Generalized Zero-Shot Learning (GZSL) addresses the challenge of classifying unseen classes in the presence of seen classes by leveraging semantic attributes to bridge the gap for unseen classes. However, in image based disease classification, such as glioma sub-typing, distinguishing between classes using image semantic attributes can be challenging. To address this challenge, we introduce a novel GZSL method that eliminates the dependency on semantic information. Specifically, we propose that the primary of most classification in clinic is risk stratification, and classes are inherently ordered rather than purely categorical. Based on this insight, we present an inter-class feature augmentation (IFA) module, where distributions of different classes are ordered by their risk levels in a learned feature space using pre-defined joint conditional Gaussian distribution model. This ordering enables the generation of unseen class features through feature mixing of adjacent seen classes, effectively transforming the zero-shot learning problem into a supervised learning task. Our method eliminates the need for explicit semantic information, avoiding the cross-modal alignment between visual and semantic features. Moreover, the IFA module for GZSL requires no structural modifications to the existing classification models. In the experiment, both in-house and public datasets are used to evaluate our method across different tasks, including glioma subtyping, Alzheimer’s disease (AD) classification and diabetic retinopathy classification. Experimental results demonstrate that our method outperforms the state-of-the-art GZSL methods with statistical significance.

Many pre-operative overall survival (OS) prediction methods have been proposed to assist personalized treatment of diffuse glioma for better prognosis. Most of them utilize pre-operative data, while post-operative data, which contains essential prognosis-related information (e.g., surgical outcomes and lesion evolution) is neglected, hindering prediction accuracy. However, incorporating post-operative data could make OS prediction inapplicable at pre-operative stage, affecting clinical utility. To address this contradiction, in this paper, we propose an effective framework that leverages longitudinal data (pre- and post-operative data) to enhance pre-operative OS prediction. Specifically, two OS prediction networks are built in a knowledge distillation framework. One is the teacher network trained with longitudinal data, and the other is the student network relying solely on pre-operative data. Distillation of deep features is conducted to align the performance of the student network with that of the teacher network. Moreover, mass effect and its distillation are adopted to incorporate lesion evolution information, further enhancing prediction performance. Based on our framework, the student network can leverage essential post-operative information without compromising its applicability at pre-operative stage. Experiments on both in-house and public datasets demonstrate that the student network outperforms all state-of-the-art methods under evaluation with statistical significance. Further ablation study reveals that distillation of mass effect and deep features play positive roles in OS prediction. Moreover, new prognosis-related factors are discovered by comparing the student network with and without distillation.

Many deep learning based methods have been proposed for brain tumor segmentation. Most studies focus on deep network internal structure to improve the segmentation accuracy, while valuable external information, such as normal brain appearance, is often ignored. Inspired by the fact that radiologists often screen lesion regions with normal appearance as reference in mind, in this paper, we propose a novel deep framework for brain tumor segmentation, where normal brain images are adopted as reference to compare with tumor brain images in a learned feature space. In this way, features at tumor regions, i.e., tumor-related features, can be highlighted and enhanced for accurate tumor segmentation. It is known that routine tumor brain images are multimodal, while normal brain images are often monomodal. This causes the feature comparison a big issue, i.e., multimodal vs. monomodal. To this end, we present a new feature alignment module (FAM) to make the feature distribution of monomodal normal brain images consistent/inconsistent with multimodal tumor brain images at normal/tumor regions, making the feature comparison effective. Both public (BraTS2022) and in-house tumor brain image datasets are used to evaluate our framework. Experimental results demonstrate that for both datasets, our framework can effectively improve the segmentation accuracy and outperforms the state-of-the-art segmentation methods. Codes are available at https://github.com/hb-liu/Normal-Brain-Boost-Tumor-Segmentation.

Deep learning based multi-atlas segmentation (DL-MA) has achieved the state-of-the-art performance in many medical image segmentation tasks, e.g., brain parcellation. In DL-MA methods, atlas-target correspondence is the key for accurate segmentation. In most existing DL-MA methods, such correspondence is usually established using traditional or deep learning based registration methods at image level with no further feature level adaption. This could cause possible atlas-target feature inconsistency. As a result, the information from atlases often has limited positive and even counteractive impact on the final segmentation results. To tackle this issue, in this paper, we propose a new DL-MA framework, where a novel differentiable atlas feature warping module with a new smooth regularization term is presented to establish feature level atlas-target correspondence. Comparing with the existing DL-MA methods, in our framework, atlas features containing anatomical prior knowledge are more relevant to the target image feature, leading the final segmentation results to a high accuracy level. We evaluate our framework in the context of brain parcellation using two public MR brain image datasets: LPBA40 and NIREP-NA0. The experimental results demonstrate that our framework outperforms both traditional multi-atlas segmentation (MAS) and state-of-the-art DL-MA methods with statistical significance. Further ablation studies confirm the effectiveness of the proposed differentiable atlas feature warping module.

