Computerized Analysis of Magnetic Resonance Images to Study Cerebral Anatomy in Developing Neonates

The study of cerebral anatomy in developing neonates is of great importance for the understanding of brain development during the early period of life. This dissertation therefore focuses on three challenges in the modelling of cerebral anatomy in neonates during brain development. The methods that have been developed all use Magnetic Resonance Images (MRI) as source data. To facilitate study of vascular development in the neonatal period, a set of image analysis algorithms are developed to automatically extract and model cerebral vessel trees. The whole process consists of cerebral vessel tracking from automatically placed seed points, vessel tree generation, and vasculature registration and matching. These algorithms have been tested on clinical Time-of- Flight (TOF) MR angiographic datasets. To facilitate study of the neonatal cortex a complete cerebral cortex segmentation and reconstruction pipeline has been developed. Segmentation of the neonatal cortex is not effectively done by existing algorithms designed for the adult brain because the contrast between grey and white matter is reversed. This causes pixels containing tissue mixtures to be incorrectly labelled by conventional methods. The neonatal cortical segmentation method that has been developed is based on a novel expectation-maximization (EM) method with explicit correction for mislabelled partial volume voxels. Based on the resulting cortical segmentation, an implicit surface evolution technique is adopted for the reconstruction of the cortex in neonates. The performance of the method is investigated by performing a detailed landmark study. To facilitate study of cortical development, a cortical surface registration algorithm for aligning the cortical surface is developed. The method first inflates extracted cortical surfaces and then performs a non-rigid surface registration using free-form deformations (FFDs) to remove residual alignment. Validation experiments using data labelled by an expert observer demonstrate that the method can capture local changes and follow the growth of specific sulcus

Deep Learning in Cardiology

The medical field is creating large amount of data that physicians are unable to decipher and use efficiently. Moreover, rule-based expert systems are inefficient in solving complicated medical tasks or for creating insights using big data. Deep learning has emerged as a more accurate and effective technology in a wide range of medical problems such as diagnosis, prediction and intervention. Deep learning is a representation learning method that consists of layers that transform the data non-linearly, thus, revealing hierarchical relationships and structures. In this review we survey deep learning application papers that use structured data, signal and imaging modalities from cardiology. We discuss the advantages and limitations of applying deep learning in cardiology that also apply in medicine in general, while proposing certain directions as the most viable for clinical use.Comment: 27 pages, 2 figures, 10 table

Retinal Vessel Segmentation Using the 2-D Morlet Wavelet and Supervised Classification

We present a method for automated segmentation of the vasculature in retinal images. The method produces segmentations by classifying each image pixel as vessel or non-vessel, based on the pixel's feature vector. Feature vectors are composed of the pixel's intensity and continuous two-dimensional Morlet wavelet transform responses taken at multiple scales. The Morlet wavelet is capable of tuning to specific frequencies, thus allowing noise filtering and vessel enhancement in a single step. We use a Bayesian classifier with class-conditional probability density functions (likelihoods) described as Gaussian mixtures, yielding a fast classification, while being able to model complex decision surfaces and compare its performance with the linear minimum squared error classifier. The probability distributions are estimated based on a training set of labeled pixels obtained from manual segmentations. The method's performance is evaluated on publicly available DRIVE and STARE databases of manually labeled non-mydriatic images. On the DRIVE database, it achieves an area under the receiver operating characteristic (ROC) curve of 0.9598, being slightly superior than that presented by the method of Staal et al.Comment: 9 pages, 7 figures and 1 table. Accepted for publication in IEEE Trans Med Imag; added copyright notic

Trainable COSFIRE filters for vessel delineation with application to retinal images

Retinal imaging provides a non-invasive opportunity for the diagnosis of several medical pathologies. The automatic segmentation of the vessel tree is an important pre-processing step which facilitates subsequent automatic processes that contribute to such diagnosis. We introduce a novel method for the automatic segmentation of vessel trees in retinal fundus images. We propose a filter that selectively responds to vessels and that we call B-COSFIRE with B standing for bar which is an abstraction for a vessel. It is based on the existing COSFIRE (Combination Of Shifted Filter Responses) approach. A B-COSFIRE filter achieves orientation selectivity by computing the weighted geometric mean of the output of a pool of Difference-of-Gaussians filters, whose supports are aligned in a collinear manner. It achieves rotation invariance efficiently by simple shifting operations. The proposed filter is versatile as its selectivity is determined from any given vessel-like prototype pattern in an automatic configuration process. We configure two B-COSFIRE filters, namely symmetric and asymmetric, that are selective for bars and bar-endings, respectively. We achieve vessel segmentation by summing up the responses of the two rotation-invariant B-COSFIRE filters followed by thresholding. The results that we achieve on three publicly available data sets (DRIVE: Se = 0.7655, Sp = 0.9704; STARE: Se = 0.7716, Sp = 0.9701; CHASE_DB1: Se = 0.7585, Sp = 0.9587) are higher than many of the state-of-the-art methods. The proposed segmentation approach is also very efficient with a time complexity that is significantly lower than existing methods.peer-reviewe

Automatic segmentation and classification methods using optical coherence tomography angiography (Octa): A review and handbook

Optical coherence tomography angiography (OCTA) is a promising technology for the non-invasive imaging of vasculature. Many studies in literature present automated algorithms to quantify OCTA images, but there is a lack of a review on the most common methods and their comparison considering multiple clinical applications (e.g., ophthalmology and dermatology). Here, we aim to provide readers with a useful review and handbook for automatic segmentation and classification methods using OCTA images, presenting a comparison of techniques found in the literature based on the adopted segmentation or classification method and on the clinical application. Another goal of this study is to provide insight into the direction of research in automated OCTA image analysis, especially in the current era of deep learning

