The Segment Anything Model (SAM) is a large-scale foundation model that has revolutionized segmentation methodology. Despite its impressive generalization ability, the segmentation accuracy of SAM on images with intricate structures is often unsatisfactory. Recent works have proposed lightweight fine-tuning using high-quality annotated data to improve accuracy on such images. However, here we provide extensive empirical evidence that this strategy leads to forgetting how to "segment anything": these models lose the original generalization abilities of SAM, in the sense that they perform worse for segmentation tasks not represented in the annotated fine-tuning set. To improve performance without forgetting, we introduce a novel framework that combines high-quality annotated data with a large unlabeled dataset. The framework relies on two methodological innovations. First, we quantify the uncertainty in the SAM pseudo labels associated with the unlabeled data and leverage it to perform uncertainty-aware fine-tuning. Second, we encode the type of segmentation task associated with each training example using a $\textit{task prompt}$ to reduce ambiguity. We evaluated the proposed Segmentation with Uncertainty Model (SUM) on a diverse test set consisting of 14 public benchmarks, where it achieves state-of-the-art results. Notably, our method consistently surpasses SAM by 3-6 points in mean IoU and 4-7 in mean boundary IoU across point-prompt interactive segmentation rounds. Code is available at https://github.com/Kangningthu/SUM

3D imaging enables accurate diagnosis by providing spatial information about organ anatomy. However, using 3D images to train AI models is computationally challenging because they consist of 10x or 100x more pixels than their 2D counterparts. To be trained with high-resolution 3D images, convolutional neural networks resort to downsampling them or projecting them to 2D. We propose an effective alternative, a neural network that enables efficient classification of full-resolution 3D medical images. Compared to off-the-shelf convolutional neural networks, our network, 3D Globally-Aware Multiple Instance Classifier (3D-GMIC), uses 77.98%-90.05% less GPU memory and 91.23%-96.02% less computation. While it is trained only with image-level labels, without segmentation labels, it explains its predictions by providing pixel-level saliency maps. On a dataset collected at NYU Langone Health, including 85,526 patients with full-field 2D mammography (FFDM), synthetic 2D mammography, and 3D mammography, 3D-GMIC achieves an AUC of 0.831 (95% CI: 0.769-0.887) in classifying breasts with malignant findings using 3D mammography. This is comparable to the performance of GMIC on FFDM (0.816, 95% CI: 0.737-0.878) and synthetic 2D (0.826, 95% CI: 0.754-0.884), which demonstrates that 3D-GMIC successfully classified large 3D images despite focusing computation on a smaller percentage of its input compared to GMIC. Therefore, 3D-GMIC identifies and utilizes extremely small regions of interest from 3D images consisting of hundreds of millions of pixels, dramatically reducing associated computational challenges. 3D-GMIC generalizes well to BCS-DBT, an external dataset from Duke University Hospital, achieving an AUC of 0.848 (95% CI: 0.798-0.896).

Learning representations for individual instances when only bag-level labels are available is a fundamental challenge in multiple instance learning (MIL). Recent works have shown promising results using contrastive self-supervised learning (CSSL), which learns to push apart representations corresponding to two different randomly-selected instances. Unfortunately, in real-world applications such as medical image classification, there is often class imbalance, so randomly-selected instances mostly belong to the same majority class, which precludes CSSL from learning inter-class differences. To address this issue, we propose a novel framework, Iterative Self-paced Supervised Contrastive Learning for MIL Representations (ItS2CLR), which improves the learned representation by exploiting instance-level pseudo labels derived from the bag-level labels. The framework employs a novel self-paced sampling strategy to ensure the accuracy of pseudo labels. We evaluate ItS2CLR on three medical datasets, showing that it improves the quality of instance-level pseudo labels and representations, and outperforms existing MIL methods in terms of both bag and instance level accuracy.11Code is available at https://github.com/Kangningthu/ItS2CLR

We hypothesize that due to the greedy nature of learning in multi-modal deep neural networks, these models tend to rely on just one modality while under-fitting the other modalities. Such behavior is counter-intuitive and hurts the models’ generalization, as we observe empirically. To estimate the model’s dependence on each modality, we compute the gain on the accuracy when the model has access to it in addition to another modality. We refer to this gain as the conditional utilization rate. In the experiments, we consistently observe an imbalance in conditional utilization rates between modalities, across multiple tasks and architectures. Since conditional utilization rate cannot be computed efficiently during training, we introduce a proxy for it based on the pace at which the model learns from each modality, which we refer to as the conditional learning speed. We propose an algorithm to balance the conditional learning speeds between modalities during training and demonstrate that it indeed addresses the issue of greedy learning. The proposed algorithm improves the model’s generalization on three datasets: Colored MNIST, ModelNet40, and NVIDIA Dynamic Hand Gesture.

