KCB-Net: A 3D knee cartilage and bone segmentation network via sparse annotation

Knee cartilage and bone segmentation is critical for physicians to analyze and diagnose articular damage and knee osteoarthritis (OA). Deep learning (DL) methods for medical image segmentation have largely outperformed traditional methods, but they often need large amounts of annotated data for model training, which is very costly and time-consuming for medical experts, especially on 3D images. In this paper, we report a new knee cartilage and bone segmentation framework, KCB-Net, for 3D MR images based on sparse annotation. KCB-Net selects a small subset of slices from 3D images for annotation, and seeks to bridge the performance gap between sparse annotation and full annotation. Specifically, it first identifies a subset of the most effective and representative slices with an unsupervised scheme; it then trains an ensemble model using the annotated slices; next, it self-trains the model using 3D images containing pseudo-labels generated by the ensemble method and improved by a bi-directional hierarchical earth mover’s distance (bi-HEMD) algorithm; finally, it fine-tunes the segmentation results using the primal–dual Internal Point Method (IPM). Experiments on four 3D MR knee joint datasets (the SKI10 dataset, OAI ZIB dataset, Iowa dataset, and iMorphics dataset) show that our new framework outperforms state-of-the-art methods on full annotation, and yields high quality results for small annotation ratios even as low as 10%.     

Suggestive annotation of brain MR images with gradient-guided sampling

Machine learning has been widely adopted for medical image analysis in recent years given its promising performance in image segmentation and classification tasks. The success of machine learning, in particular supervised learning, depends on the availability of manually annotated datasets. For medical imaging applications, such annotated datasets are not easy to acquire, it takes a substantial amount of time and resource to curate an annotated medical image set. In this paper, we propose an efficient annotation framework for brain MR images that can suggest informative sample images for human experts to annotate. We evaluate the framework on two different brain image analysis tasks, namely brain tumour segmentation and whole brain segmentation. Experiments show that for brain tumour segmentation task on the BraTS 2019 dataset, training a segmentation model with only 7% suggestively annotated image samples can achieve a performance comparable to that of training on the full dataset. For whole brain segmentation on the MALC dataset, training with 42% suggestively annotated image samples can achieve a comparable performance to training on the full dataset. The proposed framework demonstrates a promising way to save manual annotation cost and improve data efficiency in medical imaging applications.     

Vessel-CAPTCHA: An efficient learning framework for vessel annotation and segmentation

Deep learning techniques for 3D brain vessel image segmentation have not been as successful as in the segmentation of other organs and tissues. This can be explained by two factors. First, deep learning techniques tend to show poor performances at the segmentation of relatively small objects compared to the size of the full image. Second, due to the complexity of vascular trees and the small size of vessels, it is challenging to obtain the amount of annotated training data typically needed by deep learning methods. To address these problems, we propose a novel annotation-efficient deep learning vessel segmentation framework. The framework avoids pixel-wise annotations, only requiring weak patch-level labels to discriminate between vessel and non-vessel 2D patches in the training set, in a setup similar to the CAPTCHAs used to differentiate humans from bots in web applications. The user-provided weak annotations are used for two tasks: (1) to synthesize pixel-wise pseudo-labels for vessels and background in each patch, which are used to train a segmentation network, and (2) to train a classifier network. The classifier network allows to generate additional weak patch labels, further reducing the annotation burden, and it acts as a second opinion for poor quality images. We use this framework for the segmentation of the cerebrovascular tree in Time-of-Flight angiography (TOF) and Susceptibility-Weighted Images (SWI). The results show that the framework achieves state-of-the-art accuracy, while reducing the annotation time by $\sim$77% w.r.t. learning-based segmentation methods using pixel-wise labels for training.     

