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

The Use of Artificial Intelligence in the Management of Intracranial Aneurysms

The use of artificial intelligence (AI) has potential benefits in the management of intracranial aneurysms. Early detection of intracranial aneurysms is critical due to their high risk of complications such as rupture, vasospasm, and ischemia with highly impact on morbidity and mortality. The main findings suggest that AI can improve the accuracy of aneurysm detection, rupture risk prediction, and assist neurointervention in planning and performing procedures. This chapter discusses the potential for AI to improve patient care by enabling earlier diagnosis and timely treatment, reducing medical errors, costs, morbidity, and mortality. However, further validation of AI-based applications is necessary in a real-world clinical setting

Development of semi-automated steady state exogenous contrast cerebral blood volume mapping

Functional magnetic resonance imaging (fMRI) as it exists, in its many forms and vari- ants, has revolutionized the fields of neurology and psychology by revealing functional differences non-invasively. Although blood oxygenation level dependent (BOLD) fMRI is used interchangeably with fMRI, it measures one single difference in a phys- iological measurement using a set sequence. As such, there are other established changes in the brain that relate to blood movement and capacity that can also be measured using MRI. One measure, exogenous steady state cerebral blood volume, uses a bolus routine contrast agent administered intravenously alongside a pair of high resolution ‘structural-like’ MRI images to provide detailed information within small cortical and subcortical structures. In this thesis I design a semi-automated algorithm to generate maps of steady state exogenous cerebral blood volume magnetic resonance imaging datasets. To do this I developed an algorithm and tested it on existing MRI scanning protocols. A series of automated pre-processing steps are developed and tested, including automated scan flagging for artifacts and requisite vascular segmentation. Then, a methodology is developed to create cerebral blood volume (CBV) region of interest (ROI) masks that can then be applied on an existing database to test known CBV dysfunction in a group of patients at high risk for psychosis. Finally, we develop an experiment to see if template based cerebral blood alterations co-registered with class segmentation maps have any positive predictive value in determining disease state in a well characterized cohort of five age-matched groups in an Alzheimer’s disease neuroimaging study

Novel Algorithms for Merging Computational Fluid Dynamics and 4D Flow MRI

Time-resolved three-dimensional spatial encoding combined with three-directional velocity-encoded phase contrast magnetic resonance imaging (termed as 4D flow MRI), can provide valuable information for diagnosis, treatment, and monitoring of vascular diseases. The accuracy of this technique, however, is limited by errors in flow estimation due to acquisition noise as well as systematic errors. Furthermore, available spatial resolution is limited to 1.5mm - 3mm and temporal resolution is limited to 30-40ms. This is often grossly inadequate to resolve flow details in small arteries, such as those in cerebral circulation. Recently, there have been efforts to address the limitations of the spatial and temporal resolution of MR flow imaging through the use of computational fluid dynamics (CFD). While CFD is capable of providing essentially unlimited spatial and temporal resolution, numerical results are very sensitive to errors in estimation of the flow boundary conditions. In this work, we present three novel techniques that combine CFD with 4D flow MRI measurements in order to address the resolution and noise issues. The first technique is a variant of the Kalman Filter state estimator called the Ensemble Kalman Filter (EnKF). In this technique, an ensemble of patient-specific CFD solutions are used to compute filter gains. These gains are then used in a predictor-corrector scheme to not only denoise the data but also increase its temporal and spatial resolution. The second technique is based on proper orthogonal decomposition and ridge regression (POD-rr). The POD method is typically used to generate reduced order models (ROMs) in closed control applications of large degree of freedom systems that result from discretization of governing partial differential equations (PDE). The POD-rr process results in a set of basis functions (vectors), that capture the local space of solutions of the PDE in question. In our application, the basis functions are generated from an ensemble of patient-specific CFD solutions whose boundary conditions are estimated from 4D flow MRI data. The CFD solution that should be most closely representing the actual flow is generated by projecting 4D flow MRI data onto the basis vectors followed by reconstruction in both MRI and CFD resolution. The rr algorithm was used for between resolution mapping. Despite the accuracy of using rr as the mapping step, due to manual adjustment of a coefficient in the algorithm we developed the third algorithm. In this step, the rr algorithm was substituded with a dynamic mode decomposition algorithm to preserve the robustness. These algorithms have been implemented and tested using a numerical model of the flow in a cerebral aneurysm. Solutions at time intervals corresponding to the 4D flow MRI temporal resolution were collected and downsampled to the spatial resolution of the imaging data. A simulated acquisition noise was then added in k-space. Finally, the simulated data affected by noise were used as an input to the merging algorithms. Rigorous comparison to state-of-the-art techniques were conducted to assess the accuracy and performance of the proposed method. The results provided denoised flow fields with less than 1\% overall error for different signal-to-noise ratios. At the end, a small cohort of three patients were corrected and the data were reconstructed using different methods, the wall shear stress (WSS) was calculated using different reconstructed data and the results were compared. As it has been shown in chapter 5, the calculated WSS using different methods results in mutual high and low shear stress regions, however, the exact value and patterns are significantly different

