Integrated platform for multiscale molecular imaging and phenotyping of the human brain-Reference-Cited by-同舟云学术

Integrated platform for multiscale molecular imaging and phenotyping of the human brain

Published:2024-06-14 Issue:6701 Volume:384 Page:
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Park Juhyuk¹²³⁴^ORCID,Wang Ji¹³,Guan Webster²^ORCID,Gjesteby Lars A.⁵^ORCID,Pollack Dylan⁵,Kamentsky Lee¹³^ORCID,Evans Nicholas B.¹³,Stirman Jeff⁶,Gu Xinyi⁷,Zhao Chuanxi³^ORCID,Marx Slayton³^ORCID,Kim Minyoung E.⁸^ORCID,Choi Seo Woo²^ORCID,Snyder Michael⁵,Chavez David⁵,Su-Arcaro Clover³^ORCID,Tian Yuxuan²^ORCID,Park Chang Sin⁹¹⁰^ORCID,Zhang Qiangge¹¹^ORCID,Yun Dae Hee⁸^ORCID,Moukheiber Mira³^ORCID,Feng Guoping⁸¹¹,Yang X. William⁹¹⁰^ORCID,Keene C. Dirk¹²^ORCID,Hof Patrick R.¹³^ORCID,Ghosh Satrajit S.⁸¹¹¹⁴^ORCID,Frosch Matthew P.¹⁵^ORCID,Brattain Laura J.⁵,Chung Kwanghun¹²³⁸^ORCID

Affiliation:

1. Institute for Medical Engineering and Science, Massachusetts Institute of Technology (MIT), Cambridge, MA 02139, USA.

2. Department of Chemical Engineering, MIT, Cambridge, MA 02139, USA.

3. Picower Institute for Learning and Memory, MIT, Cambridge, MA 02139, USA.

4. Center for Nanomedicine, Institute for Basic Science, Seoul 03722, Republic of Korea.

5. MIT Lincoln Laboratory, Lexington, MA 02421, USA.

6. LifeCanvas Technologies, Cambridge, MA 02141, USA.

7. Department of Electrical Engineering and Computer Science, MIT, Cambridge, MA 02139, USA.

8. Department of Brain and Cognitive Sciences, MIT, Cambridge, MA 02139, USA.

9. Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.

10. Center for Neurobehavioral Genetics, Jane and Terry Semel Institute for Neuroscience, University of California, Los Angeles, CA 90024, USA.

11. McGovern Institute for Brain Research, MIT, Cambridge, MA 02139, USA.

12. Department of Laboratory Medicine and Pathology, University of Washington School of Medicine, Seattle, WA 98115, USA.

13. Nash Family Department of Neuroscience, Center for Discovery and Innovation, and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10019, USA.

14. Department of Otolaryngology, Harvard Medical School, Boston, MA 02114, USA.

15. C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.

Abstract

Understanding cellular architectures and their connectivity is essential for interrogating system function and dysfunction. However, we lack technologies for mapping the multiscale details of individual cells and their connectivity in the human organ–scale system. We developed a platform that simultaneously extracts spatial, molecular, morphological, and connectivity information of individual cells from the same human brain. The platform includes three core elements: a vibrating microtome for ultraprecision slicing of large-scale tissues without losing cellular connectivity (MEGAtome), a polymer hydrogel–based tissue processing technology for multiplexed multiscale imaging of human organ–scale tissues (mELAST), and a computational pipeline for reconstructing three-dimensional connectivity across multiple brain slabs (UNSLICE). We applied this platform for analyzing human Alzheimer’s disease pathology at multiple scales and demonstrating scalable neural connectivity mapping in the human brain.

Publisher

American Association for the Advancement of Science (AAAS)

Link

https://www.science.org/doi/pdf/10.1126/science.adh9979

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