WORD: A large scale dataset,benchmark and clinical applicable study for abdominal organ segmentation from CT image

Whole abdominal organ segmentation is important in diagnosing abdomen lesions, radiotherapy, and follow-up. However, oncologists’ delineating all abdominal organs from 3D volumes is time-consuming and very expensive. Deep learning-based medical image segmentation has shown the potential to reduce manual delineation efforts, but it still requires a large-scale fine annotated dataset for training, and there is a lack of large-scale datasets covering the whole abdomen region with accurate and detailed annotations for the whole abdominal organ segmentation. In this work, we establish a new large-scale Whole abdominal ORgan Dataset (WORD) for algorithm research and clinical application development. This dataset contains 150 abdominal CT volumes (30495 slices). Each volume has 16 organs with fine pixel-level annotations and scribble-based sparse annotations, which may be the largest dataset with whole abdominal organ annotation. Several state-of-the-art segmentation methods are evaluated on this dataset. And we also invited three experienced oncologists to revise the model predictions to measure the gap between the deep learning method and oncologists. Afterwards, we investigate the inference-efficient learning on the WORD, as the high-resolution image requires large GPU memory and a long inference time in the test stage. We further evaluate the scribble-based annotation-efficient learning on this dataset, as the pixel-wise manual annotation is time-consuming and expensive. The work provided a new benchmark for the abdominal multi-organ segmentation task, and these experiments can serve as the baseline for future research and clinical application development.     

HAL-IA: A Hybrid Active Learning framework using Interactive Annotation for medical image segmentation

High performance of deep learning models on medical image segmentation greatly relies on large amount of pixel-wise annotated data, yet annotations are costly to collect. How to obtain high accuracy segmentation labels of medical images with limited cost (e.g. time) becomes an urgent problem. Active learning can reduce the annotation cost of image segmentation, but it faces three challenges: the cold start problem, an effective sample selection strategy for segmentation task and the burden of manual annotation. In this work, we propose a Hybrid Active Learning framework using Interactive Annotation (HAL-IA) for medical image segmentation, which reduces the annotation cost both in decreasing the amount of the annotated images and simplifying the annotation process. Specifically, we propose a novel hybrid sample selection strategy to select the most valuable samples for segmentation model performance improvement. This strategy combines pixel entropy, regional consistency and image diversity to ensure that the selected samples have high uncertainty and diversity. In addition, we propose a warm-start initialization strategy to build the initial annotated dataset to avoid the cold-start problem. To simplify the manual annotation process, we propose an interactive annotation module with suggested superpixels to obtain pixel-wise label with several clicks. We validate our proposed framework with extensive segmentation experiments on four medical image datasets. Experimental results showed that the proposed framework achieves high accuracy pixel-wise annotations and models with less labeled data and fewer interactions, outperforming other state-of-the-art methods. Our method can help physicians efficiently obtain accurate medical image segmentation results for clinical analysis and diagnosis.     

Unpaired mesh-to-image translation for 3D fluorescent microscopy images of neurons

While Generative Adversarial Networks (GANs) can now reliably produce realistic images in a multitude of imaging domains, they are ill-equipped to model thin, stochastic textures present in many large 3D fluorescent microscopy (FM) images acquired in biological research. This is especially problematic in neuroscience where the lack of ground truth data impedes the development of automated image analysis algorithms for neurons and neural populations. We therefore propose an unpaired mesh-to-image translation methodology for generating volumetric FM images of neurons from paired ground truths. We start by learning unique FM styles efficiently through a Gramian-based discriminator. Then, we stylize 3D voxelized meshes of previously reconstructed neurons by successively generating slices. As a result, we effectively create a synthetic microscope and can acquire realistic FM images of neurons with control over the image content and imaging configurations. We demonstrate the feasibility of our architecture and its superior performance compared to state-of-the-art image translation architectures through a variety of texture-based metrics, unsupervised segmentation accuracy, and an expert opinion test. In this study, we use 2 synthetic FM datasets and 2 newly acquired FM datasets of retinal neurons.     

ACEnet: Anatomical context-encoding network for neuroanatomy segmentation

Segmentation of brain structures from magnetic resonance (MR) scans plays an important role in the quantification of brain morphology. Since 3D deep learning models suffer from high computational cost, 2D deep learning methods are favored for their computational efficiency. However, existing 2D deep learning methods are not equipped to effectively capture 3D spatial contextual information that is needed to achieve accurate brain structure segmentation. In order to overcome this limitation, we develop an Anatomical Context-Encoding Network (ACEnet) to incorporate 3D spatial and anatomical contexts in 2D convolutional neural networks (CNNs) for efficient and accurate segmentation of brain structures from MR scans, consisting of 1) an anatomical context encoding module to incorporate anatomical information in 2D CNNs and 2) a spatial context encoding module to integrate 3D image information in 2D CNNs. In addition, a skull stripping module is adopted to guide the 2D CNNs to attend to the brain. Extensive experiments on three benchmark datasets have demonstrated that our method achieves promising performance compared with state-of-the-art alternative methods for brain structure segmentation in terms of both computational efficiency and segmentation accuracy.     

