Time-distance vision transformers in lung cancer diagnosis from longitudinal computed tomography

Features learned from single radiologic images are unable to provide information about whether and how much a lesion may be changing over time. Time-dependent features computed from repeated images can capture those changes and help identify malignant lesions by their temporal behavior. However, longitudinal medical imaging presents the unique challenge of sparse, irregular time intervals in data acquisition. While self-attention has been shown to be a versatile and efficient learning mechanism for time series and natural images, its potential for interpreting temporal distance between sparse, irregularly sampled spatial features has not been explored. In this work, we propose two interpretations of a time-distance vision transformer (ViT) by using (1) vector embeddings of continuous time and (2) a temporal emphasis model to scale self-attention weights. The two algorithms are evaluated based on benign versus malignant lung cancer discrimination of synthetic pulmonary nodules and lung screening computed tomography studies from the National Lung Screening Trial (NLST). Experiments evaluating the time-distance ViTs on synthetic nodules show a fundamental improvement in classifying irregularly sampled longitudinal images when compared to standard ViTs. In cross-validation on screening chest CTs from the NLST, our methods (0.785 and 0.786 AUC respectively) significantly outperform a cross-sectional approach (0.734 AUC) and match the discriminative performance of the leading longitudinal medical imaging algorithm (0.779 AUC) on benign versus malignant classification. This work represents the first self-attention-based framework for classifying longitudinal medical images. Our code is available at https://github.com/tom1193/time-distance-transformer.

A Comparative Study of Confidence Calibration in Deep Learning: From Computer Vision to Medical Imaging

Although deep learning prediction models have been successful in the discrimination of different classes, they can often suffer from poor calibration across challenging domains including healthcare. Moreover, the long-tail distribution poses great challenges in deep learning classification problems including clinical disease prediction. There are approaches proposed recently to calibrate deep prediction in computer vision, but there are no studies found to demonstrate how the representative models work in different challenging contexts. In this paper, we bridge the confidence calibration from computer vision to medical imaging with a comparative study of four high-impact calibration models. Our studies are conducted in different contexts (natural image classification and lung cancer risk estimation) including in balanced vs. imbalanced training sets and in computer vision vs. medical imaging. Our results support key findings: (1) We achieve new conclusions which are not studied under different learning contexts, e.g., combining two calibration models that both mitigate the overconfident prediction can lead to under-confident prediction, and simpler calibration models from the computer vision domain tend to be more generalizable to medical imaging. (2) We highlight the gap between general computer vision tasks and medical imaging prediction, e.g., calibration methods ideal for general computer vision tasks may in fact damage the calibration of medical imaging prediction. (3) We also reinforce previous conclusions in natural image classification settings. We believe that this study has merits to guide readers to choose calibration models and understand gaps between general computer vision and medical imaging domains.

Transforming medical imaging with Transformers? A comparative review of key properties, current progresses, and future perspectives

Transformer, the latest technological advance of deep learning, has gained prevalence in natural language processing or computer vision. Since medical imaging bear some resemblance to computer vision, it is natural to inquire about the status quo of Transformers in medical imaging and ask the question: can the Transformer models transform medical imaging? In this paper, we attempt to make a response to the inquiry. After a brief introduction of the fundamentals of Transformers, especially in comparison with convolutional neural networks (CNNs), and highlighting key defining properties that characterize the Transformers, we offer a comprehensive review of the state-of-the-art Transformer-based approaches for medical imaging and exhibit current research progresses made in the areas of medical image segmentation, recognition, detection, registration, reconstruction, enhancement, etc. In particular, what distinguishes our review lies in its organization based on the Transformer's key defining properties, which are mostly derived from comparing the Transformer and CNN, and its type of architecture, which specifies the manner in which the Transformer and CNN are combined, all helping the readers to best understand the rationale behind the reviewed approaches. We conclude with discussions of future perspectives.

