改进模糊C-均值分割算法在多发性硬化症MR脑部图像中的应用

背景：脑部MR图像是一种无纹理的图像,未被噪声污染的脑部MR图像的灰度值具有分片为常数的特点。因此,在聚类过程中灰度值有趋向于在同一个分割区域中相对接近的性质。目的：寻找一个能够自动分割多发性硬化症病灶的模糊C-均值改进方法,为临床对于多发性硬化症的判断提供更方便的工具。方法：考虑到脑部MR图像相邻象素属于同一分类的概率相近的特性,在迭代过程中对8邻域数据集进行滤波以降低噪声对聚类精度的影响,提出了一种改进的模糊C-均值聚类算法。就是将模糊C-均值聚类算法迭代过程中得到的灰度值看作一个数据集,用每个象素邻域象素的灰度值修正该象索的模糊隶属度取值,从而达到利用空间信息抑制噪声的目的。结果与结论：选取了10个多发性硬化症患者的脑部MRI图像进行试验。通过对多发性硬化症患者MRT1脑部图像和T2液体衰减反转回复脑部图像的分割实验,结果显示该算法能够有效分割多发性硬化症病灶,与其他方法所做的多发性硬化症病灶分割相比,本算法更易于实现,运算时间短,同时结果与临床医生的勾画比较重叠率较高,对其临床辅助诊断具有重要作用。     

ABCnet: Adversarial bias correction network for infant brain MR images

Automatic correction of intensity nonuniformity (also termed as the bias correction) is an essential step in brain MR image analysis. Existing methods are typically developed for adult brain MR images based on the assumption that the image intensities within the same brain tissue are relatively uniform. However, this assumption is not valid in infant brain MR images, due to the dynamic and regionally-heterogeneous image contrast and appearance changes, which are caused by the underlying spatiotemporally-nonuniform myelination process. Therefore, it is not appropriate to directly use existing methods to correct the infant brain MR images. In this paper, we propose an end-to-end 3D adversarial bias correction network (ABCnet), tailored for direct prediction of bias fields from the input infant brain MR images for bias correction. The “ground-truth” bias fields for training our network are carefully defined by an improved N4 method, which integrates manually-corrected tissue segmentation maps as anatomical prior knowledge. The whole network is trained alternatively by minimizing generative and adversarial losses. To handle the heterogeneous intensity changes, our generative loss includes a tissue-aware local intensity uniformity term to reduce the local intensity variation in the corrected image. Besides, it also integrates two additional terms to enhance the smoothness of the estimated bias field and to improve the robustness of the proposed method, respectively. Comprehensive experiments with different sizes of training datasets have been carried out on a total of 1492 T1w and T2w MR images from neonates, infants, and adults, respectively. Both qualitative and quantitative evaluations on simulated and real datasets consistently demonstrate the superior performance of our ABCnet in both accuracy and efficiency, compared with popularly available methods.     

AMNet: Adaptive multi-level network for deformable registration of 3D brain MR images

Three-dimensional (3D) deformable image registration is a fundamental technique in medical image analysis tasks. Although it has been extensively investigated, current deep-learning-based registration models may face the challenges posed by deformations with various degrees of complexity. This paper proposes an adaptive multi-level registration network (AMNet) to retain the continuity of the deformation field and to achieve high-performance registration for 3D brain MR images. First, we design a lightweight registration network with an adaptive growth strategy to learn deformation field from multi-level wavelet sub-bands, which facilitates both global and local optimization and achieves registration with high performance. Second, our AMNet is designed for image-wise registration, which adapts the local importance of a region in accordance with the complexity degrees of its deformation, and thereafter improves the registration efficiency and maintains the continuity of the deformation field. Experimental results from five publicly-available brain MR datasets and a synthetic brain MR dataset show that our method achieves superior performance against state-of-the-art medical image registration approaches.     

