Simple Methods for Scanner Drift Normalization Validated for Automatic Segmentation of Knee Magnetic Resonance Imaging:with data from the Osteoarthritis Initiative

Scanner drift is a well-known magnetic resonance imaging (MRI) artifact characterized by gradual signal degradation and scan intensity changes over time. In addition, hardware and software updates may imply abrupt changes in signal. The combined effects are particularly challenging for automatic image analysis methods used in longitudinal studies. The implication is increased measurement variation and a risk of bias in the estimations (e.g. in the volume change for a structure). We proposed two quite different approaches for scanner drift normalization and demonstrated the performance for segmentation of knee MRI using the fully automatic KneeIQ framework. The validation included a total of 1975 scans from both high-field and low-field MRI. The results demonstrated that the pre-processing method denoted Atlas Affine Normalization significantly removed scanner drift effects and ensured that the cartilage volume change quantifications became consistent with manual expert scores

Assessment of Post-Treatment Imaging Changes Following Radiotherapy using Magnetic Susceptibility Techniques

Radiation therapy (RT) is a common treatment for brain neoplasms and is used alone or in combination with other therapies. The use of RT has been found to be successful in controlling tumors and extending the overall survival of patients; however, there are many unanswered questions regarding radiotherapy effects in the normal brain surrounding or infiltrated by tumor. Changes to the vascular and parenchyma have been documented, and more recently inflammatory mechanisms have been postulated to play a role in radiation injury. Traditional imaging techniques used within the clinic (CT and MRI) are often lacking in their ability to differentiate between recurrent tumor, transient treatment effects, or radiation necrosis. The primary goal of this thesis is to demonstrate an MRI acquisition method that has been shown to be sensitive to deoxygenated blood and iron content as a potential biomarker of radiation effect on the normal brain. Specifically, post-processing techniques are used to determine the applicability of qualitative images such as Susceptibility-Weighted Imaging (SWI) and quantitative methods such as Quantitative Susceptibility Mapping (QSM) and apparent traverse relaxation (R2*) using the same sequence. These methods are potential surrogate markers for vascular changes and neuroinflammatory components that could predict sub-acute and long-term radiation effects. Within this thesis, R2* is shown to be a promising marker for the prediction of radiation necrosis, whereas SWI and QSM are shown to be excellent modalities for detecting longterm effects such as microbleeds. Additionally, R2 * is shown to be a potentially useful technique in identifying post-imaging treatment changes (pseudoprogression) following chemoradiotherapy for malignant glioma. Finally, the use of this non-contrast method shows promise for integration within a clinical setting and the potential for expansion to multicenter clinical trials

Applications of Deep Learning Techniques for Automated Multiple Sclerosis Detection Using Magnetic Resonance Imaging: A Review

Multiple Sclerosis (MS) is a type of brain disease which causes visual, sensory, and motor problems for people with a detrimental effect on the functioning of the nervous system. In order to diagnose MS, multiple screening methods have been proposed so far; among them, magnetic resonance imaging (MRI) has received considerable attention among physicians. MRI modalities provide physicians with fundamental information about the structure and function of the brain, which is crucial for the rapid diagnosis of MS lesions. Diagnosing MS using MRI is time-consuming, tedious, and prone to manual errors. Research on the implementation of computer aided diagnosis system (CADS) based on artificial intelligence (AI) to diagnose MS involves conventional machine learning and deep learning (DL) methods. In conventional machine learning, feature extraction, feature selection, and classification steps are carried out by using trial and error; on the contrary, these steps in DL are based on deep layers whose values are automatically learn. In this paper, a complete review of automated MS diagnosis methods performed using DL techniques with MRI neuroimaging modalities is provided. Initially, the steps involved in various CADS proposed using MRI modalities and DL techniques for MS diagnosis are investigated. The important preprocessing techniques employed in various works are analyzed. Most of the published papers on MS diagnosis using MRI modalities and DL are presented. The most significant challenges facing and future direction of automated diagnosis of MS using MRI modalities and DL techniques are also provided

Computer aided analysis of inflammatory muscle disease using magnetic resonance imaging