On the usability of synthetic data for improving the robustness of deep learning-based segmentation of cardiac magnetic resonance images

Deep learning-based segmentation methods provide an effective and automated way for assessing the structure and function of the heart in cardiac magnetic resonance (CMR) images. However, despite their state-of-the-art performance on images acquired from the same source (same scanner or scanner vendor) as images used during training, their performance degrades significantly on images coming from different domains. A straightforward approach to tackle this issue consists of acquiring large quantities of multi-site and multi-vendor data, which is practically infeasible. Generative adversarial networks (GANs) for image synthesis present a promising solution for tackling data limitations in medical imaging and addressing the generalization capability of segmentation models. In this work, we explore the usability of synthesized short-axis CMR images generated using a segmentation-informed conditional GAN, to improve the robustness of heart cavity segmentation models in a variety of different settings. The GAN is trained on paired real images and corresponding segmentation maps belonging to both the heart and the surrounding tissue, reinforcing the synthesis of semantically-consistent and realistic images. First, we evaluate the segmentation performance of a model trained solely with synthetic data and show that it only slightly underperforms compared to the baseline trained with real data. By further combining real with synthetic data during training, we observe a substantial improvement in segmentation performance (up to 4% and 40% in terms of Dice score and Hausdorff distance) across multiple data-sets collected from various sites and scanner. This is additionally demonstrated across state-of-the-art 2D and 3D segmentation networks, whereby the obtained results demonstrate the potential of the proposed method in tackling the presence of the domain shift in medical data. Finally, we thoroughly analyze the quality of synthetic data and its ability to replace real MR images during training, as well as provide an insight into important aspects of utilizing synthetic images for segmentation.     

Fully automated left atrium segmentation from anatomical cine long-axis MRI sequences using deep convolutional neural network with unscented Kalman filter

This study proposes a fully automated approach for the left atrial segmentation from routine cine long-axis cardiac magnetic resonance image sequences using deep convolutional neural networks and Bayesian filtering. The proposed approach consists of a classification network that automatically detects the type of long-axis sequence and three different convolutional neural network models followed by unscented Kalman filtering (UKF) that delineates the left atrium. Instead of training and predicting all long-axis sequence types together, the proposed approach first identifies the image sequence type as to 2, 3 and 4 chamber views, and then performs prediction based on neural nets trained for that particular sequence type. The datasets were acquired retrospectively and ground truth manual segmentation was provided by an expert radiologist. In addition to neural net based classification and segmentation, another neural net is trained and utilized to select image sequences for further processing using UKF to impose temporal consistency over cardiac cycle. A cyclic dynamic model with time-varying angular frequency is introduced in UKF to characterize the variations in cardiac motion during image scanning. The proposed approach was trained and evaluated separately with varying amount of training data with images acquired from 20, 40, 60 and 80 patients. Evaluations over 1515 images with equal number of images from each chamber group acquired from an additional 20 patients demonstrated that the proposed model outperformed state-of-the-art and yielded a mean Dice coefficient value of 94.1%, 93.7% and 90.1% for 2, 3 and 4-chamber sequences, respectively, when trained with datasets from 80 patients.     

CAN3D: Fast 3D medical image segmentation via compact context aggregation

Direct automatic segmentation of objects in 3D medical imaging, such as magnetic resonance (MR) imaging, is challenging as it often involves accurately identifying multiple individual structures with complex geometries within a large volume under investigation. Most deep learning approaches address these challenges by enhancing their learning capability through a substantial increase in trainable parameters within their models. An increased model complexity will incur high computational costs and large memory requirements unsuitable for real-time implementation on standard clinical workstations, as clinical imaging systems typically have low-end computer hardware with limited memory and CPU resources only. This paper presents a compact convolutional neural network (CAN3D) designed specifically for clinical workstations and allows the segmentation of large 3D Magnetic Resonance (MR) images in real-time. The proposed CAN3D has a shallow memory footprint to reduce the number of model parameters and computer memory required for state-of-the-art performance and maintain data integrity by directly processing large full-size 3D image input volumes with no patches required. The proposed architecture significantly reduces computational costs, especially for inference using the CPU. We also develop a novel loss function with extra shape constraints to improve segmentation accuracy for imbalanced classes in 3D MR images. Compared to state-of-the-art approaches (U-Net3D, improved U-Net3D and V-Net), CAN3D reduced the number of parameters up to two orders of magnitude and achieved much faster inference, up to 5 times when predicting with a standard commercial CPU (instead of GPU). For the open-access OAI-ZIB knee MR dataset, in comparison with manual segmentation, CAN3D achieved Dice coefficient values of (mean = 0.87 ± 0.02 and 0.85 ± 0.04) with mean surface distance errors (mean = 0.36 ± 0.32 mm and 0.29 ± 0.10 mm) for imbalanced classes such as (femoral and tibial) cartilage volumes respectively when training volume-wise under only 12G video memory. Similarly, CAN3D demonstrated high accuracy and efficiency on a pelvis 3D MR imaging dataset for prostate cancer consisting of 211 examinations with expert manual semantic labels (bladder, body, bone, rectum, prostate) now released publicly for scientific use as part of this work.     

