LViT: Language meets Vision Transformer in Medical Image Segmentation

Deep learning has been widely used in medical image segmentation and other aspects. However, the performance of existing medical image segmentation models has been limited by the challenge of obtaining sufficient number of high-quality data with the high cost of data annotation. To overcome the limitation, we propose a new vision-language medical image segmentation model LViT (Language meets Vision Transformer). In our model, medical text annotation is introduced to compensate for the quality deficiency in image data. In addition, the text information can guide the generation of pseudo labels to a certain extent and further guarantee the quality of pseudo labels in semi-supervised learning. We also propose the Exponential Pseudo label Iteration mechanism (EPI) to help extend the semi-supervised version of LViT and the Pixel-Level Attention Module (PLAM) to preserve local features of images. In our model, LV (Language-Vision) loss is designed to supervise the training of unlabeled images using text information directly. To validate the performance of LViT, we construct multimodal medical segmentation datasets (image + text) containing pathological images, X-rays,etc. Experimental results show that our proposed LViT has better segmentation performance in both fully and semi-supervised conditions. Code and datasets are available at https://github.com/HUANGLIZI/LViT.

Comprehensive and Clinically Accurate Head and Neck Organs at Risk Delineation via Stratified Deep Learning: A Large-scale Multi-Institutional Study

Accurate organ at risk (OAR) segmentation is critical to reduce the radiotherapy post-treatment complications. Consensus guidelines recommend a set of more than 40 OARs in the head and neck (H&N) region, however, due to the predictable prohibitive labor-cost of this task, most institutions choose a substantially simplified protocol by delineating a smaller subset of OARs and neglecting the dose distributions associated with other OARs. In this work we propose a novel, automated and highly effective stratified OAR segmentation (SOARS) system using deep learning to precisely delineate a comprehensive set of 42 H&N OARs. SOARS stratifies 42 OARs into anchor, mid-level, and small & hard subcategories, with specifically derived neural network architectures for each category by neural architecture search (NAS) principles. We built SOARS models using 176 training patients in an internal institution and independently evaluated on 1327 external patients across six different institutions. It consistently outperformed other state-of-the-art methods by at least 3-5% in Dice score for each institutional evaluation (up to 36% relative error reduction in other metrics). More importantly, extensive multi-user studies evidently demonstrated that 98% of the SOARS predictions need only very minor or no revisions for direct clinical acceptance (saving 90% radiation oncologists workload), and their segmentation and dosimetric accuracy are within or smaller than the inter-user variation. These findings confirmed the strong clinical applicability of SOARS for the OAR delineation process in H&N cancer radiotherapy workflows, with improved efficiency, comprehensiveness, and quality.

Multi-institutional Validation of Two-Streamed Deep Learning Method for Automated Delineation of Esophageal Gross Tumor Volume using planning-CT and FDG-PETCT

Background: The current clinical workflow for esophageal gross tumor volume (GTV) contouring relies on manual delineation of high labor-costs and interuser variability. Purpose: To validate the clinical applicability of a deep learning (DL) multi-modality esophageal GTV contouring model, developed at 1 institution whereas tested at multiple ones. Methods and Materials: We collected 606 esophageal cancer patients from four institutions. 252 institution-1 patients had a treatment planning-CT (pCT) and a pair of diagnostic FDG-PETCT; 354 patients from other 3 institutions had only pCT. A two-streamed DL model for GTV segmentation was developed using pCT and PETCT scans of a 148 patient institution-1 subset. This built model had the flexibility of segmenting GTVs via only pCT or pCT+PETCT combined. For independent evaluation, the rest 104 institution-1 patients behaved as unseen internal testing, and 354 institutions 2-4 patients were used for external testing. We evaluated manual revision degrees by human experts to assess the contour-editing effort. The performance of the deep model was compared against 4 radiation oncologists in a multiuser study with 20 random external patients. Contouring accuracy and time were recorded for the pre-and post-DL assisted delineation process. Results: Our model achieved high segmentation accuracy in internal testing (mean Dice score: 0.81 using pCT and 0.83 using pCT+PET) and generalized well to external evaluation (mean DSC: 0.80). Expert assessment showed that the predicted contours of 88% patients need only minor or no revision. In multi-user evaluation, with the assistance of a deep model, inter-observer variation and required contouring time were reduced by 37.6% and 48.0%, respectively. Conclusions: Deep learning predicted GTV contours were in close agreement with the ground truth and could be adopted clinically with mostly minor or no changes.