Robust whole-brain segmentation: Application to traumatic brain injury

We propose a framework for the robust and fully-automatic segmentation of magnetic resonance (MR) brain images called “Multi-Atlas Label Propagation with Expectation–Maximisation based refinement” (MALP-EM). The presented approach is based on a robust registration approach (MAPER), highly performant label fusion (joint label fusion) and intensity-based label refinement using EM. We further adapt this framework to be applicable for the segmentation of brain images with gross changes in anatomy. We propose to account for consistent registration errors by relaxing anatomical priors obtained by multi-atlas propagation and a weighting scheme to locally combine anatomical atlas priors and intensity-refined posterior probabilities. The method is evaluated on a benchmark dataset used in a recent MICCAI segmentation challenge. In this context we show that MALP-EM is competitive for the segmentation of MR brain scans of healthy adults when compared to state-of-the-art automatic labelling techniques. To demonstrate the versatility of the proposed approach, we employed MALP-EM to segment 125 MR brain images into 134 regions from subjects who had sustained traumatic brain injury (TBI). We employ a protocol to assess segmentation quality if no manual reference labels are available. Based on this protocol, three independent, blinded raters confirmed on 13 MR brain scans with pathology that MALP-EM is superior to established label fusion techniques. We visually confirm the robustness of our segmentation approach on the full cohort and investigate the potential of derived symmetry-based imaging biomarkers that correlate with and predict clinically relevant variables in TBI such as the Marshall Classification (MC) or Glasgow Outcome Score (GOS). Specifically, we show that we are able to stratify TBI patients with favourable outcomes from non-favourable outcomes with 64.7% accuracy using acute-phase MR images and 66.8% accuracy using follow-up MR images. Furthermore, we are able to differentiate subjects with the presence of a mass lesion or midline shift from those with diffuse brain injury with 76.0% accuracy. The thalamus, putamen, pallidum and hippocampus are particularly affected. Their involvement predicts TBI disease progression.     

The feasibility of a common stereotactic space for children and adults in fMRI studies of development

The question of whether pediatric and adult neuroimaging data can be analyzed in a common stereotactic space is a critical issue for developmental neuroscience. Two studies were performed to address this question. In Study 1, high-resolution structural MR brain images of 20 children (7-8 years of age) and 20 young adults (18-30 years of age) were transformed to a common space. Overall brain shape was assessed by tracing the outer boundaries of the brains in three orientations, and more local anatomy was assessed by analysis of portions of 10 selected sulci. Small, but consistent, differences in location and variability were observed in specific locations of the sulcal tracings and outer-boundary sections. In Study 2, a computer simulation was used to assess the extent to which the small anatomical differences observed in Study 1 would produce spurious effects in functional imaging data. Results indicate that, assuming a functional resolution of 5 mm in images averaged across subjects, anatomical differences in either variability or location between children and adults of the magnitude obperved in Study 1 would not negatively affect functional image comparisons. We conclude that atlas-transformed brain morphology is relatively consistent between 7- and 8-year-old children and adults at a resolution appropriate to current functional imaging and that the small anatomical differences present do not limit the usefulness of comparing child and adult functional images within a common stereotactic space.     

Discriminative confidence estimation for probabilistic multi-atlas label fusion

Quantitative neuroimaging analyses often rely on the accurate segmentation of anatomical brain structures. In contrast to manual segmentation, automatic methods offer reproducible outputs and provide scalability to study large databases. Among existing approaches, multi-atlas segmentation has recently shown to yield state-of-the-art performance in automatic segmentation of brain images. It consists in propagating the labelmaps from a set of atlases to the anatomy of a target image using image registration, and then fusing these multiple warped labelmaps into a consensus segmentation on the target image. Accurately estimating the contribution of each atlas labelmap to the final segmentation is a critical step for the success of multi-atlas segmentation. Common approaches to label fusion either rely on local patch similarity, probabilistic statistical frameworks or a combination of both. In this work, we propose a probabilistic label fusion framework based on atlas label confidences computed at each voxel of the structure of interest. Maximum likelihood atlas confidences are estimated using a supervised approach, explicitly modeling the relationship between local image appearances and segmentation errors produced by each of the atlases. We evaluate different spatial pooling strategies for modeling local segmentation errors. We also present a novel type of label-dependent appearance features based on atlas labelmaps that are used during confidence estimation to increase the accuracy of our label fusion. Our approach is evaluated on the segmentation of seven subcortical brain structures from the MICCAI 2013 SATA Challenge dataset and the hippocampi from the ADNI dataset. Overall, our results indicate that the proposed label fusion framework achieves superior performance to state-of-the-art approaches in the majority of the evaluated brain structures and shows more robustness to registration errors.     