Towards annotation-efficient segmentation via image-to-image translation

An important challenge and limiting factor in deep learning methods for medical imaging segmentation is the lack of available of annotated data to properly train models. For the specific task of tumor segmentation, the process entails clinicians labeling every slice of volumetric scans for every patient, which becomes prohibitive at the scale of datasets required to train neural networks to optimal performance. To address this, we propose a novel semi-supervised framework that allows training any segmentation (encoder–decoder) model using only information readily available in radiological data, namely the presence of a tumor in the image, in addition to a few annotated images. Specifically, we conjecture that a generative model performing domain translation on this weak label — healthy vs diseased scans — helps achieve tumor segmentation. The proposed GenSeg method first disentangles tumoral tissue from healthy “background” tissue. The latent representation is separated into (1) the common background information across both domains, and (2) the unique tumoral information. GenSeg then achieves diseased-to-healthy image translation by decoding a healthy version of the image from just the common representation, as well as a residual image that allows adding back the tumors. The same decoder that produces this residual tumor image, also outputs a tumor segmentation. Implicit data augmentation is achieved by re-using the same framework for healthy-to-diseased image translation, where a residual tumor image is produced from a prior distribution. By performing both image translation and segmentation simultaneously, GenSeg allows training on only partially annotated datasets. To test the framework, we trained U-Net-like architectures using GenSeg and evaluated their performance on 3 variants of a synthetic task, as well as on 2 benchmark datasets: brain tumor segmentation in MRI (derived from BraTS) and liver metastasis segmentation in CT (derived from LiTS). Our method outperforms the baseline semi-supervised (autoencoder and mean teacher) and supervised segmentation methods, with improvements ranging between 8–14% Dice score on the brain task and 5–8% on the liver task, when only 1% of the training images were annotated. These results show the proposed framework is ideal at addressing the problem of training deep segmentation models when a large portion of the available data is unlabeled and unpaired, a common issue in tumor segmentation.     

Automated cardiac segmentation of cross-modal medical images using unsupervised multi-domain adaptation and spatial neural attention structure

Accurate cardiac segmentation of multimodal images, e.g., magnetic resonance (MR), computed tomography (CT) images, plays a pivot role in auxiliary diagnoses, treatments and postoperative assessments of cardiovascular diseases. However, training a well-behaved segmentation model for the cross-modal cardiac image analysis is challenging, due to their diverse appearances/distributions from different devices and acquisition conditions. For instance, a well-trained segmentation model based on the source domain of MR images is often failed in the segmentation of CT images. In this work, a cross-modal images-oriented cardiac segmentation scheme is proposed using a symmetric full convolutional neural network (SFCNN) with the unsupervised multi-domain adaptation (UMDA) and a spatial neural attention (SNA) structure, termed UMDA-SNA-SFCNN, having the merits of without the requirement of any annotation on the test domain. Specifically, UMDA-SNA-SFCNN incorporates SNA to the classic adversarial domain adaptation network to highlight the relevant regions, while restraining the irrelevant areas in the cross-modal images, so as to suppress the negative transfer in the process of unsupervised domain adaptation. In addition, the multi-layer feature discriminators and a predictive segmentation-mask discriminator are established to connect the multi-layer features and segmentation mask of the backbone network, SFCNN, to realize the fine-grained alignment of unsupervised cross-modal feature domains. Extensive confirmative and comparative experiments on the benchmark Multi-Modality Whole Heart Challenge dataset show that the proposed model is superior to the state-of-the-art cross-modal segmentation methods.     