Development of retinal blood vessel segmentation methodology using wavelet transforms for assessment of diabetic retinopathy

Automated image processing has the potential to assist in the early detection of diabetes, by detecting changes in blood vessel diameter and patterns in the retina. This paper describes the development of segmentation methodology in the processing of retinal blood vessel images obtained using non-mydriatic colour photography. The methods used include wavelet analysis, supervised classifier probabilities and adaptive threshold procedures, as well as morphology-based techniques. We show highly accurate identification of blood vessels for the purpose of studying changes in the vessel network that can be utilized for detecting blood vessel diameter changes associated with the pathophysiology of diabetes. In conjunction with suitable feature extraction and automated classification methods, our segmentation method could form the basis of a quick and accurate test for diabetic retinopathy, which would have huge benefits in terms of improved access to screening people for risk or presence of diabetes

Gap Filling of 3-D Microvascular Networks by Tensor Voting

We present a new algorithm which merges discontinuities in 3-D images of tubular structures presenting undesirable gaps. The application of the proposed method is mainly associated to large 3-D images of microvascular networks. In order to recover the real network topology, we need to fill the gaps between the closest discontinuous vessels. The algorithm presented in this paper aims at achieving this goal. This algorithm is based on the skeletonization of the segmented network followed by a tensor voting method. It permits to merge the most common kinds of discontinuities found in microvascular networks. It is robust, easy to use, and relatively fast. The microvascular network images were obtained using synchrotron tomography imaging at the European Synchrotron Radiation Facility. These images exhibit samples of intracortical networks. Representative results are illustrated

Signal Processing Methods for Quantitative Power Doppler Microvascular Angiography

Operator-dependent instrument settings and the likelihood of image artifacts are two challenges for reliably using three-dimensional (3-D) power Doppler angiography in flow depiction and quantification applications. To address the operator-dependent settings challenge, an automated method for wall filter cut-off selection, the wall filter selection curve (WFSC) method, was developed using flow-phantom images. The flow-phantom WFSCs guided the development of a theoretical signal model relating color pixel density (CPD) and wall filter cut-off frequency. Simulations using the theoretical model were used to define criteria for the WFSC method to be applied to unprocessed power Doppler signals from 3-D vasculature. The adapted WFSC method was combined with a 3-D skeletonization and vessel network reconstruction method to present a two-stage processing method aimed at improving vascular detection, visualization and quantification. The two-stage method was evaluated using two in vivo models; a murine tumor model was used to test the performance of the method in a flow quantification application and a chick embryo chorioallantoic membrane (CAM) model was used to evaluate the method’s value for flow depiction applications. Applying the WFSC method to flow-phantom images improved vessel delineation and vascular quantification to within 3% of the vascular volume fraction of the phantom. Criteria for the WFSC method from the simulations were to assess at least 100 cut-off frequencies and that the CPD variability should be less than 5% to ensure quantification accuracy. Large variations in the cut-off frequency selected using the WFSC among images acquired at different time points and across different animals in the murine tumor model signified the relevance of spatially and temporally adjusting the cut-off frequency. The two-stage method improved visualization of the vascular network and significantly reduced artifacts in both the tumor and CAM models in comparison to images using conventional Doppler processing. In the CAM model, vessel diameters measured in two-stage processed images were more accurate than measurements in images exported from a commercial scanner. The proposed signal processing methods increase accuracy and robustness of qualitative and quantitative studies using 3-D power Doppler angiography to assess vascular networks for flow depiction and quantification

Automated Vascular Smooth Muscle Segmentation, Reconstruction, Classification and Simulation on Whole-Slide Histology

Histology of the microvasculature depicts detailed characteristics relevant to tissue perfusion. One important histologic feature is the smooth muscle component of the microvessel wall, which is responsible for controlling vessel caliber. Abnormalities can cause disease and organ failure, as seen in hypertensive retinopathy, diabetic ischemia, Alzheimer’s disease and improper cardiovascular development. However, assessments of smooth muscle cell content are conventionally performed on selected fields of view on 2D sections, which may lead to measurement bias. We have developed a software platform for automated (1) 3D vascular reconstruction, (2) detection and segmentation of muscularized microvessels, (3) classification of vascular subtypes, and (4) simulation of function through blood flow modeling. Vessels were stained for α-actin using 3,3\u27-Diaminobenzidine, assessing both normal (n=9 mice) and regenerated vasculature (n=5 at day 14, n=4 at day 28). 2D locally adaptive segmentation involved vessel detection, skeletonization, and fragment connection. 3D reconstruction was performed using our novel nucleus landmark-based registration. Arterioles and venules were categorized using supervised machine learning based on texture and morphometry. Simulation of blood flow for the normal and regenerated vasculature was performed at baseline and during demand based on the structural measures obtained from the above tools. Vessel medial area and vessel wall thickness were found to be greater in the normal vasculature as compared to the regenerated vasculature (p\u3c0.001) and a higher density of arterioles was found in the regenerated tissue (p\u3c0.05). Validation showed: a Dice coefficient of 0.88 (compared to manual) for the segmentations, a 3D reconstruction target registration error of 4 μm, and area under the receiver operator curve of 0.89 for vessel classification. We found 89% and 67% decreases in the blood flow through the network for the regenerated vasculature during increased oxygen demand as compared to the normal vasculature, respectively for 14 and 28 days post-ischemia. We developed a software platform for automated vasculature histology analysis involving 3D reconstruction, segmentation, and arteriole vs. venule classification. This advanced the knowledge of conventional histology sampling compared to whole slide analysis, the morphological and density differences in the regenerated vasculature, and the effect of the differences on blood flow and function