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.     

Multicontext fuzzy clustering for separation of brain tissues in magnetic resonance images

A local image model is proposed to eliminate the adverse impact of both artificial and inherent intensity inhomogeneities in magnetic resonance imaging on intensity-based image segmentation methods. The estimation and correction procedures for intensity inhomogeneities are no longer indispensable because the highly convoluted spatial distribution of different tissues in the brain is taken into consideration. On the basis of the local image model, multicontext fuzzy clustering (MCFC) is proposed for classifying 2D and 3D MR data into tissues of white matter, gray matter, and cerebral spinal fluid automatically. In MCFC, multiple clustering contexts are generated for each pixel, and fuzzy clustering is independently performed in each context to calculate the degree of membership of a pixel to each tissue class. To maintain the statistical reliability and spatial continuity of membership distributions, a fusion strategy is adopted to integrate the clustering outcomes from different contexts. The fusion result is taken as the final membership value of the pixel. Experimental results on both real MR images and simulated volumetric MR data show that MCFC outperforms the classic fuzzy c-means (FCM) as well as other segmentation methods that deal with intensity inhomogeneities.     

TWave: high-order analysis of functional MRI

The traditional approach to functional image analysis models images as matrices of raw voxel intensity values. Although such a representation is widely utilized and heavily entrenched both within neuroimaging and in the wider data mining community, the strong interactions among space, time, and categorical modes such as subject and experimental task inherent in functional imaging yield a dataset with "high-order" structure, which matrix models are incapable of exploiting. Reasoning across all of these modes of data concurrently requires a high-order model capable of representing relationships between all modes of the data in tandem. We thus propose to model functional MRI data using tensors, which are high-order generalizations of matrices equivalent to multidimensional arrays or data cubes. However, several unique challenges exist in the high-order analysis of functional medical data: na?ve tensor models are incapable of exploiting spatiotemporal locality patterns, standard tensor analysis techniques exhibit poor efficiency, and mixtures of numeric and categorical modes of data are very often present in neuroimaging experiments. Formulating the problem of image clustering as a form of Latent Semantic Analysis and using the WaveCluster algorithm as a baseline, we propose a comprehensive hybrid tensor and wavelet framework for clustering, concept discovery, and compression of functional medical images which successfully addresses these challenges. Our approach reduced runtime and dataset size on a 9.3GB finger opposition motor task fMRI dataset by up to 98% while exhibiting improved spatiotemporal coherence relative to standard tensor, wavelet, and voxel-based approaches. Our clustering technique was capable of automatically differentiating between the frontal areas of the brain responsible for task-related habituation and the motor regions responsible for executing the motor task, in contrast to a widely used fMRI analysis program, SPM, which only detected the latter region. Furthermore, our approach discovered latent concepts suggestive of subject handedness nearly 100× faster than standard approaches. These results suggest that a high-order model is an integral component to accurate scalable functional neuroimaging.     

模糊K-均值聚类算法及其在磁共振颅脑图像分割中的应用研究

目的　介绍一种动态模糊聚类算法并利用该算法对磁共振图像进行分割研究。方法　首先对磁共振颅脑图像进行预处理去掉颅骨和肌肉等非脑组织,只保留大脑组织,然后利用模糊Ｋ－ 均值聚类算法计算脑白质、脑灰质和脑脊液的模糊类属函数。结果　模糊Ｋ－ 均值聚类算法能很好地分割出磁共振颅脑图像中的灰质、白质和脑脊液。结论　利用模糊Ｋ－ 均值聚类算法分割磁共振颅脑图像能获得较好的分割效果。     

CLASSIC: consistent longitudinal alignment and segmentation for serial image computing

This paper proposes a temporally consistent and spatially adaptive longitudinal MR brain image segmentation algorithm, referred to as CLASSIC, which aims at obtaining accurate measurements of rates of change of regional and global brain volumes from serial MR images. The algorithm incorporates image-adaptive clustering, spatiotemporal smoothness constraints, and image warping to jointly segment a series of 3-D MR brain images of the same subject that might be undergoing changes due to development, aging, or disease. Morphological changes, such as growth or atrophy, are also estimated as part of the algorithm. Experimental results on simulated and real longitudinal MR brain images show both segmentation accuracy and longitudinal consistency.     

