A joint ventricle and WMH segmentation from MRI for evaluation of healthy and pathological changes in the aging brain.

Age-related changes in brain structure include atrophy of the brain parenchyma and white matter changes of presumed vascular origin. Enlargement of the ventricles may occur due to atrophy or impaired cerebrospinal fluid (CSF) circulation. The co-occurrence of these changes in neurodegenerative diseases and in aging brains often requires investigators to take both into account when studying the brain, however, automated segmentation of enlarged ventricles and white matter hyperintensities (WMHs) can be a challenging task. Here, we present a hybrid multi-atlas segmentation and convolutional autoencoder approach for joint ventricle parcellation and WMH segmentation from magnetic resonance images (MRIs). Our fully automated approach uses a convolutional autoencoder to generate a standardized image of grey matter, white matter, CSF, and WMHs, which, in conjunction with labels generated by a multi-atlas segmentation approach, is then fed into a convolutional neural network to parcellate the ventricular system. Hence, our approach does not depend on manually delineated training data for new data sets. The segmentation pipeline was validated on both healthy elderly subjects and subjects with normal pressure hydrocephalus using ground truth manual labels and compared with state-of-the-art segmentation methods. We then applied the method to a cohort of 2401 elderly brains to investigate associations of ventricle volume and WMH load with various demographics and clinical biomarkers, using a multiple regression model. Our results indicate that the ventricle volume and WMH load are both highly variable in a cohort of elderly subjects and there is an independent association between the two, which highlights the importance of taking both the possibility of enlarged ventricles and WMHs into account when studying the aging brain.

SegAE: Unsupervised white matter lesion segmentation from brain MRIs using a CNN autoencoder.

White matter hyperintensities (WMHs) of presumed vascular origin are frequently observed in magnetic resonance images (MRIs) of the elderly. Detection and quantification of WMHs is important to help doctors make diagnoses and evaluate prognosis of their elderly patients, and once quantified, these can act as biomarkers in clinical research studies. Manual delineation of WMHs can be both time-consuming and inconsistent, hence, automatic segmentation methods are often preferred. However, fully automatic methods can be challenging to construct due to the variability in lesion load, placement of lesions, and voxel intensities. Several state-of-the-art lesion segmentation methods based on supervised Convolutional Neural Networks (CNNs) have been proposed. These approaches require manually delineated lesions for training the parameters of the network. Here we present a novel approach for WMH segmentation using a CNN trained in an unsupervised manner, by reconstructing multiple MRI sequences as weighted sums of segmentations of WMHs and tissues present in the images. After training, our method can be used to segment new images that are not part of the training set to provide fast and robust segmentation of WMHs in a matter of seconds per subject. Comparisons with state-of-the-art WMH segmentation methods evaluated on ground truth manual labels from two distinct data sets and six different scanners indicate that the proposed method works well at generating accurate WMH segmentations without the need for manual delineations.

Applications of a deep learning method for anti-aliasing and super-resolution in MRI.

Magnetic resonance (MR) images with both high resolutions and high signal-to-noise ratios (SNRs) are desired in many clinical and research applications. However, acquiring such images takes a long time, which is both costly and susceptible to motion artifacts. Acquiring MR images with good in-plane resolution and poor through-plane resolution is a common strategy that saves imaging time, preserves SNR, and provides one viewpoint with good resolution in two directions. Unfortunately, this strategy also creates orthogonal viewpoints that have poor resolution in one direction and, for 2D MR acquisition protocols, also creates aliasing artifacts. A deep learning approach called SMORE that carries out both anti-aliasing and super-resolution on these types of acquisitions using no external atlas or exemplars has been previously reported but not extensively validated. This paper reviews the SMORE algorithm and then demonstrates its performance in four applications with the goal to demonstrate its potential for use in both research and clinical scenarios. It is first shown to improve the visualization of brain white matter lesions in FLAIR images acquired from multiple sclerosis patients. Then it is shown to improve the visualization of scarring in cardiac left ventricular remodeling after myocardial infarction. Third, its performance on multi-view images of the tongue is demonstrated and finally it is shown to improve performance in parcellation of the brain ventricular system. Both visual and selected quantitative metrics of resolution enhancement are demonstrated.