We propose generative multitask learning (GMTL), a simple and scalable approach to causal machine learning in the multitask setting. Our approach makes a minor change to the conventional multitask inference objective, and improves robustness to target shift. Since GMTL only modifies the inference objective, it can be used with existing multitask learning methods without requiring additional training. The improvement in robustness comes from mitigating unobserved confounders that cause the targets, but not the input. We refer to them as \emph{target-causing confounders}. These confounders induce spurious dependencies between the input and targets. This poses a problem for conventional multitask learning, due to its assumption that the targets are conditionally independent given the input. GMTL mitigates target-causing confounding at inference time, by removing the influence of the joint target distribution, and predicting all targets jointly. This removes the spurious dependencies between the input and targets, where the degree of removal is adjustable via a single hyperparameter. This flexibility is useful for managing the trade-off between in- and out-of-distribution generalization. Our results on the Attributes of People and Taskonomy datasets reflect an improved robustness to target shift across four multitask learning methods.

The early phase of training a deep neural network has a dramatic effect on the local curvature of the loss function. For instance, using a small learning rate does not guarantee stable optimization because the optimization trajectory has a tendency to steer towards regions of the loss surface with increasing local curvature. We ask whether this tendency is connected to the widely observed phenomenon that the choice of the learning rate strongly influences generalization. We first show that stochastic gradient descent (SGD) implicitly penalizes the trace of the Fisher Information Matrix (FIM), a measure of the local curvature, from the start of training. We argue it is an implicit regularizer in SGD by showing that explicitly penalizing the trace of the FIM can significantly improve generalization. We highlight that poor final generalization coincides with the trace of the FIM attaining a large value early in training, to which we refer as catastrophic Fisher explosion. Finally, to gain insight into the regularization effect of penalizing the trace of the FIM, we show that it limits memorization by reducing the learning speed of examples with noisy labels more than that of the examples with clean labels.

MOTIVATION: Registration of histology images from multiple sources is a pressing problem in large-scale studies of spatial -omics data. Researchers often perform 'common coordinate registration', akin to segmentation, in which samples are partitioned based on tissue type to allow for quantitative comparison of similar regions across samples. Accuracy in such registration requires both high image resolution and global awareness, which mark a difficult balancing act for contemporary deep learning architectures. RESULTS: We present a novel convolutional neural network (CNN) architecture that combines (i) a local classification CNN that extracts features from image patches sampled sparsely across the tissue surface and (ii) a global segmentation CNN that operates on these extracted features. This hybrid network can be trained in an end-to-end manner, and we demonstrate its relative merits over competing approaches on a reference histology dataset as well as two published spatial transcriptomics datasets. We believe that this paradigm will greatly enhance our ability to process spatial -omics data, and has general purpose applications for the processing of high-resolution histology images on commercially available GPUs. AVAILABILITY AND IMPLEMENTATION: All code is publicly available at https://github.com/flatironinstitute/st_gridnet. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Medical images differ from natural images in significantly higher resolutions and smaller regions of interest. Because of these differences, neural network architectures that work well for natural images might not be applicable to medical image analysis. In this work, we propose a novel neural network model to address these unique properties of medical images. This model first uses a low-capacity, yet memory-efficient, network on the whole image to identify the most informative regions. It then applies another higher-capacity network to collect details from chosen regions. Finally, it employs a fusion module that aggregates global and local information to make a prediction. While existing methods often require lesion segmentation during training, our model is trained with only image-level labels and can generate pixel-level saliency maps indicating possible malignant findings. We apply the model to screening mammography interpretation: predicting the presence or absence of benign and malignant lesions. On the NYU Breast Cancer Screening Dataset, our model outperforms (AUC = 0.93) ResNet-34 and Faster R-CNN in classifying breasts with malignant findings. On the CBIS-DDSM dataset, our model achieves performance (AUC = 0.858) on par with state-of-the-art approaches. Compared to ResNet-34, our model is 4.1x faster for inference while using 78.4% less GPU memory. Furthermore, we demonstrate, in a reader study, that our model surpasses radiologist-level AUC by a margin of 0.11.

