Thesis (Ph. D. in Physics)--Vanderbilt University, Dec. 2007. / Title from title screen. Includes bibliographical references.

Despite their unmatched soft-tissue contrast, Magnetic Resonance (MR) images suffer from wide-ranging image distortions; this has raised questions about their suitability as an imaging modality upon which to base conformal radiation therapy treatment plans. This thesis addresses image distortion as it relates to the implementation of MR-based radiation therapy treatment planning (MR-RTP). A grid phantom was imaged at 3T to determine the 3D distortion field using in-house software. Using multiple images, both machine- and object-related sources of distortion were separated such that individual evaluation of distortion sources is possible. Over the imaging volume, nonlinearities in the gradients led to peak-to-peak image distortions of up to 11 mm. For in-vivo distortion quantification, the method was augmented with a modified gradient echo sequence which measures the phase evolution due to underlying field inhomogeneities. The amount of distortion measured using this technique is dependent upon both patient anatomy and sequence parameters, but was found to contribute 5.7 mm at maximum. The methods presented can be combined to provide comprehensive distortion rectification such that mean residual image distortion is reduced to well below the pixel resolution. Finally, distortion quantification and correction methods were applied to a clinical MR-RTP study of prostate patients. The dosimetric consequences of distortion correction were investigated by comparing 3D conformal and intensity modulated radiation therapy plans developed based on both uncorrected and corrected MRI data sets. Total image distortions and those directly affecting the prostate and organs at risk (OARs) were assessed and target doses, OAR doses, and dose volume histograms were compared. Maximum distortion (from all sources) was 7.8 mm. With the exception of two patients, changes in plan dosimetry were insignificant (<2% / <1Gy). Two patients who were poorly position suffered larger distortions in the target region which led to dosimetric differences of up to 4.2%. / Medical Physics

Aims : Patients with mild heart failure (HF) who are clinically compensated may have normal left ventricular (LV) stroke volume (SV). Despite this, altered intra-ventricular flow patterns have been recognized in these subjects. We hypothesized that, compared with normal LVs, flow in myopathic LVs would demonstrate a smaller proportion of inflow volume passing directly to ejection and diminished the end-diastolic preservation of the inflow kinetic energy (KE). Methods and results : In 10 patients with dilated cardiomyopathy (DCM) (49 ± 14 years, six females) and 10 healthy subjects (44 ± 17 years, four females), four-dimensional MRI velocity and morphological data were acquired. A previously validated method was used to separate the LV end-diastolic volume (EDV) into four flow components based on the blood's locations at the beginning and end of the cardiac cycle. KE was calculated over the cardiac cycle for each component. The EDV was larger (P = 0.021) and the ejection fraction smaller (P &lt; 0.001) in DCM compared with healthy subjects; the SV was equivalent (DCM: 77 ± 19, healthy: 79 ± 16 mL). The proportion of the total LV inflow that passed directly to ejection was smaller in DCM (P = 0.000), but the end-diastolic KE/mL of the direct flow was not different in the two groups (NS). Conclusion : Despite equivalent LVSVs, HF patients with mild LV remodelling demonstrate altered diastolic flow routes through the LV and impaired preservation of inflow KE at pre-systole compared with healthy subjects. These unique flow-specific changes in the flow route and energetics are detectable despite clinical compensation, and may prove useful as subclinical markers of LV dysfunction.

It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

Magnetic Resonance Imaging instruments rely on a contrast agent to provide high-resolution images of tissues in vivo. However, current clinical contrast agents are hindered by low relaxivity and fast correlation time, necessitating high injection dosages. These concerns, among others, have driven the development of a class of protein-based contrast agents (ProCAs), by design of lanthanide binding sites into a scaffold protein. ProCA1 has a higher reported relaxivity and dosage efficiency than current contrast agents. In this study, expression and Glutathione-S-Transferase purification procedures were optimized, and a refolding method for rapid production of ProCA1 has been developed to enable studies of conformation, metal binding, relaxivity, and in vivo applications. Several ProCA1 variants with 4-5 charged ligand residues were shown to have strong gadolinium binding affinity (Kd of 10-12 M) and metal selectivity. Several options to improve ProCA1 have been explored, including addition of a polyethylene chain or a bombesin tag.

