Generalizable deep learning based medical image segmentation

Deep learning is revolutionizing medical image analysis and interpretation. However, its real-world deployment is often hindered by the poor generalization to unseen domains (new imaging modalities and protocols). This lack of generalization ability is further exacerbated by the scarcity of labeled datasets for training: Data collection and annotation can be prohibitively expensive in terms of labor and costs because label quality heavily dependents on the expertise of radiologists. Additionally, unreliable predictions caused by poor model generalization pose safety risks to clinical downstream applications. To mitigate labeling requirements, we investigate and develop a series of techniques to strengthen the generalization ability and the data efficiency of deep medical image computing models. We further improve model accountability and identify unreliable predictions made on out-of-domain data, by designing probability calibration techniques. In the first and the second part of thesis, we discuss two types of problems for handling unexpected domains: unsupervised domain adaptation and single-source domain generalization. For domain adaptation we present a data-efficient technique that adapts a segmentation model trained on a labeled source domain (e.g., MRI) to an unlabeled target domain (e.g., CT), using a small number of unlabeled training images from the target domain. For domain generalization, we focus on both image reconstruction and segmentation. For image reconstruction, we design a simple and effective domain generalization technique for cross-domain MRI reconstruction, by reusing image representations learned from natural image datasets. For image segmentation, we perform causal analysis of the challenging cross-domain image segmentation problem. Guided by this causal analysis we propose an effective data-augmentation-based generalization technique for single-source domains. The proposed method outperforms existing approaches on a large variety of cross-domain image segmentation scenarios. In the third part of the thesis, we present a novel self-supervised method for learning generic image representations that can be used to analyze unexpected objects of interest. The proposed method is designed together with a novel few-shot image segmentation framework that can segment unseen objects of interest by taking only a few labeled examples as references. Superior flexibility over conventional fully-supervised models is demonstrated by our few-shot framework: it does not require any fine-tuning on novel objects of interest. We further build a publicly available comprehensive evaluation environment for few-shot medical image segmentation. In the fourth part of the thesis, we present a novel probability calibration model. To ensure safety in clinical settings, a deep model is expected to be able to alert human radiologists if it has low confidence, especially when confronted with out-of-domain data. To this end we present a plug-and-play model to calibrate prediction probabilities on out-of-domain data. It aligns the prediction probability in line with the actual accuracy on the test data. We evaluate our method on both artifact-corrupted images and images from an unforeseen MRI scanning protocol. Our method demonstrates improved calibration accuracy compared with the state-of-the-art method. Finally, we summarize the major contributions and limitations of our works. We also suggest future research directions that will benefit from the works in this thesis.Open Acces

Tailored for Real-World: A Whole Slide Image Classification System Validated on Uncurated Multi-Site Data Emulating the Prospective Pathology Workload.

Standard of care diagnostic procedure for suspected skin cancer is microscopic examination of hematoxylin & eosin stained tissue by a pathologist. Areas of high inter-pathologist discordance and rising biopsy rates necessitate higher efficiency and diagnostic reproducibility. We present and validate a deep learning system which classifies digitized dermatopathology slides into 4 categories. The system is developed using 5,070 images from a single lab, and tested on an uncurated set of 13,537 images from 3 test labs, using whole slide scanners manufactured by 3 different vendors. The system\u27s use of deep-learning-based confidence scoring as a criterion to consider the result as accurate yields an accuracy of up to 98%, and makes it adoptable in a real-world setting. Without confidence scoring, the system achieved an accuracy of 78%. We anticipate that our deep learning system will serve as a foundation enabling faster diagnosis of skin cancer, identification of cases for specialist review, and targeted diagnostic classifications

