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.

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.

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.

Background Knee osteoarthritis is a degenerative joint disease characterized by damaged cartilage, tendons, ligaments, synovium, and bone. Knee osteoarthritis causes joint pain, reduced joint function, and decreased quality of life and is the leading cause of chronic disability in older adults. Two of the major risk factors for knee osteoarthritis are increasing age and obesity. To decrease the occurrence of knee osteoarthritis in our aging population, it is important that we identify exercises that are safe for people with or at risk of knee osteoarthritis. Purpose The main purpose of this thesis was to compare the acute response of knee cartilage composition to two common aerobic activities, running and bicycling, of equal total load. To address the primary purpose, we first sought to determine the reliability and validity of measuring loading repetition during running (steps) and bicycling (pedal-revolutions) using accelerometry. Methods 1) Twenty-two healthy adults completed running and bicycling activity bouts (five-minutes) while wearing six accelerometers: two at each the waist, thigh and shank. Accelerometer and video data were collected during each activity. 2) Fifteen healthy men completed running and bicycling activities of equal cumulative load that were preceded and followed by a series of magnetic resonance images. Results 1) Excellent reliability (ICC≥.99; SEM≤1.0) and validity (Pearson≥.99) were found for step and pedal revolution measurements taken by an accelerometer placed at the shank. 2) Bicycling did not cause significant changes in cartilage composition (p=0.274); however, running did cause a change in cartilage composition (p=0.002). Conclusion Findings from this thesis suggest that to acquire reliable and valid step and pedal revolution measurement, accelerometers should be placed on the shank. Furthermore, bicycling causes no statistical changes in knee cartilage, while running does. Bicycling may therefore be used to combat obesity and maintain cardiovascular health in individuals with compromised joint health. / Thesis / Master of Science (MSc) / Knee osteoarthritis is a degenerative joint disease that affects all knee tissues, particularly articular cartilage. This “wear and tear” condition reduces mobility and creates pain, collectively decreasing quality of life. Two important risk factors for knee osteoarthritis are age and obesity. While we cannot stop aging, exercise can have a positive impact on weight, particularly among adults with knee osteoarthritis. This thesis provides foundational information on how running and bicycling affects knee cartilage. First, we identified a useful method of measuring steps during running and pedal revolutions during bicycling. Second, we compared the effect of running and bicycling of equal cumulative load on knee cartilage, using MRI. The running activity was 1/3 the length of the bicycling activity but despite shorter exposure, running caused changes in cartilage shape and composition, while bicycling did not. These findings suggest that bicycling is a suitable aerobic activity that reduces loading at the knee.

