Harini Veeraraghavan

Jue Jiang, Neelam Tyagi, Kathryn Tringale et al.

Vision transformers, with their ability to more efficiently model long-range context, have demonstrated impressive accuracy gains in several computer vision and medical image analysis tasks including segmentation. However, such methods need large labeled datasets for training, which is hard to obtain for medical image analysis. Self-supervised learning (SSL) has demonstrated success in medical image segmentation using convolutional networks. In this work, we developed a \underline{s}elf-distillation learning with \underline{m}asked \underline{i}mage modeling method to perform SSL for vision \underline{t}ransformers (SMIT) applied to 3D multi-organ segmentation from CT and MRI. Our contribution is a dense pixel-wise regression within masked patches called masked image prediction, which we combined with masked patch token distillation as pretext task to pre-train vision transformers. We show our approach is more accurate and requires fewer fine tuning datasets than other pretext tasks. Unlike prior medical image methods, which typically used image sets arising from disease sites and imaging modalities corresponding to the target tasks, we used 3,643 CT scans (602,708 images) arising from head and neck, lung, and kidney cancers as well as COVID-19 for pre-training and applied it to abdominal organs segmentation from MRI pancreatic cancer patients as well as publicly available 13 different abdominal organs segmentation from CT. Our method showed clear accuracy improvement (average DSC of 0.875 from MRI and 0.878 from CT) with reduced requirement for fine-tuning datasets over commonly used pretext tasks. Extensive comparisons against multiple current SSL methods were done. Code will be made available upon acceptance for publication.

Jue Jiang, Jun Hong, Kathryn Tringale et al.

Method: ProRSeg was trained using 5-fold cross-validation with 110 T2-weighted MRI acquired at 5 treatment fractions from 10 different patients, taking care that same patient scans were not placed in training and testing folds. Segmentation accuracy was measured using Dice similarity coefficient (DSC) and Hausdorff distance at 95th percentile (HD95). Registration consistency was measured using coefficient of variation (CV) in displacement of OARs. Ablation tests and accuracy comparisons against multiple methods were done. Finally, applicability of ProRSeg to segment cone-beam CT (CBCT) scans was evaluated on 80 scans using 5-fold cross-validation. Results: ProRSeg processed 3D volumes (128 $\times$ 192 $\times$ 128) in 3 secs on a NVIDIA Tesla V100 GPU. It's segmentations were significantly more accurate ($p<0.001$) than compared methods, achieving a DSC of 0.94 $\pm$0.02 for liver, 0.88$\pm$0.04 for large bowel, 0.78$\pm$0.03 for small bowel and 0.82$\pm$0.04 for stomach-duodenum from MRI. ProRSeg achieved a DSC of 0.72$\pm$0.01 for small bowel and 0.76$\pm$0.03 for stomach-duodenum from CBCT. ProRSeg registrations resulted in the lowest CV in displacement (stomach-duodenum $CV_{x}$: 0.75\%, $CV_{y}$: 0.73\%, and $CV_{z}$: 0.81\%; small bowel $CV_{x}$: 0.80\%, $CV_{y}$: 0.80\%, and $CV_{z}$: 0.68\%; large bowel $CV_{x}$: 0.71\%, $CV_{y}$ : 0.81\%, and $CV_{z}$: 0.75\%). ProRSeg based dose accumulation accounting for intra-fraction (pre-treatment to post-treatment MRI scan) and inter-fraction motion showed that the organ dose constraints were violated in 4 patients for stomach-duodenum and for 3 patients for small bowel. Study limitations include lack of independent testing and ground truth phantom datasets to measure dose accumulation accuracy.

Maxime Kayser, Maksim Gridnev, Wanting Wang et al.