A CAD system for early diagnosis of autism using different imaging modalities.

The term “autism spectrum disorder” (ASD) refers to a collection of neuro-developmental disorders that affect linguistic, behavioral, and social skills. Autism has many symptoms, most prominently, social impairment and repetitive behaviors. It is crucial to diagnose autism at an early stage for better assessment and investigation of this complex syndrome. There have been a lot of efforts to diagnose ASD using different techniques, such as imaging modalities, genetic techniques, and behavior reports. Imaging modalities have been extensively exploited for ASD diagnosis, and one of the most successful ones is Magnetic resonance imaging(MRI),where it has shown promise for the early diagnosis of the ASD related abnormalities in particular. Magnetic resonance imaging (MRI) modalities have emerged as powerful means that facilitate non-invasive clinical diagnostics of various diseases and abnormalities since their inception in the 1980s. After the advent in the nineteen eighties, MRI soon became one of the most promising non- invasive modalities for visualization and diagnostics of ASD-related abnormalities. Along with its main advantage of no exposure to radiation, high contrast, and spatial resolution, the recent advances to MRI modalities have notably increased diagnostic certainty. Multiple MRI modalities, such as different types of structural MRI (sMRI) that examines anatomical changes, and functional MRI (fMRI) that examines brain activity by monitoring blood flow changes,have been employed to investigate facets of ASD in order to better understand this complex syndrome. This work aims at developing a new computer-aided diagnostic (CAD) system for autism diagnosis using different imaging modalities. It mainly relies on making use of structural magnetic resonance images for extracting notable shape features from parts of the brainthat proved to correlate with ASD from previous neuropathological studies. Shape features from both the cerebral cortex (Cx) and cerebral white matter(CWM)are extracted. Fusion of features from these two structures is conducted based on the recent findings suggesting that Cx changes in autism are related to CWM abnormalities. Also, when fusing features from more than one structure, this would increase the robustness of the CAD system. Moreover, fMRI experiments are done and analyzed to find areas of activation in the brains of autistic and typically developing individuals that are related to a specific task. All sMRI findings are fused with those of fMRI to better understand ASD in terms of both anatomy and functionality,and thus better classify the two groups. This is one aspect of the novelty of this CAD system, where sMRI and fMRI studies are both applied on subjects from different ages to diagnose ASD. In order to build such a CAD system, three main blocks are required. First, 3D brain segmentation is applied using a novel hybrid model that combines shape, intensity, and spatial information. Second, shape features from both Cx and CWM are extracted and anf MRI reward experiment is conducted from which areas of activation that are related to the task of this experiment are identified. Those features were extracted from local areas of the brain to provide an accurate analysis of ASD and correlate it with certain anatomical areas. Third and last, fusion of all the extracted features is done using a deep-fusion classification network to perform classification and obtain the diagnosis report. Fusing features from all modalities achieved a classification accuracy of 94.7%, which emphasizes the significance of combining structures/modalities for ASD diagnosis. To conclude, this work could pave the pathway for better understanding of the autism spectrum by finding local areas that correlate to the disease. The idea of personalized medicine is emphasized in this work, where the proposed CAD system holds the promise to resolve autism endophenotypes and help clinicians deliver personalized treatment to individuals affected with this complex syndrome