Abstract Cartilage-related diseases such as osteoarthritis (OA) are a major cause of disability and decrease in the quality of life. Moreover OA causes a heavy economical burden on the social welfare and health care systems. Conventional magnetic resonance imaging (MRI) provides accurate noninvasive method of morphological evaluation of the articular cartilage. However, there are early degenerative changes in the articular cartilage that can be evaluated with modern quantitative MRI methods prior to the signs of cartilage loss. In this study, T2 relaxation time of the articular cartilage was further evaluated in 1.5T in vivo using clinical patients and asymptomatic volunteers. The detection of focal patellar cartilage lesions in T2 mapping as compared to standard clinical MRI was evaluated. T2 mapping showed more lesions than the clinical MRI, and in T2 maps the lesions appeared generally wider. This suggests that T2-mapping is feasible in the clinical setting and may reveal cartilage lesions not seen in the standard knee MRI. The normal topographical variation of T2 relaxation time of articular cartilage in different compartments of the knee joint and at different zones of cartilage in young healthy adults was assessed. T2 values were significantly higher in the superficial zone as compared to the deep tissue at all locations and there was remarkable variation in T2 relaxation between different locations. The normal variation in cartilage T2 within a joint is significant and should be acknowledged when pathology-related T2 changes are investigated. The short- and long-term repeatability of T2 relaxation time measurements of articular cartilage in the knee joint was assessed. The results showed mostly good repeatability, and with careful patient positioning T2 relaxation time at the different cartilage surfaces of the knee can be accurately determined. / Tiivistelmä Nivelrikko, joka usein liittyy nivelruston vaurioitumiseen, aiheuttaa merkittävää toimintakyvyn ja elämänlaadun heikentymistä ikääntyvässä väestössä. Lisäksi nivelrikosta aiheutuu merkittäviä kustannuksia sosiaali- ja terveydenhuollolle. Magneettikuvaus on tarkka kajoamaton menetelmä rustovaurioiden arvioimiseksi. Kuitenkin rustovaurion alkuvaiheessa tapahtuu ruston sisäisiä rakenteellisia ja biokemiallisia muutoksia, joita on mahdollista arvioida uusilla kvantitatiivisilla magneettikuvausmenetelmillä ennen varsinaisten rustopuutosten kehittymistä. Tässä tutkimuksessa tutkittiin ruston T2-relaksaatioaikamittausta 1.5T magneettikuvauslaitteella sekä potilasaineistossa että vapaaehtoisilla. Tutkimuksessa verrattiin paikallisten rustomuutosten havaitsemisen herk¬kyyttä T2-relaksaatioaikakartoituksen ja tavanomaisen kliinisen magneetti¬kuvauksen välillä kliinisessä potilasaineistossa. T2-relaksaatiomittaus osoitti useampia muutoksia kuin kliininen magneettikuvaus ja muutokset olivat yleensä laajempia. Voidaan olettaa, että T2-relaksaatioaikamittaus soveltuu kliiniseen käyttöön ja voi osoittaa tavanomaisessa magneettikuvauksessa näkymättömiä rustomuutoksia. Tutkimuksessa arvioitiin ruston T2-relaksaatioajan paikkakohtaista ja kerroksittaista vaihtelua polven nivelpintojen eri alueilla nuorten vapaaehtoisten aineistossa. T2-relaksaatioaika oli merkitsevästi pidempi ruston pinnallisessa kuin syvässä kerroksessa kaikilla nivelpintojen alueilla. Lisäksi T2-relaksaatioajassa oli merkittävää normaalia vaihtelua eri alueiden välillä ja tämä tulisi huomioida ruston patologisia muutoksia arvioitaessa. Tutkimuksessa arvioitiin polven ruston T2-relaksaatioajan lyhyen ja pitkän aikavälin toistettavuutta vapaaehtoisaineistossa. Tulokset osoittivat enimmäkseen hyvää toistettavuutta ja huolellisella asettelulla voidaan ruston T2-relaksaatioaika mitata luotettavasti polven nivelpintojen eri alueilla.

Computed Tomography (CT) is often used for building 3D biomechanical models of human anatomy. This method exposes the subject to a significant x-ray dose and provides limited soft-tissue contrast. Magnetic Resonance Imaging (MRI) is a potential alternative to CT for this application, as MRI offers significantly better soft-tissue contrast and does not expose the subject to ionizing radiation. However, MRI requires long scan times to achieve 3D images at sufficient resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). These long scan times can make subject motion a problem. This thesis describes my work to reduce scan time while achieving sufficient resolution, SNR, and CNR for 3D biomechanical modeling of (1) the human larynx, and (2) the human hip. I focused on two important strategies for reducing scan time and improving SNR and CNR: the design of RF coils optimized to detect MRI signals from the anatomy of interest, and the determination of MRI relaxation properties of the tissues being imaged (allowing optimization of imaging parameters to improve CNR between tissues). Work on the larynx was done in collaboration with the Thomson group in Mechanical Engineering at BYU. To produce a high-resolution 3D image of the larynx, a 2-channel phased array was constructed. Eight different coil element designs were analyzed for use in the array, and one chosen that provided the highest Q-ratio while still meeting the mechanical constraints of the problem. The phased array was tested by imaging a pig larynx, a good substitute for the human larynx. Excellent image quality was achieved and MR relaxometry was then performed on tissues in the larynx. The work on the hip was done in collaboration with the Anderson group in orthopedics at the University of Utah, who are building models of femoral acetabular impingement (FAI). Accurate imaging of hip cartilage requires injection of fluid into the hip joint capsule while in traction. To optimize contrast, MR relaxometry measurements were performed on saline, isovue, and lidocaine solutions (all typically injected into the hip). Our analysis showed that these substances actually should not be used for MR imaging of the hip, and alternate strategies should be explored as a result.

