DIRBoost–An algorithm for boosting deformable image registration: Application to lung CT intra-subject registration

We introduce a boosting algorithm to improve on existing methods for deformable image registration (DIR). The proposed DIRBoost algorithm is inspired by the theory on hypothesis boosting, well known in the field of machine learning. DIRBoost utilizes a method for automatic registration error detection to obtain estimates of local registration quality. All areas detected as erroneously registered are subjected to boosting, i.e. undergo iterative registrations by employing boosting masks on both the fixed and moving image. We validated the DIRBoost algorithm on three different DIR methods (ANTS gSyn, NiftyReg, and DROP) on three independent reference datasets of pulmonary image scan pairs. DIRBoost reduced registration errors significantly and consistently on all reference datasets for each DIR algorithm, yielding an improvement of the registration accuracy by 5–34% depending on the dataset and the registration algorithm employed.     

TransMorph: Transformer for unsupervised medical image registration

In the last decade, convolutional neural networks (ConvNets) have been a major focus of research in medical image analysis. However, the performances of ConvNets may be limited by a lack of explicit consideration of the long-range spatial relationships in an image. Recently, Vision Transformer architectures have been proposed to address the shortcomings of ConvNets and have produced state-of-the-art performances in many medical imaging applications. Transformers may be a strong candidate for image registration because their substantially larger receptive field enables a more precise comprehension of the spatial correspondence between moving and fixed images. Here, we present TransMorph, a hybrid Transformer-ConvNet model for volumetric medical image registration. This paper also presents diffeomorphic and Bayesian variants of TransMorph: the diffeomorphic variants ensure the topology-preserving deformations, and the Bayesian variant produces a well-calibrated registration uncertainty estimate. We extensively validated the proposed models using 3D medical images from three applications: inter-patient and atlas-to-patient brain MRI registration and phantom-to-CT registration. The proposed models are evaluated in comparison to a variety of existing registration methods and Transformer architectures. Qualitative and quantitative results demonstrate that the proposed Transformer-based model leads to a substantial performance improvement over the baseline methods, confirming the effectiveness of Transformers for medical image registration.     

DragNet: Learning-based deformable registration for realistic cardiac MR sequence generation from a single frame

Deformable image registration (DIR) can be used to track cardiac motion. Conventional DIR algorithms aim to establish a dense and non-linear correspondence between independent pairs of images. They are, nevertheless, computationally intensive and do not consider temporal dependencies to regulate the estimated motion in a cardiac cycle. In this paper, leveraging deep learning methods, we formulate a novel hierarchical probabilistic model, termed DragNet, for fast and reliable spatio-temporal registration in cine cardiac magnetic resonance (CMR) images and for generating synthetic heart motion sequences. DragNet is a variational inference framework, which takes an image from the sequence in combination with the hidden states of a recurrent neural network (RNN) as inputs to an inference network per time step. As part of this framework, we condition the prior probability of the latent variables on the hidden states of the RNN utilised to capture temporal dependencies. We further condition the posterior of the motion field on a latent variable from hierarchy and features from the moving image. Subsequently, the RNN updates the hidden state variables based on the feature maps of the fixed image and the latent variables. Different from traditional methods, DragNet performs registration on unseen sequences in a forward pass, which significantly expedites the registration process. Besides, DragNet enables generating a large number of realistic synthetic image sequences given only one frame, where the corresponding deformations are also retrieved. The probabilistic framework allows for computing spatio-temporal uncertainties in the estimated motion fields. Our results show that DragNet performance is comparable with state-of-the-art methods in terms of registration accuracy, with the advantage of offering analytical pixel-wise motion uncertainty estimation across a cardiac cycle and being a motion generator. We will make our code publicly available.     