Diverse data augmentation for learning image segmentation with cross-modality annotations

The dearth of annotated data is a major hurdle in building reliable image segmentation models. Manual annotation of medical images is tedious, time-consuming, and significantly variable across imaging modalities. The need for annotation can be ameliorated by leveraging an annotation-rich source modality in learning a segmentation model for an annotation-poor target modality. In this paper, we introduce a diverse data augmentation generative adversarial network (DDA-GAN) to train a segmentation model for an unannotated target image domain by borrowing information from an annotated source image domain. This is achieved by generating diverse augmented data for the target domain by one-to-many source-to-target translation. The DDA-GAN uses unpaired images from the source and target domains and is an end-to-end convolutional neural network that (i) explicitly disentangles domain-invariant structural features related to segmentation from domain-specific appearance features, (ii) combines structural features from the source domain with appearance features randomly sampled from the target domain for data augmentation, and (iii) train the segmentation model with the augmented data in the target domain and the annotations from the source domain. The effectiveness of our method is demonstrated both qualitatively and quantitatively in comparison with the state of the art for segmentation of craniomaxillofacial bony structures via MRI and cardiac substructures via CT.     

Deep dense multi-path neural network for prostate segmentation in magnetic resonance imaging

Purpose

We propose an approach of 3D convolutional neural network to segment the prostate in MR images.

Methods

A 3D deep dense multi-path convolutional neural network that follows the framework of the encoder–decoder design is proposed. The encoder is built based upon densely connected layers that learn the high-level feature representation of the prostate. The decoder interprets the features and predicts the whole prostate volume by utilizing a residual layout and grouped convolution. A set of sub-volumes of MR images, centered at the prostate, is generated and fed into the proposed network for training purpose. The performance of the proposed network is compared to previously reported approaches.

Results

Two independent datasets were employed to assess the proposed network. In quantitative evaluations, the proposed network achieved 95.11 and 89.01 Dice coefficients for the two datasets. The segmentation results were robust to variations in MR images. In comparison experiments, the segmentation performance of the proposed network was comparable to the previously reported approaches. In qualitative evaluations, the segmentation results by the proposed network were well matched to the ground truth provided by human experts.

Conclusions

The proposed network is capable of segmenting the prostate in an accurate and robust manner. This approach can be applied to other types of medical images.

     

Segmentation only uses sparse annotations: Unified weakly and semi-supervised learning in medical images

Since segmentation labeling is usually time-consuming and annotating medical images requires professional expertise, it is laborious to obtain a large-scale, high-quality annotated segmentation dataset. We propose a novel weakly- and semi-supervised framework named SOUSA (Segmentation Only Uses Sparse Annotations), aiming at learning from a small set of sparse annotated data and a large amount of unlabeled data. The proposed framework contains a teacher model and a student model. The student model is weakly supervised by scribbles and a Geodesic distance map derived from scribbles. Meanwhile, a large amount of unlabeled data with various perturbations are fed to student and teacher models. The consistency of their output predictions is imposed by Mean Square Error (MSE) loss and a carefully designed Multi-angle Projection Reconstruction (MPR) loss. Extensive experiments are conducted to demonstrate the robustness and generalization ability of our proposed method. Results show that our method outperforms weakly- and semi-supervised state-of-the-art methods on multiple datasets. Furthermore, our method achieves a competitive performance with some fully supervised methods with dense annotation when the size of the dataset is limited.     

ImUnity: A generalizable VAE-GAN solution for multicenter MR image harmonization

ImUnity is an original 2.5D deep-learning model designed for efficient and flexible MR image harmonization. A VAE-GAN network, coupled with a confusion module and an optional biological preservation module, uses multiple 2D slices taken from different anatomical locations in each subject of the training database, as well as image contrast transformations for its training. It eventually generates ‘corrected’ MR images that can be used for various multi-center population studies. Using 3 open source databases (ABIDE, OASIS and SRPBS), which contain MR images from multiple acquisition scanner types or vendors and a large range of subjects ages, we show that ImUnity: (1) outperforms state-of-the-art methods in terms of quality of images generated using traveling subjects; (2) removes sites or scanner biases while improving patients classification; (3) harmonizes data coming from new sites or scanners without the need for an additional fine-tuning and (4) allows the selection of multiple MR reconstructed images according to the desired applications. Tested here on T1-weighted images, ImUnity could be used to harmonize other types of medical images.     