Inflammatory muscle disease (myositis) is characterised by inflammation and a gradual increase in muscle weakness. Diagnosis typically requires a range of clinical tests, including magnetic resonance imaging of the thigh muscles to assess the disease severity. In the past, this has been measured by manually counting the number of muscles affected. In this work, a computer-aided analysis of inflammatory muscle disease is presented to help doctors diagnose and monitor the disease. Methods to quantify the level of oedema and fat infiltration from magnetic resonance scans are proposed and the disease quantities determined are shown to have positive correlation against expert medical opinion. The methods have been designed and tested on a database of clinically acquired T1 and STIR sequences, and are proven to be robust despite suboptimal image quality. General background information is first introduced, giving an overview of the medical, technical, and theoretical topics necessary to understand the problem domain. Next, a detailed introduction to the physics of magnetic resonance imaging is given. A review of important literature from similar and related domains is presented, with valuable insights that are utilised at a later stage. Scans are carefully pre-processed to bring all slices in to a common frame of reference and the methods to quantify the level of oedema and fat infiltration are defined and shown to have good positive correlation with expert medical opinion. A number of validation tests are performed with re-scanned subjects to indicate the level of repeatability. The disease quantities, together with statistical features from the T1-STIR joint histogram, are used for automatic classification of the disease severity. Automatic classification is shown to be successful on out of sample data for both the oedema and fat infiltration problems

Adaptive kernel estimation for enhanced filtering and pattern classification of magnetic resonance imaging: novel techniques for evaluating the biomechanics and pathologic conditions of the lumbar spine

This dissertation investigates the contribution the lumbar spine musculature has on etiological and pathogenic characteristics of low back pain and lumbar spondylosis. This endeavor necessarily required a two-step process: 1) design of an accurate post-processing method for extracting relevant information via magnetic resonance images and 2) determine pathological trends by elucidating high-dimensional datasets through multivariate pattern classification. The lumbar musculature was initially evaluated by post-processing and segmentation of magnetic resonance (MR) images of the lumbar spine, which characteristically suffer from nonlinear corruption of the signal intensity. This so called intensity inhomogeneity degrades the efficacy of traditional intensity-based segmentation algorithms. Proposed in this dissertation is a solution for filtering individual MR images by extracting a map of the underlying intensity inhomogeneity to adaptively generate local estimates of the kernel’s optimal bandwidth. The adaptive kernel is implemented and tested within the structure of the non-local means filter, but also generalized and extended to the Gaussian and anisotropic diffusion filters. Testing of the proposed filters showed that the adaptive kernel significantly outperformed their non-adaptive counterparts. A variety of performance metrics were utilized to measure either fine feature preservation or accuracy of post-processed segmentation. Based on these metrics the adaptive filters proposed in this dissertation significantly outperformed the non-adaptive versions. Using the proposed filter, the MR data was semi-automatically segmented to delineate between adipose and lean muscle tissues. Two important findings were reached utilizing this data. First, a clear distinction between the musculature of males and females was established that provided 100% accuracy in being able to predict gender. Second, degenerative lumbar spines were accurately predicted at a rate of up to 92% accuracy. These results solidify prior assumptions made regarding sexual dimorphic anatomy and the pathogenic nature of degenerative spine disease

Probing resting-state functional connectivity in the infant brain: methods and potentiality

Early brain development is characterized by rapid growth and perpetual reconfiguration, driven by a dynamic milieu of heterogeneous processes. Moreover, potent postnatal brain plasticity engenders increased vulnerability to environmental stimuli. However, little is known regarding the ontogeny and temporal manifestations of inter- and intra-regional functional connectivity that comprise functional brain networks. Recently, resting-state functional magnetic resonance imaging (fMRI) emerged as a promising non-invasive neuroinvestigative tool, measuring spontaneous fluctuations in blood oxygen level dependent (BOLD) signal at rest that reflect baseline neuronal activity. Its application has expanded to infant populations in the past decade, providing unprecedented insight into functional organization of the developing brain, as well as early biomarkers of abnormal/ disease states. However, rapid extension of the resting-state technique to infant populations leaves many methodological issues need to be resolved prior to standardization of the technique. The purpose of this thesis is to describe a protocol for intrinsic functional connectivity analysis, and extraction of resting-state networks in infants <12 months of age using the data-driven approach independent component analysis (ICA). To begin, we review the evolution of resting-state fMRI application in infant populations, including the biological premise for neural networks. Next, we present a protocol designed such that investigators without previous knowledge in the field can implement the analysis and reliably obtain viable results consistent with previous literature. Presented protocol provides detailed, albeit basic framework for RSN analysis, with interwoven discussion of basic theory behind each technique, as well as the rationale behind selecting parameters. The overarching goal is to catalyze efforts towards development of robust, infant-specific acquisition and preprocessing pipelines, as well as promote greater transparency by researchers regarding methods used. Finally, we review the literature, current methodological challenges and potential future directions for the field of infant resting-state fMRI

