Label-free automated three-dimensional imaging of whole organs by microtomy-assisted photoacoustic microscopy
Abstract
Three-dimensional (3D) optical imaging of whole biological organs with microscopic resolution has remained a challenge. Most versions of such imaging techniques require special preparation of the tissue specimen. Here we demonstrate microtomy-assisted photoacoustic microscopy (mPAM) of mouse brains and other organs, which automatically acquires serial distortion-free and registration-free images with endogenous absorption contrasts. Without tissue staining or clearing, mPAM generates micrometer-resolution 3D images of paraffin- or agarose-embedded whole organs with high fidelity, achieved by label-free simultaneous sensing of DNA/RNA, hemoglobins, and lipids. mPAM provides histology-like imaging of cell nuclei, blood vessels, axons, and other anatomical structures, enabling the application of histopathological interpretation at the organelle level to analyze a whole organ. Its deep tissue imaging capability leads to less sectioning, resulting in negligible sectioning artifact. mPAM offers a new way to better understand complex biological organs.
Additional Information
© 2017 The Authors. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. Received: 03 April 2017; Accepted: 05 October 2017; Published online: 09 November 2017. The authors appreciate Prof. James Ballard's close reading of the manuscript and Yang Li's preparation of the system schematic. This work was sponsored in part by National Institutes of Health grants DP1 EB016986 (NIH Director's Pioneer Award) and R01 CA186567 (NIH Director's Transformative Research Award). Part of the work was performed at the Alafi Neuroimaging Laboratory, the Hope Center for Neurological Disorders, which is supported by the NIH Neuroscience Blueprint Center Core Grant P30 NS057105. Author Contributions: T.T.W.W., R.Z., C.Z. and L.V.W. conceived of the study. T.T.W.W., R.Z., C.Z. and K.I.M. designed the imaging system. T.T.W.W., R.Z. and C.Z. built the imaging system. L.W. and J.S. wrote the operating software. R.C., K.K.S. and Q.Z. fabricated the ultrasonic transducer. T.T.W.W., R.Z. and C.Z. performed the imaging experiments. T.T.W.W. and R.Z. analyzed the data. T.T.W.W., R.Z., C.Z. and H.-C.H. processed the data. T.T.W.W. and L.V.W. wrote the manuscript. L.V.W. supervised the whole study. Competing interests: L.V.W. has a financial interest in MicroPhotoAcoustics, CalPACT, LLC, and Union Photoacoustic Technologies, which, however, did not support this work. K.I.M. has a financial interest in MicroPhotoAcoustics. The remaining authors declare no competing financial interests.Attached Files
Published - s41467-017-01649-3.pdf
Supplemental Material - 41467_2017_1649_MOESM1_ESM.pdf
Supplemental Material - 41467_2017_1649_MOESM2_ESM.pdf
Supplemental Material - 41467_2017_1649_MOESM3_ESM.pdf
Supplemental Material - 41467_2017_1649_MOESM4_ESM.mp4
Supplemental Material - 41467_2017_1649_MOESM5_ESM.mp4
Supplemental Material - 41467_2017_1649_MOESM6_ESM.mp4
Supplemental Material - 41467_2017_1649_MOESM7_ESM.mp4
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Additional details
- PMCID
- PMC5680318
- Eprint ID
- 83140
- Resolver ID
- CaltechAUTHORS:20171113-084411285
- DP1 EB016986
- NIH
- R01 CA186567
- NIH
- P30 NS057105
- NIH
- Created
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2017-11-14Created from EPrint's datestamp field
- Updated
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2022-03-21Created from EPrint's last_modified field