Random Multi-Channel Image Synthesis for Multiplexed Immunofluorescence Imaging

TL;DR

This paper introduces a novel high-resolution GAN-based method for digital image synthesis to recover missing stains in multiplex immunofluorescence imaging, reducing tissue depletion and enabling comprehensive cell analysis.

Contribution

It presents a unified deep network framework with an N-to-N strategy for efficient multi-stain image synthesis, significantly reducing computational time and advancing MxIF imaging capabilities.

Findings

Effective synthesis of missing stains in MxIF images.

Reduction of computational time from four years to 20 hours.

First comprehensive experimental study on cross-stain synthesis in MxIF.

Abstract

Multiplex immunofluorescence (MxIF) is an emerging imaging technique that produces the high sensitivity and specificity of single-cell mapping. With a tenet of 'seeing is believing', MxIF enables iterative staining and imaging extensive antibodies, which provides comprehensive biomarkers to segment and group different cells on a single tissue section. However, considerable depletion of the scarce tissue is inevitable from extensive rounds of staining and bleaching ('missing tissue'). Moreover, the immunofluorescence (IF) imaging can globally fail for particular rounds ('missing stain''). In this work, we focus on the 'missing stain' issue. It would be appealing to develop digital image synthesis approaches to restore missing stain images without losing more tissue physically. Herein, we aim to develop image synthesis approaches for eleven MxIF structural molecular markers (i.e., epithelial and stromal) on real samples. We propose a novel multi-channel high-resolution image synthesis approach, called pixN2N-HD, to tackle possible missing stain scenarios via a high-resolution generative adversarial network (GAN). Our contribution is three-fold: (1) a single deep network framework is proposed to tackle missing stain in MxIF; (2) the proposed 'N-to-N' strategy reduces theoretical four years of computational time to 20 hours when covering all possible missing stains scenarios, with up to five missing stains (e.g., '(N-1)-to-1', '(N-2)-to-2'); and (3) this work is the first comprehensive experimental study of investigating cross-stain synthesis in MxIF. Our results elucidate a promising direction of advancing MxIF imaging with deep image synthesis.