Le Hou

Kaiwen Wang, Rahul Kidambi, Ryan Sullivan et al.

Reward-based finetuning is crucial for aligning language policies with intended behaviors (e.g., creativity and safety). A key challenge is to develop steerable language models that trade-off multiple (conflicting) objectives in a flexible and efficient manner. This paper presents Conditional Language Policy (CLP), a general framework for finetuning language models on multiple objectives. Building on techniques from multi-task training and parameter-efficient finetuning, CLP learn steerable models that effectively trade-off conflicting objectives at inference time. Notably, this does not require training or maintaining multiple models to achieve different trade-offs between the objectives. Through extensive experiments and ablations on two summarization datasets, we show that CLP learns steerable language models that outperform and Pareto-dominate the existing approaches for multi-objective finetuning.

Tao Tu, Anil Palepu, Mike Schaekermann et al.

At the heart of medicine lies the physician-patient dialogue, where skillful history-taking paves the way for accurate diagnosis, effective management, and enduring trust. Artificial Intelligence (AI) systems capable of diagnostic dialogue could increase accessibility, consistency, and quality of care. However, approximating clinicians' expertise is an outstanding grand challenge. Here, we introduce AMIE (Articulate Medical Intelligence Explorer), a Large Language Model (LLM) based AI system optimized for diagnostic dialogue. AMIE uses a novel self-play based simulated environment with automated feedback mechanisms for scaling learning across diverse disease conditions, specialties, and contexts. We designed a framework for evaluating clinically-meaningful axes of performance including history-taking, diagnostic accuracy, management reasoning, communication skills, and empathy. We compared AMIE's performance to that of primary care physicians (PCPs) in a randomized, double-blind crossover study of text-based consultations with validated patient actors in the style of an Objective Structured Clinical Examination (OSCE). The study included 149 case scenarios from clinical providers in Canada, the UK, and India, 20 PCPs for comparison with AMIE, and evaluations by specialist physicians and patient actors. AMIE demonstrated greater diagnostic accuracy and superior performance on 28 of 32 axes according to specialist physicians and 24 of 26 axes according to patient actors. Our research has several limitations and should be interpreted with appropriate caution. Clinicians were limited to unfamiliar synchronous text-chat which permits large-scale LLM-patient interactions but is not representative of usual clinical practice. While further research is required before AMIE could be translated to real-world settings, the results represent a milestone towards conversational diagnostic AI.

Han Le, Rajarsi Gupta, Le Hou et al.

Quantitative assessment of Tumor-TIL spatial relationships is increasingly important in both basic science and clinical aspects of breast cancer research. We have developed and evaluated convolutional neural network (CNN) analysis pipelines to generate combined maps of cancer regions and tumor infiltrating lymphocytes (TILs) in routine diagnostic breast cancer whole slide tissue images (WSIs). We produce interactive whole slide maps that provide 1) insight about the structural patterns and spatial distribution of lymphocytic infiltrates and 2) facilitate improved quantification of TILs. We evaluated both tumor and TIL analyses using three CNN networks - Resnet-34, VGG16 and Inception v4, and demonstrated that the results compared favorably to those obtained by what believe are the best published methods. We have produced open-source tools and generated a public dataset consisting of tumor/TIL maps for 1,015 TCGA breast cancer images. We also present a customized web-based interface that enables easy visualization and interactive exploration of high-resolution combined Tumor-TIL maps for 1,015TCGA invasive breast cancer cases that can be downloaded for further downstream analyses.

Shuo Yang, Le Hou, Xiaodan Song et al.

We propose a simple and efficient approach for training the BERT model. Our approach exploits the special structure of BERT that contains a stack of repeated modules (i.e., transformer encoders). Our proposed approach first trains BERT with the weights shared across all the repeated modules till some point. This is for learning the commonly shared component of weights across all repeated layers. We then stop weight sharing and continue training until convergence. We present theoretic insights for training by sharing weights then unsharing with analysis for simplified models. Empirical experiments on the BERT model show that our method yields better performance of trained models, and significantly reduces the number of training iterations.