Currently available methods for extracting saliency maps identify parts of the input which are the most important to a specific fixed classifier. We show that this strong dependence on a given classifier hinders their performance. To address this problem, we propose classifier-agnostic saliency map extraction, which finds all parts of the image that any classifier could use, not just one given in advance. We observe that the proposed approach extracts higher quality saliency maps than prior work while being conceptually simple and easy to implement. The method sets the new state of the art result for localization task on the ImageNet data, outperforming all existing weakly-supervised localization techniques, despite not using the ground truth labels at the inference time. The code reproducing the results is available at https://github.com/kondiz/casme.

We present a deep convolutional neural network for breast cancer screening exam classification, trained, and evaluated on over 200000 exams (over 1000000 images). Our network achieves an AUC of 0.895 in predicting the presence of cancer in the breast, when tested on the screening population. We attribute the high accuracy to a few technical advances. 1) Our network's novel two-stage architecture and training procedure, which allows us to use a high-capacity patch-level network to learn from pixel-level labels alongside a network learning from macroscopic breast-level labels. 2) A custom ResNet-based network used as a building block of our model, whose balance of depth and width is optimized for high-resolution medical images. 3) Pretraining the network on screening BI-RADS classification, a related task with more noisy labels. 4) Combining multiple input views in an optimal way among a number of possible choices. To validate our model, we conducted a reader study with 14 readers, each reading 720 screening mammogram exams, and show that our model is as accurate as experienced radiologists when presented with the same data. We also show that a hybrid model, averaging the probability of malignancy predicted by a radiologist with a prediction of our neural network, is more accurate than either of the two separately. To further understand our results, we conduct a thorough analysis of our network's performance on different subpopulations of the screening population, the model's design, training procedure, errors, and properties of its internal representations. Our best models are publicly available at https://github.com/nyukat/breast_cancer_classifier.

Extracting saliency maps, which indicate parts of the image important to classification, requires many tricks to achieve satisfactory performance when using classifier-dependent methods. Instead, we propose classifier-agnostic saliency map extraction. This allows to find all parts of the image that any classifier could use, not just one given in advance. This way we extract much higher quality saliency maps.

Breast density classification is an essential part of breast cancer screening. Although a lot of prior work considered this problem as a task for learning algorithms, to our knowledge, all of them used small and not clinically realistic data both for training and evaluation of their models. In this work, we explored the limits of this task with a data set coming from over 200,000 breast cancer screening exams. We used this data to train and evaluate a strong convolutional neural network classifier. In a reader study, we found that our model can perform this task comparably to a human expert.

Deep neural networks have achieved great successes on various machine learning tasks, however, there are many open fundamental questions to be answered. In this paper, we tackle the problem of quantifying the quality of learned wights of different networks with possibly different architectures, going beyond considering the final classification error as the only metric. We introduce \emphExtended Data Jacobian Matrix to help analyze properties of networks of various structures, finding that, the spectrum of the extended data jacobian matrix is a strong discriminating factor for networks of different structures and performance. Based on such observation, we propose a novel regularization method, which manages to improve the network performance comparably to dropout, which in turn verifies the observation.

Cross-validation is an essential tool in machine learning and statistics. The typical procedure, in which data points are randomly assigned to one of the test sets, makes an implicit assumption that the data are exchangeable. A common case in which this does not hold is when the data come from multiple sources, in the sense used in transfer learning. In this case it is common to arrange the cross-validation procedure in a way that takes the source structure into account. Although common in practice, this procedure does not appear to have been theoretically analysed. We present new estimators of the variance of the cross-validation, both in the multiple-source setting and in the standard iid setting. These new estimators allow for much more accurate confidence intervals and hypothesis tests to compare algorithms.