Semantic similarity metrics for image registration

Image registration aims to find geometric transformations that align images. Most algorithmic and deep learning-based methods solve the registration problem by minimizing a loss function, consisting of a similarity metric comparing the aligned images, and a regularization term ensuring smoothness of the transformation. Existing similarity metrics like Euclidean Distance or Normalized Cross-Correlation focus on aligning pixel intensity values or correlations, giving difficulties with low intensity contrast, noise, and ambiguous matching. We propose a semantic similarity metric for image registration, focusing on aligning image areas based on semantic correspondence instead. Our approach learns dataset-specific features that drive the optimization of a learning-based registration model. We train both an unsupervised approach extracting features with an auto-encoder, and a semi-supervised approach using supplemental segmentation data. We validate the semantic similarity metric using both deep-learning-based and algorithmic image registration methods. Compared to existing methods across four different image modalities and applications, the method achieves consistently high registration accuracy and smooth transformation fields.     

Predict brain MR image registration via sparse learning of appearance and transformation

We propose a new approach to register the subject image with the template by leveraging a set of intermediate images that are pre-aligned to the template. We argue that, if points in the subject and the intermediate images share similar local appearances, they may have common correspondence in the template. In this way, we learn the sparse representation of a certain subject point to reveal several similar candidate points in the intermediate images. Each selected intermediate candidate can bridge the correspondence from the subject point to the template space, thus predicting the transformation associated with the subject point at the confidence level that relates to the learned sparse coefficient. Following this strategy, we first predict transformations at selected key points, and retain multiple predictions on each key point, instead of allowing only a single correspondence. Then, by utilizing all key points and their predictions with varying confidences, we adaptively reconstruct the dense transformation field that warps the subject to the template. We further embed the prediction–reconstruction protocol above into a multi-resolution hierarchy. In the final, we refine our estimated transformation field via existing registration method in effective manners. We apply our method to registering brain MR images, and conclude that the proposed framework is competent to improve registration performances substantially.     

Volumetric memory network for interactive medical image segmentation

Despite recent progress of automatic medical image segmentation techniques, fully automatic results usually fail to meet clinically acceptable accuracy, thus typically require further refinement. To this end, we propose a novel Volumetric Memory Network, dubbed as VMN, to enable segmentation of 3D medical images in an interactive manner. Provided by user hints on an arbitrary slice, a 2D interaction network is firstly employed to produce an initial 2D segmentation for the chosen slice. Then, the VMN propagates the initial segmentation mask bidirectionally to all slices of the entire volume. Subsequent refinement based on additional user guidance on other slices can be incorporated in the same manner. To facilitate smooth human-in-the-loop segmentation, a quality assessment module is introduced to suggest the next slice for interaction based on the segmentation quality of each slice produced in the previous round. Our VMN demonstrates two distinctive features: First, the memory-augmented network design offers our model the ability to quickly encode past segmentation information, which will be retrieved later for the segmentation of other slices; Second, the quality assessment module enables the model to directly estimate the quality of each segmentation prediction, which allows for an active learning paradigm where users preferentially label the lowest-quality slice for multi-round refinement. The proposed network leads to a robust interactive segmentation engine, which can generalize well to various types of user annotations (e.g., scribble, bounding box, extreme clicking). Extensive experiments have been conducted on three public medical image segmentation datasets (i.e., MSD, KiTS₁₉, CVC-ClinicDB), and the results clearly confirm the superiority of our approach in comparison with state-of-the-art segmentation models. The code is made publicly available at https://github.com/0liliulei/Mem3D.     

Cross-modal attention for multi-modal image registration

In the past few years, convolutional neural networks (CNNs) have been proven powerful in extracting image features crucial for medical image registration. However, challenging applications and recent advances in computer vision suggest that CNNs are limited in their ability to understand the spatial correspondence between features, which is at the core of image registration. The issue is further exaggerated when it comes to multi-modal image registration, where the appearances of input images can differ significantly. This paper presents a novel cross-modal attention mechanism for correlating features extracted from the multi-modal input images and mapping such correlation to image registration transformation. To efficiently train the developed network, a contrastive learning-based pre-training method is also proposed to aid the network in extracting high-level features across the input modalities for the following cross-modal attention learning. We validated the proposed method on transrectal ultrasound (TRUS) to magnetic resonance (MR) registration, a clinically important procedure that benefits prostate cancer biopsy. Our experimental results demonstrate that for MR-TRUS registration, a deep neural network embedded with the cross-modal attention block outperforms other advanced CNN-based networks with ten times its size. We also incorporated visualization techniques to improve the interpretability of our network, which helps bring insights into the deep learning based image registration methods. The source code of our work is available at https://github.com/DIAL-RPI/Attention-Reg.     