We present brat (brain report alignment transformer), a multi-view representation learning framework for brain magnetic resonance imaging (MRI) trained on MRIs paired with clinical reports. Brain MRIs present unique challenges due to the presence of numerous, highly varied, and often subtle abnormalities that are localized to a few slices within a 3D volume. To address these challenges, we introduce a brain MRI dataset $10\times$ larger than existing ones, containing approximately 80,000 3D scans with corresponding radiology reports, and propose a multi-view pre-training approach inspired by advances in document retrieval. We develop an implicit query-feature matching mechanism and adopt concepts from quality-diversity to obtain multi-view embeddings of MRIs that are aligned with the clinical features given by report sentences. We evaluate our approach across multiple vision-language and vision tasks, demonstrating substantial performance improvements. The brat foundation models are publicly released.

Hyemin Um, Jue Jiang, Maria Thor et al.

We implemented and evaluated a multiple resolution residual network (MRRN) for multiple normal organs-at-risk (OAR) segmentation from computed tomography (CT) images for thoracic radiotherapy treatment (RT) planning. Our approach simultaneously combines feature streams computed at multiple image resolutions and feature levels through residual connections. The feature streams at each level are updated as the images are passed through various feature levels. We trained our approach using 206 thoracic CT scans of lung cancer patients with 35 scans held out for validation to segment the left and right lungs, heart, esophagus, and spinal cord. This approach was tested on 60 CT scans from the open-source AAPM Thoracic Auto-Segmentation Challenge dataset. Performance was measured using the Dice Similarity Coefficient (DSC). Our approach outperformed the best-performing method in the grand challenge for hard-to-segment structures like the esophagus and achieved comparable results for all other structures. Median DSC using our method was 0.97 (interquartile range [IQR]: 0.97-0.98) for the left and right lungs, 0.93 (IQR: 0.93-0.95) for the heart, 0.78 (IQR: 0.76-0.80) for the esophagus, and 0.88 (IQR: 0.86-0.89) for the spinal cord.

Jue Jiang, Jason Hu, Neelam Tyagi et al.

Lung tumors, especially those located close to or surrounded by soft tissues like the mediastinum, are difficult to segment due to the low soft tissue contrast on computed tomography images. Magnetic resonance images contain superior soft-tissue contrast information that can be leveraged if both modalities were available for training. Therefore, we developed a cross-modality educed learning approach where MR information that is educed from CT is used to hallucinate MRI and improve CT segmentation. Our approach, called cross-modality educed deep learning segmentation (CMEDL) combines CT and pseudo MR produced from CT by aligning their features to obtain segmentation on CT. Features computed in the last two layers of parallelly trained CT and MR segmentation networks are aligned. We implemented this approach on U-net and dense fully convolutional networks (dense-FCN). Our networks were trained on unrelated cohorts from open-source the Cancer Imaging Archive CT images (N=377), an internal archive T2-weighted MR (N=81), and evaluated using separate validation (N=304) and testing (N=333) CT-delineated tumors. Our approach using both networks were significantly more accurate (U-net $P <0.001$; denseFCN $P <0.001$) than CT-only networks and achieved an accuracy (Dice similarity coefficient) of 0.71$\pm$0.15 (U-net), 0.74$\pm$0.12 (denseFCN) on validation and 0.72$\pm$0.14 (U-net), 0.73$\pm$0.12 (denseFCN) on the testing sets. Our novel approach demonstrated that educing cross-modality information through learned priors enhances CT segmentation performance

Sudharsan Madhavan, Chengcheng Gui, Lando Bosma et al.