Brain ventricle parcellation using a deep neural network: Application to patients with ventriculomegaly.

Numerous brain disorders are associated with ventriculomegaly, including both neuro-degenerative diseases and cerebrospinal fluid disorders. Detailed evaluation of the ventricular system is important for these conditions to help understand the pathogenesis of ventricular enlargement and elucidate novel patterns of ventriculomegaly that can be associated with different diseases. One such disease is normal pressure hydrocephalus (NPH), a chronic form of hydrocephalus in older adults that causes dementia. Automatic parcellation of the ventricular system into its sub-compartments in patients with ventriculomegaly is quite challenging due to the large variation of the ventricle shape and size. Conventional brain labeling methods are time-consuming and often fail to identify the boundaries of the enlarged ventricles. We propose a modified 3D U-Net method to perform accurate ventricular parcellation, even with grossly enlarged ventricles, from magnetic resonance images (MRIs). We validated our method on a data set of healthy controls as well as a cohort of 95 patients with NPH with mild to severe ventriculomegaly and compared with several state-of-the-art segmentation methods. On the healthy data set, the proposed network achieved mean Dice similarity coefficient (DSC) of 0.895 ±â€¯0.03 for the ventricular system. On the NPH data set, we achieved mean DSC of 0.973 ±â€¯0.02, which is significantly (p < 0.005) higher than four state-of-the-art segmentation methods we compared with. Furthermore, the typical processing time on CPU-base implementation of the proposed method is 2 min, which is much lower than the several hours required by the other methods. Results indicate that our method provides: 1) highly robust parcellation of the ventricular system that is comparable in accuracy to state-of-the-art methods on healthy controls; 2) greater robustness and significantly more accurate results on cases of ventricular enlargement; and 3) a tool that enables computation of novel imaging biomarkers for dilated ventricular spaces that characterize the ventricular system.

Shortcomings of Ventricle Segmentation Using Deep Convolutional Networks.

Normal Pressure Hydrocephalus (NPH) is a brain disorder that can present with ventriculomegaly and dementia-like symptoms, which often can be reversed through surgery. Having accurate segmentation of the ventricular system into its sub-compartments from magnetic resonance images (MRI) would be beneficial to better characterize the condition of NPH patients. Previous segmentation algorithms need long processing time and often fail to accurately segment severely enlarged ventricles in NPH patients. Recently, deep convolutional neural network (CNN) methods have been reported to have fast and accurate performance on medical image segmentation tasks. In this paper, we present a 3D U-net CNN-based network to segment the ventricular system in MRI. We trained three networks on different data sets and compared their performances. The networks trained on healthy controls (HC) failed in patients with NPH pathology, even in patients with normal appearing ventricles. The network trained on images from HC and NPH patients provided superior performance against state-of-the-art methods when evaluated on images from both data sets.

Multi-atlas segmentation of the hydrocephalus brain using an adaptive ventricle atlas.

Normal pressure hydrocephalus (NPH) is a brain disorder caused by disruption of the flow of cerebrospinal fluid (CSF). The dementia-like symptoms of NPH are often mistakenly attributed to Alzheimer's disease. However, if correctly diagnosed, NPH patients can potentially be treated and their symptoms reversed through surgery. Observing the dilated ventricles through magnetic resonance imaging (MRI) is one element in diagnosing NPH. Diagnostic accuracy therefore benefits from accurate, automatic parcellation of the ventricular system into its sub-compartments. We present an improvement to a whole brain segmentation approach designed for subjects with enlarged and deformed ventricles. Our method incorporates an adaptive ventricle atlas from an NPH-atlas-based segmentation as a prior and uses a more robust relaxation scheme for the multi-atlas label fusion approach that accurately labels the four sub-compartments of the ventricular system. We validated our method on NPH patients, demonstrating improvement over state-of-the-art segmentation techniques.

Deformable model reconstruction of the subarachnoid space.