SAME: Deformable Image Registration based on Self-supervised Anatomical Embeddings

In this work, we introduce a fast and accurate method for unsupervised 3D medical image registration. This work is built on top of a recent algorithm SAM, which is capable of computing dense anatomical/semantic correspondences between two images at the pixel level. Our method is named SAME, which breaks down image registration into three steps: affine transformation, coarse deformation, and deep deformable registration. Using SAM embeddings, we enhance these steps by finding more coherent correspondences, and providing features and a loss function with better semantic guidance. We collect a multi-phase chest computed tomography dataset with 35 annotated organs for each patient and conduct inter-subject registration for quantitative evaluation. Results show that SAME outperforms widely-used traditional registration techniques (Elastix FFD, ANTs SyN) and learning based VoxelMorph method by at least 4.7% and 2.7% in Dice scores for two separate tasks of within-contrast-phase and across-contrast-phase registration, respectively. SAME achieves the comparable performance to the best traditional registration method, DEEDS (from our evaluation), while being orders of magnitude faster (from 45 seconds to 1.2 seconds).

DeepStationing: Thoracic Lymph Node Station Parsing in CT Scans using Anatomical Context Encoding and Key Organ Auto-Search

Lymph node station (LNS) delineation from computed tomography (CT) scans is an indispensable step in radiation oncology workflow. High inter-user variabilities across oncologists and prohibitive laboring costs motivated the automated approach. Previous works exploit anatomical priors to infer LNS based on predefined ad-hoc margins. However, without voxel-level supervision, the performance is severely limited. LNS is highly context-dependent - LNS boundaries are constrained by anatomical organs - we formulate it as a deep spatial and contextual parsing problem via encoded anatomical organs. This permits the deep network to better learn from both CT appearance and organ context. We develop a stratified referencing organ segmentation protocol that divides the organs into anchor and non-anchor categories and uses the former's predictions to guide the later segmentation. We further develop an auto-search module to identify the key organs that opt for the optimal LNS parsing performance. Extensive four-fold cross-validation experiments on a dataset of 98 esophageal cancer patients (with the most comprehensive set of 12 LNSs + 22 organs in thoracic region to date) are conducted. Our LNS parsing model produces significant performance improvements, with an average Dice score of 81.1% +/- 6.1%, which is 5.0% and 19.2% higher over the pure CT-based deep model and the previous representative approach, respectively.

Self-supervised Learning of Pixel-wise Anatomical Embeddings in Radiological Images

Radiological images such as computed tomography (CT) and X-rays render anatomy with intrinsic structures. Being able to reliably locate the same anatomical or semantic structure across varying images is a fundamental task in medical image analysis. In principle it is possible to use landmark detection or semantic segmentation for this task, but to work well these require large numbers of labeled data for each anatomical structure and sub-structure of interest. A more universal approach would discover the intrinsic structure from unlabeled images. We introduce such an approach, called Self-supervised Anatomical eMbedding (SAM). SAM generates semantic embeddings for each image pixel that describes its anatomical location or body part. To produce such embeddings, we propose a pixel-level contrastive learning framework. A coarse-to-fine strategy ensures both global and local anatomical information are encoded. Negative sample selection strategies are designed to enhance the discriminability among different body parts. Using SAM, one can label any point of interest on a template image, and then locate the same body part in other images by simple nearest neighbor searching. We demonstrate the effectiveness of SAM in multiple tasks with 2D and 3D image modalities. On a chest CT dataset with 19 landmarks, SAM outperforms widely-used registration algorithms while being 200 times faster. On two X-ray datasets, SAM, with only one labeled template image, outperforms supervised methods trained on 50 labeled images. We also apply SAM on whole-body follow-up lesion matching in CT and obtain an accuracy of 91%.

Learning from Multiple Datasets with Heterogeneous and Partial Labels for Universal Lesion Detection in CT

Large-scale datasets with high-quality labels are desired for training accurate deep learning models. However, due to annotation costs, medical imaging datasets are often either partially-labeled or small. For example, DeepLesion is a large-scale CT image dataset with lesions of various types, but it also has many unlabeled lesions (missing annotations). When training a lesion detector on a partially-labeled dataset, the missing annotations will generate incorrect negative signals and degrade performance. Besides DeepLesion, there are several small single-type datasets, such as LUNA for lung nodules and LiTS for liver tumors. Such datasets have heterogeneous label scopes, i.e., different lesion types are labeled in different datasets with other types ignored. In this work, we aim to tackle the problem of heterogeneous and partial labels, and develop a universal lesion detection algorithm to detect a comprehensive variety of lesions. First, we build a simple yet effective lesion detection framework named Lesion ENSemble (LENS). LENS can efficiently learn from multiple heterogeneous lesion datasets in a multi-task fashion and leverage their synergy by feature sharing and proposal fusion. Next, we propose strategies to mine missing annotations from partially-labeled datasets by exploiting clinical prior knowledge and cross-dataset knowledge transfer. Finally, we train our framework on four public lesion datasets and evaluate it on 800 manually-labeled sub-volumes in DeepLesion. On this challenging task, our method brings a relative improvement of 49% compared to the current state-of-the-art approach.

