Multi-Contrast Computed Tomography Atlas of Healthy Pancreas

With the substantial diversity in population demographics, such as differences in age and body composition, the volumetric morphology of pancreas varies greatly, resulting in distinctive variations in shape and appearance. Such variations increase the difficulty at generalizing population-wide pancreas features. A volumetric spatial reference is needed to adapt the morphological variability for organ-specific analysis. Here, we proposed a high-resolution computed tomography (CT) atlas framework specifically optimized for the pancreas organ across multi-contrast CT. We introduce a deep learning-based pre-processing technique to extract the abdominal region of interests (ROIs) and leverage a hierarchical registration pipeline to align the pancreas anatomy across populations. Briefly, DEEDs affine and non-rigid registration are performed to transfer patient abdominal volumes to a fixed high-resolution atlas template. To generate and evaluate the pancreas atlas template, multi-contrast modality CT scans of 443 subjects (without reported history of pancreatic disease, age: 15-50 years old) are processed. Comparing with different registration state-of-the-art tools, the combination of DEEDs affine and non-rigid registration achieves the best performance for the pancreas label transfer across all contrast phases. We further perform external evaluation with another research cohort of 100 de-identified portal venous scans with 13 organs labeled, having the best label transfer performance of 0.504 Dice score in unsupervised setting. The qualitative representation (e.g., average mapping) of each phase creates a clear boundary of pancreas and its distinctive contrast appearance. The deformation surface renderings across scales (e.g., small to large volume) further illustrate the generalizability of the proposed atlas template.

Region-based Contrastive Pretraining for Medical Image Retrieval with Anatomic Query

We introduce a novel Region-based contrastive pretraining for Medical Image Retrieval (RegionMIR) that demonstrates the feasibility of medical image retrieval with similar anatomical regions. RegionMIR addresses two major challenges for medical image retrieval i) standardization of clinically relevant searching criteria (e.g., anatomical, pathology-based), and ii) localization of anatomical area of interests that are semantically meaningful. In this work, we propose an ROI image retrieval image network that retrieves images with similar anatomy by extracting anatomical features (via bounding boxes) and evaluate similarity between pairwise anatomy-categorized features between the query and the database of images using contrastive learning. ROI queries are encoded using a contrastive-pretrained encoder that was fine-tuned for anatomy classification, which generates an anatomical-specific latent space for region-correlated image retrieval. During retrieval, we compare the anatomically encoded query to find similar features within a feature database generated from training samples, and retrieve images with similar regions from training samples. We evaluate our approach on both anatomy classification and image retrieval tasks using the Chest ImaGenome Dataset. Our proposed strategy yields an improvement over state-of-the-art pretraining and co-training strategies, from 92.24 to 94.12 (2.03%) classification accuracy in anatomies. We qualitatively evaluate the image retrieval performance demonstrating generalizability across multiple anatomies with different morphology.

Longitudinal Multimodal Transformer Integrating Imaging and Latent Clinical Signatures From Routine EHRs for Pulmonary Nodule Classification

The accuracy of predictive models for solitary pulmonary nodule (SPN) diagnosis can be greatly increased by incorporating repeat imaging and medical context, such as electronic health records (EHRs). However, clinically routine modalities such as imaging and diagnostic codes can be asynchronous and irregularly sampled over different time scales which are obstacles to longitudinal multimodal learning. In this work, we propose a transformer-based multimodal strategy to integrate repeat imaging with longitudinal clinical signatures from routinely collected EHRs for SPN classification. We perform unsupervised disentanglement of latent clinical signatures and leverage time-distance scaled self-attention to jointly learn from clinical signatures expressions and chest computed tomography (CT) scans. Our classifier is pretrained on 2,668 scans from a public dataset and 1,149 subjects with longitudinal chest CTs, billing codes, medications, and laboratory tests from EHRs of our home institution. Evaluation on 227 subjects with challenging SPNs revealed a significant AUC improvement over a longitudinal multimodal baseline (0.824 vs 0.752 AUC), as well as improvements over a single cross-section multimodal scenario (0.809 AUC) and a longitudinal imaging-only scenario (0.741 AUC). This work demonstrates significant advantages with a novel approach for co-learning longitudinal imaging and non-imaging phenotypes with transformers.

Scaling Up 3D Kernels with Bayesian Frequency Re-parameterization for Medical Image Segmentation