Understanding molecular and ion dynamics in soft materials used for fuel cell, battery, and drug delivery vehicle applications on multiple time and length scales provides critical information for the development of next generation materials. In this dissertation, new insights into transport and kinetic processes such as diffusion coefficients, translational activation energies (Ea), and rate constants for molecular exchange, as well as how these processes depend on material chemistry and morphology are shown. This dissertation also aims to serve as a guide for material scientists wanting to expand their research capabilities via nuclear magnetic resonance (NMR) techniques. By employing variable temperature pulsed-field-gradient (PFG) NMR diffusometry, which can probe molecular transport over nm – μm length scales, I first explore transport and morphology on a series of ion-conducting materials: an organic ionic plastic crystal, a proton-exchange membrane, and a polymer-gel electrolyte. These studies show the dependencies of small molecule and ion transport on modulations to material parameters, including thermal or magnetic treatment, water content, and/or crosslink density. I discuss the fundamental significance of the length scale over which translational Ea reports on these systems (~ 1 nm) and the resulting implications for using the Arrhenius equation parameters to understand and rationally design new ion-conductors. Next, I describe how NMR spectroscopy can be utilized to investigate the effect of loading a small molecule into the core of a spherical block copolymer micelle (to mimic, e.g., drug loading) on the hydrodynamic radius (rH) and polymer chain dynamics. In particular, I present spin-lattice relaxation (T1) results that directly measure single chain exchange rate kexch between micelles and diffusion results that inform on the unimer exchange mechanism. These convenient NMR methods thus offer an economical alternative (or complement) to time-resolved small angle neutron scattering (TR-SANS). / Ph. D.

The aim of the thesis is to define the dependency of the classification of patients affected by neurodegenerative diseases on the choice of the parcellation atlas. Part of this thesis is the application of the functional connectivity analysis and the calculation of graph metrics according to the method published by Olaf Sporns and Mikail Rubinov [1] on fMRI data measured at CEITEC MU. The application is preceded by the theoretical research of parcellation atlases for brain segmentation from fMRI frames and the research of mathematical methods for classification as well as classifiers of neurodegenerative diseases. The first chapters of the thesis brings a theoretical basis of knowledge from the field of magnetic and functional magnetic resonance imaging. The physical principles of the method, the conditions and the course of acquisition of image data are defined. The third chapter summarizes the graph metrics used in the diploma thesis for analyzing and classifying graphs. The paper presents a brief overview of the brain segmentation methods, with the focuse on the atlas-based segmentation. After a theoretical research of functional connectivity methods and mathematical classification methods, the findings were used for segmentation, calculation of graph metrics and for classification of fMRI images obtained from 96 subjects into the one of two classes using Binary classifications by support vector machines and linear discriminatory analysis. The data classified in this study was measured on patiens with Parkinson’s disease (PD), Alzheimer’s disease (AD), Mild cognitive impairment (MCI), a combination of PD and MCI and subjects belonging to the control group of healthy individuals. For pre-processing and analysis, the MATLAB environment, the SPM12 toolbox and The Brain Connectivity Toolbox were used.

