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Iron is the most abundant trace metal in the brain and is essential for many biological processes, such as neurotransmitter synthesis and myelin formation. This thesis investigates small, multifocal hypointensities that are apparent on T2*- weighted (T2*w) MRI in the basal ganglia, where presumably most iron enters the brain via the blood-brain-barrier along the penetrating arteries. These basal ganglia T2*w hypointensities are believed to arise from iron-rich microvascular mineral deposits, which are frequently found in community-dwelling elderly subjects and are associated with age-related cognitive decline. This thesis documents the characteristic spatial distribution and morphology of basal ganglia T2*w hypointensities of 98 community-dwelling, elderly subjects in their seventies, as well as their imaging signatures on T1-weighted (T1w) and T2- weighted (T2w) MRI. A fully automated, novel method is introduced for the segmentation of basal ganglia T2*w hypointensities, which was developed to reduce the high intra- and inter-rater variability associated with current semi-automated segmentation methods and to facilitate the segmentation of these features in other single- and multi-centre studies. This thesis also presents a multi parametric quantitative MRI relaxometry methodology for conventional clinical MRI scanners that was developed and validated to improve the characterisation of brain iron. Lastly, this thesis describes the application of the developed methods in the segmentation of basal ganglia T2*w hypointensities of 243 community-dwelling participants of the Austrian Stroke Prevention Study Family (ASPS-Fam) and their analysis on R2* (=1/T2*) relaxation rate and Larmor frequency shift maps. This work confirms that basal ganglia T2*w hypointensities, especially in the globus pallidus, are potentially MRI markers of microvascular mineralization. Furthermore, the ASPS-Fam results show that basal ganglia mineral deposits mainly consist of paramagnetic particles, which presumably arise from an imbalance in the brain iron homeostasis. Hence, basal ganglia T2*w hypointensities are possibly an indicator of age-related microvascular dysfunction with iron accumulation, which might help to explain the variability of cognitive decline in normal ageing.

Software used in medical settings operate in complex and variable environments. Programs need to integrate well not only with their electrical and mechanical components, but also within the socio-technological setting they participate in. In this Master's Thesis, a modular software architecture for controlling surgical robot systems within magnetic resonance scanners is designed and implemented. The C++ program runs on a sbRIO 9651 real-time operating system and an object oriented design is taken. Robot kinematics and controls are put into effect in software and validated. Communication with up to ten daughter cards occurs via SPI and external information is exchanged via OpenIGTLink. A web-based engineering console made with ReactJS is also constructed to provide a visual interface for actuating motor axes and executing robot functionality. Documentation of the code is provided and the program was validated quantitatively with software tests and qualitatively through experimentation in MRI suites.

There are unmet needs in evaluating treatment response of hepatocellular carcinoma in research protocols. Early predictors, such as imaging biomarkers, could allow for earlier judgment of treatment effect. Currently RECIST is the most widely accepted criterion in clinical trials. A modified RECIST (mRECIST) criterion was developed to take into account the unique imaging characteristics of HCC lesions. Much discussion has occurred regarding linear measurements and their appropriateness for evaluating change in tumor burden over time. The simplicity of currently accepted criteria differs with the increasing sophistication of imaging techniques. Tumor volume change on 3D imaging can provide insight into actual action of treatment rather than an estimate of action as shown by linear and bi-dimensional measurements. It was the aim of this study to determine whether linear, bi-dimensional, and volumetric percent changes of HCC lesions, in both the arterial and portal venous phases, are significantly comparable. 27 HCC lesions (identified on 25 subjects) were measured at two timepoints by each method on 3D GRE MRI scans in both phases. Percent change was calculated per lesion for each measurement type in both the arterial and portal venous phases. Signed rank tests, paired t tests, and comparison of change tests were run to evaluate the data. Significant differences between the percent changes of linear measurements versus volumetric measurements were observed using a Wilcoxon signed-rank test which showed p = 0.0000. A simple correlation assessment showed positive correlations for all measurements, with the lowest being correlations 0.8679 for the arterial linear percent change versus the arterial volumetric percent change and 0.8434 for the portal venous linear percent change versus the portal venous volumetric percent change. Differences between percent changes of linear versus bi-dimensional measurements and bi-dimensional versus volumetric measurements were significant as well (Linear versus bi-dimensional p = 0.0001, bi-dimensional versus volumetric p = 0.0004). To conclude, the differences in the percent changes when comparing the measurement types are statistically significant, particularly when comparing linear and volumetric measurements. Establishing a reproducible volumetric criterion could lead to improvements in the implementation of clinical trials.

