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3D Digital Pathology for a Chemical-Functional Analysis of Glomeruli in Health and Pathology

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    3D Digital Pathology for a Chemical-Functional Analysis of Glomeruli in Health and Pathology
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    • Hsiang-Hsin Chen
      Hsiang-Hsin Chen
      Academia Sinica, Institute of Physics, 128 Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan
      University of Bordeaux, Inserm U1029 LAMC, Allée Geoffroy Saint-Hillaire, Bat. B2, F33600 Pessac-Cedex, France
      More by Hsiang-Hsin Chen
    • Tsung-Tse Lee
      Tsung-Tse Lee
      Academia Sinica, Institute of Physics, 128 Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan
      More by Tsung-Tse Lee
    • Ann Chen
      Ann Chen
      Graduate Institute of Life Sciences, National Defense Medical Center, 161 Section 6, Minquan East Road, Neihu District, 114, Taipei City, Taiwan
      More by Ann Chen
    • Yeukuang Hwu
      Yeukuang Hwu
      Academia Sinica, Institute of Physics, 128 Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan
      More by Yeukuang Hwu
    • Cyril Petibois*
      Cyril Petibois
      Academia Sinica, Institute of Physics, 128 Sec. 2, Academia Road, Nankang, Taipei 11529, Taiwan
      University of Bordeaux, Inserm U1029 LAMC, Allée Geoffroy Saint-Hillaire, Bat. B2, F33600 Pessac-Cedex, France
      *E-mail: [email protected]
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      Orcidhttp://orcid.org/0000-0001-9027-4192
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    Analytical Chemistry

    Cite this: Anal. Chem. 2018, 90, 6, 3811–3818
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    https://doi.org/10.1021/acs.analchem.7b04265
    Published March 5, 2018
    Copyright © 2018 American Chemical Society
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    Abstract

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    Determining the filtration function and biochemical status of kidney at the single glomerulus level remains hardly accessible, even from biopsies. Here, we provide evidence that IR spectro-microscopy is a suitable method to account for the filtration capacity of individual glomeruli along with related physio-pathological condition. A ∼4 μm voxel resolution 3D IR image reconstruction is built from consecutive tissue sections, thus, providing a 3D IR spectrum matrix of an individual glomerulus. The filtration capacity of glomeruli was quantitatively determined after BaSO4 perfusion, and additional chemical data could be used to determined oxidative stress effects and fibrosis, thus, combining functional and biochemical information from the same 3D IR spectrum matrix. This analytical approach was applied on mice with unilateral ureteral obstruction (UUO) inducing chronic kidney disease. Compared to the healthy condition, UUO induced a significant drop in glomeruli filtration capacity (−17 ± 8% at day 4 and −48 ± 14% at day 14) and volume (36 ± 10% at day 4 and 67 ± 13% at day 14), along a significant increase of oxidative stress (+61 ± 19% at day 4 and +84 ± 17% at day 14) and a change in the lipid-to-protein ratio (−8.2 ± 3.6% at day 4 and −18.1 ± 5.9% at day 14). Therefore, IR spectro-microscopy might be developed as a new 3D pathology resource for analyzing functional and biochemical parameters of glomeruli.

    Copyright © 2018 American Chemical Society

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    Supporting Information

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    Videos of single glomeruli, 3D chemical images. Video-S1:3D absorption of BaSO4 for a normal glomerulus. Video-S2:3D absorption from fatty acyl chain unsaturations for a normal glomerulus. Video-S3: Merged 3D absorptions of BaSO4 and fatty acyl chain unsaturations for a normal glomerulus. Videos-4 to −6 are UUO counterparts. The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.analchem.7b04265.

    • Figure S1: Mean IR spectra of glomeruli at different time points of CKD development compared to the healthy condition (marked “normal”). The spectra have been offset on absorbance axis for readability. The main BaSO4 absorptions are indicated and did not affect the proteins and lipids absorptions chosen for chemical mapping (PDF).

    • Video S1: 3D chemical imaging of a healthy kidney glomerulus perfusion using the BaSO4 IR absorption (1160–1220 cm–1) (MPG).

    • Video S2: 3D chemical imaging of a healthy kidney glomerulus fatty acyl chain unsaturation level using the −C=C<H to CH3 absorptions ratio (extracted from curve-fitting of the 3050–2800 cm–1 spectral interval (MPG).

    • Video S3: Merged 3D chemical images of a healthy glomerulus revealing its perfusion level and fatty acyl chain unsaturation (MPG).

    • Video S4: 3D chemical imaging of a UUO kidney glomerulus perfusion using the BaSO4 IR absorption (1160–1220 cm–1) (MPG).

    • Video S5: 3D chemical imaging of a UUO kidney glomerulus fatty acyl chain unsaturation level using the −C=C<H to CH3 absorptions ratio (extracted from curve-fitting of the 3050–2800 cm–1 spectral interval (MPG).

    • Video S6: Merged 3D chemical images of a UUO glomerulus revealing its perfusion level and fatty acyl chain unsaturation (MPG).

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    This article is cited by 7 publications.

    1. Anton P.J. Stampfl, Zhongdong Liu, Jun Hu, Kei Sawada, H. Takano, Yoshiki Kohmura, Tetsuya Ishikawa, Jae-Hong Lim, Jung-Ho Je, Chian-Ming Low, Alvin Teo, Eng Soon Tok, Tin Wee Tan, Kenneth Ban, Camilo Libedinsky, Francis Chee Kuan Tan, Kuan-Peng Chen, An-Cheng Yang, Chao-Chun Chuang, Nan-Yow Chen, Chi-Tin Shih, Ting-Kuo Lee, De-Nian Yang, Hsu-Chao Lai, Hong-Han Shuai, Chang-Chieh Cheng, Yu-Tai Ching, Chia-Wei Li, Ching-Che Charng, Chung-Chuan Lo, Ann-Shyn Chiang, Benoit Recur, Cyril Petibois, Chia-Liang Cheng, Hsiang-Hsin Chen, Shun-Min Yang, Yeukuang Hwu, Catleya Rojviriya, Supagorn Rugmai, Saroj Rujirawat, Giorgio Margaritondo. SYNAPSE: An international roadmap to large brain imaging. Physics Reports 2023, 999 , 1-60. https://doi.org/10.1016/j.physrep.2022.11.003
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    7. Peter Lasch, Isao Noda. Two-Dimensional Correlation Spectroscopy (2D-COS) for Analysis of Spatially Resolved Vibrational Spectra. Applied Spectroscopy 2019, 73 (4) , 359-379. https://doi.org/10.1177/0003702818819880
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    Analytical Chemistry

    Cite this: Anal. Chem. 2018, 90, 6, 3811–3818
    Click to copy citationCitation copied!
    https://doi.org/10.1021/acs.analchem.7b04265
    Published March 5, 2018
    Copyright © 2018 American Chemical Society
    Request reuse permissions

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