Current quantitative nuclear magnetic resonance (NMR) technics offer biomarkers that allow performing non-invasive longitudinal studies for the follow up of therapeutic trials in neuromuscular disorders (NMD). In contrast to fat degeneration, the mechanisms of inflammation/oedema/necrosis and fibrosis are characteristic signs of disease activity, which makes their quantification a promising source of crucial biomarkers for longitudinal studies. This thesis work consisted on the implementation of more precise quantitative NMR methods adapted to the clinical study of skeletal muscle (SKM) for : (i) detection and quantification of sites of disease activity by T2-mapping of muscle water ; (ii) investigation of the different pathophysiological mechanisms underlying T2 alterations ; and (iii) Detection and quantification of muscle fibrosis. We implemented two methods for T2 mapping of muscle water. The first one is based on a multi-spin-echo sequence du type CPMG. In this method the 1H-NMR signals from water and lipids are acquired simultaneously. The acquired data are fitted to a tri-exponential model, in which water and fat signals are separated by exploring the T2 difference between water and fat. This method allows extraction of muscle water T2-value in the presence of fat infiltration. The second method is based on a " partially spoiled steady state free precession " (pSSFP) sequence. In contrast to the first method, which demands a sophisticated post-treatment of images acquired at 17 different echo-times, with the pSSFP a T2-mapping is extracted from two 3D data sets. 3D acquisition is compatible with spectrally selective water excitation, which eliminates signal contribution from lipids. Both methods were validated experimentally on patients and healthy subjects. The results demonstrated their capacity to detect and quantify disease activity sites. This 2 works have been published in two international journals : Azzabou, de Sousa, Araujo, & Carlier, 2014. Journal of Magnetic Resonance Imaging. DOI 10.1002/jmri.24613 (in press); et de Sousa, Vignaud, Araujo, & Carlier . 2012. Magnetic Resonance in Medicine. 67:1379-1390. Although it was shown to reveal disease activity, mono-exponential T2 of muscle water is non-specific to what concerns the mechanisms underlying its alterations. It has been long known that T2 relaxation in SKM tissue is multi-exponential. This is currently accepted to reveal anatomical compartmentation of myowater. We implemented a method for localized spectroscopic CPMG acquisition. CPMG data respect echo-time sampling and signal to noise ration limits for allowing robust multiexponential analysis. This work allowed us to establish a compartmentation model that perfectly explains the multi-exponential T2 relaxation observed in SKM tissue. This work was published in the " Biophysical Journal " (Araujo, Fromes & Carlier 2014. New Insights on skeletal muscle tissue compartments revealed by T2 NMR relaxometry. (In press)). Pilot studies performed in patients show promising results and suggest potential application of the method in clinical studies. Fibrosis starts with an excessive accumulation of intramuscular connective tissue (IMCT). We have explored the " Ultrashort time to echo " (UTE) method with the aim to detect and characterize the signal from IMCT. In a first study we characterized in vivo a short T2 component (~500 µs) in SKM, and we collected evidences suggesting that this component might reflect IMCT. Then we implemented a methodology that allowed imaging this short component in SKM tissue for the first time.

The task of this thesis is to study the subject of perfusion analysis based on dynamic imaging with T2/T2* contrast. The focus was on the acquisition commonly used for DSC-MRI and especially in the acquisition pulse sequences that use images with different echo time, so called Multi-echo sequence. Principles of dynamic measurement by magnetic resonance imaging, the role of contrast agents and their influence on the relaxation times are described. It also describes the problems perfusion analysis, measurement and mathematical modeling parameters entering to the convolution dependency for getting perfusion parametersIn the experimental part is developed automatic algorithm to gain curves relaxation time T2 *. Next, the synthetic data are created and tested robustness estimate perfusion parameters against noise. In the next phase of work there are compared real scanned objects with using a conversion with T2 * and free of T2*. In the last phase of work is compared influence of length of used echo times on concentration curves and after perfusion analysis influence on resulting perfusion parameters.