With the inspiration of vision transformers, the concept of depth-wise convolution revisits to provide a large Effective Receptive Field (ERF) using Large Kernel (LK) sizes for medical image segmentation. However, the segmentation performance might be saturated and even degraded as the kernel sizes scaled up (e.g., $21\times 21\times 21$) in a Convolutional Neural Network (CNN). We hypothesize that convolution with LK sizes is limited to maintain an optimal convergence for locality learning. While Structural Re-parameterization (SR) enhances the local convergence with small kernels in parallel, optimal small kernel branches may hinder the computational efficiency for training. In this work, we propose RepUX-Net, a pure CNN architecture with a simple large kernel block design, which competes favorably with current network state-of-the-art (SOTA) (e.g., 3D UX-Net, SwinUNETR) using 6 challenging public datasets. We derive an equivalency between kernel re-parameterization and the branch-wise variation in kernel convergence. Inspired by the spatial frequency in the human visual system, we extend to vary the kernel convergence into element-wise setting and model the spatial frequency as a Bayesian prior to re-parameterize convolutional weights during training. Specifically, a reciprocal function is leveraged to estimate a frequency-weighted value, which rescales the corresponding kernel element for stochastic gradient descent. From the experimental results, RepUX-Net consistently outperforms 3D SOTA benchmarks with internal validation (FLARE: 0.929 to 0.944), external validation (MSD: 0.901 to 0.932, KiTS: 0.815 to 0.847, LiTS: 0.933 to 0.949, TCIA: 0.736 to 0.779) and transfer learning (AMOS: 0.880 to 0.911) scenarios in Dice Score.

Single Slice Thigh CT Muscle Group Segmentation with Domain Adaptation and Self-Training

Objective: Thigh muscle group segmentation is important for assessment of muscle anatomy, metabolic disease and aging. Many efforts have been put into quantifying muscle tissues with magnetic resonance (MR) imaging including manual annotation of individual muscles. However, leveraging publicly available annotations in MR images to achieve muscle group segmentation on single slice computed tomography (CT) thigh images is challenging. Method: We propose an unsupervised domain adaptation pipeline with self-training to transfer labels from 3D MR to single CT slice. First, we transform the image appearance from MR to CT with CycleGAN and feed the synthesized CT images to a segmenter simultaneously. Single CT slices are divided into hard and easy cohorts based on the entropy of pseudo labels inferenced by the segmenter. After refining easy cohort pseudo labels based on anatomical assumption, self-training with easy and hard splits is applied to fine tune the segmenter. Results: On 152 withheld single CT thigh images, the proposed pipeline achieved a mean Dice of 0.888(0.041) across all muscle groups including sartorius, hamstrings, quadriceps femoris and gracilis. muscles Conclusion: To our best knowledge, this is the first pipeline to achieve thigh imaging domain adaptation from MR to CT. The proposed pipeline is effective and robust in extracting muscle groups on 2D single slice CT thigh images.The container is available for public use at https://github.com/MASILab/DA_CT_muscle_seg

Adaptive Contrastive Learning with Dynamic Correlation for Multi-Phase Organ Segmentation

Recent studies have demonstrated the superior performance of introducing ``scan-wise" contrast labels into contrastive learning for multi-organ segmentation on multi-phase computed tomography (CT). However, such scan-wise labels are limited: (1) a coarse classification, which could not capture the fine-grained ``organ-wise" contrast variations across all organs; (2) the label (i.e., contrast phase) is typically manually provided, which is error-prone and may introduce manual biases of defining phases. In this paper, we propose a novel data-driven contrastive loss function that adapts the similar/dissimilar contrast relationship between samples in each minibatch at organ-level. Specifically, as variable levels of contrast exist between organs, we hypothesis that the contrast differences in the organ-level can bring additional context for defining representations in the latent space. An organ-wise contrast correlation matrix is computed with mean organ intensities under one-hot attention maps. The goal of adapting the organ-driven correlation matrix is to model variable levels of feature separability at different phases. We evaluate our proposed approach on multi-organ segmentation with both non-contrast CT (NCCT) datasets and the MICCAI 2015 BTCV Challenge contrast-enhance CT (CECT) datasets. Compared to the state-of-the-art approaches, our proposed contrastive loss yields a substantial and significant improvement of 1.41% (from 0.923 to 0.936, p-value$<$0.01) and 2.02% (from 0.891 to 0.910, p-value$<$0.01) on mean Dice scores across all organs with respect to NCCT and CECT cohorts. We further assess the trained model performance with the MICCAI 2021 FLARE Challenge CECT datasets and achieve a substantial improvement of mean Dice score from 0.927 to 0.934 (p-value$<$0.01). The code is available at: https://github.com/MASILab/DCC_CL

3D UX-Net: A Large Kernel Volumetric ConvNet Modernizing Hierarchical Transformer for Medical Image Segmentation