Local contrastive loss with pseudo-label based self-training for semi-supervised medical image segmentation

Supervised deep learning-based methods yield accurate results for medical image segmentation. However, they require large labeled datasets for this, and obtaining them is a laborious task that requires clinical expertise. Semi/self-supervised learning-based approaches address this limitation by exploiting unlabeled data along with limited annotated data. Recent self-supervised learning methods use contrastive loss to learn good global level representations from unlabeled images and achieve high performance in classification tasks on popular natural image datasets like ImageNet. In pixel-level prediction tasks such as segmentation, it is crucial to also learn good local level representations along with global representations to achieve better accuracy. However, the impact of the existing local contrastive loss-based methods remains limited for learning good local representations because similar and dissimilar local regions are defined based on random augmentations and spatial proximity; not based on the semantic label of local regions due to lack of large-scale expert annotations in the semi/self-supervised setting. In this paper, we propose a local contrastive loss to learn good pixel level features useful for segmentation by exploiting semantic label information obtained from pseudo-labels of unlabeled images alongside limited annotated images with ground truth (GT) labels. In particular, we define the proposed contrastive loss to encourage similar representations for the pixels that have the same pseudo-label/GT label while being dissimilar to the representation of pixels with different pseudo-label/GT label in the dataset. We perform pseudo-label based self-training and train the network by jointly optimizing the proposed contrastive loss on both labeled and unlabeled sets and segmentation loss on only the limited labeled set. We evaluated the proposed approach on three public medical datasets of cardiac and prostate anatomies, and obtain high segmentation performance with a limited labeled set of one or two 3D volumes. Extensive comparisons with the state-of-the-art semi-supervised and data augmentation methods and concurrent contrastive learning methods demonstrate the substantial improvement achieved by the proposed method. The code is made publicly available at https://github.com/krishnabits001/pseudo_label_contrastive_training.     

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.     

3D image segmentation by using statistical deformation models and level sets

Purpose Improved segmentation of soft objects was sought using a new method that combines level set segmentation with statistical deformation models, using prior knowledge of the shape of an object as well as information derived from the input image. Methods Statistical deformation models were created using Euclidian distance functions of binary data and a multi-hierarchical registration approach based on mutual information metric and demons deformable registration. This approach is motivated by the fact that models based on signed distance maps, traditionally combined with level set segmentation can result in irregular shapes and do not establish explicit correspondences. By using statistical deformation models as representation of shape and a maximum a posteriori (MAP) estimation model to estimate the MAP shape of the object to be segmented, a robust segmentation algorithm using accurate shape models could be developed. Results The accuracy and correctness of the synthesized models was evaluated on different 3D objects (cardiac MRI and spinal CT vertebral segment) and the segmentation algorithm was validated by performing different segmentation tasks using various image modalities. The results of this evaluation are very promising and show the potential utility of the approach. Conclusion Initial results demonstrate the approach is feasible and may be advantageous over alternative segmentation methods. Extensions of the model, which also incorporate prior knowledge about the spatial distribution of grey values, are currently under development.     

SpineRegNet: Spine Registration Network for volumetric MR and CT image by the joint estimation of an affine-elastic deformation field