Multi-stage segmentation of white matter hyperintensity, cortical and lacunar infarcts

Cerebral abnormalities such as white matter hyperintensity (WMH), cortical infarct (CI), and lacunar infarct (LI) are of clinical importance and frequently present in patients with stroke and dementia. Up to date, there are limited algorithms available to automatically delineate these cerebral abnormalities partially due to their complex appearance in MR images. In this paper, we describe an automated multi-stage segmentation approach for labeling the WMH, CI, and LI using multi-modal MR images. We first automatically segment brain tissues (white matter, gray matter, and CSF) based on the T1-weighted image and then identify hyperintense voxels based on the fluid attenuated inversion recovery (FLAIR) image. We finally label the WMH, CI, and LI based on the T1-weighted, T2-weighted, and FLAIR images. The segmentation accuracy is evaluated using a community-based sample of 272 old adults. Our results show that the automated segmentation of the WMH, CI, and LI is comparable with manual labeling in terms of spatial location, volume, and the number of lacunes. Additionally, the WMH volume is highly correlated with the visual grading score based on the Age-Related White Matter Changes (ARWMC) protocol. The evaluations against the manual labeling and ARWMC visual grading suggest that our algorithm provides reasonable segmentation accuracy for the WMH, CI, and LI.     

Magnetic resonance image tissue classification using a partial volume model

We describe a sequence of low-level operations to isolate and classify brain tissue within T1-weighted magnetic resonance images (MRI). Our method first removes nonbrain tissue using a combination of anisotropic diffusion filtering, edge detection, and mathematical morphology. We compensate for image nonuniformities due to magnetic field inhomogeneities by fitting a tricubic B-spline gain field to local estimates of the image nonuniformity spaced throughout the MRI volume. The local estimates are computed by fitting a partial volume tissue measurement model to histograms of neighborhoods about each estimate point. The measurement model uses mean tissue intensity and noise variance values computed from the global image and a multiplicative bias parameter that is estimated for each region during the histogram fit. Voxels in the intensity-normalized image are then classified into six tissue types using a maximum a posteriori classifier. This classifier combines the partial volume tissue measurement model with a Gibbs prior that models the spatial properties of the brain. We validate each stage of our algorithm on real and phantom data. Using data from the 20 normal MRI brain data sets of the Internet Brain Segmentation Repository, our method achieved average kappa indices of kappa = 0.746 +/- 0.114 for gray matter (GM) and kappa = 0.798 +/- 0.089 for white matter (WM) compared to expert labeled data. Our method achieved average kappa indices kappa = 0.893 +/- 0.041 for GM and kappa = 0.928 +/- 0.039 for WM compared to the ground truth labeling on 12 volumes from the Montreal Neurological Institute's BrainWeb phantom.     

Multi-modal image set registration and atlas formation

In this paper, we present a Bayesian framework for both generating inter-subject large deformation transformations between two multi-modal image sets of the brain and for forming multi-class brain atlases. In this framework, the estimated transformations are generated using maximal information about the underlying neuroanatomy present in each of the different modalities. This modality independent registration framework is achieved by jointly estimating the posterior probabilities associated with the multi-modal image sets and the high-dimensional registration transformations mapping these posteriors. To maximally use the information present in all the modalities for registration, Kullback-Leibler divergence between the estimated posteriors is minimized. Registration results for image sets composed of multi-modal MR images of healthy adult human brains are presented. Atlas formation results are presented for a population of five infant human brains.     

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.     

Automated classification of brain tumor type in whole-slide digital pathology images using local representative tiles

