Medical image colorization for better visualization and segmentation

Medical images contain precious anatomical information for clinical procedures. Improved understanding of medical modality may contribute significantly in arena of medical image analysis. This paper investigates enhancement of monochromatic medical modality into colorized images. Improving the contrast of anatomical structures facilitates precise segmentation. The proposed framework starts with pre-processing to remove noise and improve edge information. Then colour information is embedded to each pixel of a subject image. A resulting image has a potential to portray better anatomical information than a conventional monochromatic image. To evaluate the performance of colorized medical modality, the structural similarity index and the peak signal to noise ratio are computed. Supremacy of proposed colorization is validated by segmentation experiments and compared with greyscale monochromatic images

Lattice-gas cellular automata for the analysis of cancer invasion

Cancer cells display characteristic traits acquired in a step-wise manner during carcinogenesis. Some of these traits are autonomous growth, induction of angiogenesis, invasion and metastasis. In this thesis, the focus is on one of the latest stages of tumor progression, tumor invasion. Tumor invasion emerges from the combined effect of tumor cell-cell and cell-microenvironment interactions, which can be studied with the help of mathematical analysis. Cellular automata (CA) can be viewed as simple models of self-organizing complex systems in which collective behavior can emerge out of an ensemble of many interacting "simple" components. In particular, we focus on an important class of CA, the so-called lattice-gas cellular automata (LGCA). In contrast to traditional CA, LGCA provide a straightforward and intuitive implementation of particle transport and interactions. Additionally, the structure of LGCA facilitates the mathematical analysis of their behavior. Here, the principal tools of mathematical analysis of LGCA are the mean-field approximation and the corresponding Lattice Boltzmann equation. The main objective of this thesis is to investigate important aspects of tumor invasion, under the microscope of mathematical modeling and analysis: Impact of the tumor environment: We introduce a LGCA as a microscopic model of tumor cell migration together with a mathematical description of different tumor environments. We study the impact of the various tumor environments (such as extracellular matrix) on tumor cell migration by estimating the tumor cell dispersion speed for a given environment. Effect of tumor cell proliferation and migration: We study the effect of tumor cell proliferation and migration on the tumor’s invasive behavior by developing a simplified LGCA model of tumor growth. In particular, we derive the corresponding macroscopic dynamics and we calculate the tumor’s invasion speed in terms of tumor cell proliferation and migration rates. Moreover, we calculate the width of the invasive zone, where the majority of mitotic activity is concentrated, and it is found to be proportional to the invasion speed. Mechanisms of tumor invasion emergence: We investigate the mechanisms for the emergence of tumor invasion in the course of cancer progression. We conclude that the response of a microscopic intracellular mechanism (migration/proliferation dichotomy) to oxygen shortage, i.e. hypoxia, maybe responsible for the transition from a benign (proliferative) to a malignant (invasive) tumor. Computing in vivo tumor invasion: Finally, we propose an evolutionary algorithm that estimates the parameters of a tumor growth LGCA model based on time-series of patient medical data (in particular Magnetic Resonance and Diffusion Tensor Imaging data). These parameters may allow to reproduce clinically relevant tumor growth scenarios for a specific patient, providing a prediction of the tumor growth at a later time stage.Krebszellen zeigen charakteristische Merkmale, die sie in einem schrittweisen Vorgang während der Karzinogenese erworben haben. Einige dieser Merkmale sind autonomes Wachstum, die Induktion von Angiogenese, Invasion und Metastasis. Der Schwerpunkt dieser Arbeit liegt auf der Tumorinvasion, einer der letzten Phasen der Tumorprogression. Die Tumorinvasion ensteht aus der kombinierten Wirkung von den Wechselwirkungen Tumorzelle-Zelle und Zelle-Mikroumgebung, die mit die Hilfe von mathematischer Analyse untersucht werden können. Zelluläre Automaten (CA) können als einfache Modelle von selbst-organisierenden komplexen Systemen betrachtet werden, in denen kollektives Verhalten aus einer Kombination von vielen interagierenden "einfachen" Komponenten entstehen kann. Insbesondere konzentrieren wir uns auf eine wichtige CA-Klasse, die sogenannten Zelluläre Gitter-Gas Automaten (LGCA). Im Gegensatz zu traditionellen CA bieten LGCA eine einfache und intuitive Umsetzung der Teilchen und Wechselwirkungen. Zusätzlich erleichtert die Struktur der LGCA die mathematische Analyse ihres Verhaltens. Die wichtigsten Werkzeuge der mathematischen Analyse der LGCA sind hier die Mean-field Approximation und die entsprechende Lattice - Boltzmann - Gleichung. Das wichtigste Ziel dieser Arbeit ist es, wichtige Aspekte der Tumorinvasion unter dem Mikroskop der mathematischen Modellierung und Analyse zu erforschen: Auswirkungen der Tumorumgebung: Wir stellen einen LGCA als mikroskopisches Modell der Tumorzellen-Migration in Verbindung mit einer mathematischen Beschreibung der verschiedenen Tumorumgebungen vor. Wir untersuchen die Auswirkungen der verschiedenen Tumorumgebungen (z. B. extrazellulären Matrix) auf die Migration von Tumorzellen dürch Schätzung der Tumorzellen-Dispersionsgeschwindigkeit in einem gegebenen Umfeld. Wirkung von Tumor-Zellenproliferation und Migration: Wir untersuchen die Wirkung von Tumorzellenproliferation und Migration auf das invasive Verhalten der Tumorzellen durch die Entwicklung eines vereinfachten LGCA Tumorwachstumsmodells. Wir leiten die entsprechende makroskopische Dynamik und berechnen die Tumorinvasionsgeschwindigkeit im Hinblick auf die Tumorzellenproliferation- und Migrationswerte. Darüber hinaus berechnen wir die Breite der invasiven Zone, wo die Mehrheit der mitotischer Aktivität konzentriert ist, und es wird festgestellt, dass diese proportional zu den Invasionsgeschwindigkeit ist. Mechanismen der Tumorinvasion Entstehung: Wir untersuchen Mechanismen, die für die Entstehung von Tumorinvasion im Verlauf des Krebs zuständig sind. Wir kommen zu dem Schluss, dass die Reaktion eines mikroskopischen intrazellulären Mechanismus (Migration/Proliferation Dichotomie) zu Sauerstoffmangel, d.h. Hypoxie, möglicheweise für den Übergang von einem gutartigen (proliferative) zu einer bösartigen (invasive) Tumor verantwortlich ist. Berechnung der in-vivo Tumorinvasion: Schließlich schlagen wir einen evolutionären Algorithmus vor, der die Parameter eines LGCA Modells von Tumorwachstum auf der Grundlage von medizinischen Daten des Patienten für mehrere Zeitpunkte (insbesondere die Magnet-Resonanz-und Diffusion Tensor Imaging Daten) ermöglicht. Diese Parameter erlauben Szenarien für einen klinisch relevanten Tumorwachstum für einen bestimmten Patienten zu reproduzieren, die eine Vorhersage des Tumorwachstums zu einem späteren Zeitpunkt möglich machen