Improved 3D MR Image Acquisition and Processing in Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect, affecting about 1% of the population. MRI is an essential tool in the assessment of CHD, including diagnosis, intervention planning and follow-up. Three-dimensional MRI can provide particularly rich visualization and information. However, it is often complicated by long scan times, cardiorespiratory motion, injection of contrast agents, and complex and time-consuming postprocessing. This thesis comprises four pieces of work that attempt to respond to some of these challenges. The first piece of work aims to enable fast acquisition of 3D time-resolved cardiac imaging during free breathing. Rapid imaging was achieved using an efficient spiral sequence and a sparse parallel imaging reconstruction. The feasibility of this approach was demonstrated on a population of 10 patients with CHD, and areas of improvement were identified. The second piece of work is an integrated software tool designed to simplify and accelerate the development of machine learning (ML) applications in MRI research. It also exploits the strengths of recently developed ML libraries for efficient MR image reconstruction and processing. The third piece of work aims to reduce contrast dose in contrast-enhanced MR angiography (MRA). This would reduce risks and costs associated with contrast agents. A deep learning-based contrast enhancement technique was developed and shown to improve image quality in real low-dose MRA in a population of 40 children and adults with CHD. The fourth and final piece of work aims to simplify the creation of computational models for hemodynamic assessment of the great arteries. A deep learning technique for 3D segmentation of the aorta and the pulmonary arteries was developed and shown to enable accurate calculation of clinically relevant biomarkers in a population of 10 patients with CHD

Measuring blood flow and pulsatility with MRI: optimisation, validation and application in cerebral small vessel disease

Cerebral small vessel disease (SVD) is the breakdown of the small blood vessels of the brain, leading to many cases of stroke and dementia. The pathophysiology of SVD is largely unknown, although several mechanisms have been suggested. One such mechanism is the role of increased blood flow pulsatility into the brain, caused by vessel stiffening, leading to damage of the microvasculature. Magnetic resonance imaging (MRI) allows us to non-invasively measure blood flow and velocity using a technique called phase contrast-MRI – traditionally used with 2D slices across the vessel(s) of interest. An advanced form of phase-contrast MRI, known as 4D flow, has emerged in recent years that allows for a volume of data to be acquired, containing velocity information in all directions. However, to keep scan times practical when collecting this amount of data, spatiotemporal resolution has to be sacrificed. The main aim of this thesis was to assess 4D flow’s capabilities, including comparing it to the more well-established 2D method in healthy volunteers, patients, and phantom experiments, so as to better understand its role in investigating SVD. Another aim was to learn more about the role of flow and pulsatility in SVD development in patients using data acquired in the longitudinal Mild Stroke Study 3 (MSS3). Firstly, I systematically reviewed studies that have assessed the human brain using 4D flow. Across 61 relevant studies, I found a general consensus for the current use of the technique in this context. I then optimised the Siemens prototype 4D flow sequence (N = 11 healthy volunteers), testing different parameters to find the combination that best balanced scan quality and duration. I then assessed the test-retest repeatability and intra-rater reliability of both 2D and 4D methods (N = 11 healthy volunteers), as well as differences between them. Following this, I performed the same 4D-2D comparison on SVD patients (N = 10). Absolute flow measurements using 4D flow were shown to have moderate repeatability and reliability, while flow pulsatility measurements showed acceptable repeatability and reliability. Furthermore, 2D arterial pulsatility was measured higher than with 4D, while 4D often measured higher flow rates than 2D. 4D flow was shown to be feasible when used on SVD patients, with no noticeable issues caused by potential patient movement. Flow data analysis from the longitudinal SVD study MSS3 showed that intracranial pulsatility is associated with cross-sectional SVD lesion volume but not longitudinal lesion growth, with stronger associations seen in the arteries of the neck compared to the venous sinuses