Pseudo-Label Guided Multi-Contrast Generalization for Non-Contrast Organ-Aware Segmentation

Non-contrast computed tomography (NCCT) is commonly acquired for lung cancer screening, assessment of general abdominal pain or suspected renal stones, trauma evaluation, and many other indications. However, the absence of contrast limits distinguishing organ in-between boundaries. In this paper, we propose a novel unsupervised approach that leverages pairwise contrast-enhanced CT (CECT) context to compute non-contrast segmentation without ground-truth label. Unlike generative adversarial approaches, we compute the pairwise morphological context with CECT to provide teacher guidance instead of generating fake anatomical context. Additionally, we further augment the intensity correlations in 'organ-specific' settings and increase the sensitivity to organ-aware boundary. We validate our approach on multi-organ segmentation with paired non-contrast & contrast-enhanced CT scans using five-fold cross-validation. Full external validations are performed on an independent non-contrast cohort for aorta segmentation. Compared with current abdominal organs segmentation state-of-the-art in fully supervised setting, our proposed pipeline achieves a significantly higher Dice by 3.98% (internal multi-organ annotated), and 8.00% (external aorta annotated) for abdominal organs segmentation. The code and pretrained models are publicly available at https://github.com/MASILab/ContrastMix.

Characterizing Renal Structures with 3D Block Aggregate Transformers

Efficiently quantifying renal structures can provide distinct spatial context and facilitate biomarker discovery for kidney morphology. However, the development and evaluation of the transformer model to segment the renal cortex, medulla, and collecting system remains challenging due to data inefficiency. Inspired by the hierarchical structures in vision transformer, we propose a novel method using a 3D block aggregation transformer for segmenting kidney components on contrast-enhanced CT scans. We construct the first cohort of renal substructures segmentation dataset with 116 subjects under institutional review board (IRB) approval. Our method yields the state-of-the-art performance (Dice of 0.8467) against the baseline approach of 0.8308 with the data-efficient design. The Pearson R achieves 0.9891 between the proposed method and manual standards and indicates the strong correlation and reproducibility for volumetric analysis. We extend the proposed method to the public KiTS dataset, the method leads to improved accuracy compared to transformer-based approaches. We show that the 3D block aggregation transformer can achieve local communication between sequence representations without modifying self-attention, and it can serve as an accurate and efficient quantification tool for characterizing renal structures.

Swin UNETR: Swin Transformers for Semantic Segmentation of Brain Tumors in MRI Images

Semantic segmentation of brain tumors is a fundamental medical image analysis task involving multiple MRI imaging modalities that can assist clinicians in diagnosing the patient and successively studying the progression of the malignant entity. In recent years, Fully Convolutional Neural Networks (FCNNs) approaches have become the de facto standard for 3D medical image segmentation. The popular "U-shaped" network architecture has achieved state-of-the-art performance benchmarks on different 2D and 3D semantic segmentation tasks and across various imaging modalities. However, due to the limited kernel size of convolution layers in FCNNs, their performance of modeling long-range information is sub-optimal, and this can lead to deficiencies in the segmentation of tumors with variable sizes. On the other hand, transformer models have demonstrated excellent capabilities in capturing such long-range information in multiple domains, including natural language processing and computer vision. Inspired by the success of vision transformers and their variants, we propose a novel segmentation model termed Swin UNEt TRansformers (Swin UNETR). Specifically, the task of 3D brain tumor semantic segmentation is reformulated as a sequence to sequence prediction problem wherein multi-modal input data is projected into a 1D sequence of embedding and used as an input to a hierarchical Swin transformer as the encoder. The swin transformer encoder extracts features at five different resolutions by utilizing shifted windows for computing self-attention and is connected to an FCNN-based decoder at each resolution via skip connections. We have participated in BraTS 2021 segmentation challenge, and our proposed model ranks among the top-performing approaches in the validation phase. Code: https://monai.io/research/swin-unetr

Self-Supervised Pre-Training of Swin Transformers for 3D Medical Image Analysis

Vision Transformers (ViT)s have shown great performance in self-supervised learning of global and local representations that can be transferred to downstream applications. Inspired by these results, we introduce a novel self-supervised learning framework with tailored proxy tasks for medical image analysis. Specifically, we propose: (i) a new 3D transformer-based model, dubbed Swin UNEt TRansformers (Swin UNETR), with a hierarchical encoder for self-supervised pre-training; (ii) tailored proxy tasks for learning the underlying pattern of human anatomy. We demonstrate successful pre-training of the proposed model on 5,050 publicly available computed tomography (CT) images from various body organs. The effectiveness of our approach is validated by fine-tuning the pre-trained models on the Beyond the Cranial Vault (BTCV) Segmentation Challenge with 13 abdominal organs and segmentation tasks from the Medical Segmentation Decathlon (MSD) dataset. Our model is currently the state-of-the-art (i.e. ranked 1st) on the public test leaderboards of both MSD and BTCV datasets. Code: https://monai.io/research/swin-unetr

