Magnetic resonance spectroscopic imaging (MRSI) is a non-invasive technique that offers a unique ability to provide the spatial distribution of relevant biochemical compounds (metabolites). The ‘spectrum’ of information provided by MRSI is used as biomarkers for the differential diagnosis of several diseases such as cancer or neurological disorders. Treatment responsive brain tumors can appear similar to non-responsive tumors on conventional anatomical MR images, earlier in the therapy, leading to a poor prognosis for many patients. Biomarkers such as lactate are particularly of interest in the oncological studies of solid tumors to determine their energy metabolism, blood flow, and hypoxia. Despite the capability of nearly all clinical MRI scanners to perform MRSI only limited integration of MRSI into routine clinical studies has occurred to date. The major challenges affecting its true potential are the inherently long acquisition time, low signal-to-noise (SNR) of the signals, overlapping of spectral lines, or the presence of artifacts. The goal of this dissertation work is to facilitate MRSI in routine clinical studies without affecting the current patient throughput. In this work, the Compressed Sensing (CS) strategy was used to accelerate conventional Point RESolved Spectroscopy (PRESS) MRSI by sampling well below the Shannon-Nyquist limit. Two undersampling strategies, namely the pseudo-random variable density and a novel a priori method was developed and implemented on a clinical scanner. Prospectively undersampled MRSI data was acquired from patients with various brain-related concerns. Spatial-spectral post-processing and CS reconstruction pipeline was developed for multi-channel undersampled data. The fidelity of the CS-MRSI method was determined by comparing the CS reconstructed data to the fully sampled data. Statistical results showed that the a priori approach maintained high spectral fidelity compared to the fully sampled reference for an 80% reduction in scan time. Next, an improvement to the CS-MRSI reconstruction was achieved by incorporating coil sensitivity maps as support in the iterative process. Further, a CS-MRSI-based fast lactate spectroscopic imaging method was developed and implemented to achieve complete water and fat suppression for accurate spatial localization and quantification of lactate in tumors. In vitro phantoms were developed, and the sequence was tested to determine the efficacy of CS-MRSI for low SNR signals, the efficacy of the CS acceleration was determined with statistical analysis.

Magnetic resonance spectroscopic imaging (MRSI) is a valuable technique for assessing the in vivo spatial profiles of metabolites like N-acetylaspartate (NAA), creatine, choline, and lactate. Changes in metabolite concentrations can help identify tissue heterogeneity, providing prognostic and diagnostic information to the clinician. The increased uptake of glucose by solid tumors as compared to normal tissues and its conversion to lactate can be exploited for tumor diagnostics, anti-cancer therapy, and in the detection of metastasis. Lactate levels in cancer cells are suggestive of altered metabolism, tumor recurrence, and poor outcome. A dedicated technique like MRSI could contribute to an improved assessment of metabolic abnormalities in the clinical setting, and introduce the possibility of employing non-invasive lactate imaging as a powerful prognostic marker.

However, the long acquisition time in MRSI is a deterrent to its inclusion in clinical protocols due to associated costs, patient discomfort (especially in pediatric patients under anesthesia), and higher susceptibility to motion artifacts. Acceleration strategies like compressed sensing (CS) permit faithful reconstructions even when the k-space is undersampled well below the Nyquist limit. CS is apt for MRSI as spectroscopic data are inherently sparse in multiple dimensions of space and frequency in an appropriate transform domain, for e.g. the wavelet domain. The objective of this research was three-fold: firstly on the preclinical front, to prospectively speed-up spectrally-edited MRSI using CS for rapid mapping of lactate and capture associated changes in response to therapy. Secondly, to retrospectively evaluate CS-MRSI in pediatric patients scanned for various brain-related concerns. Thirdly, to implement prospective CS-MRSI acquisitions on a clinical magnetic resonance imaging (MRI) scanner for fast spectroscopic imaging studies. Both phantom and in vivo results demonstrated a reduction in the scan time by up to 80%, with the accelerated CS-MRSI reconstructions maintaining high spectral fidelity and statistically insignificant errors as compared to the fully sampled reference dataset. Optimization of CS parameters involved identifying an optimal sampling mask for CS-MRSI at each acceleration factor. It is envisioned that time-efficient MRSI realized with optimized CS acceleration would facilitate the clinical acceptance of routine MRSI exams for a quantitative mapping of important biomarkers.

This research reports on the investigation into the synthesis and stabilization of

iron oxide nanoparticles for theranostic applications using amine-epoxide polymers. Although theranostic agents such as magnetic nanoparticles have been designed and developed for a few decades, there is still more work that needs to be done with the type of materials that can be used to stabilize or functionalize these particles if they are to be used for applications such as drug delivery, imaging and hyperthermia. For in-vivo applications, it is crucial that organic coatings enclose the nanoparticles in order to prevent aggregation and facilitate efficient removal from the body as well as protect the body from toxic material.

The objective of this thesis is to design polymer coated magnetite nanoparticles with polymers that are biocompatible and can stabilize the iron oxide nanoparticle to help create mono-dispersed particles in solution. It is desirable to also have these nanoparticles possess high magnetic susceptibility in response to an applied magnetic field. The co- precipitation method was selected because it is probably the simplest and most efficient chemical pathway to obtain magnetic nanoparticles.

In literature, cationic polymers such as Polyethylenimine (PEI), which is the industry standard, have been used to stabilize IONPs because they can be used in magnetofections to deliver DNA or RNA. PEI however is known to interact very strongly with proteins and is cytotoxic, so as mentioned previously the Iron Oxide nanoparticles

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(IONPs) synthesized in this study were stabilized with amine-epoxide polymers because of the limitations of PEI.

Four different amine-epoxide polymers which have good water solubility, biodegradability and less toxic than PEI were synthesized and used in the synthesis and stabilization of the magnetic nanoparticles and compared to PEI templated IONPs. These polymer-templated magnetic nanoparticles were also characterized by size, surface charge, Iron oxide content (ICP analysis) and superconducting quantum interference devices (SQUID) analysis to determine the magnetization values. TEM images were also used to determine the shape and size of the nanoparticles. All this was done in an effort to choose two or three leads that could be used in future work for magnetofections or drug delivery research.

Ionizing radiation, such as gamma rays and X-rays, are becoming more widely used. These high-energy forms of electromagnetic radiation are present in nuclear energy, astrophysics, and the medical field. As more and more people have the opportunity to be exposed to ionizing radiation, the necessity for coming up with simple and quick methods of radiation detection is increasing. In this work, two systems were explored for their ability to simply detect ionizing radiation. Gold nanoparticles were formed via radiolysis of water in the presence of Elastin-like polypeptides (ELPs) and also in the presence of cationic polymers. Gold nanoparticle formation is an indicator of the presence of radiation. The system with ELP was split into two subsystems: those samples including isopropyl alcohol (IPA) and acetone, and those without IPA and acetone. The samples were exposed to certain radiation doses and gold nanoparticles were formed. Gold nanoparticle formation was deemed to have occurred when the sample changed color from light yellow to a red or purple color. Nanoparticle formation was also checked by absorbance measurements. In the cationic polymer system, gold nanoparticles were also formed after exposing the experimental system to certain radiation doses. Unique to the polymer system was the ability of some of the cationic polymers to form gold nanoparticles without the samples being irradiated. Future work to be done on this project is further characterization of the gold nanoparticles formed by both systems.