GBM Volumetry using the 3D Slicer Medical Image Computing Platform

Volumetric change in glioblastoma multiforme (GBM) over time is a critical factor in treatment decisions. Typically, the tumor volume is computed on a slice-by-slice basis using MRI scans obtained at regular intervals. (3D)Slicer – a free platform for biomedical research – provides an alternative to this manual slice-by-slice segmentation process, which is significantly faster and requires less user interaction. In this study, 4 physicians segmented GBMs in 10 patients, once using the competitive region-growing based GrowCut segmentation module of Slicer, and once purely by drawing boundaries completely manually on a slice-by-slice basis. Furthermore, we provide a variability analysis for three physicians for 12 GBMs. The time required for GrowCut segmentation was on an average 61% of the time required for a pure manual segmentation. A comparison of Slicer-based segmentation with manual slice-by-slice segmentation resulted in a Dice Similarity Coefficient of 88.43 ± 5.23% and a Hausdorff Distance of 2.32 ± 5.23 mm

Numerical simulations in 3-dimensions of reaction–diffusion models for brain tumour growth

We work with a well-known model of reaction–diffusion type for brain tumour growth and accomplish full 3-dimensional (3d) simulations of the tumour in time on two types of imaging data, the 3d Shepp–Logan head phantom image and an MRI T1-weighted brain scan from the Internet Brain Segmentation Repository. The source term is such that we have logistic growth. These simulations are obtained using standard finite difference approximations with novel calculations to increase speed and accuracy. Moreover, biological background to the model, its well-posedness together with a variational formulation are given. The variational formulation enable the feasibility of different derivations and modifications of the model

