Generalizing AI-driven Assessment of Immunohistochemistry across Immunostains and Cancer Types: A Universal Immunohistochemistry Analyzer

Despite advancements in methodologies, immunohistochemistry (IHC) remains the most utilized ancillary test for histopathologic and companion diagnostics in targeted therapies. However, objective IHC assessment poses challenges. Artificial intelligence (AI) has emerged as a potential solution, yet its development requires extensive training for each cancer and IHC type, limiting versatility. We developed a Universal IHC (UIHC) analyzer, an AI model for interpreting IHC images regardless of tumor or IHC types, using training datasets from various cancers stained for PD-L1 and/or HER2. This multi-cohort trained model outperforms conventional single-cohort models in interpreting unseen IHCs (Kappa score 0.578 vs. up to 0.509) and consistently shows superior performance across different positive staining cutoff values. Qualitative analysis reveals that UIHC effectively clusters patches based on expression levels. The UIHC model also quantitatively assesses c-MET expression with MET mutations, representing a significant advancement in AI application in the era of personalized medicine and accumulating novel biomarkers.

Bayesian Optimization Meets Self-Distillation

Bayesian optimization (BO) has contributed greatly to improving model performance by suggesting promising hyperparameter configurations iteratively based on observations from multiple training trials. However, only partial knowledge (i.e., the measured performances of trained models and their hyperparameter configurations) from previous trials is transferred. On the other hand, Self-Distillation (SD) only transfers partial knowledge learned by the task model itself. To fully leverage the various knowledge gained from all training trials, we propose the BOSS framework, which combines BO and SD. BOSS suggests promising hyperparameter configurations through BO and carefully selects pre-trained models from previous trials for SD, which are otherwise abandoned in the conventional BO process. BOSS achieves significantly better performance than both BO and SD in a wide range of tasks including general image classification, learning with noisy labels, semi-supervised learning, and medical image analysis tasks.

OCELOT: Overlapped Cell on Tissue Dataset for Histopathology

Cell detection is a fundamental task in computational pathology that can be used for extracting high-level medical information from whole-slide images. For accurate cell detection, pathologists often zoom out to understand the tissue-level structures and zoom in to classify cells based on their morphology and the surrounding context. However, there is a lack of efforts to reflect such behaviors by pathologists in the cell detection models, mainly due to the lack of datasets containing both cell and tissue annotations with overlapping regions. To overcome this limitation, we propose and publicly release OCELOT, a dataset purposely dedicated to the study of cell-tissue relationships for cell detection in histopathology. OCELOT provides overlapping cell and tissue annotations on images acquired from multiple organs. Within this setting, we also propose multi-task learning approaches that benefit from learning both cell and tissue tasks simultaneously. When compared against a model trained only for the cell detection task, our proposed approaches improve cell detection performance on 3 datasets: proposed OCELOT, public TIGER, and internal CARP datasets. On the OCELOT test set in particular, we show up to 6.79 improvement in F1-score. We believe the contributions of this paper, including the release of the OCELOT dataset at https://lunit-io.github.io/research/publications/ocelot are a crucial starting point toward the important research direction of incorporating cell-tissue relationships in computation pathology.

Benchmarking Self-Supervised Learning on Diverse Pathology Datasets

Computational pathology can lead to saving human lives, but models are annotation hungry and pathology images are notoriously expensive to annotate. Self-supervised learning has shown to be an effective method for utilizing unlabeled data, and its application to pathology could greatly benefit its downstream tasks. Yet, there are no principled studies that compare SSL methods and discuss how to adapt them for pathology. To address this need, we execute the largest-scale study of SSL pre-training on pathology image data, to date. Our study is conducted using 4 representative SSL methods on diverse downstream tasks. We establish that large-scale domain-aligned pre-training in pathology consistently out-performs ImageNet pre-training in standard SSL settings such as linear and fine-tuning evaluations, as well as in low-label regimes. Moreover, we propose a set of domain-specific techniques that we experimentally show leads to a performance boost. Lastly, for the first time, we apply SSL to the challenging task of nuclei instance segmentation and show large and consistent performance improvements under diverse settings.

Improving Multi-fidelity Optimization with a Recurring Learning Rate for Hyperparameter Tuning

Despite the evolution of Convolutional Neural Networks (CNNs), their performance is surprisingly dependent on the choice of hyperparameters. However, it remains challenging to efficiently explore large hyperparameter search space due to the long training times of modern CNNs. Multi-fidelity optimization enables the exploration of more hyperparameter configurations given budget by early termination of unpromising configurations. However, it often results in selecting a sub-optimal configuration as training with the high-performing configuration typically converges slowly in an early phase. In this paper, we propose Multi-fidelity Optimization with a Recurring Learning rate (MORL) which incorporates CNNs' optimization process into multi-fidelity optimization. MORL alleviates the problem of slow-starter and achieves a more precise low-fidelity approximation. Our comprehensive experiments on general image classification, transfer learning, and semi-supervised learning demonstrate the effectiveness of MORL over other multi-fidelity optimization methods such as Successive Halving Algorithm (SHA) and Hyperband. Furthermore, it achieves significant performance improvements over hand-tuned hyperparameter configuration within a practical budget.

