Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

CODA: quantitative 3D reconstruction of large tissues at cellular resolution. Nat Methods 2022 Nov;19(11):1490-1499

Date

10/26/2022

Pubmed ID

36280719

Pubmed Central ID

PMC10500590

DOI

10.1038/s41592-022-01650-9

Scopus ID

2-s2.0-85140470848 (requires institutional sign-in at Scopus site)   54 Citations

Abstract

A central challenge in biology is obtaining high-content, high-resolution information while analyzing tissue samples at volumes relevant to disease progression. We address this here with CODA, a method to reconstruct exceptionally large (up to multicentimeter cubed) tissues at subcellular resolution using serially sectioned hematoxylin and eosin-stained tissue sections. Here we demonstrate CODA's ability to reconstruct three-dimensional (3D) distinct microanatomical structures in pancreas, skin, lung and liver tissues. CODA allows creation of readily quantifiable tissue volumes amenable to biological research. As a testbed, we assess the microanatomy of the human pancreas during tumorigenesis within the branching pancreatic ductal system, labeling ten distinct structures to examine heterogeneity and structural transformation during neoplastic progression. We show that pancreatic precancerous lesions develop into distinct 3D morphological phenotypes and that pancreatic cancer tends to spread far from the bulk tumor along collagen fibers that are highly aligned to the 3D curves of ductal, lobular, vascular and neural structures. Thus, CODA establishes a means to transform broadly the structural study of human diseases through exploration of exhaustively labeled 3D microarchitecture.

Author List

Kiemen AL, Braxton AM, Grahn MP, Han KS, Babu JM, Reichel R, Jiang AC, Kim B, Hsu J, Amoa F, Reddy S, Hong SM, Cornish TC, Thompson ED, Huang P, Wood LD, Hruban RH, Wirtz D, Wu PH

Author

Toby Charles Cornish MD, PhD Professor in the Pathology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Humans
Imaging, Three-Dimensional
Pancreas
Pancreatic Neoplasms