Trabalhos anteriores sobre a síntese de imagens de difusão por ressonância magnética se limitaram a estudos sobre estruturas microscópicas, menores que as dimensões típicas de um voxel (e.g., [BF08] [BF13] [LFS + 10] e [BA94]). Isto decorre em parte devido às metodologias utilizadas, que têm como ponto em comum serem simulações de tipo Monte Carlo, nas quais os elementos mínimos da simulação são as partículas de água. Portanto o custo computacional destas simulações é proporcional ao número de partículas a simular, e isto limita os volumes que podem ser simulados a tamanhos microscópicos. Propomos uma metodologia alternativa, que utiliza a imagem T 2 de uma amostra para sintetizar imagens de difusão por ressonância magnética. Os elementos mínimos desta nova metodologia são os pontos da imagem T 2 , e portanto seu custo computacional é proporcional à resolução da imagem T 2 utilizada, o que permite a síntese a partir de amostras de qualquer tamanho físico. Estas sínteses são realizadas por meio da integração numérica da equação do artigo seminal de Stejskal e Tanner [ST65] que relaciona a atenuação do sinal de ressonância magnética devida à difusão com os parâmetros da sequência de pulsos PGSE. Usamos os parâmetros típicos dessa sequência (b, gamma, tau\', g 0, g, delta e Delta), que podem ser configurados explicitamente em máquinas de ressonância magnética, para calcular valores do coeficiente de difusão aparente D em direções arbitrárias. Desenvolvemos software, disponibilizado [Bor] por licença GPL [Fou07], para realizar estas simulações, e para especificar uma máscara de direções, útil para modelar a difusão de uma amostra. Estas ferramentas permitem o estudo sistemático das variações dos parâmetros na síntese de imagens de difusão por ressonância magnética. Apresentamos um estudo de um fantoma de capilares imersos em água, exemplificando como utilizar as ferramentas para investigar a influência destes parâmetros na difusão da água da amostra. / Previous work on the synthesis of diffusion-weighted magnetic resonance imaging are limited to microscopic structures, smaller than the typical dimensions of a single voxel (e.g., [BF08] [BF13] [LFS + 10] and [BA94]). This is consequence, in part, of the methodologies used, that have in common the adoption of Monte Carlo simulation strategies, in which the minimal elements of simulation are the water particles. Therefore the computational cost of these simulations is proportional to the number of particles to simulate, and this limits the volume to be simulated to microscopic sizes. We propose a novel methodology, that uses the T 2 image from a sample to synthesize diffusion-weighted magnetic resonance images. The mininal elements of this novel methodology are the points of the T 2 image, and therefore its computational cost is proportional to the resolution of the T 2 image to be used, which allows the synthesis from samples of any physical size. These syntheses are made through numerical integration of the equation from the seminal article by Stejskal and Tanner [ST65] that relates the attenuation of the magnetic resonance signal due to diffusion to the parameters of the PGSE pulse sequence. We use the typical parameters of this sequence (b, gamma, tau\', g 0, g, delta and Delta), that can be explicitly configured in magnetic resonance machines, to calculate apparent diffusion coefficients D in arbitrary directions. We developed software, available [Bor] through GPL license [Fou07], to run these simulations, and to specify a mask of directions useful to model diffusion. These tools allow the systematic study of parameter variation in the synthesis of diffusion-weighted magnetic resonance images. We present a case study of a phantom made of capillary tubes immersed in water, to exemplify the use of these tools and how to investigate the influence of parameter variation on diffusion in the sample.

Obtaining high spatial or spatiotemporal resolution along with good slice coverage is challenging in dynamic magnetic resonance imaging, MRI, due to the slow nature of the acquisition process. In recent years, there has been a rapid growth of MRI techniques that allow faster scan speed by exploiting spatial or spatiotemporal redundancy of the images. These techniques can improve the performance of imaging significantly across multiple clinical applications, including cardiac functional examinations, perfusion imaging, blood flow assessment, contrast-enhanced angiography, functional MRI, and interventional imaging, among others. The ultimate goal of this thesis is to develop novel algorithms to reconstruct heavily undersampled sparse imaging. The designed schemes aim to achieve a shorter scan duration, higher spatial resolution, increased temporal resolution, signal-to-noise ratio and coverage in multidimensional multichannel MRI. In addition to improving patients comfort and compliance while imaging under the MRI device, the newly developed schemes will allow patients with arrhythmia problems, pediatric and obese subjects to breath freely without the need for any breath-hold scans. Shortening examination periods also reduces patient's stress, lowers the entire visit to the clinic and finally decreases the associated economic costs. Rapid imaging acquisitions will also allow for efficient extraction of quantitative information needed for the patients' diagnosis eg. tumor characterization and veins blockages through myocardial perfusion MRI. Current applications of interests include real-time CINE MRI and contrast changing perfusion MRI.