Interactive Multi-Class Tiny-Object Detection

Annotating tens or hundreds of tiny objects in a given image is laborious yet crucial for a multitude of Computer Vision tasks. Such imagery typically contains objects from various categories, yet the multi-class interactive annotation setting for the detection task has thus far been unexplored. To address these needs, we propose a novel interactive annotation method for multiple instances of tiny objects from multiple classes, based on a few point-based user inputs. Our approach, C3Det, relates the full image context with annotator inputs in a local and global manner via late-fusion and feature-correlation, respectively. We perform experiments on the Tiny-DOTA and LCell datasets using both two-stage and one-stage object detection architectures to verify the efficacy of our approach. Our approach outperforms existing approaches in interactive annotation, achieving higher mAP with fewer clicks. Furthermore, we validate the annotation efficiency of our approach in a user study where it is shown to be 2.85x faster and yield only 0.36x task load (NASA-TLX, lower is better) compared to manual annotation. The code is available at https://github.com/ChungYi347/Interactive-Multi-Class-Tiny-Object-Detection.

Learning Visual Context by Comparison

Finding diseases from an X-ray image is an important yet highly challenging task. Current methods for solving this task exploit various characteristics of the chest X-ray image, but one of the most important characteristics is still missing: the necessity of comparison between related regions in an image. In this paper, we present Attend-and-Compare Module (ACM) for capturing the difference between an object of interest and its corresponding context. We show that explicit difference modeling can be very helpful in tasks that require direct comparison between locations from afar. This module can be plugged into existing deep learning models. For evaluation, we apply our module to three chest X-ray recognition tasks and COCO object detection & segmentation tasks and observe consistent improvements across tasks. The code is available at https://github.com/mk-minchul/attend-and-compare.

Reducing Domain Gap via Style-Agnostic Networks

Deep learning models often fail to maintain their performance on new test domains. This problem has been regarded as a critical limitation of deep learning for real-world applications. One of the main causes of this vulnerability to domain changes is that the model tends to be biased to image styles (i.e. textures). To tackle this problem, we propose Style-Agnostic Networks (SagNets) to encourage the model to focus more on image contents (i.e. shapes) shared across domains but ignore image styles. SagNets consist of three novel techniques: style adversarial learning, style blending and style consistency learning, each of which prevents the model from making decisions based upon style information. In collaboration with a few additional training techniques and an ensemble of several model variants, the proposed method won the 1st place in the semi-supervised domain adaptation task of the Visual Domain Adaptation 2019 (VisDA-2019) Challenge.

Visuomotor Understanding for Representation Learning of Driving Scenes

Dashboard cameras capture a tremendous amount of driving scene video each day. These videos are purposefully coupled with vehicle sensing data, such as from the speedometer and inertial sensors, providing an additional sensing modality for free. In this work, we leverage the large-scale unlabeled yet naturally paired data for visual representation learning in the driving scenario. A representation is learned in an end-to-end self-supervised framework for predicting dense optical flow from a single frame with paired sensing data. We postulate that success on this task requires the network to learn semantic and geometric knowledge in the ego-centric view. For example, forecasting a future view to be seen from a moving vehicle requires an understanding of scene depth, scale, and movement of objects. We demonstrate that our learned representation can benefit other tasks that require detailed scene understanding and outperforms competing unsupervised representations on semantic segmentation.

PseudoEdgeNet: Nuclei Segmentation only with Point Annotations

Nuclei segmentation is one of the important tasks for whole slide image analysis in digital pathology. With the drastic advance of deep learning, recent deep networks have demonstrated successful performance of the nuclei segmentation task. However, a major bottleneck to achieving good performance is the cost for annotation. A large network requires a large number of segmentation masks, and this annotation task is given to pathologists, not the public. In this paper, we propose a weakly supervised nuclei segmentation method, which requires only point annotations for training. This method can scale to large training set as marking a point of a nucleus is much cheaper than the fine segmentation mask. To this end, we introduce a novel auxiliary network, called PseudoEdgeNet, which guides the segmentation network to recognize nuclei edges even without edge annotations. We evaluate our method with two public datasets, and the results demonstrate that the method consistently outperforms other weakly supervised methods.