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Science, Jun 14 2024, 384 (6701) | https://doi.org/10.1126/science.adh9979 Integrated platform for multiscale molecular imaging and phenotyping of the human brain

Juhyuk Park ^#,1,2,3,4, Ji Wang ^#,1,3, Webster Guan ^#,2, Lars A Gjesteby ⁵, Dylan Pollack ⁵, Lee Kamentsky ^1,3, Nicholas B. Evans ^1,3, Jeff Stirman ⁶, Xinyi Gu ⁷, Chuanxi Zhao ³, Slayton Marx³, Minyoung E. Kim ⁸, Seo Woo Choi ², Michael Snyder ⁵, David Chavez⁵, Clover Su-Arcaro ³, Yuxuan Tian ², Chang Sin Park ^9,10, Qiangge Zhang ¹¹, Dae Hee Yun ⁸, Mira Moukheiber ³, Guoping Feng ^8,11, X William Yang ^9,10, C Dirk Keene ¹², Patrick R Hof ¹³, Satrajit S. Ghosh ^8,11,14, Matthew P Frosch ¹⁵, Laura J Brattain ⁵, Kwanghun Chung^*,1,2,3,8

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

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

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

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

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

⁶LifeCanvas Technologies, Cambridge, MA 02141, USA.

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

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

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

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

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

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

¹³Nash 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.

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

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

^#Contributed equally.

^*Corresponding author : Kwanghun Chung

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-17)
연구진국내+국외 연구진
분야 바이오·의료융합 > 바이오소재

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