Vision transformers (ViTs) have quickly superseded convolutional networks (ConvNets) as the current state-of-the-art (SOTA) models for medical image segmentation. Hierarchical transformers (e.g., Swin Transformers) reintroduced several ConvNet priors and further enhanced the practical viability of adapting volumetric segmentation in 3D medical datasets. The effectiveness of hybrid approaches is largely credited to the large receptive field for non-local self-attention and the large number of model parameters. In this work, we propose a lightweight volumetric ConvNet, termed 3D UX-Net, which adapts the hierarchical transformer using ConvNet modules for robust volumetric segmentation. Specifically, we revisit volumetric depth-wise convolutions with large kernel size (e.g. starting from $7\times7\times7$) to enable the larger global receptive fields, inspired by Swin Transformer. We further substitute the multi-layer perceptron (MLP) in Swin Transformer blocks with pointwise depth convolutions and enhance model performances with fewer normalization and activation layers, thus reducing the number of model parameters. 3D UX-Net competes favorably with current SOTA transformers (e.g. SwinUNETR) using three challenging public datasets on volumetric brain and abdominal imaging: 1) MICCAI Challenge 2021 FLARE, 2) MICCAI Challenge 2021 FeTA, and 3) MICCAI Challenge 2022 AMOS. 3D UX-Net consistently outperforms SwinUNETR with improvement from 0.929 to 0.938 Dice (FLARE2021) and 0.867 to 0.874 Dice (Feta2021). We further evaluate the transfer learning capability of 3D UX-Net with AMOS2022 and demonstrates another improvement of $2.27\%$ Dice (from 0.880 to 0.900). The source code with our proposed model are available at https://github.com/MASILab/3DUX-Net.

Reducing Positional Variance in Cross-sectional Abdominal CT Slices with Deep Conditional Generative Models

2D low-dose single-slice abdominal computed tomography (CT) slice enables direct measurements of body composition, which are critical to quantitatively characterizing health relationships on aging. However, longitudinal analysis of body composition changes using 2D abdominal slices is challenging due to positional variance between longitudinal slices acquired in different years. To reduce the positional variance, we extend the conditional generative models to our C-SliceGen that takes an arbitrary axial slice in the abdominal region as the condition and generates a defined vertebral level slice by estimating the structural changes in the latent space. Experiments on 1170 subjects from an in-house dataset and 50 subjects from BTCV MICCAI Challenge 2015 show that our model can generate high quality images in terms of realism and similarity. External experiments on 20 subjects from the Baltimore Longitudinal Study of Aging (BLSA) dataset that contains longitudinal single abdominal slices validate that our method can harmonize the slice positional variance in terms of muscle and visceral fat area. Our approach provides a promising direction of mapping slices from different vertebral levels to a target slice to reduce positional variance for single slice longitudinal analysis. The source code is available at: https://github.com/MASILab/C-SliceGen.

UNesT: Local Spatial Representation Learning with Hierarchical Transformer for Efficient Medical Segmentation

Transformer-based models, capable of learning better global dependencies, have recently demonstrated exceptional representation learning capabilities in computer vision and medical image analysis. Transformer reformats the image into separate patches and realize global communication via the self-attention mechanism. However, positional information between patches is hard to preserve in such 1D sequences, and loss of it can lead to sub-optimal performance when dealing with large amounts of heterogeneous tissues of various sizes in 3D medical image segmentation. Additionally, current methods are not robust and efficient for heavy-duty medical segmentation tasks such as predicting a large number of tissue classes or modeling globally inter-connected tissues structures. Inspired by the nested hierarchical structures in vision transformer, we proposed a novel 3D medical image segmentation method (UNesT), employing a simplified and faster-converging transformer encoder design that achieves local communication among spatially adjacent patch sequences by aggregating them hierarchically. We extensively validate our method on multiple challenging datasets, consisting anatomies of 133 structures in brain, 14 organs in abdomen, 4 hierarchical components in kidney, and inter-connected kidney tumors). We show that UNesT consistently achieves state-of-the-art performance and evaluate its generalizability and data efficiency. Particularly, the model achieves whole brain segmentation task complete ROI with 133 tissue classes in single network, outperforms prior state-of-the-art method SLANT27 ensembled with 27 network tiles, our model performance increases the mean DSC score of the publicly available Colin and CANDI dataset from 0.7264 to 0.7444 and from 0.6968 to 0.7025, respectively.

Longitudinal Variability Analysis on Low-dose Abdominal CT with Deep Learning-based Segmentation

Metabolic health is increasingly implicated as a risk factor across conditions from cardiology to neurology, and efficiency assessment of body composition is critical to quantitatively characterizing these relationships. 2D low dose single slice computed tomography (CT) provides a high resolution, quantitative tissue map, albeit with a limited field of view. Although numerous potential analyses have been proposed in quantifying image context, there has been no comprehensive study for low-dose single slice CT longitudinal variability with automated segmentation. We studied a total of 1816 slices from 1469 subjects of Baltimore Longitudinal Study on Aging (BLSA) abdominal dataset using supervised deep learning-based segmentation and unsupervised clustering method. 300 out of 1469 subjects that have two year gap in their first two scans were pick out to evaluate longitudinal variability with measurements including intraclass correlation coefficient (ICC) and coefficient of variation (CV) in terms of tissues/organs size and mean intensity. We showed that our segmentation methods are stable in longitudinal settings with Dice ranged from 0.821 to 0.962 for thirteen target abdominal tissues structures. We observed high variability in most organ with ICC<0.5, low variability in the area of muscle, abdominal wall, fat and body mask with average ICC>0.8. We found that the variability in organ is highly related to the cross-sectional position of the 2D slice. Our efforts pave quantitative exploration and quality control to reduce uncertainties in longitudinal analysis.