Magnetic resonance imaging is utilized as an important tool in radiation oncology for delineation of healthy and cancerous tissues, and evaluating the functionality of those tissues, structures, and organs. Currently, the clinical imaging protocol at Virginia Commonwealth University includes anatomical imaging for tissue and structure delineation, and to observe treatment induced changes. Diffusion weighted imaging (DWI) is also acquired for calculation of apparent diffusion coefficient (ADC) values to provide quantitative information on tissue diffusivity and microstructure. However, anatomical images and ADC values may not display the true extent of changes in tissue. This work seeks to further utilize the capabilities of MRI and expand its role in treatment response monitoring for liver cancer patients treated with stereotactic body radiotherapy (SBRT). To do so, an imaging protocol and image analysis methodology to evaluate treatment changes on pre- and post-treatment image sets was developed. An extension of DWI, termed intravoxel incoherent motion (IVIM) imaging, was utilized to quantitatively assess levels of perfusion and diffusion within the liver and tumor. Acquisition of high-quality diffusion weighted images of the liver necessitated the development of an MR safe respiratory motion management device, which was designed, constructed and evaluated in this work. An imaging protocol was developed providing anatomical and functional images of the liver, acquired under breath hold, utilizing the respiratory motion management device. An IVIM parameter calculation and texture analysis workflow was developed using MATLAB, and applied to acquired data sets from multiple studies, including past clinical cases, investigator, healthy volunteer, and liver cancer patient . Differences in IVIM and texture analysis parameters were investigated for healthy and diseased tissue, and for select dose regions from pre- and post-treatment imaging sessions. Significant differences, at a voxel level, were found between healthy and diseased tissue, and pre- and post-treatment volumes, for multiple parameters, including apparent diffusion coefficient, pure diffusion, and perfusion, as well as for various texture features. Overall, this study showed the potential of IVIM and texture analysis to be used for discriminating between healthy and diseased tissues in the liver, and for indication of treatment response.

<p>Methods for measuring deformation and motion of the human heart in-vivo are crucial in the assessment of cardiac function. Applications ranging from basic physiological research, through early detection of disease to follow-up studies, all benefit from improved methods of measuring the dynamics of the heart. This thesis presents new methods for acquisition, reconstruction and visualization of cardiac motion and deformation, based on magnetic resonance imaging.</p><p>Local heart wall deformation can be quantified in a strain rate tensor field. This tensor field describes the local deformation excluding rigid body translation and rotation. The drawback of studying this tensor-valued quantity, as opposed to a velocity vector field, is the high dimensionality of the tensor. The problem of visualizing the tensor field is approached by combining a local visualization that displays all degrees of freedom for a single tensor with an overview visualization using a scalar field representation of the complete tensor field. The scalar field is obtained by iterated adaptive filtering of a noise field.</p><p>Several methods for synchronizing the magnetic resonance imaging acquisition to the heart beat have previously been used to resolve individual heart phases from multiple cardiac cycles. In the present work, one of these techniques is extended to resolve two temporal dimensions simultaneously, the cardiac cycle and the respiratory cycle. This is combined with volumetric imaging to produce a five-dimensional data set. Furthermore, the acquisition order is optimized in order to reduce eddy current artifacts.</p><p>The five-dimensional acquisition either requires very long scan times or can only provide low spatiotemporal resolution. A method that exploits the variation in temporal bandwidth over the imaging volume, k-t BLAST, is described and extended to two simultaneous temporal dimensions. The new method, k-t2 BLAST, allows simultaneous reduction of scan time and improvement of spatial resolution.</p> / Report code: LIU-TEK-LIC-2006:43