Random Multi-Channel Image Synthesis for Multiplexed Immunofluorescence Imaging

Multiplex immunofluorescence (MxIF) is an emerging imaging technique that produces the high sensitivity and specificity of single-cell mapping. With a tenet of 'seeing is believing', MxIF enables iterative staining and imaging extensive antibodies, which provides comprehensive biomarkers to segment and group different cells on a single tissue section. However, considerable depletion of the scarce tissue is inevitable from extensive rounds of staining and bleaching ('missing tissue'). Moreover, the immunofluorescence (IF) imaging can globally fail for particular rounds ('missing stain''). In this work, we focus on the 'missing stain' issue. It would be appealing to develop digital image synthesis approaches to restore missing stain images without losing more tissue physically. Herein, we aim to develop image synthesis approaches for eleven MxIF structural molecular markers (i.e., epithelial and stromal) on real samples. We propose a novel multi-channel high-resolution image synthesis approach, called pixN2N-HD, to tackle possible missing stain scenarios via a high-resolution generative adversarial network (GAN). Our contribution is three-fold: (1) a single deep network framework is proposed to tackle missing stain in MxIF; (2) the proposed 'N-to-N' strategy reduces theoretical four years of computational time to 20 hours when covering all possible missing stains scenarios, with up to five missing stains (e.g., '(N-1)-to-1', '(N-2)-to-2'); and (3) this work is the first comprehensive experimental study of investigating cross-stain synthesis in MxIF. Our results elucidate a promising direction of advancing MxIF imaging with deep image synthesis.

Technical Report: Quality Assessment Tool for Machine Learning with Clinical CT

Image Quality Assessment (IQA) is important for scientific inquiry, especially in medical imaging and machine learning. Potential data quality issues can be exacerbated when human-based workflows use limited views of the data that may obscure digital artifacts. In practice, multiple factors such as network issues, accelerated acquisitions, motion artifacts, and imaging protocol design can impede the interpretation of image collections. The medical image processing community has developed a wide variety of tools for the inspection and validation of imaging data. Yet, IQA of computed tomography (CT) remains an under-recognized challenge, and no user-friendly tool is commonly available to address these potential issues. Here, we create and illustrate a pipeline specifically designed to identify and resolve issues encountered with large-scale data mining of clinically acquired CT data. Using the widely studied National Lung Screening Trial (NLST), we have identified approximately 4% of image volumes with quality concerns out of 17,392 scans. To assess robustness, we applied the proposed pipeline to our internal datasets where we find our tool is generalizable to clinically acquired medical images. In conclusion, the tool has been useful and time-saving for research study of clinical data, and the code and tutorials are publicly available at https://github.com/MASILab/QA_tool.

Lung Cancer Risk Estimation with Incomplete Data: A Joint Missing Imputation Perspective

Data from multi-modality provide complementary information in clinical prediction, but missing data in clinical cohorts limits the number of subjects in multi-modal learning context. Multi-modal missing imputation is challenging with existing methods when 1) the missing data span across heterogeneous modalities (e.g., image vs. non-image); or 2) one modality is largely missing. In this paper, we address imputation of missing data by modeling the joint distribution of multi-modal data. Motivated by partial bidirectional generative adversarial net (PBiGAN), we propose a new Conditional PBiGAN (C-PBiGAN) method that imputes one modality combining the conditional knowledge from another modality. Specifically, C-PBiGAN introduces a conditional latent space in a missing imputation framework that jointly encodes the available multi-modal data, along with a class regularization loss on imputed data to recover discriminative information. To our knowledge, it is the first generative adversarial model that addresses multi-modal missing imputation by modeling the joint distribution of image and non-image data. We validate our model with both the national lung screening trial (NLST) dataset and an external clinical validation cohort. The proposed C-PBiGAN achieves significant improvements in lung cancer risk estimation compared with representative imputation methods (e.g., AUC values increase in both NLST (+2.9\%) and in-house dataset (+4.3\%) compared with PBiGAN, p$<$0.05).