Multi-atlas parcellation (MAP) is carried out on a brain image by propagating and fusing labelled regions from brain atlases. Typical nonlinear registration-based label propagation is time-consuming and sensitive to inter-subject differences. Recently, deep learning parcellation (DLP) has been proposed to avoid nonlinear registration for better efficiency and robustness than MAP. However, most existing DLP methods neglect using brain atlases, which contain high-level information (e.g., manually labelled brain regions), to provide auxiliary features for improving the parcellation accuracy. In this paper, we propose a novel multi-atlas DLP method for brain parcellation. Our method is based on fully convolutional networks (FCN) and squeeze-and-excitation (SE) modules. It can automatically and adaptively select features from the most relevant brain atlases to guide parcellation. Moreover, our method is trained via a generative adversarial network (GAN), where a convolutional neural network (CNN) with multi-scale l1loss is used as the discriminator. Benefiting from brain atlases, our method outperforms MAP and state-of-the-art DLP methods on two public image datasets (LPBA40 and NIREP-NA0).

Dynamic functional connectivity (dFC) analysis using resting-state functional Magnetic Resonance Imaging (rs-fMRI) is currently an advanced technique for capturing the dynamic changes of neural activities in brain disease identification. Most existing dFC modeling methods extract dynamic interaction information by using the sliding window-based correlation, whose performance is very sensitive to window parameters. Because few studies can convincingly identify the optimal combination of window parameters, sliding window-based correlation may not be the optimal way to capture the temporal variability of brain activity. In this paper, we propose a novel adaptive dFC model, aided by a deep spatial-temporal feature fusion method, for mild cognitive impairment (MCI) identification. Specifically, we adopt an adaptive Ultra-weighted-lasso recursive least squares algorithm to estimate the adaptive dFC, which effectively alleviates the problem of parameter optimization. Then, we extract temporal and spatial features from the adaptive dFC. In order to generate coarser multi-domain representations for subsequent classification, the temporal and spatial features are further mapped into comprehensive fused features with a deep feature fusion method. Experimental results show that the classification accuracy of our proposed method is reached to 87.7%, which is at least 5.5% improvement than the state-of-the-art methods. These results elucidate the superiority of the proposed method for MCI classification, indicating its effectiveness in the early identification of brain abnormalities.

Glioblastoma (GBM) is the most common and deadly malignant brain tumor. For personalized treatment, an accurate pre-operative prognosis for GBM patients is highly desired. Recently, many machine learning-based methods have been adopted to predict overall survival (OS) time based on the pre-operative mono- or multi-modal imaging phenotype. The genotypic information of GBM has been proven to be strongly indicative of the prognosis; however, this has not been considered in the existing imaging-based OS prediction methods. The main reason is that the tumor genotype is unavailable pre-operatively unless deriving from craniotomy. In this paper, we propose a new deep learning-based OS prediction method for GBM patients, which can derive tumor genotype-related features from pre-operative multimodal magnetic resonance imaging (MRI) brain data and feed them to OS prediction. Specifically, we propose a multi-task convolutional neural network (CNN) to accomplish both tumor genotype and OS prediction tasks jointly. As the network can benefit from learning tumor genotype-related features for genotype prediction, the accuracy of predicting OS time can be prominently improved. In the experiments, multimodal MRI brain dataset of 120 GBM patients, with as many as four different genotypic/molecular biomarkers, are used to evaluate our method. Our method achieves the highest OS prediction accuracy compared to other state-of-the-art methods.

Using multi-atlas registration (MAR), information carried by atlases can be transferred onto a new input image for the tasks of region of interest (ROI) segmentation, anatomical landmark detection, and so on. Conventional atlases used in MAR methods are monomodal and contain only normal anatomical structures. Therefore, the majority of MAR methods cannot handle input multimodal pathological images, which are often collected in routine image-based diagnosis. This is because registering monomodal atlases with normal appearances to multimodal pathological images involves two major problems: (1) missing imaging modalities in the monomodal atlases, and (2) influence from pathological regions. In this paper, we propose a new MAR framework to tackle these problems. In this framework, a deep learning based image synthesizers are applied for synthesizing multimodal normal atlases from conventional monomodal normal atlases. To reduce the influence from pathological regions, we further propose a multimodal lowrank approach to recover multimodal normal-looking images from multimodal pathological images. Finally, the multimodal normal atlases can be registered to the recovered multimodal images in a multi-channel way. We evaluate our MAR framework via brain ROI segmentation of multimodal tumor brain images. Due to the utilization of multimodal information and the reduced influence from pathological regions, experimental results show that registration based on our method is more accurate and robust, leading to significantly improved brain ROI segmentation compared with state-of-the-art methods.

We introduce a new multi-atlas segmentation (MAS) framework for MR tumor brain images. The basic idea of MAS is to register and fuse label information from multiple normal brain atlases to a new brain image for segmentation. Many MAS methods have been proposed with success. However, most of them are developed for normal brain images, and tumor brain images usually pose a great challenge for them. This is because tumors cause difficulties in registration of normal brain atlases to the tumor brain image. To address this challenge, in the first step of our MAS framework, a new low-rank method is used to get the recovered image of normal-looking brain from the MR tumor brain image based on the information of normal brain atlases. Different from conventional low-rank methods that produce the recovered image with distorted normal brain regions, our low-rank method harnesses a spatial constraint to get the recovered image with preserved normal brain regions. Then in the second step, normal brain atlases can be registered to the recovered image without influence from tumors. These two steps are iteratively proceeded until convergence, for obtaining the final segmentation of the tumor brain image. During the iteration, both the recovered image and the registration of normal brain atlases to the recovered image are gradually refined. We have compared our proposed method with state-of-the-art methods by using both synthetic and real MR tumor brain images. Experimental results show that our proposed method can get effectively recovered images and also improves segmentation accuracy.