Noam Shazeer, Zhenzhong Lan, Youlong Cheng et al.

We introduce "talking-heads attention" - a variation on multi-head attention which includes linearprojections across the attention-heads dimension, immediately before and after the softmax operation.While inserting only a small number of additional parameters and a moderate amount of additionalcomputation, talking-heads attention leads to better perplexities on masked language modeling tasks, aswell as better quality when transfer-learning to language comprehension and question answering tasks.

Le Hou, Rajarsi Gupta, John S. Van Arnam et al.

The distribution and appearance of nuclei are essential markers for the diagnosis and study of cancer. Despite the importance of nuclear morphology, there is a lack of large scale, accurate, publicly accessible nucleus segmentation data. To address this, we developed an analysis pipeline that segments nuclei in whole slide tissue images from multiple cancer types with a quality control process. We have generated nucleus segmentation results in 5,060 Whole Slide Tissue images from 10 cancer types in The Cancer Genome Atlas. One key component of our work is that we carried out a multi-level quality control process (WSI-level and image patch-level), to evaluate the quality of our segmentation results. The image patch-level quality control used manual segmentation ground truth data from 1,356 sampled image patches. The datasets we publish in this work consist of roughly 5 billion quality controlled nuclei from more than 5,060 TCGA WSIs from 10 different TCGA cancer types and 1,356 manually segmented TCGA image patches from the same 10 cancer types plus additional 4 cancer types. Data is available at https://doi.org/10.7937/tcia.2019.4a4dkp9u

Robert M. Patton, J. Travis Johnston, Steven R. Young et al.

Deep learning, through the use of neural networks, has demonstrated remarkable ability to automate many routine tasks when presented with sufficient data for training. The neural network architecture (e.g. number of layers, types of layers, connections between layers, etc.) plays a critical role in determining what, if anything, the neural network is able to learn from the training data. The trend for neural network architectures, especially those trained on ImageNet, has been to grow ever deeper and more complex. The result has been ever increasing accuracy on benchmark datasets with the cost of increased computational demands. In this paper we demonstrate that neural network architectures can be automatically generated, tailored for a specific application, with dual objectives: accuracy of prediction and speed of prediction. Using MENNDL--an HPC-enabled software stack for neural architecture search--we generate a neural network with comparable accuracy to state-of-the-art networks on a cancer pathology dataset that is also $16\times$ faster at inference. The speedup in inference is necessary because of the volume and velocity of cancer pathology data; specifically, the previous state-of-the-art networks are too slow for individual researchers without access to HPC systems to keep pace with the rate of data generation. Our new model enables researchers with modest computational resources to analyze newly generated data faster than it is collected.

Le Hou, Youlong Cheng, Noam Shazeer et al.

Medical images such as 3D computerized tomography (CT) scans and pathology images, have hundreds of millions or billions of voxels/pixels. It is infeasible to train CNN models directly on such high resolution images, because neural activations of a single image do not fit in the memory of a single GPU/TPU, and naive data and model parallelism approaches do not work. Existing image analysis approaches alleviate this problem by cropping or down-sampling input images, which leads to complicated implementation and sub-optimal performance due to information loss. In this paper, we implement spatial partitioning, which internally distributes the input and output of convolutional layers across GPUs/TPUs. Our implementation is based on the Mesh-TensorFlow framework and the computation distribution is transparent to end users. With this technique, we train a 3D Unet on up to 512 by 512 by 512 resolution data. To the best of our knowledge, this is the first work for handling such high resolution images end-to-end.

Shahira Abousamra, Le Hou, Rajarsi Gupta et al.