Background: Accurate deformable image registration (DIR) is required for contour propagation and dose accumulation in MR-guided adaptive radiotherapy (MRgART). This study trained and evaluated a deep learning DIR method for domain invariant MR-MR registration. Methods: A progressively refined registration and segmentation (ProRSeg) method was trained with 262 pairs of 3T MR simulation scans from prostate cancer patients using weighted segmentation consistency loss. ProRSeg was tested on same- (58 pairs), cross- (72 1.5T MR Linac pairs), and mixed-domain (42 MRSim-MRL pairs) datasets for contour propagation accuracy of clinical target volume (CTV), bladder, and rectum. Dose accumulation was performed for 42 patients undergoing 5-fraction MRgART. Results: ProRSeg demonstrated generalization for bladder with similar Dice Similarity Coefficients across domains (0.88, 0.87, 0.86). For rectum and CTV, performance was domain-dependent with higher accuracy on cross-domain MRL dataset (DSCs 0.89) versus same-domain data. The model's strong cross-domain performance prompted us to study the feasibility of using it for dose accumulation. Dose accumulation showed 83.3% of patients met CTV coverage (D95 >= 40.0 Gy) and bladder sparing (D50 <= 20.0 Gy) constraints. All patients achieved minimum mean target dose (>40.4 Gy), but only 9.5% remained under upper limit (<42.0 Gy). Conclusions: ProRSeg showed reasonable multi-domain MR-MR registration performance for prostate cancer patients with preliminary feasibility for evaluating treatment compliance to clinical constraints.

Jue Jiang, Aneesh Rangnekar, Harini Veeraraghavan

Self-supervised learning (SSL) is an approach to extract useful feature representations from unlabeled data, and enable fine-tuning on downstream tasks with limited labeled examples. Self-pretraining is a SSL approach that uses the curated task dataset for both pretraining the networks and fine-tuning them. Availability of large, diverse, and uncurated public medical image sets provides the opportunity to apply SSL in the "wild" and potentially extract features robust to imaging variations. However, the benefit of wild- vs self-pretraining has not been studied for medical image analysis. In this paper, we compare robustness of wild versus self-pretrained transformer (vision transformer [ViT] and hierarchical shifted window [Swin]) models to computed tomography (CT) imaging differences for non-small cell lung cancer (NSCLC) segmentation. Wild-pretrained Swin models outperformed self-pretrained Swin for the various imaging acquisitions. ViT resulted in similar accuracy for both wild- and self-pretrained models. Masked image prediction pretext task that forces networks to learn the local structure resulted in higher accuracy compared to contrastive task that models global image information. Wild-pretrained models resulted in higher feature reuse at the lower level layers and feature differentiation close to output layer after fine-tuning. Hence, we conclude: Wild-pretrained networks were more robust to analyzed CT imaging differences for lung tumor segmentation than self-pretrained methods. Swin architecture benefited from such pretraining more than ViT.

Jorge Tapias Gomez, Aneesh Rangnekar, Hannah Williams et al.

Endoscopic images are used at various stages of rectal cancer treatment starting from cancer screening, diagnosis, during treatment to assess response and toxicity from treatments such as colitis, and at follow up to detect new tumor or local regrowth (LR). However, subjective assessment is highly variable and can underestimate the degree of response in some patients, subjecting them to unnecessary surgery, or overestimate response that places patients at risk of disease spread. Advances in deep learning has shown the ability to produce consistent and objective response assessment for endoscopic images. However, methods for detecting cancers, regrowth, and monitoring response during the entire course of patient treatment and follow-up are lacking. This is because, automated diagnosis and rectal cancer response assessment requires methods that are robust to inherent imaging illumination variations and confounding conditions (blood, scope, blurring) present in endoscopy images as well as changes to the normal lumen and tumor during treatment. Hence, a hierarchical shifted window (Swin) transformer was trained to distinguish rectal cancer from normal lumen using endoscopy images. Swin as well as two convolutional (ResNet-50, WideResNet-50), and vision transformer (ViT) models were trained and evaluated on follow-up longitudinal images to detect LR on private dataset as well as on out-of-distribution (OOD) public colonoscopy datasets to detect pre/non-cancerous polyps. Color shifts were applied using optimal transport to simulate distribution shifts. Swin and ResNet models were similarly accurate in the in-distribution dataset. Swin was more accurate than other methods (follow-up: 0.84, OOD: 0.83) even when subject to color shifts (follow-up: 0.83, OOD: 0.87), indicating capability to provide robust performance for longitudinal cancer assessment.

Aneesh Rangnekar, Nishant Nadkarni, Jue Jiang et al.