During fetal development, the hippocampal structures are folded forming the hippocampal sulcus which penetrates into the temporal lobe and then the entity rotates.  During this process, the hippocampal sulcus will be closed and the inverted hippocampus takes a rounded form. After complete inversion, the hippocampus has an oval form in a plane perpendicular to its long axis. If this process has not been completed the hippocampus remains the rounded form. That condition is called incomplete hippocampal inversion (IHI). The aims of this study was to evaluate the frequency of IHI in non-epileptic and epileptic children and adults and to explore the development of the hippocampal region by studying premature neonates and fetuses. Magnetic resonance (MR) images of 201 epilepsy patients and 150 non-epileptic subjects were evaluated without knowing clinical data. IHI was found in 19 % in seizure free controls (20 left-sided and 8 bilateral). 30% of the 201 epilepsy patients had IHI (40 left-sided, 4 right-sided, 16 bilateral). The difference was statistically significant (p&lt;0.02). 25% of the temporal lobe epilepsy patients had IHI. The frequency was not significantly higher than in controls. There is no causality between temporal lobe epilepsy and IHI. 44% of the Rolandic epilepsy patients and 57% of the cryptogenic generalized epilepsy patients had IHI. IHI can be a sign of possible disturbed cerebral development in other parts of the brain. Cranial ultrasound examinations of 160 premature children were analyzed. The age at examination was 23-24 GW in 24 children, 25-28 GW in 72 children, and 29-36 GW in 64 children. IHI was found in 50%, 25% and 14%, respectively. The frequency difference between the children &lt; 25 GW and &gt; 25 GW was statistically significant (p&lt; 0.001). From 25 GW onwards, the frequency and laterality of IHI is similar to that in the adult population. MRIs of 63 fetuses without intracranial pathology were reviewed independently by two radiologists. Three MRIs were performed post mortem at gestation week (GW) 17-18 and 60 in utero at GW 19-35. The hippocampal sulcus was open, bi- or unilaterally, in 35 fetuses at GW 17-32. The oldest of them was at GW 32.  The sulcus was closed at GW 21 at the earliest, unilaterally, and always from GW 33 onwards bilaterally. In 26/63 fetuses (41%), the hippocampal development was asymmetric and in 23 fetuses, the right side had developed faster.

Spinal cord injury (SCI) leads to axonal damage and limits the ability of the brain to communicate with the rest of the body. Several bioengineered approaches have been developed for the recovery of SCI. Among these techniques, degradable guidance tubes have shown promising results. However, design of nerve guide tubes requires several design considerations and has been a significant challenge. To assess the efficacy of a prototypical implanted nerve guide tubes, it is essential to perform continuous monitoring. In this respect, magnetic resonance imaging (MRI) is one of the most reliable imaging techniques as it offers the ability to achieve extraordinary high temporal and spatial resolution in addition to its non-invasive features. In spite of the excellent image quality of non-enhanced MRI various types of contrast agents have been developed to further enhance the contrast and allow improved visualization. The MRI contrast agents principally work by shortening the T1 or T2 relaxation times of protons located nearby. The presented study was intended to evaluate the in vitro degradation of the nerve guide tubes made of poly (lactic-co-glycolic acid) (PLGA). PLGA tubes incorporated with different concentrations of superparamagnetic iron oxide (SPIO) were scanned by MRI 3T on weekly basis during the degradation period. Spin-echo (SE) sequence with various echo times (TEs) ranged from 13.3 to 314.4 msec was applied. T2 mapping was computed using in-house algorithm developed in Matlab. Least square fit was used to find the slope of the decay curve by plotting log intensity on the y-axis and echo time on the x-axis. The average T2 values were calculated. Mass loss and water uptake of the degrading tubes were also measured weekly. Moreover, the micro-structural changes of the tubes were investigated using the scanning electron microscope (SEM). The MRI results showed that the concentration of SPIO affects the signal intensity of the T2 weighted images reducing the T2 relaxation time value. Accordingly, a linear correlation between SPIO concentration and T2 relaxation time was found. At the beginning of degradation, the SPIO nanoparticles were trapped within the polymeric network. Therefore, water penetration was the predominant factor affecting the T2 relaxation times. At week 5, a significant mass loss was observed. From this stage onwards, the trapped SPIO were released from the polymeric network increasing T2 relaxation time dramatically. According to SEM images, the size of the pores in PLGA guide tubes was increased with the degradation. Approaching the end of degradation, shrinkage of the tubes was observed and the degraded nerve guide tubes were shown to be collapsed. Similar shape variation was observed in T2 weighted MR images. In summary, this study provided an approach to non-invasive monitoring of degradation behavior of nerve guide tubes using contrast enhancement. The developed technique is of great importance since it opened an insight to non-invasive monitoring of tissue engineered scaffolds for in vivo studies.