Neuroimaging of structural pathology and connectomics in traumatic brain injury: Toward personalized outcome prediction.

Recent contributions to the body of knowledge on traumatic brain injury (TBI) favor the view that multimodal neuroimaging using structural and functional magnetic resonance imaging (MRI and fMRI, respectively) as well as diffusion tensor imaging (DTI) has excellent potential to identify novel biomarkers and predictors of TBI outcome. This is particularly the case when such methods are appropriately combined with volumetric/morphometric analysis of brain structures and with the exploration of TBI-related changes in brain network properties at the level of the connectome. In this context, our present review summarizes recent developments on the roles of these two techniques in the search for novel structural neuroimaging biomarkers that have TBI outcome prognostication value. The themes being explored cover notable trends in this area of research, including (1) the role of advanced MRI processing methods in the analysis of structural pathology, (2) the use of brain connectomics and network analysis to identify outcome biomarkers, and (3) the application of multivariate statistics to predict outcome using neuroimaging metrics. The goal of the review is to draw the community's attention to these recent advances on TBI outcome prediction methods and to encourage the development of new methodologies whereby structural neuroimaging can be used to identify biomarkers of TBI outcome

Brain Lesion Segmentation through Image Synthesis and Outlier Detection

Cerebral small vessel disease (SVD) can manifest in a number of ways. Many of these result in hyperintense regions visible on T2-weighted magnetic resonance (MR) images. The automatic segmentation of these lesions has been the focus of many studies. However, previous methods tended to be limited to certain types of pathology, as a consequence of either restricting the search to the white matter, or by training on an individual pathology. Here we present an unsupervised abnormality detection method which is able to detect abnormally hyperintense regions on FLAIR regardless of the underlying pathology or location. The method uses a combination of image synthesis, Gaussian mixture models and one class support vector machines, and needs only be trained on healthy tissue. We evaluate our method by comparing segmentation results from 127 subjects with SVD with three established methods and report significantly superior performance across a number of metrics

Developing advanced mathematical models for detecting abnormalities in 2D/3D medical structures.

Detecting abnormalities in two-dimensional (2D) and three-dimensional (3D) medical structures is among the most interesting and challenging research areas in the medical imaging field. Obtaining the desired accurate automated quantification of abnormalities in medical structures is still very challenging. This is due to a large and constantly growing number of different objects of interest and associated abnormalities, large variations of their appearances and shapes in images, different medical imaging modalities, and associated changes of signal homogeneity and noise for each object. The main objective of this dissertation is to address these problems and to provide proper mathematical models and techniques that are capable of analyzing low and high resolution medical data and providing an accurate, automated analysis of the abnormalities in medical structures in terms of their area/volume, shape, and associated abnormal functionality. This dissertation presents different preliminary mathematical models and techniques that are applied in three case studies: (i) detecting abnormal tissue in the left ventricle (LV) wall of the heart from delayed contrast-enhanced cardiac magnetic resonance images (MRI), (ii) detecting local cardiac diseases based on estimating the functional strain metric from cardiac cine MRI, and (iii) identifying the abnormalities in the corpus callosum (CC) brain structure—the largest fiber bundle that connects the two hemispheres in the brain—for subjects that suffer from developmental brain disorders. For detecting the abnormal tissue in the heart, a graph-cut mathematical optimization model with a cost function that accounts for the object’s visual appearance and shape is used to segment the the inner cavity. The model is further integrated with a geometric model (i.e., a fast marching level set model) to segment the outer border of the myocardial wall (the LV). Then the abnormal tissue in the myocardium wall (also called dead tissue, pathological tissue, or infarct area) is identified based on a joint Markov-Gibbs random field (MGRF) model of the image and its region (segmentation) map that accounts for the pixel intensities and the spatial interactions between the pixels. Experiments with real in-vivo data and comparative results with ground truth (identified by a radiologist) and other approaches showed that the proposed framework can accurately detect the pathological tissue and can provide useful metrics for radiologists and clinicians. To estimate the strain from cardiac cine MRI, a novel method based on tracking the LV wall geometry is proposed. To achieve this goal, a partial differential equation (PDE) method is applied to track the LV wall points by solving the Laplace equation between the LV contours of each two successive image frames over the cardiac cycle. The main advantage of the proposed tracking method over traditional texture-based methods is its ability to track the movement and rotation of the LV wall based on tracking the geometric features of the inner, mid-, and outer walls of the LV. This overcomes noise sources that come from scanner and heart motion. To identify the abnormalities in the CC from brain MRI, the CCs are aligned using a rigid registration model and are segmented using a shape-appearance model. Then, they are mapped to a simple unified space for analysis. This work introduces a novel cylindrical mapping model, which is conformal (i.e., one to one transformation and bijective), that enables accurate 3D shape analysis of the CC in the cylindrical domain. The framework can detect abnormalities in all divisions of the CC (i.e., splenium, rostrum, genu and body). In addition, it offers a whole 3D analysis of the CC abnormalities instead of only area-based analysis as done by previous groups. The initial classification results based on the centerline length and CC thickness suggest that the proposed CC shape analysis is a promising supplement to the current techniques for diagnosing dyslexia. The proposed techniques in this dissertation have been successfully tested on complex synthetic and MR images and can be used to advantage in many of today’s clinical applications of computer-assisted medical diagnostics and intervention