Medical image foundation models have shown the ability to segment organs and tumors with minimal fine-tuning. These models are typically evaluated on task-specific in-distribution (ID) datasets. However, reliable performance on ID datasets does not guarantee robust generalization on out-of-distribution (OOD) datasets. Importantly, once deployed for clinical use, it is impractical to have `ground truth' delineations to assess ongoing performance drifts, especially when images fall into the OOD category due to different imaging protocols. Hence, we introduced a comprehensive set of computationally fast metrics to evaluate the performance of multiple foundation models (Swin UNETR, SimMIM, iBOT, SMIT) trained with self-supervised learning (SSL). All models were fine-tuned on identical datasets for lung tumor segmentation from computed tomography (CT) scans. The evaluation was performed on two public lung cancer datasets (LRAD: n = 140, 5Rater: n = 21) with different image acquisitions and tumor stages compared to training data (n = 317 public resource with stage III-IV lung cancers) and a public non-cancer dataset containing volumetric CT scans of patients with pulmonary embolism (n = 120). All models produced similarly accurate tumor segmentation on the lung cancer testing datasets. SMIT produced the highest F1-score (LRAD: 0.60, 5Rater: 0.64) and lowest entropy (LRAD: 0.06, 5Rater: 0.12), indicating higher tumor detection rate and confident segmentations. In the OOD dataset, SMIT misdetected the least number of tumors, marked by a median volume occupancy of 5.67 cc compared to the best method SimMIM of 9.97 cc. Our analysis shows that additional metrics such as entropy and volume occupancy may help better understand model performance on mixed domain datasets.

Jue Jiang, Harini Veeraraghavan

Image-guided adaptive lung radiotherapy requires accurate tumor and organs segmentation from during treatment cone-beam CT (CBCT) images. Thoracic CBCTs are hard to segment because of low soft-tissue contrast, imaging artifacts, respiratory motion, and large treatment induced intra-thoracic anatomic changes. Hence, we developed a novel Patient-specific Anatomic Context and Shape prior or PACS-aware 3D recurrent registration-segmentation network for longitudinal thoracic CBCT segmentation. Segmentation and registration networks were concurrently trained in an end-to-end framework and implemented with convolutional long-short term memory models. The registration network was trained in an unsupervised manner using pairs of planning CT (pCT) and CBCT images and produced a progressively deformed sequence of images. The segmentation network was optimized in a one-shot setting by combining progressively deformed pCT (anatomic context) and pCT delineations (shape context) with CBCT images. Our method, one-shot PACS was significantly more accurate (p$<$0.001) for tumor (DSC of 0.83 $\pm$ 0.08, surface DSC [sDSC] of 0.97 $\pm$ 0.06, and Hausdorff distance at $95^{th}$ percentile [HD95] of 3.97$\pm$3.02mm) and the esophagus (DSC of 0.78 $\pm$ 0.13, sDSC of 0.90$\pm$0.14, HD95 of 3.22$\pm$2.02) segmentation than multiple methods. Ablation tests and comparative experiments were also done.

Harini Veeraraghavan, Jue Jiang, Sharif Elguindi et al.

Although deep convolutional networks have been widely studied for head and neck (HN) organs at risk (OAR) segmentation, their use for routine clinical treatment planning is limited by a lack of robustness to imaging artifacts, low soft tissue contrast on CT, and the presence of abnormal anatomy. In order to address these challenges, we developed a computationally efficient nested block self-attention (NBSA) method that can be combined with any convolutional network. Our method achieves computational efficiency by performing non-local calculations within memory blocks of fixed spatial extent. Contextual dependencies are captured by passing information in a raster scan order between blocks, as well as through a second attention layer that causes bi-directional attention flow. We implemented our approach on three different networks to demonstrate feasibility. Following training using 200 cases, we performed comprehensive evaluations using conventional and clinical metrics on a separate set of 172 test scans sourced from external and internal institution datasets without any exclusion criteria. NBSA required a similar number of computations (15.7 gflops) as the most efficient criss-cross attention (CCA) method and generated significantly more accurate segmentations for brain stem (Dice of 0.89 vs. 0.86) and parotid glands (0.86 vs. 0.84) than CCA. NBSA's segmentations were less variable than multiple 3D methods, including for small organs with low soft-tissue contrast such as the submandibular glands (surface Dice of 0.90).