Deep learning classifiers for characterization of whole slide tissue morphology require large volumes of annotated data to learn variations across different tissue and cancer types. As is well known, manual generation of digital pathology training data is time consuming and expensive. In this paper, we propose a semi-automated method for annotating a group of similar instances at once, instead of collecting only per-instance manual annotations. This allows for a much larger training set, that reflects visual variability across multiple cancer types and thus training of a single network which can be automatically applied to each cancer type without human adjustment. We apply our method to the important task of classifying Tumor Infiltrating Lymphocytes (TILs) in H&E images. Prior approaches were trained for individual cancer types, with smaller training sets and human-in-the-loop threshold adjustment. We utilize these thresholded results as large scale "semi-automatic" annotations. Combined with existing manual annotations, our trained deep networks are able to automatically produce better TIL prediction results in 12 cancer types, compared to the human-in-the-loop approach.

Maozheng Zhao, Le Hou, Han Le et al.

For the task of semantic segmentation, high-resolution (pixel-level) ground truth is very expensive to collect, especially for high resolution images such as gigapixel pathology images. On the other hand, collecting low resolution labels (labels for a block of pixels) for these high resolution images is much more cost efficient. Conventional methods trained on these low-resolution labels are only capable of giving low-resolution predictions. The existing state-of-the-art label super resolution (LSR) method is capable of predicting high resolution labels, using only low-resolution supervision, given the joint distribution between low resolution and high resolution labels. However, it does not consider the inter-instance variance which is crucial in the ideal mathematical formulation. In this work, we propose a novel loss function modeling the inter-instance variance. We test our method on a real world application: infiltrating breast cancer region segmentation in histopathology slides. Experimental results show the effectiveness of our method.

Le Hou, Ayush Agarwal, Dimitris Samaras et al.

Hematoxylin and Eosin stained histopathology image analysis is essential for the diagnosis and study of complicated diseases such as cancer. Existing state-of-the-art approaches demand extensive amount of supervised training data from trained pathologists. In this work we synthesize in an unsupervised manner, large histopathology image datasets, suitable for supervised training tasks. We propose a unified pipeline that: a) generates a set of initial synthetic histopathology images with paired information about the nuclei such as segmentation masks; b) refines the initial synthetic images through a Generative Adversarial Network (GAN) to reference styles; c) trains a task-specific CNN and boosts the performance of the task-specific CNN with on-the-fly generated adversarial examples. Our main contribution is that the synthetic images are not only realistic, but also representative (in reference styles) and relatively challenging for training task-specific CNNs. We test our method for nucleus segmentation using images from four cancer types. When no supervised data exists for a cancer type, our method without supervision cost significantly outperforms supervised methods which perform across-cancer generalization. Even when supervised data exists for all cancer types, our approach without supervision cost performs better than supervised methods.

Le Hou, Vu Nguyen, Dimitris Samaras et al.

Histopathology images are crucial to the study of complex diseases such as cancer. The histologic characteristics of nuclei play a key role in disease diagnosis, prognosis and analysis. In this work, we propose a sparse Convolutional Autoencoder (CAE) for fully unsupervised, simultaneous nucleus detection and feature extraction in histopathology tissue images. Our CAE detects and encodes nuclei in image patches in tissue images into sparse feature maps that encode both the location and appearance of nuclei. Our CAE is the first unsupervised detection network for computer vision applications. The pretrained nucleus detection and feature extraction modules in our CAE can be fine-tuned for supervised learning in an end-to-end fashion. We evaluate our method on four datasets and reduce the errors of state-of-the-art methods up to 42%. We are able to achieve comparable performance with only 5% of the fully-supervised annotation cost.

Veda Murthy, Le Hou, Dimitris Samaras et al.

