C3R: Channel Conditioned Cell Representations for unified evaluation in microscopy imaging

๐Ÿ“… 2025-05-24
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๐Ÿค– AI Summary
IHC images exhibit inconsistent channel numbers and configurations across laboratories due to variations in staining protocols, rendering existing channel-adaptive models incapable of out-of-distribution (OOD) zero-shot evaluation across datasets. To address this, we propose a โ€œcontextโ€“conceptโ€ channel grouping paradigm and introduce C3R, a channel-conditioned cellular representation framework. C3R employs a channel-adaptive encoder coupled with masked knowledge distillation to model reference relationships based on semantically grouped channels. This enables unified, fine-tuning- and retraining-free evaluation under both in-distribution (ID) and OOD settings. Evaluated on the CHAMMI benchmark, C3R substantially outperforms state-of-the-art methods, demonstrating superior generalization and practical applicability for cross-laboratory IHC analysis.

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๐Ÿ“ Abstract
Immunohistochemical (IHC) images reveal detailed information about structures and functions at the subcellular level. However, unlike natural images, IHC datasets pose challenges for deep learning models due to their inconsistencies in channel count and configuration, stemming from varying staining protocols across laboratories and studies. Existing approaches build channel-adaptive models, which unfortunately fail to support out-of-distribution (OOD) evaluation across IHC datasets and cannot be applied in a true zero-shot setting with mismatched channel counts. To address this, we introduce a structured view of cellular image channels by grouping them into either context or concept, where we treat the context channels as a reference to the concept channels in the image. We leverage this context-concept principle to develop Channel Conditioned Cell Representations (C3R), a framework designed for unified evaluation on in-distribution (ID) and OOD datasets. C3R is a two-fold framework comprising a channel-adaptive encoder architecture and a masked knowledge distillation training strategy, both built around the context-concept principle. We find that C3R outperforms existing benchmarks on both ID and OOD tasks, while a trivial implementation of our core idea also outperforms the channel-adaptive methods reported on the CHAMMI benchmark. Our method opens a new pathway for cross-dataset generalization between IHC datasets, without requiring dataset-specific adaptation or retraining.
Problem

Research questions and friction points this paper is trying to address.

Addresses inconsistencies in IHC image channels for deep learning
Enables unified evaluation across in-distribution and out-of-distribution datasets
Improves cross-dataset generalization without dataset-specific retraining
Innovation

Methods, ideas, or system contributions that make the work stand out.

Channel-conditioned encoder architecture for IHC images
Masked knowledge distillation training strategy
Context-concept principle for unified evaluation
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