Jue Jiang, Sadegh Riyahi Alam, Ishita Chen et al.

Despite the widespread availability of in-treatment room cone beam computed tomography (CBCT) imaging, due to the lack of reliable segmentation methods, CBCT is only used for gross set up corrections in lung radiotherapies. Accurate and reliable auto-segmentation tools could potentiate volumetric response assessment and geometry-guided adaptive radiation therapies. Therefore, we developed a new deep learning CBCT lung tumor segmentation method. Methods: The key idea of our approach called cross modality educed distillation (CMEDL) is to use magnetic resonance imaging (MRI) to guide a CBCT segmentation network training to extract more informative features during training. We accomplish this by training an end-to-end network comprised of unpaired domain adaptation (UDA) and cross-domain segmentation distillation networks (SDN) using unpaired CBCT and MRI datasets. Feature distillation regularizes the student network to extract CBCT features that match the statistical distribution of MRI features extracted by the teacher network and obtain better differentiation of tumor from background.} We also compared against an alternative framework that used UDA with MR segmentation network, whereby segmentation was done on the synthesized pseudo MRI representation. All networks were trained with 216 weekly CBCTs and 82 T2-weighted turbo spin echo MRI acquired from different patient cohorts. Validation was done on 20 weekly CBCTs from patients not used in training. Independent testing was done on 38 weekly CBCTs from patients not used in training or validation. Segmentation accuracy was measured using surface Dice similarity coefficient (SDSC) and Hausdroff distance at 95th percentile (HD95) metrics.

Jue Jiang, Harini Veeraraghavan

Our contribution is a unified cross-modality feature disentagling approach for multi-domain image translation and multiple organ segmentation. Using CT as the labeled source domain, our approach learns to segment multi-modal (T1-weighted and T2-weighted) MRI having no labeled data. Our approach uses a variational auto-encoder (VAE) to disentangle the image content from style. The VAE constrains the style feature encoding to match a universal prior (Gaussian) that is assumed to span the styles of all the source and target modalities. The extracted image style is converted into a latent style scaling code, which modulates the generator to produce multi-modality images according to the target domain code from the image content features. Finally, we introduce a joint distribution matching discriminator that combines the translated images with task-relevant segmentation probability maps to further constrain and regularize image-to-image (I2I) translations. We performed extensive comparisons to multiple state-of-the-art I2I translation and segmentation methods. Our approach resulted in the lowest average multi-domain image reconstruction error of 1.34$\pm$0.04. Our approach produced an average Dice similarity coefficient (DSC) of 0.85 for T1w and 0.90 for T2w MRI for multi-organ segmentation, which was highly comparable to a fully supervised MRI multi-organ segmentation network (DSC of 0.86 for T1w and 0.90 for T2w MRI).

Jue Jiang, Yu Chi Hu, Neelam Tyagi et al.

We developed a new joint probabilistic segmentation and image distribution matching generative adversarial network (PSIGAN) for unsupervised domain adaptation (UDA) and multi-organ segmentation from magnetic resonance (MRI) images. Our UDA approach models the co-dependency between images and their segmentation as a joint probability distribution using a new structure discriminator. The structure discriminator computes structure of interest focused adversarial loss by combining the generated pseudo MRI with probabilistic segmentations produced by a simultaneously trained segmentation sub-network. The segmentation sub-network is trained using the pseudo MRI produced by the generator sub-network. This leads to a cyclical optimization of both the generator and segmentation sub-networks that are jointly trained as part of an end-to-end network. Extensive experiments and comparisons against multiple state-of-the-art methods were done on four different MRI sequences totalling 257 scans for generating multi-organ and tumor segmentation. The experiments included, (a) 20 T1-weighted (T1w) in-phase mdixon and (b) 20 T2-weighted (T2w) abdominal MRI for segmenting liver, spleen, left and right kidneys, (c) 162 T2-weighted fat suppressed head and neck MRI (T2wFS) for parotid gland segmentation, and (d) 75 T2w MRI for lung tumor segmentation. Our method achieved an overall average DSC of 0.87 on T1w and 0.90 on T2w for the abdominal organs, 0.82 on T2wFS for the parotid glands, and 0.77 on T2w MRI for lung tumors.

