CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain

Lin Yuan Zhang, Pan Lin, Jiaji Pan, Yuanyuan Ma, Zhenyu Wei, Lu Jiang, Liping Wang, Yaying Song, Yongting Wang, Zhijun Zhang, Kunlin Jin, Qian Wang, Guo Yuan Yang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.

Original languageEnglish
Pages (from-to)262-272
Number of pages11
JournalAging and Disease
Volume9
Issue number2
DOIs
StatePublished - 1 Apr 2018

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Blood Vessels
Brain
Three-Dimensional Imaging
Middle Cerebral Artery Infarction
Normal Distribution
Microvessels
Inbred C57BL Mouse
Brain Injuries
Transgenic Mice
Software

Keywords

  • Brain
  • Clarity
  • Imaging process
  • Mouse
  • Vasculature

Cite this

Zhang, L. Y., Lin, P., Pan, J., Ma, Y., Wei, Z., Jiang, L., ... Yang, G. Y. (2018). CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain. Aging and Disease, 9(2), 262-272. https://doi.org/10.14336/AD.2017.0613
Zhang, Lin Yuan ; Lin, Pan ; Pan, Jiaji ; Ma, Yuanyuan ; Wei, Zhenyu ; Jiang, Lu ; Wang, Liping ; Song, Yaying ; Wang, Yongting ; Zhang, Zhijun ; Jin, Kunlin ; Wang, Qian ; Yang, Guo Yuan. / CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain. In: Aging and Disease. 2018 ; Vol. 9, No. 2. pp. 262-272.
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abstract = "Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.",
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Zhang, LY, Lin, P, Pan, J, Ma, Y, Wei, Z, Jiang, L, Wang, L, Song, Y, Wang, Y, Zhang, Z, Jin, K, Wang, Q & Yang, GY 2018, 'CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain', Aging and Disease, vol. 9, no. 2, pp. 262-272. https://doi.org/10.14336/AD.2017.0613

CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain. / Zhang, Lin Yuan; Lin, Pan; Pan, Jiaji; Ma, Yuanyuan; Wei, Zhenyu; Jiang, Lu; Wang, Liping; Song, Yaying; Wang, Yongting; Zhang, Zhijun; Jin, Kunlin; Wang, Qian; Yang, Guo Yuan.

In: Aging and Disease, Vol. 9, No. 2, 01.04.2018, p. 262-272.

Research output: Contribution to journalArticle

TY - JOUR

T1 - CLARITY for high-resolution imaging and quantification of vasculature in the whole mouse brain

AU - Zhang, Lin Yuan

AU - Lin, Pan

AU - Pan, Jiaji

AU - Ma, Yuanyuan

AU - Wei, Zhenyu

AU - Jiang, Lu

AU - Wang, Liping

AU - Song, Yaying

AU - Wang, Yongting

AU - Zhang, Zhijun

AU - Jin, Kunlin

AU - Wang, Qian

AU - Yang, Guo Yuan

PY - 2018/4/1

Y1 - 2018/4/1

N2 - Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.

AB - Elucidating the normal structure and distribution of cerebral vascular system is fundamental for understanding its function. However, studies on visualization and whole-brain quantification of vasculature with cellular resolution are limited. Here, we explored the structure of vasculature at the whole-brain level using the newly developed CLARITY technique. Adult male C57BL/6J mice undergoing transient middle cerebral artery occlusion and Tie2-RFP transgenic mice were used. Whole mouse brains were extracted for CLARITY processing. Immunostaining was performed to label vessels. Customized MATLAB code was used for image processing and quantification. Three-dimensional images were visualized using the Vaa3D software. Our results showed that whole mouse brain became transparent using the CLARITY method. Three-dimensional imaging and visualization of vasculature were achieved at the whole-brain level with a 1-μm voxel resolution. The quantitative results showed that the fractional vascular volume was 0.018 ± 0.004 mm3 per mm3, the normalized vascular length was 0.44 ± 0.04 m per mm3, and the mean diameter of the microvessels was 4.25 ± 0.08 μm. Furthermore, a decrease in the fractional vascular volume and a decrease in the normalized vascular length were found in the penumbra of ischemic mice compared to controls (p < 0.05). In conclusion, CLARITY provides a novel approach for mapping vasculature in the whole mouse brain at cellular resolution. CLARITY-optimized algorithms facilitate the assessment of structural change in vasculature after brain injury.

KW - Brain

KW - Clarity

KW - Imaging process

KW - Mouse

KW - Vasculature

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