Computerized analysis of digital pathology images offers the potential of improving clinical care (e.g. automated diagnosis) and catalyzing research (e.g. discovering disease subtypes). There are two key challenges thwarting computerized analysis of digital pathology images: first, whole slide pathology images are massive, making computerized analysis inefficient, and second, diverse tissue regions in whole slide images that are not directly relevant to the disease may mislead computerized diagnosis algorithms. We propose a method to overcome both of these challenges that utilizes a coarse-to-fine analysis of the localized characteristics in pathology images. An initial surveying stage analyzes the diversity of coarse regions in the whole slide image. This includes extraction of spatially localized features of shape, color and texture from tiled regions covering the slide. Dimensionality reduction of the features assesses the image diversity in the tiled regions and clustering creates representative groups. A second stage provides a detailed analysis of a single representative tile from each group. An Elastic Net classifier produces a diagnostic decision value for each representative tile. A weighted voting scheme aggregates the decision values from these tiles to obtain a diagnosis at the whole slide level. We evaluated our method by automatically classifying 302 brain cancer cases into two possible diagnoses (glioblastoma multiforme (N = 182) versus lower grade glioma (N = 120)) with an accuracy of 93.1 % (p << 0.001). We also evaluated our method in the dataset provided for the 2014 MICCAI Pathology Classification Challenge, in which our method, trained and tested using 5-fold cross validation, produced a classification accuracy of 100% (p << 0.001). Our method showed high stability and robustness to parameter variation, with accuracy varying between 95.5% and 100% when evaluated for a wide range of parameters. Our approach may be useful to automatically differentiate between the two cancer subtypes.     

MRI noise estimation and denoising using non-local PCA

This paper proposes a novel method for MRI denoising that exploits both the sparseness and self-similarity properties of the MR images. The proposed method is a two-stage approach that first filters the noisy image using a non local PCA thresholding strategy by automatically estimating the local noise level present in the image and second uses this filtered image as a guide image within a rotationally invariant non-local means filter. The proposed method internally estimates the amount of local noise presents in the images that enables applying it automatically to images with spatially varying noise levels and also corrects the Rician noise induced bias locally. The proposed approach has been compared with related state-of-the-art methods showing competitive results in all the studied cases.     

2D probabilistic undersampling pattern optimization for MR image reconstruction

With 3D magnetic resonance imaging (MRI), a tradeoff exists between higher image quality and shorter scan time. One way to solve this problem is to reconstruct high-quality MRI images from undersampled k-space. There have been many recent studies exploring effective k-space undersampling patterns and designing MRI reconstruction methods from undersampled k-space, which are two necessary steps. Most studies separately considered these two steps, although in theory, their performance is dependent on each other. In this study, we propose a joint optimization model, trained end-to-end, to simultaneously optimize the undersampling pattern in the Fourier domain and the reconstruction model in the image domain. A 2D probabilistic undersampling layer was designed to optimize the undersampling pattern and probability distribution in a differentiable manner. A 2D inverse Fourier transform layer was implemented to connect the Fourier domain and the image domain during the forward and back propagation. Finally, we discovered an optimized relationship between the probability distribution of the undersampling pattern and its corresponding sampling rate. Further testing was performed using 3D T1-weighted MR images of the brain from the MICCAI 2013 Grand Challenge on Multi-Atlas Labeling dataset and locally acquired brain 3D T1-weighted MR images of healthy volunteers and contrast-enhanced 3D T1-weighted MR images of high-grade glioma patients. The results showed that the recovered MR images using our 2D probabilistic undersampling pattern (with or without the reconstruction network) significantly outperformed those using the existing start-of-the-art undersampling strategies for both qualitative and quantitative comparison, suggesting the advantages and some extent of the generalization of our proposed method.     

Variational, geometric, and statistical methods for modeling brain anatomy and function

We survey the recent activities of the Odyssée Laboratory in the area of the application of mathematics to the design of models for studying brain anatomy and function. We start with the problem of reconstructing sources in MEG and EEG, and discuss the variational approach we have developed for solving these inverse problems. This motivates the need for geometric models of the head. We present a method for automatically and accurately extracting surface meshes of several tissues of the head from anatomical magnetic resonance (MR) images. Anatomical connectivity can be extracted from diffusion tensor magnetic resonance images but, in the current state of the technology, it must be preceded by a robust estimation and regularization stage. We discuss our work based on variational principles and show how the results can be used to track fibers in the white matter (WM) as geodesics in some Riemannian space. We then go to the statistical modeling of functional magnetic resonance imaging (fMRI) signals from the viewpoint of their decomposition in a pseudo-deterministic and stochastic part that we then use to perform clustering of voxels in a way that is inspired by the theory of support vector machines and in a way that is grounded in information theory. Multimodal image matching is discussed next in the framework of image statistics and partial differential equations (PDEs) with an eye on registering fMRI to the anatomy. The paper ends with a discussion of a new theory of random shapes that may prove useful in building anatomical and functional atlases.