Validation of White Matter Hyperintensities automatic segmentation methods

Treballs finals del Màster de Fonaments de Ciència de Dades, Facultat de matemàtiques, Universitat de Barcelona, Any: 2020, Tutor: Eloi Puertas i Prats i Joaquim Raduà[en] This master’s thesis seeks to review and objectively evaluate the current white matter hyperintensities (WMH) automatic segmentation methods published journals. To this end, the methods have been systematically searched in scientific databases, and those meeting inclusion criteria have been evaluated. The evaluation has consisted in applying the method to detect WMH in our dataset of patients with bipolar disorder and healthy controls, in which an experienced neuroradiologist had manually coded all WMH. After the systematic search, we selected all available methods that were ready for use with standard MRI data by a standard user. Four methods met these criteria. We then applied these methods to detect WMH in our dataset, and compared the results with the neuroradiologist-based ground truth deriving several evaluation metrics. This master’s thesis also include a discussion section, in which we compare the results of our evaluations with the results of the WMH Segmentation Challenge held in 2017, which included substantially different datasets. The most relevant conclusion of this master’s thesis is that no method seems to be accurate enough for clinical implementation, although the low performance of the methods may be related to the differences between our data and the data that were used to train them. Besides, realizing the huge improvement made in the field during the last few years after the appearance of deep neural networks, we anticipate that a method with sufficient accuracy might be available soon. The codes used to obtain the results and graphs displayed in this project together with some guidelines to run them are available through PFM-WMH 1

Simultaneous lesion and neuroanatomy segmentation in Multiple Sclerosis using deep neural networks

Segmentation of both white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. Typically these tasks are performed separately: in this paper we present a single segmentation solution based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of multimodal magnetic resonance images into lesion classes and normal-appearing grey- and white-matter structures. We show substantial, statistically significant improvements in both Dice coefficient and in lesion-wise specificity and sensitivity, compared to previous approaches, and agreement with individual human raters in the range of human inter-rater variability. The method is trained on data gathered from a single centre: nonetheless, it performs well on data from centres, scanners and field-strengths not represented in the training dataset. A retrospective study found that the classifier successfully identified lesions missed by the human raters. Lesion labels were provided by human raters, while weak labels for other brain structures (including CSF, cortical grey matter, cortical white matter, cerebellum, amygdala, hippocampus, subcortical GM structures and choroid plexus) were provided by Freesurfer 5.3. The segmentations of these structures compared well, not only with Freesurfer 5.3, but also with FSL-First and Freesurfer 6.0

Differentiation of calcified regions and iron deposits in the ageing brain on conventional structural MR images:Calcium and Iron on Conventional MRI