It was hypothesized that superparamagnetic nanoparticles encapsulated in a silica shell with a fluorescent dye could be functionalized with axonal tracers and could be used for serial, non-invasive imaging with magnetic resonance imaging (MRI) for axon tract tracing. Nanoparticles functionalized with amine, octadecyl, silica, and biotinylated dextran amine were manufactured and characterized with MRI, scanning electron microscopy, and UV-visible, infrared, and fluorescence spectroscopy. Nanoparticle concentrations of 10 mM were not toxic to adult rat neural progenitor cells (NPCs) and labeled approximately 90% of cells. Nanoparticles were assessed for anterograde and retrograde tract tracing in adult rat models. With MRI and microscopy, the nanoparticles did not appear to trace axons but did provide an MRI signal for up to 3 weeks post implantation. While functionalized nanoparticles did not appear to trace axons, they are not toxic to NPCs and may be used as a MRI contrast agent in the neural axis.

この論文は，筆頭著者の博士論文（膝蓋大腿関節痛を有する成人女性の膝蓋骨可動性についての研究（http://hdl.handle.net/2237/10676）の副論文として提出された。和文によるタイトル，抄録は博士論文提出の際に付けられた。

There is an increasing interest for nanomaterials in biomedical applications and in this work, nanoparticles of gadolinium oxide (Gd2O3) have been investigated as a novel contrast agent for Magnetic Resonance Imaging (MRI). Relaxation properties have been studied in aqueous solutions as well as in cell culture medium and the nanoparticles have been explored as cell labeling agents. The fluorescent properties of the particles were used to visualize the internalization in cells and doped particles were also investigated as a multimodal agent that could work as a fluorescent marker for microscopy and as a contrast enhancer for MRI. Results show that in aqueous solutions, there is a twofold increase in relaxivity for Gd2O3 compared to commercial agent Gd-DTPA. In cell culture medium as well as in cells, there is a clear T1 effect and a distinct increase in signal intensity in T1-mapped images. Fluorescent studies show that the Gd2O3 nanoparticles doped with 5% terbium have interesting fluorescent properties and that these particles could work as a multimodal contrast agent. This study shows that Gd2O3 nanoparticles possess excellent relaxation properties that are retained in more biological environments. Gd2O3 particles are suitable as a T1 contrast agent, but seem also be adequate for T2 enhancement in for instance cell labeling experiments.

Background: Hip fractures are a major health problem in Canada, and two main contributors to hip fracture are weak bone strength and fall. Weak muscles also negatively affect bone strength and increase the likelihood of falling. Advanced imaging techniques, such as magnetic resonance imaging (MRI), offer in vivo measurement of bone strength and muscle area at the proximal femur. However, it is not known if MRI-based measurements of bone and muscle properties are repeatable (i.e. precise). Methods: The femoral neck and shaft of 14 healthy participants were scanned three times, using a 1.5T MRI with repositioning between scans. Boundaries of the femoral neck, shaft and four muscle groups were delineated semi-automatically. Geometrical and strength properties of bone and area of muscle groups were determined based on segmented images. The short-term precision errors (root mean square coefficient of variation; CVrms%) between the repeated measures were calculated accordingly. Results: MRI-based measures of bone geometry and strength and muscle area at the proximal femur demonstrated in vivo precision errors < 7.6%. The average CVrms% for bone measures and muscle area were less than 4% and 2.5% respectively. Higher CVrms% (e.g. average: 4.8%) was obtained for bone strength properties. Conclusion: This is the first study to evaluate the in vivo performance of MRI on application to the proximal femur and surrounding muscles. Results demonstrate that MRI is a promising non-ionizing technique that offers precise measures of bone and muscle at the proximal femur.

Magnetic Resonance Imaging (MRI) is a common medical imaging tool that have beenused in clinical industry for diagnostic and research purposes. These images are subjectto noises while capturing the data that can eect the image quality and diagnostics.Therefore, improving the quality of the generated images from both resolution andsignal to noise ratio (SNR) perspective is critical. Wavelet based denoising technique isone of the common tools to remove the noise in the MRI images. The noise is eliminatedfrom the detailed coecients of the signal in the wavelet domain. This can be done byapplying thresholding methods. The main task here is to nd an optimal threshold andkeep all the coecients larger than this threshold as the noiseless ones. Noise InvalidationDenoising technique is a method in which the optimal threshold is found by comparingthe noisy signal to a noise signature (function of noise statistics). The original NIDeapproach is developed for one dimensional signals with additive Gaussian noise. In thiswork, the existing NIDe approach has been generalized for applications in MRI imageswith dierent noise distribution. The developed algorithm was tested on simulated datafrom the Brainweb database and compared with the well-known Non Local Mean lteringmethod for MRI. The results indicated better detailed structural preserving forthe NIDe approach on the magnitude data while the signal to noise ratio is compatible.The algorithm shows an important advantageous which is less computational complexitythan the NLM method. On the other hand, the Unbiased NLM technique is combinedwith the proposed technique, it can yield the same structural similarity while the signalto noise ratio is improved.