The subarachnoid space is a layer in the meninges that surrounds the brain and is filled with trabeculae and cerebrospinal fluid. Quantifying the volume and thickness of the subarachnoid space is of interest in order to study the pathogenesis of neurodegenerative diseases and compare with healthy subjects. We present an automatic method to reconstruct the subarachnoid space with subvoxel accuracy using a nested deformable model. The method initializes the deformable model using the convex hull of the union of the outer surfaces of the cerebrum, cerebellum and brainstem. A region force is derived from the subject's Tl-weighted and T2-weighted MRI to drive the deformable model to the outer surface of the subarachnoid space. The proposed method is compared to a semi-automatic delineation from the subject's T2-weighted MRI and an existing multi-atlas-based method. A small pilot study comparing the volume and thickness measurements in a set of age-matched subjects with normal pressure hydrocephalus and healthy controls is presented to show the efficacy of the proposed method.

Longitudinal multiple sclerosis lesion segmentation data resource.

The data presented in this article is related to the research article entitled "Longitudinal multiple sclerosis lesion segmentation: Resource and challenge" (Carass et al., 2017) [1]. In conjunction with the 2015 International Symposium on Biomedical Imaging, we organized a longitudinal multiple sclerosis (MS) lesion segmentation challenge providing training and test data to registered participants. The training data consists of five subjects with a mean of 4.4 (±0.55) time-points, and test data of fourteen subjects with a mean of 4.4 (±0.67) time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. The training data including multi-modal scans and manually delineated lesion masks is available for download. In addition, the testing data is also being made available in conjunction with a website for evaluating the automated analysis of the testing data.

Longitudinal multiple sclerosis lesion segmentation: Resource and challenge.

In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4.4 time-points, and test data of fourteen subjects with a mean of 4.4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website2 as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.

Whole Brain Parcellation with Pathology: Validation on Ventriculomegaly Patients.

Numerous brain disorders are associated with ventriculomegaly; normal pressure hydrocephalus (NPH) is one example. NPH presents with dementia-like symptoms and is often misdiagnosed as Alzheimer's due to its chronic nature and nonspecific presenting symptoms. However, unlike other forms of dementia NPH can be treated surgically with an over 80% success rate on appropriately selected patients. Accurate assessment of the ventricles, in particular its sub-compartments, is required to diagnose the condition. Existing segmentation algorithms fail to accurately identify the ventricles in patients with such extreme pathology. We present an improvement to a whole brain segmentation approach that accurately identifies the ventricles and parcellates them into four sub-compartments. Our work is a combination of patch-based tissue segmentation and multi-atlas registration-based labeling. We include a validation on NPH patients, demonstrating superior performance against state-of-the-art methods.

Segmentation and labeling of the ventricular system in normal pressure hydrocephalus using patch-based tissue classification and multi-atlas labeling.

Normal pressure hydrocephalus (NPH) affects older adults and is thought to be caused by obstruction of the normal flow of cerebrospinal fluid (CSF). NPH typically presents with cognitive impairment, gait dysfunction, and urinary incontinence, and may account for more than five percent of all cases of dementia. Unlike most other causes of dementia, NPH can potentially be treated and the neurological dysfunction reversed by shunt surgery or endoscopic third ventriculostomy (ETV), which drain excess CSF. However, a major diagnostic challenge remains to robustly identify shunt-responsive NPH patients from patients with enlarged ventricles due to other neurodegenerative diseases. Currently, radiologists grade the severity of NPH by detailed examination and measurement of the ventricles based on stacks of 2D magnetic resonance images (MRIs). Here we propose a new method to automatically segment and label different compartments of the ventricles in NPH patients from MRIs. While this task has been achieved in healthy subjects, the ventricles in NPH are both enlarged and deformed, causing current algorithms to fail. Here we combine a patch-based tissue classification method with a registration-based multi-atlas labeling method to generate a novel algorithm that labels the lateral, third, and fourth ventricles in subjects with ventriculomegaly. The method is also applicable to other neurodegenerative diseases such as Alzheimer's disease; a condition considered in the differential diagnosis of NPH. Comparison with state of the art segmentation techniques demonstrate substantial improvements in labeling the enlarged ventricles, indicating that this strategy may be a viable option for the diagnosis and characterization of NPH.

Robust deformable image registration using prior shape information for atlas to patient registration.