Purpose: In the human brain, minerals such as iron and calcium accumulate increasingly with age. They typically appear hypointense on T2*‐weighted MRI sequences. This study aims to explore the differentiation and association between calcified regions and noncalcified iron deposits on clinical brain MRI in elderly, otherwise healthy subjects. Materials and Methods: Mineral deposits were segmented on co‐registered T1‐ and T2*‐weighted sequences from 100 1.5 Tesla MRI datasets of community‐dwelling individuals in their 70s. To differentiate calcified regions from noncalcified iron deposits we developed a method based on their appearance on T1‐weighted images, which was validated with a purpose‐designed phantom. Joint T1‐ and T2*‐weighted intensity histograms were constructed to measure the similarity between the calcified and noncalcified iron deposits using a Euclidean distance based metric. Results: We found distinct distributions for calcified regions and noncalcified iron deposits in the cumulative joint T1‐ and T2*‐weighted intensity histograms across all subjects (correlations ranging from 0.02 to 0.86; mean = 0.26 ± 0.16; t = 16.93; P < 0.001) consistent with differences in iron and calcium signal in the phantom. The mean volumes of affected tissue per subject for calcified and noncalcified deposits were 236.74 ± 309.70 mm3 and 283.76 ± 581.51 mm3; respectively. There was a positive association between the mineral depositions (β = 0.32, P < 0.005), consistent with existing literature reports. Conclusion: Calcified mineral deposits and noncalcified iron deposits can be distinguished from each other by signal intensity changes on conventional 1.5T T1‐weighted MRI and are significantly associated in brains of elderly, otherwise healthy subjects

The Developing Human Connectome Project: a minimal processing pipeline for neonatal cortical surface reconstruction

The Developing Human Connectome Project (dHCP) seeks to create the first 4-dimensional connectome of early life. Understanding this connectome in detail may provide insights into normal as well as abnormal patterns of brain development. Following established best practices adopted by the WU-MINN Human Connectome Project (HCP), and pioneered by FreeSurfer, the project utilises cortical surface-based processing pipelines. In this paper, we propose a fully automated processing pipeline for the structural Magnetic Resonance Imaging (MRI) of the developing neonatal brain. This proposed pipeline consists of a refined framework for cortical and sub-cortical volume segmentation, cortical surface extraction, and cortical surface inflation, which has been specifically designed to address considerable differences between adult and neonatal brains, as imaged using MRI. Using the proposed pipeline our results demonstrate that images collected from 465 subjects ranging from 28 to 45 weeks post-menstrual age (PMA) can be processed fully automatically; generating cortical surface models that are topologically correct, and correspond well with manual evaluations of tissue boundaries in 85% of cases. Results improve on state-of-the-art neonatal tissue segmentation models and significant errors were found in only 2% of cases, where these corresponded to subjects with high motion. Downstream, these surfaces will enhance comparisons of functional and diffusion MRI datasets, supporting the modelling of emerging patterns of brain connectivity

Influence of threshold selection and image sequence in in-vivo segmentation of enlarged perivascular spaces

BACKGROUND: Growing interest surrounds perivascular spaces (PVS) as a clinical biomarker of brain dysfunction given their association with cerebrovascular risk factors and disease. Neuroimaging techniques allowing quick and reliable quantification are being developed, but, in practice, they require optimisation as their limits of validity are usually unspecified.NEW METHOD: We evaluate modifications and alternatives to a state-of-the-art (SOTA) PVS segmentation method that uses a vesselness filter to enhance PVS discrimination, followed by thresholding of its response, applied to brain magnetic resonance images (MRI) from patients with sporadic small vessel disease acquired at 3 T.RESULTS: The method is robust against inter-observer differences in threshold selection, but separate thresholds for each region of interest (i.e., basal ganglia, centrum semiovale, and midbrain) are required. Noise needs to be assessed prior to selecting these thresholds, as effect of noise and imaging artefacts can be mitigated with a careful optimisation of these thresholds. PVS segmentation from T1-weighted images alone, misses small PVS, therefore, underestimates PVS count, may overestimate individual PVS volume especially in the basal ganglia, and is susceptible to the inclusion of calcified vessels and mineral deposits. Visual analyses indicated the incomplete and fragmented detection of long and thin PVS as the primary cause of errors, with the Frangi filter coping better than the Jerman filter.COMPARISON WITH EXISTING METHODS: Limits of validity to a SOTA PVS segmentation method applied to 3 T MRI with confounding pathology are given.CONCLUSIONS: Evidence presented reinforces the STRIVE-2 recommendation of using T2-weighted images for PVS assessment wherever possible. The Frangi filter is recommended for PVS segmentation from MRI, offering robust output against variations in threshold selection and pathology presentation.</p