Computational pathology can lead to saving human lives, but models are annotation hungry and pathology images are notoriously expensive to annotate. Self-supervised learning (SSL) 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. We release the pre-trained model weights11https://lunit-io.github.io/research/publications/pathology_ssl.

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.

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 unex-plored. 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 in-puts. Our approach, C3Det, relates the full image context with annotator inputs in a local and global manner via late-fusion andfeature-correlation, respectively. We perform ex-periments 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 outper-forms 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.

Fully convolutional networks have been achieving remarkable results in image semantic segmentation, while being efficient. Such efficiency results from the capability of segmenting several voxels in a single forward pass. So, there is a direct spatial correspondence between a unit in a feature map and the voxel in the same location. In a convolutional layer, the kernel spans over all channels and extracts information from them. We observe that linear recombination of feature maps by increasing the number of channels followed by compression may enhance their discriminative power. Moreover, not all feature maps have the same relevance for the classes being predicted. In order to learn the inter-channel relationships and recalibrate the channels to suppress the less relevant ones, squeeze and excitation blocks were proposed in the context of image classification with convolutional neural networks. However, this is not well adapted for segmentation with fully convolutional networks since they segment several objects simultaneously, hence a feature map may contain relevant information only in some locations. In this paper, we propose recombination of features and a spatially adaptive recalibration block that is adapted for semantic segmentation with fully convolutional networks- the SegSE block. Feature maps are recalibrated by considering the cross-channel information together with spatial relevance. The experimental results indicate that recombination and recalibration improve the results of a competitive baseline, and generalize across three different problems: brain tumor segmentation, stroke penumbra estimation, and ischemic stroke lesion outcome prediction. The obtained results are competitive or outperform the state of the art in the three applications.

Among brain tumors, gliomas are the most common and aggressive, leading to a very short life expectancy in their highest grade. Thus, treatment planning is a key stage to improve the quality of life of oncological patients. Magnetic resonance imaging (MRI) is a widely used imaging technique to assess these tumors, but the large amount of data produced by MRI prevents manual segmentation in a reasonable time, limiting the use of precise quantitative measurements in the clinical practice. So, automatic and reliable segmentation methods are required; however, the large spatial and structural variability among brain tumors make automatic segmentation a challenging problem. In this paper, we propose an automatic segmentation method based on Convolutional Neural Networks (CNN), exploring small 3 ×3 kernels. The use of small kernels allows designing a deeper architecture, besides having a positive effect against overfitting, given the fewer number of weights in the network. We also investigated the use of intensity normalization as a pre-processing step, which though not common in CNN-based segmentation methods, proved together with data augmentation to be very effective for brain tumor segmentation in MRI images. Our proposal was validated in the Brain Tumor Segmentation Challenge 2013 database (BRATS 2013), obtaining simultaneously the first position for the complete, core, and enhancing regions in Dice Similarity Coefficient metric (0.88, 0.83, 0.77) for the Challenge data set. Also, it obtained the overall first position by the online evaluation platform. We also participated in the on-site BRATS 2015 Challenge using the same model, obtaining the second place, with Dice Similarity Coefficient metric of 0.78, 0.65, and 0.75 for the complete, core, and enhancing regions, respectively.

In this paper we report the set-up and results of the Multimodal Brain Tumor Image Segmentation Benchmark (BRATS) organized in conjunction with the MICCAI 2012 and 2013 conferences. Twenty state-of-the-art tumor segmentation algorithms were applied to a set of 65 multi-contrast MR scans of low- and high-grade glioma patients-manually annotated by up to four raters-and to 65 comparable scans generated using tumor image simulation software. Quantitative evaluations revealed considerable disagreement between the human raters in segmenting various tumor sub-regions (Dice scores in the range 74%-85%), illustrating the difficulty of this task. We found that different algorithms worked best for different sub-regions (reaching performance comparable to human inter-rater variability), but that no single algorithm ranked in the top for all sub-regions simultaneously. Fusing several good algorithms using a hierarchical majority vote yielded segmentations that consistently ranked above all individual algorithms, indicating remaining opportunities for further methodological improvements. The BRATS image data and manual annotations continue to be publicly available through an online evaluation system as an ongoing benchmarking resource.