Altered Neurocircuitry in the Dopamine Transporter Knockout Mouse Brain

The plasma membrane transporters for the monoamine neurotransmitters dopamine, serotonin, and norepinephrine modulate the dynamics of these monoamine neurotransmitters. Thus, activity of these transporters has significant consequences for monoamine activity throughout the brain and for a number of neurological and psychiatric disorders. Gene knockout (KO) mice that reduce or eliminate expression of each of these monoamine transporters have provided a wealth of new information about the function of these proteins at molecular, physiological and behavioral levels. In the present work we use the unique properties of magnetic resonance imaging (MRI) to probe the effects of altered dopaminergic dynamics on meso-scale neuronal circuitry and overall brain morphology, since changes at these levels of organization might help to account for some of the extensive pharmacological and behavioral differences observed in dopamine transporter (DAT) KO mice. Despite the smaller size of these animals, voxel-wise statistical comparison of high resolution structural MR images indicated little morphological change as a consequence of DAT KO. Likewise, proton magnetic resonance spectra recorded in the striatum indicated no significant changes in detectable metabolite concentrations between DAT KO and wild-type (WT) mice. In contrast, alterations in the circuitry from the prefrontal cortex to the mesocortical limbic system, an important brain component intimately tied to function of mesolimbic/mesocortical dopamine reward pathways, were revealed by manganese-enhanced MRI (MEMRI). Analysis of co-registered MEMRI images taken over the 26 hours after introduction of Mn^(2+) into the prefrontal cortex indicated that DAT KO mice have a truncated Mn^(2+) distribution within this circuitry with little accumulation beyond the thalamus or contralateral to the injection site. By contrast, WT littermates exhibit Mn^(2+) transport into more posterior midbrain nuclei and contralateral mesolimbic structures at 26 hr post-injection. Thus, DAT KO mice appear, at this level of anatomic resolution, to have preserved cortico-striatal-thalamic connectivity but diminished robustness of reward-modulating circuitry distal to the thalamus. This is in contradistinction to the state of this circuitry in serotonin transporter KO mice where we observed more robust connectivity in more posterior brain regions using methods identical to those employed here

Assessment and optimisation of MRI measures of atrophy as potential markers of disease progression in multiple sclerosis

There is a need for sensitive measures of disease progression in multiple sclerosis (MS) to monitor treatment effects and understand disease evolution. MRI measures of brain atrophy have been proposed for this purpose. This thesis investigates a number of measurement techniques to assess their relative ability to monitor disease progression in clinically isolated syndromes (CIS) and early relapsing remitting MS (RRMS). Presented, is work demonstrating that measurement techniques and MR acquisitions can be optimised to give small but significant improvements in measurement sensitivity and precision, which provided greater statistical power. Direct comparison of numerous techniques demonstrated significant differences between them. Atrophy measurements from SIENA and the BBSI (registration-based techniques) were significantly more precise than segmentation and subtraction of brain volumes, although larger percentage losses were observed in grey matter fraction. Ventricular enlargement (VE) gave similar statistical power and these techniques were robust and reliable; scan-rescan measurement error was <0.01% of brain volume for BBSI and SIENA and <0.04ml for VE. Annual atrophy rates (using SIENA) were -0.78% in RRMS and -0.52% in CIS patients who progressed to MS, which were significantly greater than the rate observed in controls (-0.07%). Sample size calculations for future trials of disease-modifying treatments in RRMS, using brain atrophy as an outcome measure, are described. For SIENA, the BBSI and VE respectively, an estimated 123, 157 and 140 patients per treatment arm respectively would be required to show a 30% slowing of atrophy rate over two years. In CIS subjects brain atrophy rate was a significant prognostic factor, independent of T2 MRI lesions at baseline, for development of MS by five year follow-up. It was also the most significant MR predictor of disability in RRMS subjects. Cognitive assessment of RRMS patients at five year follow-up is described, and brain atrophy rate was a significant predictor of overall cognitive performance, and more specifically, of performance in tests of memory. The work in this thesis has identified methods for sensitively measuring progressive brain atrophy in MS. It has shown that brain atrophy changes in early MS are related to early clinical evolution, providing complementary information to clinical assessment that could be utilised to monitor disease progression

The Rotterdam Scan Study: design update 2016 and main findings

Imaging plays an essential role in research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to elucidate the causes of neurological disease by performing imaging of the brain in a prospective population-based setting. Initially, in 1995 and 1999, random subsamples of participants from the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. Moreover, we describe the imaging protocol, image post-processing techniques, and the main findings to date. Finally, we provide recommendations for future research, which will also be topics of investigation in the Rotterdam Scan Study