kikinis, “3D Slicer as an image computing platform for the Quantitative Imaging Network,” Magn. Reson. Imaging 30(9), 1323–1341 (2012).
[Crossref] [PubMed]

Microvasc. Res. (1)

R. Dickie, R. M. Bachoo, M. A. Rupnick, S. M. Dallabrida, G. M. Deloid, J. Lai, R. A. Depinho, and R. A. Rogers, “Three-dimensional visualization of microvessel architecture of whole-mount tissue by confocal microscopy,” Microvasc. Res. 72(1-2), 20–26 (2006).
[Crossref] [PubMed]

Nat. Methods (2)

P. J. Verveer, J. Swoger, F. Pampaloni, K. Greger, M. Marcello, and E. H. K. Stelzer, “High-resolution three-dimensional imaging of large specimens with light sheet-based microscopy,” Nat. Methods 4(4), 311–313 (2007).
[PubMed]

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Supplementary Material (3)

NameDescription
» Visualization 1: MP4 (8689 KB)      Visualization 1. 3D imaging of the vasculature obtained with SPIM following anti-CD31 labelling
» Visualization 2: MP4 (5656 KB)      Visualization 2. 3D imaging of the vasculature obtained with SPIM following perfusion with FITC-labelled lectin
» Visualization 3: MP4 (5569 KB)      Visualization 2. 3D imaging of the vasculature obtained with SPIM following perfusion with 647-labelled lectin

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Figures (4)

Fig. 1
Fig. 1

CUBIC- and BABB-clearing in cardiac mouse tissue. A, Adapted CUBIC-clearing protocol for lectin-perfusion and clearing in mouse hearts. B, Stepwise enhancement of the sample transparency following the CUBIC-clearing protocol. C, Box-plot of the transparency measurement at different time points of the clearing protocol and at the end of BABB-clearing. D, Transparency measurement with Beer-Lambert law. I0, initial light intensity; I, light intensity after traversing the uncleared/cleared tissue; L, tissue thickness; µ, absorption coefficient. E, F, Weight (E) and volume (F) measurements of the mouse hearts before, during and after the CUBIC- and BABB-clearing protocol. d, days in R1. n = 3. *p<0.05, **p<0.005, ***<0.0005, unpaired t-test vs control samples.

Fig. 2
Fig. 2

CUBIC- and BABB-clearing in cardiac tissue at cellular- and subcellular level. A, Hematoxylin and eosin staining (H&E) of uncleared heart tissue in 20x and 40x magnification (upper row), CUBIC-cleared tissue (middle) and BABB-cleared tissue (bottom). B, Electron microscopy images of uncleared, CUBIC- and BABB-cleared cardiac tissue. Scale bars, 10 µm (left), 3 µm (middle) and 500 nm (right). Green and orange arrows indicate contrast loss; red arrows indicate, formation of cavities.

Fig. 3
Fig. 3

Illumination correction of SPIM images. A, Schematic representing the multiplication of the original image. The intensity loss in y (left) with the correction factor matrix (middle) leads to the illumination-corrected image (right). B, Intensity profiles along the yellow lines shown in the images in A. Blue, Intensity profile along the yellow line of the original SPIM image where the intensity loss along the light path can be observed. Red, Intensity profile of the N4-algorithm corrected image. Green, Intensity profile of the image that was corrected using the described algorithm implemented in Matlab. All images show the 405 nm laser excitation channel (DAPI), in which the highest Rayleigh scattering is present.

Fig. 4
Fig. 4

3D imaging of the vasculature obtained with SPIM. A, Maximum intensity projection of an anti-CD31 labeled mouse heart apex. SPIM-excitation laser, 635nm; emission filter, 670 nm. B, 3D-visualization the same data shown in A. C.1, Single SPIM image of a FITC-lectin labeled mouse heart. The low contrast between background (BG) and labeled vasculature makes it difficult to distinguish between them. Autofluorecence and stripes artifact harm the image quality. C.2, SPIM-image of a lectin-647 labeled mouse heart. The BG is minimized significantly by the absence of autofluorecence in the far-red channel. The stripes artifact almost entirely disappear. D, Single image of a SPIM image stack in which the macro- and micro-vasculature were both labeled with FITC-lectin (white). E, 3D volume rendering of the stained vasculature, stack size: 1945x1214x380 mm, visualized with VolView3 software (Bangham laboratory). F, Zoom of the indicated zone in E. All scale bars in all images, 100µm.

Equations (2)

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I=  I 0 e μ L
c f ( Δx ) = 1 e ( μ x Δx )

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