Lymph Node Gross Tumor Volume Detection in Oncology Imaging via Relationship Learning Using Graph Neural Network

Determining the spread of GTV$_{LN}$ is essential in defining the respective resection or irradiating regions for the downstream workflows of surgical resection and radiotherapy for many cancers. Different from the more common enlarged lymph node (LN), GTV$_{LN}$ also includes smaller ones if associated with high positron emission tomography signals and/or any metastasis signs in CT. This is a daunting task. In this work, we propose a unified LN appearance and inter-LN relationship learning framework to detect the true GTV$_{LN}$. This is motivated by the prior clinical knowledge that LNs form a connected lymphatic system, and the spread of cancer cells among LNs often follows certain pathways. Specifically, we first utilize a 3D convolutional neural network with ROI-pooling to extract the GTV$_{LN}$'s instance-wise appearance features. Next, we introduce a graph neural network to further model the inter-LN relationships where the global LN-tumor spatial priors are included in the learning process. This leads to an end-to-end trainable network to detect by classifying GTV$_{LN}$. We operate our model on a set of GTV$_{LN}$ candidates generated by a preliminary 1st-stage method, which has a sensitivity of $>85\%$ at the cost of high false positive (FP) ($>15$ FPs per patient). We validate our approach on a radiotherapy dataset with 142 paired PET/RTCT scans containing the chest and upper abdominal body parts. The proposed method significantly improves over the state-of-the-art (SOTA) LN classification method by $5.5\%$ and $13.1\%$ in F1 score and the averaged sensitivity value at $2, 3, 4, 6$ FPs per patient, respectively.

Lymph Node Gross Tumor Volume Detection and Segmentation via Distance-based Gating using 3D CT/PET Imaging in Radiotherapy

Finding, identifying and segmenting suspicious cancer metastasized lymph nodes from 3D multi-modality imaging is a clinical task of paramount importance. In radiotherapy, they are referred to as Lymph Node Gross Tumor Volume (GTVLN). Determining and delineating the spread of GTVLN is essential in defining the corresponding resection and irradiating regions for the downstream workflows of surgical resection and radiotherapy of various cancers. In this work, we propose an effective distance-based gating approach to simulate and simplify the high-level reasoning protocols conducted by radiation oncologists, in a divide-and-conquer manner. GTVLN is divided into two subgroups of tumor-proximal and tumor-distal, respectively, by means of binary or soft distance gating. This is motivated by the observation that each category can have distinct though overlapping distributions of appearance, size and other LN characteristics. A novel multi-branch detection-by-segmentation network is trained with each branch specializing on learning one GTVLN category features, and outputs from multi-branch are fused in inference. The proposed method is evaluated on an in-house dataset of $141$ esophageal cancer patients with both PET and CT imaging modalities. Our results validate significant improvements on the mean recall from $72.5\%$ to $78.2\%$, as compared to previous state-of-the-art work. The highest achieved GTVLN recall of $82.5\%$ at $20\%$ precision is clinically relevant and valuable since human observers tend to have low sensitivity (around $80\%$ for the most experienced radiation oncologists, as reported by literature).

Robust Pancreatic Ductal Adenocarcinoma Segmentation with Multi-Institutional Multi-Phase Partially-Annotated CT Scans

Accurate and automated tumor segmentation is highly desired since it has the great potential to increase the efficiency and reproducibility of computing more complete tumor measurements and imaging biomarkers, comparing to (often partial) human measurements. This is probably the only viable means to enable the large-scale clinical oncology patient studies that utilize medical imaging. Deep learning approaches have shown robust segmentation performances for certain types of tumors, e.g., brain tumors in MRI imaging, when a training dataset with plenty of pixel-level fully-annotated tumor images is available. However, more than often, we are facing the challenge that only (very) limited annotations are feasible to acquire, especially for hard tumors. Pancreatic ductal adenocarcinoma (PDAC) segmentation is one of the most challenging tumor segmentation tasks, yet critically important for clinical needs. Previous work on PDAC segmentation is limited to the moderate amounts of annotated patient images (n<300) from venous or venous+arterial phase CT scans. Based on a new self-learning framework, we propose to train the PDAC segmentation model using a much larger quantity of patients (n~=1,000), with a mix of annotated and un-annotated venous or multi-phase CT images. Pseudo annotations are generated by combining two teacher models with different PDAC segmentation specialties on unannotated images, and can be further refined by a teaching assistant model that identifies associated vessels around the pancreas. A student model is trained on both manual and pseudo annotated multi-phase images. Experiment results show that our proposed method provides an absolute improvement of 6.3% Dice score over the strong baseline of nnUNet trained on annotated images, achieving the performance (Dice = 0.71) similar to the inter-observer variability between radiologists.