Spine registration for volumetric magnetic resonance (MR) and computed tomography (CT) images plays a significant role in surgical planning and surgical navigation system for the radiofrequency ablation of spine intervertebral discs. The affine transformation of each vertebra and elastic deformation of the intervertebral disc exist at the same time. This situation is a major challenge in spine registration. Existing spinal image registration methods failed to solve the optimal affine-elastic deformation field (AEDF) simultaneously, only consider the overall rigid or elastic alignment with the help of a manual spine mask, and encounter difficulty in meeting the accuracy requirements of clinical registration application. In this study, we propose a novel affine-elastic registration framework named SpineRegNet. The SpineRegNet consists of a Multiple Affine Matrices Estimation (MAME) Module for multiple vertebrae alignment, an Affine-Elastic Fusion (AEF) Module for joint estimation of the overall AEDF, and a Local Rigidity Constraint (LRC) Module for preserving the rigidity of each vertebra. Experiments on T2-weighted volumetric MR and CT images show that the proposed approach achieves impressive performance with mean Dice similarity coefficients of 91.36%, 81.60%, and 83.08% for the mask of the vertebrae on Datasets A-C, respectively. The proposed technique does not require a mask or manual participation during the tests and provides a useful tool for clinical spinal disease surgical planning and surgical navigation systems.     

Multi-modal contrastive mutual learning and pseudo-label re-learning for semi-supervised medical image segmentation

Semi-supervised learning has a great potential in medical image segmentation tasks with a few labeled data, but most of them only consider single-modal data. The excellent characteristics of multi-modal data can improve the performance of semi-supervised segmentation for each image modality. However, a shortcoming for most existing multi-modal solutions is that as the corresponding processing models of the multi-modal data are highly coupled, multi-modal data are required not only in the training but also in the inference stages, which thus limits its usage in clinical practice. Consequently, we propose a semi-supervised contrastive mutual learning (Semi-CML) segmentation framework, where a novel area-similarity contrastive (ASC) loss leverages the cross-modal information and prediction consistency between different modalities to conduct contrastive mutual learning. Although Semi-CML can improve the segmentation performance of both modalities simultaneously, there is a performance gap between two modalities, i.e., there exists a modality whose segmentation performance is usually better than that of the other. Therefore, we further develop a soft pseudo-label re-learning (PReL) scheme to remedy this gap. We conducted experiments on two public multi-modal datasets. The results show that Semi-CML with PReL greatly outperforms the state-of-the-art semi-supervised segmentation methods and achieves a similar (and sometimes even better) performance as fully supervised segmentation methods with 100% labeled data, while reducing the cost of data annotation by 90%. We also conducted ablation studies to evaluate the effectiveness of the ASC loss and the PReL module.     

Segmentation ability map: Interpret deep features for medical image segmentation

Deep convolutional neural networks (CNNs) have been widely used for medical image segmentation. In most studies, only the output layer is exploited to compute the final segmentation results and the hidden representations of the deep learned features have not been well understood. In this paper, we propose a prototype segmentation (ProtoSeg) method to compute a binary segmentation map based on deep features. We measure the segmentation abilities of the features by computing the Dice between the feature segmentation map and ground-truth, named as the segmentation ability score (SA score for short). The corresponding SA score can quantify the segmentation abilities of deep features in different layers and units to understand the deep neural networks for segmentation. In addition, our method can provide a mean SA score which can give a performance estimation of the output on the test images without ground-truth. Finally, we use the proposed ProtoSeg method to compute the segmentation map directly on input images to further understand the segmentation ability of each input image. Results are presented on segmenting tumors in brain MRI, lesions in skin images, COVID-related abnormality in CT images, prostate segmentation in abdominal MRI, and pancreatic mass segmentation in CT images. Our method can provide new insights for interpreting and explainable AI systems for medical image segmentation. Our code is available on: https://github.com/shengfly/ProtoSeg.     

可变形图像配准的CT与MRI对肝癌体积测定的前瞻性比较

目的  通过比较MRI与CT对肝癌肿瘤的诊断情况,进而进行高精度放疗计划。方法  选择2020年7月~2022年7月收治的26例不可切除的肝转移(n=8)、肝细胞癌(n=10)和胆管癌(n=8)患者作为研究对象,患者在放疗计划时进行了具有诊断质量的MRI扫描和三期CT扫描,并确定了肝内解剖参考点。在最能显示肿瘤的CT和MRI系列中,勾画了肝脏和肿瘤体积,确定了肝内解剖参考点。采用形变配准对CT和MRI的肝脏进行配准。结果  5例肝癌CT病灶数量与MRI有差异,MRI病灶多3例,CT病灶多2例。肝脏变形配准后,CT肿瘤表面与MRI肿瘤表面平均距离的人群中位数为3.7（2.2~21.3）mm。肿瘤表面积相差5 mm的中位百分比为26%(38%~86%)。转移瘤的中位符合率为81%(77%~86%),肝细胞癌的一致性为78%（44%~86%）,胆管癌的一致性为69%（25%~85%）。结论  MRI诊断的肝癌肿瘤体积与CT诊断的肝癌肿瘤体积存在显著差异,且在原发性肝癌中更为常见。     

