WeakSTIL: Weak whole-slide image level stromal tumor infiltrating lymphocyte scores are all you need

We present WeakSTIL, an interpretable two-stage weak label deep learning pipeline for scoring the percentage of stromal tumor infiltrating lymphocytes (sTIL%) in H&E-stained whole-slide images (WSIs) of breast cancer tissue. The sTIL% score is a prognostic and predictive biomarker for many solid tumor types. However, due to the high labeling efforts and high intra- and interobserver variability within and between expert annotators, this biomarker is currently not used in routine clinical decision making. WeakSTIL compresses tiles of a WSI using a feature extractor pre-trained with self-supervised learning on unlabeled histopathology data and learns to predict precise sTIL% scores for each tile in the tumor bed by using a multiple instance learning regressor that only requires a weak WSI-level label. By requiring only a weak label, we overcome the large annotation efforts required to train currently existing TIL detection methods. We show that WeakSTIL is at least as good as other TIL detection methods when predicting the WSI-level sTIL% score, reaching a coefficient of determination of $0.45\pm0.15$ when compared to scores generated by an expert pathologist, and an AUC of $0.89\pm0.05$ when treating it as the clinically interesting sTIL-high vs sTIL-low classification task. Additionally, we show that the intermediate tile-level predictions of WeakSTIL are highly interpretable, which suggests that WeakSTIL pays attention to latent features related to the number of TILs and the tissue type. In the future, WeakSTIL may be used to provide consistent and interpretable sTIL% predictions to stratify breast cancer patients into targeted therapy arms.

Deep MRI Reconstruction with Radial Subsampling

In spite of its extensive adaptation in almost every medical diagnostic and examinatorial application, Magnetic Resonance Imaging (MRI) is still a slow imaging modality which limits its use for dynamic imaging. In recent years, Parallel Imaging (PI) and Compressed Sensing (CS) have been utilised to accelerate the MRI acquisition. In clinical settings, subsampling the k-space measurements during scanning time using Cartesian trajectories, such as rectilinear sampling, is currently the most conventional CS approach applied which, however, is prone to producing aliased reconstructions. With the advent of the involvement of Deep Learning (DL) in accelerating the MRI, reconstructing faithful images from subsampled data became increasingly promising. Retrospectively applying a subsampling mask onto the k-space data is a way of simulating the accelerated acquisition of k-space data in real clinical setting. In this paper we compare and provide a review for the effect of applying either rectilinear or radial retrospective subsampling on the quality of the reconstructions outputted by trained deep neural networks. With the same choice of hyper-parameters, we train and evaluate two distinct Recurrent Inference Machines (RIMs), one for each type of subsampling. The qualitative and quantitative results of our experiments indicate that the model trained on data with radial subsampling attains higher performance and learns to estimate reconstructions with higher fidelity paving the way for other DL approaches to involve radial subsampling.

DeepSMILE: Self-supervised heterogeneity-aware multiple instance learning for DNA damage response defect classification directly from H&E whole-slide images

We propose a Deep learning-based weak label learning method for analysing whole slide images (WSIs) of Hematoxylin and Eosin (H&E) stained tumorcells not requiring pixel-level or tile-level annotations using Self-supervised pre-training and heterogeneity-aware deep Multiple Instance LEarning (DeepSMILE). We apply DeepSMILE to the task of Homologous recombination deficiency (HRD) and microsatellite instability (MSI) prediction. We utilize contrastive self-supervised learning to pre-train a feature extractor on histopathology tiles of cancer tissue. Additionally, we use variability-aware deep multiple instance learning to learn the tile feature aggregation function while modeling tumor heterogeneity. Compared to state-of-the-art genomic label classification methods, DeepSMILE improves classification performance for HRD from $70.43\pm4.10\%$ to $83.79\pm1.25\%$ AUC and MSI from $78.56\pm6.24\%$ to $90.32\pm3.58\%$ AUC in a multi-center breast and colorectal cancer dataset, respectively. These improvements suggest we can improve genomic label classification performance without collecting larger datasets. In the future, this may reduce the need for expensive genome sequencing techniques, provide personalized therapy recommendations based on widely available WSIs of cancer tissue, and improve patient care with quicker treatment decisions - also in medical centers without access to genome sequencing resources.