Jue Jiang, Elguindi Sharif, Hyemin Um et al.

We developed a new and computationally simple local block-wise self attention based normal structures segmentation approach applied to head and neck computed tomography (CT) images. Our method uses the insight that normal organs exhibit regularity in their spatial location and inter-relation within images, which can be leveraged to simplify the computations required to aggregate feature information. We accomplish this by using local self attention blocks that pass information between each other to derive the attention map. We show that adding additional attention layers increases the contextual field and captures focused attention from relevant structures. We developed our approach using U-net and compared it against multiple state-of-the-art self attention methods. All models were trained on 48 internal headneck CT scans and tested on 48 CT scans from the external public domain database of computational anatomy dataset. Our method achieved the highest Dice similarity coefficient segmentation accuracy of 0.85$\pm$0.04, 0.86$\pm$0.04 for left and right parotid glands, 0.79$\pm$0.07 and 0.77$\pm$0.05 for left and right submandibular glands, 0.93$\pm$0.01 for mandible and 0.88$\pm$0.02 for the brain stem with the lowest increase of 66.7\% computing time per image and 0.15\% increase in model parameters compared with standard U-net. The best state-of-the-art method called point-wise spatial attention, achieved \textcolor{black}{comparable accuracy but with 516.7\% increase in computing time and 8.14\% increase in parameters compared with standard U-net.} Finally, we performed ablation tests and studied the impact of attention block size, overlap of the attention blocks, additional attention layers, and attention block placement on segmentation performance.

Peter Klages, Ilyes Benslimane, Sadegh Riyahi et al.

A total of twenty paired CT and MR images were used in this study to investigate two conditional generative adversarial networks, Pix2Pix, and Cycle GAN, for generating synthetic CT images for Headand Neck cancer cases. Ten of the patient cases were used for training and included such common artifacts as dental implants; the remaining ten testing cases were used for testing and included a larger range of image features commonly found in clinical head and neck cases. These features included strong metal artifacts from dental implants, one case with a metal implant, and one case with abnormal anatomy. The original CT images were deformably registered to the mDixon FFE MR images to minimize the effects of processing the MR images. The sCT generation accuracy and robustness were evaluated using Mean Absolute Error (MAE) based on the Hounsfield Units (HU) for three regions (whole body, bone, and air within the body), Mean Error (ME) to observe systematic average offset errors in the sCT generation, and dosimetric evaluation of all clinically relevant structures. For the test set the MAE for the Pix2Pix and Cycle GAN models were 92.4 $\pm$ 13.5 HU, and 100.7 $\pm$ 14.6 HU, respectively, for the body region, 166.3 $\pm$ 31.8 HU, and 184 $\pm$ 31.9 HU, respectively, for the bone region, and 183.7 $\pm$ 41.3 HU and 185.4 $\pm$ 37.9 HU for the air regions. The ME for Pix2Pix and Cycle GAN were 21.0 $\pm$ 11.8 HU and 37.5 $\pm$ 14.9 HU, respectively. Absolute Percent Mean/Max Dose Errors were less than 2% for the PTV and all critical structures for both models, and DRRs generated from these models looked qualitatively similar to CT generated DRRs showing these methods are promising for MR-only planning.

Jan Egger, Tina Kapur, Andriy Fedorov et al.

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer - a free platform for biomedical research - provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 +/- 5.23% and a Hausdorff Distance of 2.32 +/- 5.23 mm.