Deep label fusion: A generalizable hybrid multi-atlas and deep convolutional neural network for medical image segmentation

Deep convolutional neural networks (DCNN) achieve very high accuracy in segmenting various anatomical structures in medical images but often suffer from relatively poor generalizability. Multi-atlas segmentation (MAS), while less accurate than DCNN in many applications, tends to generalize well to unseen datasets with different characteristics from the training dataset. Several groups have attempted to integrate the power of DCNN to learn complex data representations and the robustness of MAS to changes in image characteristics. However, these studies primarily focused on replacing individual components of MAS with DCNN models and reported marginal improvements in accuracy. In this study we describe and evaluate a 3D end-to-end hybrid MAS and DCNN segmentation pipeline, called Deep Label Fusion (DLF). The DLF pipeline consists of two main components with learnable weights, including a weighted voting subnet that mimics the MAS algorithm and a fine-tuning subnet that corrects residual segmentation errors to improve final segmentation accuracy. We evaluate DLF on five datasets that represent a diversity of anatomical structures (medial temporal lobe subregions and lumbar vertebrae) and imaging modalities (multi-modality, multi-field-strength MRI and Computational Tomography). These experiments show that DLF achieves comparable segmentation accuracy to nnU-Net (Isensee et al., 2020), the state-of-the-art DCNN pipeline, when evaluated on a dataset with similar characteristics to the training datasets, while outperforming nnU-Net on tasks that involve generalization to datasets with different characteristics (different MRI field strength or different patient population). DLF is also shown to consistently improve upon conventional MAS methods. In addition, a modality augmentation strategy tailored for multimodal imaging is proposed and demonstrated to be beneficial in improving the segmentation accuracy of learning-based methods, including DLF and DCNN, in missing data scenarios in test time as well as increasing the interpretability of the contribution of each individual modality.     

基于深度学习与多模态医学影像融合识别阈下抑郁患者

目的 基于深度学习（DL）卷积神经网络（CNN）算法，利用医学影像数据实现识别阈下抑郁（StD）患者。方法 对56例StD患者和70名正常人采集MRI和fMRI数据，分别输入所构建的CNN，利用网络融合技术对2种不同模态数据进行综合分析，得到分类结果；最后调整网络结构与模型参数，实现分类效果最优化。结果 单独MRI数据模型分类精度为73.02%，单独fMRI数据模型分类精度为65.08%；2种模态结合，最终分类精度升至78.57%。结论 利用DL可识别StD患者与正常人；采用多种模态输入法可提高分类准确度。     

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.     

Case-based similar image retrieval for weakly annotated large histopathological images of malignant lymphoma using deep metric learning

In the present study, we propose a novel case-based similar image retrieval (SIR) method for hematoxylin and eosin (H&E) stained histopathological images of malignant lymphoma. When a whole slide image (WSI) is used as an input query, it is desirable to be able to retrieve similar cases by focusing on image patches in pathologically important regions such as tumor cells. To address this problem, we employ attention-based multiple instance learning, which enables us to focus on tumor-specific regions when the similarity between cases is computed. Moreover, we employ contrastive distance metric learning to incorporate immunohistochemical (IHC) staining patterns as useful supervised information for defining appropriate similarity between heterogeneous malignant lymphoma cases. In the experiment with 249 malignant lymphoma patients, we confirmed that the proposed method exhibited higher evaluation measures than the baseline case-based SIR methods. Furthermore, the subjective evaluation by pathologists revealed that our similarity measure using IHC staining patterns is appropriate for representing the similarity of H&E stained tissue images for malignant lymphoma.