Cross-dimensional transfer learning in medical image segmentation with deep learning

Over the last decade, convolutional neural networks have emerged and advanced the state-of-the-art in various image analysis and computer vision applications. The performance of 2D image classification networks is constantly improving and being trained on databases made of millions of natural images. Conversely, in the field of medical image analysis, the progress is also remarkable but has mainly slowed down due to the relative lack of annotated data and besides, the inherent constraints related to the acquisition process. These limitations are even more pronounced given the volumetry of medical imaging data. In this paper, we introduce an efficient way to transfer the efficiency of a 2D classification network trained on natural images to 2D, 3D uni- and multi-modal medical image segmentation applications. In this direction, we designed novel architectures based on two key principles: weight transfer by embedding a 2D pre-trained encoder into a higher dimensional U-Net, and dimensional transfer by expanding a 2D segmentation network into a higher dimension one. The proposed networks were tested on benchmarks comprising different modalities: MR, CT, and ultrasound images. Our 2D network ranked first on the CAMUS challenge dedicated to echo-cardiographic data segmentation and surpassed the state-of-the-art. Regarding 2D/3D MR and CT abdominal images from the CHAOS challenge, our approach largely outperformed the other 2D-based methods described in the challenge paper on Dice, RAVD, ASSD, and MSSD scores and ranked third on the online evaluation platform. Our 3D network applied to the BraTS 2022 competition also achieved promising results, reaching an average Dice score of 91.69% (91.22%) for the whole tumor, 83.23% (84.77%) for the tumor core and 81.75% (83.88%) for enhanced tumor using the approach based on weight (dimensional) transfer. Experimental and qualitative results illustrate the effectiveness of our methods for multi-dimensional medical image segmentation.     

Structured patch model for a unified automatic and interactive segmentation framework

We present a novel interactive segmentation framework incorporating a priori knowledge learned from training data. The knowledge is learned as a structured patch model (StPM) comprising sets of corresponding local patch priors and their pairwise spatial distribution statistics which represent the local shape and appearance along its boundary and the global shape structure, respectively. When successive user annotations are given, the StPM is appropriately adjusted in the target image and used together with the annotations to guide the segmentation. The StPM reduces the dependency on the placement and quantity of user annotations with little increase in complexity since the time-consuming StPM construction is performed offline. Furthermore, a seamless learning system can be established by directly adding the patch priors and the pairwise statistics of segmentation results to the StPM. The proposed method was evaluated on three datasets, respectively, of 2D chest CT, 3D knee MR, and 3D brain MR. The experimental results demonstrate that within an equal amount of time, the proposed interactive segmentation framework outperforms recent state-of-the-art methods in terms of accuracy, while it requires significantly less computing and editing time to obtain results with comparable accuracy.     

Multimodal image synthesis based on disentanglement representations of anatomical and modality specific features,learned using uncooperative relativistic GAN

Growing number of methods for attenuation-coefficient map estimation from magnetic resonance (MR) images have recently been proposed because of the increasing interest in MR-guided radiotherapy and the introduction of positron emission tomography (PET) MR hybrid systems. We propose a deep-network ensemble incorporating stochastic-binary-anatomical encoders and imaging-modality variational autoencoders, to disentangle image-latent spaces into a space of modality-invariant anatomical features and spaces of modality attributes. The ensemble integrates modality-modulated decoders to normalize features and image intensities based on imaging modality. Besides promoting disentanglement, the architecture fosters uncooperative learning, offering ability to maintain anatomical structure in a cross-modality reconstruction. Introduction of a modality-invariant structural consistency constraint further enforces faithful embedding of anatomy. To improve training stability and fidelity of synthesized modalities, the ensemble is trained in a relativistic generative adversarial framework incorporating multiscale discriminators. Analyses of priors and network architectures as well as performance validation were performed on computed tomography (CT) and MR pelvis datasets. The proposed method demonstrated robustness against intensity inhomogeneity, improved tissue-class differentiation, and offered synthetic CT in Hounsfield units with intensities consistent and smooth across slices compared to the state-of-the-art approaches, offering median normalized mutual information of 1.28, normalized cross correlation of 0.97, and gradient cross correlation of 0.59 over 324 images.