An Unsupervised Learning Model for Deformable Medical Image Registration

We present a fast learning-based algorithm for deformable, pairwise 3D medical image registration. Current registration methods optimize an objective function independently for each pair of images, which can be time-consuming for large data. We define registration as a parametric function, and optimize its parameters given a set of images from a collection of interest. Given a new pair of scans, we can quickly compute a registration field by directly evaluating the function using the learned parameters. We model this function using a convolutional neural network (CNN), and use a spatial transform layer to reconstruct one image from another while imposing smoothness constraints on the registration field. The proposed method does not require supervised information such as ground truth registration fields or anatomical landmarks. We demonstrate registration accuracy comparable to state-of-the-art 3D image registration, while operating orders of magnitude faster in practice. Our method promises to significantly speed up medical image analysis and processing pipelines, while facilitating novel directions in learning-based registration and its applications. Our code is available at https://github.com/balakg/voxelmorph .Comment: 9 pages, in CVPR 201

Domain Generalization for Medical Image Analysis: A Survey

Medical Image Analysis (MedIA) has become an essential tool in medicine and healthcare, aiding in disease diagnosis, prognosis, and treatment planning, and recent successes in deep learning (DL) have made significant contributions to its advances. However, DL models for MedIA remain challenging to deploy in real-world situations, failing for generalization under the distributional gap between training and testing samples, known as a distribution shift problem. Researchers have dedicated their efforts to developing various DL methods to adapt and perform robustly on unknown and out-of-distribution data distributions. This paper comprehensively reviews domain generalization studies specifically tailored for MedIA. We provide a holistic view of how domain generalization techniques interact within the broader MedIA system, going beyond methodologies to consider the operational implications on the entire MedIA workflow. Specifically, we categorize domain generalization methods into data-level, feature-level, model-level, and analysis-level methods. We show how those methods can be used in various stages of the MedIA workflow with DL equipped from data acquisition to model prediction and analysis. Furthermore, we include benchmark datasets and applications used to evaluate these approaches and analyze the strengths and weaknesses of various methods, unveiling future research opportunities

MLA-BIN: Model-level Attention and Batch-instance Style Normalization for Domain Generalization of Federated Learning on Medical Image Segmentation

The privacy protection mechanism of federated learning (FL) offers an effective solution for cross-center medical collaboration and data sharing. In multi-site medical image segmentation, each medical site serves as a client of FL, and its data naturally forms a domain. FL supplies the possibility to improve the performance of seen domains model. However, there is a problem of domain generalization (DG) in the actual de-ployment, that is, the performance of the model trained by FL in unseen domains will decrease. Hence, MLA-BIN is proposed to solve the DG of FL in this study. Specifically, the model-level attention module (MLA) and batch-instance style normalization (BIN) block were designed. The MLA represents the unseen domain as a linear combination of seen domain models. The atten-tion mechanism is introduced for the weighting coefficient to obtain the optimal coefficient ac-cording to the similarity of inter-domain data features. MLA enables the global model to gen-eralize to unseen domain. In the BIN block, batch normalization (BN) and instance normalization (IN) are combined to perform the shallow layers of the segmentation network for style normali-zation, solving the influence of inter-domain image style differences on DG. The extensive experimental results of two medical image seg-mentation tasks demonstrate that the proposed MLA-BIN outperforms state-of-the-art methods.Comment: 9 pages, 8 figures, 2 table

Domain Generalization in Vision: A Survey

Generalization to out-of-distribution (OOD) data is a capability natural to humans yet challenging for machines to reproduce. This is because most learning algorithms strongly rely on the i.i.d.~assumption on source/target data, which is often violated in practice due to domain shift. Domain generalization (DG) aims to achieve OOD generalization by using only source data for model learning. Since first introduced in 2011, research in DG has made great progresses. In particular, intensive research in this topic has led to a broad spectrum of methodologies, e.g., those based on domain alignment, meta-learning, data augmentation, or ensemble learning, just to name a few; and has covered various vision applications such as object recognition, segmentation, action recognition, and person re-identification. In this paper, for the first time a comprehensive literature review is provided to summarize the developments in DG for computer vision over the past decade. Specifically, we first cover the background by formally defining DG and relating it to other research fields like domain adaptation and transfer learning. Second, we conduct a thorough review into existing methods and present a categorization based on their methodologies and motivations. Finally, we conclude this survey with insights and discussions on future research directions.Comment: v4: includes the word "vision" in the title; improves the organization and clarity in Section 2-3; adds future directions; and mor