Sparse-Shot Learning for Extremely Many Localisations

Object localisation is typically considered in the context of regular images, for instance depicting objects like people or cars. In these images there is typically a relatively small number of instances per image per class, which usually is manageable to annotate. However, outside the realm of regular images we are often confronted with a different situation. In computational pathology digitised tissue sections are extremely large images, whose dimensions quickly exceed 250'000x250'000 pixels, where relevant objects, such as tumour cells or lymphocytes can quickly number in the millions. Annotating them all is practically impossible and annotating sparsely a few, out of many more, is the only possibility. Unfortunately, learning from sparse annotations, or sparse-shot learning, clashes with standard supervised learning because what is not annotated is treated as a negative. However, assigning negative labels to what are true positives leads to confusion in the gradients and biased learning. To this end, we present exclusive cross entropy, which slows down the biased learning by examining the second-order loss derivatives in order to drop the loss terms corresponding to likely biased terms. Experiments on nine datasets and two different localisation tasks, detection with YOLLO and segmentation with Unet, show that we obtain considerable improvements compared to cross entropy or focal loss, while often reaching the best possible performance for the model with only 10-40 of annotations.

Automatic Breast Lesion Detection in Ultrafast DCE-MRI Using Deep Learning

Purpose: We propose a deep learning-based computer-aided detection (CADe) method to detect breast lesions in ultrafast DCE-MRI sequences. This method uses both the three-dimensional spatial information and temporal information obtained from the early-phase of the dynamic acquisition.Methods: The proposed CADe method, based on a modified 3D RetinaNet model, operates on ultrafast T1 weighted sequences, which are preprocessed for motion compensation, temporal normalization, and are cropped before passing into the model. The model is optimized to enable the detection of relatively small breast lesions in a screening setting, focusing on detection of lesions that are harder to differentiate from confounding structures inside the breast.Results: The method was developed based on a dataset consisting of 489 ultrafast MRI studies obtained from 462 patients containing a total of 572 lesions (365 malignant, 207 benign) and achieved a detection rate, sensitivity, and detection rate of benign lesions of 0.90, 0.95, and 0.86 at 4 false positives per normal breast with a 10-fold cross-validation, respectively.Conclusions: The deep learning architecture used for the proposed CADe application can efficiently detect benign and malignant lesions on ultrafast DCE-MRI. Furthermore, utilizing the less visible hard-to detect-lesions in training improves the learning process and, subsequently, detection of malignant breast lesions.

State-of-the-Art Machine Learning MRI Reconstruction in 2020: Results of the Second fastMRI Challenge

Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community.

State-of-the-art Machine Learning MRI Reconstruction in 2020: Results of the Second fastMRI Challenge

Accelerating MRI scans is one of the principal outstanding problems in the MRI research community. Towards this goal, we hosted the second fastMRI competition targeted towards reconstructing MR images with subsampled k-space data. We provided participants with data from 7,299 clinical brain scans (de-identified via a HIPAA-compliant procedure by NYU Langone Health), holding back the fully-sampled data from 894 of these scans for challenge evaluation purposes. In contrast to the 2019 challenge, we focused our radiologist evaluations on pathological assessment in brain images. We also debuted a new Transfer track that required participants to submit models evaluated on MRI scanners from outside the training set. We received 19 submissions from eight different groups. Results showed one team scoring best in both SSIM scores and qualitative radiologist evaluations. We also performed analysis on alternative metrics to mitigate the effects of background noise and collected feedback from the participants to inform future challenges. Lastly, we identify common failure modes across the submissions, highlighting areas of need for future research in the MRI reconstruction community.

Multi-channel MR Reconstruction (MC-MRRec) Challenge -- Comparing Accelerated MR Reconstruction Models and Assessing Their Genereralizability to Datasets Collected with Different Coils

The 2020 Multi-channel Magnetic Resonance Reconstruction (MC-MRRec) Challenge had two primary goals: 1) compare different MR image reconstruction models on a large dataset and 2) assess the generalizability of these models to datasets acquired with a different number of receiver coils (i.e., multiple channels). The challenge had two tracks: Track 01 focused on assessing models trained and tested with 12-channel data. Track 02 focused on assessing models trained with 12-channel data and tested on both 12-channel and 32-channel data. While the challenge is ongoing, here we describe the first edition of the challenge and summarise submissions received prior to 5 September 2020. Track 01 had five baseline models and received four independent submissions. Track 02 had two baseline models and received two independent submissions. This manuscript provides relevant comparative information on the current state-of-the-art of MR reconstruction and highlights the challenges of obtaining generalizable models that are required prior to clinical adoption. Both challenge tracks remain open and will provide an objective performance assessment for future submissions. Subsequent editions of the challenge are proposed to investigate new concepts and strategies, such as the integration of potentially available longitudinal information during the MR reconstruction process. An outline of the proposed second edition of the challenge is presented in this manuscript.