Doctor of Philosophy

dissertationConfocal microscopy has become a popular imaging technique in biology research in recent years. It is often used to study three-dimensional (3D) structures of biological samples. Confocal data are commonly multichannel, with each channel resulting from a different fluorescent staining. This technique also results in finely detailed structures in 3D, such as neuron fibers. Despite the plethora of volume rendering techniques that have been available for many years, there is a demand from biologists for a flexible tool that allows interactive visualization and analysis of multichannel confocal data. Together with biologists, we have designed and developed FluoRender. It incorporates volume rendering techniques such as a two-dimensional (2D) transfer function and multichannel intermixing. Rendering results can be enhanced through tone-mappings and overlays. To facilitate analyses of confocal data, FluoRender provides interactive operations for extracting complex structures. Furthermore, we developed the Synthetic Brainbow technique, which takes advantage of the asynchronous behavior in Graphics Processing Unit (GPU) framebuffer loops and generates random colorizations for different structures in single-channel confocal data. The results from our Synthetic Brainbows, when applied to a sequence of developing cells, can then be used for tracking the movements of these cells. Finally, we present an application of FluoRender in the workflow of constructing anatomical atlases

Longitudinal Brain Tumor Tracking, Tumor Grading, and Patient Survival Prediction Using MRI

This work aims to develop novel methods for brain tumor classification, longitudinal brain tumor tracking, and patient survival prediction. Consequently, this dissertation proposes three tasks. First, we develop a framework for brain tumor segmentation prediction in longitudinal multimodal magnetic resonance imaging (mMRI) scans, comprising two methods: feature fusion and joint label fusion (JLF). The first method fuses stochastic multi-resolution texture features with tumor cell density features, in order to obtain tumor segmentation predictions in follow-up scans from a baseline pre-operative timepoint. The second method utilizes JLF to combine segmentation labels obtained from (i) the stochastic texture feature-based and Random Forest (RF)-based tumor segmentation method; and (ii) another state-of-the-art tumor growth and segmentation method known as boosted Glioma Image Segmentation and Registration (GLISTRboost, or GB). With the advantages of feature fusion and label fusion, we achieve state-of-the-art brain tumor segmentation prediction. Second, we propose a deep neural network (DNN) learning-based method for brain tumor type and subtype grading using phenotypic and genotypic data, following the World Health Organization (WHO) criteria. In addition, the classification method integrates a cellularity feature which is derived from the morphology of a pathology image to improve classification performance. The proposed method achieves state-of-the-art performance for tumor grading following the new CNS tumor grading criteria. Finally, we investigate brain tumor volume segmentation, tumor subtype classification, and overall patient survival prediction, and then we propose a new context- aware deep learning method, known as the Context Aware Convolutional Neural Network (CANet). Using the proposed method, we participated in the Multimodal Brain Tumor Segmentation Challenge 2019 (BraTS 2019) for brain tumor volume segmentation and overall survival prediction tasks. In addition, we also participated in the Radiology-Pathology Challenge 2019 (CPM-RadPath 2019) for Brain Tumor Subtype Classification, organized by the Medical Image Computing & Computer Assisted Intervention (MICCAI) Society. The online evaluation results show that the proposed methods offer competitive performance from their use of state-of-the-art methods in tumor volume segmentation, promising performance on overall survival prediction, and state-of-the-art performance on tumor subtype classification. Moreover, our result was ranked second place in the testing phase of the CPM-RadPath 2019

Spectral-spatial classification of n-dimensional images in real-time based on segmentation and mathematical morphology on GPUs

The objective of this thesis is to develop efficient schemes for spectral-spatial n-dimensional image classification. By efficient schemes, we mean schemes that produce good classification results in terms of accuracy, as well as schemes that can be executed in real-time on low-cost computing infrastructures, such as the Graphics Processing Units (GPUs) shipped in personal computers. The n-dimensional images include images with two and three dimensions, such as images coming from the medical domain, and also images ranging from ten to hundreds of dimensions, such as the multiand hyperspectral images acquired in remote sensing. In image analysis, classification is a regularly used method for information retrieval in areas such as medical diagnosis, surveillance, manufacturing and remote sensing, among others. In addition, as the hyperspectral images have been widely available in recent years owing to the reduction in the size and cost of the sensors, the number of applications at lab scale, such as food quality control, art forgery detection, disease diagnosis and forensics has also increased. Although there are many spectral-spatial classification schemes, most are computationally inefficient in terms of execution time. In addition, the need for efficient computation on low-cost computing infrastructures is increasing in line with the incorporation of technology into everyday applications. In this thesis we have proposed two spectral-spatial classification schemes: one based on segmentation and other based on wavelets and mathematical morphology. These schemes were designed with the aim of producing good classification results and they perform better than other schemes found in the literature based on segmentation and mathematical morphology in terms of accuracy. Additionally, it was necessary to develop techniques and strategies for efficient GPU computing, for example, a block–asynchronous strategy, resulting in an efficient implementation on GPU of the aforementioned spectral-spatial classification schemes. The optimal GPU parameters were analyzed and different data partitioning and thread block arrangements were studied to exploit the GPU resources. The results show that the GPU is an adequate computing platform for on-board processing of hyperspectral information