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Automatic detection of lesion load change in Multiple Sclerosis using convolutional neural networks with segmentation confidence

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 Added by Richard McKinley
 Publication date 2019
and research's language is English




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The detection of new or enlarged white-matter lesions in multiple sclerosis is a vital task in the monitoring of patients undergoing disease-modifying treatment for multiple sclerosis. However, the definition of new or enlarged is not fixed, and it is known that lesion-counting is highly subjective, with high degree of inter- and intra-rater variability. Automated methods for lesion quantification hold the potential to make the detection of new and enlarged lesions consistent and repeatable. However, the majority of lesion segmentation algorithms are not evaluated for their ability to separate progressive from stable patients, despite this being a pressing clinical use-case. In this paper we show that change in volumetric measurements of lesion load alone is not a good method for performing this separation, even for highly performing segmentation methods. Instead, we propose a method for identifying lesion changes of high certainty, and establish on a dataset of longitudinal multiple sclerosis cases that this method is able to separate progressive from stable timepoints with a very high level of discrimination (AUC = 0.99), while changes in lesion volume are much less able to perform this separation (AUC = 0.71). Validation of the method on a second external dataset confirms that the method is able to generalize beyond the setting in which it was trained, achieving an accuracy of 83% in separating stable and progressive timepoints. Both lesion volume and count have previously been shown to be strong predictors of disease course across a population. However, we demonstrate that for individual patients, changes in these measures are not an adequate means of establishing no evidence of disease activity. Meanwhile, directly detecting tissue which changes, with high confidence, from non-lesion to lesion is a feasible methodology for identifying radiologically active patients.

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Multiple Sclerosis (MS) is an autoimmune disease that leads to lesions in the central nervous system. Magnetic resonance (MR) images provide sufficient imaging contrast to visualize and detect lesions, particularly those in the white matter. Quantitative measures based on various features of lesions have been shown to be useful in clinical trials for evaluating therapies. Therefore robust and accurate segmentation of white matter lesions from MR images can provide important information about the disease status and progression. In this paper, we propose a fully convolutional neural network (CNN) based method to segment white matter lesions from multi-contrast MR images. The proposed CNN based method contains two convolutional pathways. The first pathway consists of multiple parallel convolutional filter banks catering to multiple MR modalities. In the second pathway, the outputs of the first one are concatenated and another set of convolutional filters are applied. The output of this last pathway produces a membership function for lesions that may be thresholded to obtain a binary segmentation. The proposed method is evaluated on a dataset of 100 MS patients, as well as the ISBI 2015 challenge data consisting of 14 patients. The comparison is performed against four publicly available MS lesion segmentation methods. Significant improvement in segmentation quality over the competing methods is demonstrated on various metrics, such as Dice and false positive ratio. While evaluating on the ISBI 2015 challenge data, our method produces a score of 90.48, where a score of 90 is considered to be comparable to a human rater.
Segmentation of white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. In this paper we explore segmentation solutions based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of lesions and grey-matter structures in multi-modal MR imaging, and the performance of these methods when applied to out-of-centre data. We trained two state-of-the-art fully convolutional CNN architectures on the 2016 MSSEG training dataset, which was annotated by seven independent human raters: a reference implementation of a 3D Unet, and a more recently proposed 3D-to-2D architecture (DeepSCAN). We then retrained those methods on a larger dataset from a single centre, with and without labels for other brain structures. We quantified changes in performance owing to dataset shift, and changes in performance by adding the additional brain-structure labels. We also compared performance with freely available reference methods. Both fully-convolutional CNN methods substantially outperform other approaches in the literature when trained and evaluated in cross-validation on the MSSEG dataset, showing agreement with human raters in the range of human inter-rater variability. Both architectures showed drops in performance when trained on single-centre data and tested on the MSSEG dataset. When trained with the addition of weak anatomical labels derived from Freesurfer, the performance of the 3D Unet degraded, while the performance of the DeepSCAN net improved. Overall, the DeepSCAN network predicting both lesion and anatomical labels was the best-performing network examined.
The spinal cord is frequently affected by atrophy and/or lesions in multiple sclerosis (MS) patients. Segmentation of the spinal cord and lesions from MRI data provides measures of damage, which are key criteria for the diagnosis, prognosis, and longitudinal monitoring in MS. Automating this operation eliminates inter-rater variability and increases the efficiency of large-throughput analysis pipelines. Robust and reliable segmentation across multi-site spinal cord data is challenging because of the large variability related to acquisition parameters and image artifacts. The goal of this study was to develop a fully-automatic framework, robust to variability in both image parameters and clinical condition, for segmentation of the spinal cord and intramedullary MS lesions from conventional MRI data. Scans of 1,042 subjects (459 healthy controls, 471 MS patients, and 112 with other spinal pathologies) were included in this multi-site study (n=30). Data spanned three contrasts (T1-, T2-, and T2*-weighted) for a total of 1,943 volumes. The proposed cord and lesion automatic segmentation approach is based on a sequence of two Convolutional Neural Networks (CNNs). To deal with the very small proportion of spinal cord and/or lesion voxels compared to the rest of the volume, a first CNN with 2D dilated convolutions detects the spinal cord centerline, followed by a second CNN with 3D convolutions that segments the spinal cord and/or lesions. When compared against manual segmentation, our CNN-based approach showed a median Dice of 95% vs. 88% for PropSeg, a state-of-the-art spinal cord segmentation method. Regarding lesion segmentation on MS data, our framework provided a Dice of 60%, a relative volume difference of -15%, and a lesion-wise detection sensitivity and precision of 83% and 77%, respectively. The proposed framework is open-source and readily available in the Spinal Cord Toolbox.
Multiple sclerosis (MS) lesions occupy a small fraction of the brain volume, and are heterogeneous with regards to shape, size and locations, which poses a great challenge for training deep learning based segmentation models. We proposed a new geometric loss formula to address the data imbalance and exploit the geometric property of MS lesions. We showed that traditional region-based and boundary-aware loss functions can be associated with the formula. We further develop and instantiate two loss functions containing first- and second-order geometric information of lesion regions to enforce regularization on optimizing deep segmentation models. Experimental results on two MS lesion datasets with different scales, acquisition protocols and resolutions demonstrated the superiority of our proposed methods compared to other state-of-the-art methods.
Automatic segmentation of the liver and its lesion is an important step towards deriving quantitative biomarkers for accurate clinical diagnosis and computer-aided decision support systems. This paper presents a method to automatically segment liver and lesions in CT abdomen images using cascaded fully convolutional neural networks (CFCNs) and dense 3D conditional random fields (CRFs). We train and cascade two FCNs for a combined segmentation of the liver and its lesions. In the first step, we train a FCN to segment the liver as ROI input for a second FCN. The second FCN solely segments lesions from the predicted liver ROIs of step 1. We refine the segmentations of the CFCN using a dense 3D CRF that accounts for both spatial coherence and appearance. CFCN models were trained in a 2-fold cross-validation on the abdominal CT dataset 3DIRCAD comprising 15 hepatic tumor volumes. Our results show that CFCN-based semantic liver and lesion segmentation achieves Dice scores over 94% for liver with computation times below 100s per volume. We experimentally demonstrate the robustness of the proposed method as a decision support system with a high accuracy and speed for usage in daily clinical routine.
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