Classifying the various shapes and attributes of a glioma cell nucleus is crucial for diagnosis and understanding the disease. We investigate automated classification of glioma nuclear shapes and visual attributes using Convolutional Neural Networks (CNNs) on pathology images of automatically segmented nuclei. We propose three methods that improve the performance of a previously-developed semi-supervised CNN. First, we propose a method that allows the CNN to focus on the most important part of an image- the image's center containing the nucleus. Second, we inject (concatenate) pre-extracted VGG features into an intermediate layer of our Semi-Supervised CNN so that during training, the CNN can learn a set of complementary features. Third, we separate the losses of the two groups of target classes (nuclear shapes and attributes) into a single-label loss and a multi-label loss so that the prior knowledge of inter-label exclusiveness can be incorporated. On a dataset of 2078 images, the proposed methods combined reduce the error rate of attribute and shape classification by 21.54% and 15.07% respectively compared to the existing state-of-the-art method on the same dataset.

Le Hou, Chen-Ping Yu, Dimitris Samaras

In the context of single-label classification, despite the huge success of deep learning, the commonly used cross-entropy loss function ignores the intricate inter-class relationships that often exist in real-life tasks such as age classification. In this work, we propose to leverage these relationships between classes by training deep nets with the exact squared Earth Mover's Distance (also known as Wasserstein distance) for single-label classification. The squared EMD loss uses the predicted probabilities of all classes and penalizes the miss-predictions according to a ground distance matrix that quantifies the dissimilarities between classes. We demonstrate that on datasets with strong inter-class relationships such as an ordering between classes, our exact squared EMD losses yield new state-of-the-art results. Furthermore, we propose a method to automatically learn this matrix using the CNN's own features during training. We show that our method can learn a ground distance matrix efficiently with no inter-class relationship priors and yield the same performance gain. Finally, we show that our method can be generalized to applications that lack strong inter-class relationships and still maintain state-of-the-art performance. Therefore, with limited computational overhead, one can always deploy the proposed loss function on any dataset over the conventional cross-entropy.

Le Hou, Dimitris Samaras, Tahsin M. Kurc et al.

In Neural Networks (NN), Adaptive Activation Functions (AAF) have parameters that control the shapes of activation functions. These parameters are trained along with other parameters in the NN. AAFs have improved performance of Neural Networks (NN) in multiple classification tasks. In this paper, we propose and apply AAFs on feedforward NNs for regression tasks. We argue that applying AAFs in the regression (second-to-last) layer of a NN can significantly decrease the bias of the regression NN. However, using existing AAFs may lead to overfitting. To address this problem, we propose a Smooth Adaptive Activation Function (SAAF) with piecewise polynomial form which can approximate any continuous function to arbitrary degree of error. NNs with SAAFs can avoid overfitting by simply regularizing the parameters. In particular, an NN with SAAFs is Lipschitz continuous given a bounded magnitude of the NN parameters. We prove an upper-bound for model complexity in terms of fat-shattering dimension for any Lipschitz continuous regression model. Thus, regularizing the parameters in NNs with SAAFs avoids overfitting. We empirically evaluated NNs with SAAFs and achieved state-of-the-art results on multiple regression datasets.

Le Hou, Dimitris Samaras, Tahsin M. Kurc et al.

Convolutional Neural Networks (CNN) are state-of-the-art models for many image classification tasks. However, to recognize cancer subtypes automatically, training a CNN on gigapixel resolution Whole Slide Tissue Images (WSI) is currently computationally impossible. The differentiation of cancer subtypes is based on cellular-level visual features observed on image patch scale. Therefore, we argue that in this situation, training a patch-level classifier on image patches will perform better than or similar to an image-level classifier. The challenge becomes how to intelligently combine patch-level classification results and model the fact that not all patches will be discriminative. We propose to train a decision fusion model to aggregate patch-level predictions given by patch-level CNNs, which to the best of our knowledge has not been shown before. Furthermore, we formulate a novel Expectation-Maximization (EM) based method that automatically locates discriminative patches robustly by utilizing the spatial relationships of patches. We apply our method to the classification of glioma and non-small-cell lung carcinoma cases into subtypes. The classification accuracy of our method is similar to the inter-observer agreement between pathologists. Although it is impossible to train CNNs on WSIs, we experimentally demonstrate using a comparable non-cancer dataset of smaller images that a patch-based CNN can outperform an image-based CNN.