Statistical atlases enable the individualization of atlas information for patient specific applications such as surgical planning. In this paper, a statistical atlas comprising a point distribution model defined on the vertices of a tetrahedral mesh is registered to a subject's computed tomography scan of the human pelvis. The approach consists of a volumetric deformable registration method augmented to maintain the topology of the atlas mesh after deformation as well as incorporating the dominant three-dimensional shape modes in the atlas. Experimental results demonstrate that incorporation of the statistical shape atlas helps to stabilize the registration and improves robustness and registration accuracy.

Mjolnir: extending HAMMER using a diffusion transformation model and histogram equalization for deformable image registration.

Image registration is a crucial step in many medical image analysis procedures such as image fusion, surgical planning, segmentation and labeling, and shape comparison in population or longitudinal studies. A new approach to volumetric intersubject deformable image registration is presented. The method, called Mjolnir, is an extension of the highly successful method HAMMER. New image features in order to better localize points of correspondence between the two images are introduced as well as a novel approach to generate a dense displacement field based upon the weighted diffusion of automatically derived feature correspondences. An extensive validation of the algorithm was performed on T1-weighted SPGR MR brain images from the NIREP evaluation database. The results were compared with results generated by HAMMER and are shown to yield significant improvements in cortical alignment as well as reduced computation time.

Statistical atlases of bone anatomy: construction, iterative improvement and validation.

We present an iterative bootstrapping framework to create and analyze statistical atlases of bony anatomy such as the human pelvis from a large collection of CT data sets. We create an initial tetrahedral mesh representation of the target anatomy and use deformable intensity-based registration to create an initial atlas. This atlas is used as prior information to assist in deformable registration/segmentation of our subject image data sets, and the process is iterated several times to remove any bias from the initial choice of template subject and to improve the stability and consistency of mean shape and variational modes. We also present a framework to validate the statistical models. Using this method, we have created a statistical atlas of full pelvis anatomy with 110 healthy patient CT scans. Our analysis shows that any given pelvis shape can be approximated up to an average accuracy of 1.5036 mm using the first 15 principal modes of variation. Although a particular intensity-based deformable registration algorithm was used to produce these results, we believe that the basic method may be adapted readily for use with any registration method with broadly similar characteristics.

Transposon-derived repeats in the human genome and 5-methylcytosine-associated mutations in adjacent genes.

Transposon-derived repeats (TDR) represent approximately 50% of the human genome. A transposon suppression system has been proposed to explain why transposon-derived repeats (TDR) seldom cause mutations in humans. If this system is based on DNA methylation, a correlation might exist between amount of TDR adjacent to genes and frequency of coding sequence mutations due to m5C deaminations. To test this hypothesis we selected 385 genes based on availability of accurate information on their genome structure and mutation patterns (at least 10 mutations described in the Human Gene Mutation Database (HGMD)). The CENSOR program was used to estimate amount and class of TDR for the gene region and an arbitrarily selected 1 KB from each end. We assumed all C --> T transitions to be possible 5-methylcytosine-associated mutations (MAM) and calculated the number and proportion of MAM in the 385 genes. If there is a strong correlation between methylation of certain CpX dinuclecotides and TDR we might be able to detect it despite limitations of available data for this analysis. We found statistically significant correlations between: i) TDR and number of MAM in genes (r = 0.118, p = 0.02), ii) SINE-TDR and proportion of CpG --> TpG (r = 0.11, p = 0.03); limited to MIR elements only (r = 0.14, p = 0.006), and iii) LINE-TDR and proportion of CpT --> TpT (r = 0.166, p = 0.04). The group of genes with no TDR had a statistically significant lower proportion of MAM (184/479, 0.38 vs. 6466/14524, 0.46; p = 0.009) with differences noted for CpA --> TpA (35/479, 0.073 vs. 1380/11474; p = 0.003). In addition, CpT --> TpT were least common in genes with no TDR (8/479, 0.017), intermediate in genes with TDR in genomic sequence but not mRNA (337/11474, 0.029) and most common in genes with TDR within mature mRNA (121/3050, 0.040; p for trend = 0.003). Our data suggest that TDR adjacent to genes may sometimes influence methylation of cytosines in coding sequences to a degree that it affects mutation patterns. These observations should be followed up with further database analysis and biochemical studies.