Yes / Background: Skeletal muscles undergo changes with ageing which can cause sarcopenia that can result in frailty. Quantitative MRI may detect the muscle-deficit component of frailty which could help improve the understanding of ageing muscles. Aims: To investigate whether quantitative MRI measures of T2, fat fraction (FF), diffusion tensor imaging and muscle volume can detect differences within the muscles between three age groups, and to assess how these measures compare with frailty index, gait speed and muscle power. Methods: 18 ‘young’ (18–30 years), 18 ‘middle-aged’ (31–68 years) and 18 ‘older’ (> 69 years) healthy participants were recruited. Participants had an MRI of their dominant thigh. Knee extension and flexion power and handgrip strength were measured. Frailty (English Longitudinal Study of Ageing frailty index) and gait speed were measured in the older participants. Results: Young participants had a lower muscle MRI T2, FF and mean diffusivity than middle-aged and older participants; middle-aged participants had lower values than older participants. Young participants had greater muscle flexion and extension power, muscle volume and stronger hand grip than middle-aged and older participants; middle-aged participants had greater values than the older participants. Quantitative MRI measurements correlated with frailty index, gait speed, grip strength and muscle power. Discussion: Quantitative MRI and strength measurements can detect muscle differences due to ageing. Older participants had raised T2, FF and mean diffusivity and lower muscle volume, grip strength and muscle power. Conclusions: Quantitative MRI measurements correlate with frailty and muscle function and could be used for identifying differences across age groups within muscle. / JDB is funded by a National Institute for Health Research (NIHR) (and Health Education England) Clinical Lectureship. This paper presents independent research funded/supported by the National Institute for Health Research (NIHR) Leeds Biomedical Research Centre (BRC). AC and LB are funded as part of the NIHR Collaboration for Leadership in Applied Health Research and Care, Yorkshire and Humber (NIHR CLAHRC YH).

Técnicas de aquisição paralelas e hardware dedicados vem sendo desenvolvidos desde a década de 1980 para reduzir o tempo de aquisição de imagens via ressonância magnética (IRM). Uma bobina do tipo phased array é um dispositivo do tipo receptor, que usa múltiplas bobinas (canais) cada qual com seu próprio circuito de detecção para adquirir simultaneamente os sinais que formam uma imagem ou espectro via IRM. Exemplos de técnica de imagem paralela que usa bobinas tipo phased array são Sensitivy Enconding (SENSE) e GeneRalized Autocalibrating Partial Parallel Acquisition (GRAPPA). Sampled array é o nome de um método proposto neste trabalho em que cada canal de uma bobina multicanal é responsável por adquirir de forma independente o sinal da sua amostra de modo que cada sinal de amostra é endereçado ao seu canal específico. Neste trabalho, descrevemos o desenvolvimento de uma bobina phased array de quatro canais para anatomia de cabeça de rato usando circuito impresso flexível para operar em um sistema de IRM pré-clínico de 2T com objetivo de validar o método de construção e uso de circuito flexível como bobina de recepção. Também desenvolvemos uma bobina de quatro canais para realizar simultaneamente a imagem de quatro sementes na mesma varredura para validar o método Sampled Array com objetivo de melhorar a qualidade da imagem e simultaneamente acelerar experimentos de múltiplas amostras. Os resultados mostram que a bobina de circuito impresso phased array, em comparação com uma bobina de enrolamento de fio regular, forneceu uma boa relação sinal / ruído (RSR) e possui geometria mais adequada à anatomia por ser flexível. Além disso, o processo de fabricação da bobina seja facilitado desde que toda a bobina é construída como um protótipo de circuito impresso. Os bons resultados da bobina sampled array mostraram o método como promissor para imageamento de múltiplas amostras com aumento de RSR e diminuição de tempo de experimentos em relação ao uso de bobinas de canal único. / Parallel techniques and dedicated hardware has been developed since the 1980s to reduce acquisition time on Magnetic Resonance Imaging (MRI) scanners. A phased array is a receiver only mode device concept, which uses multiple channels (coils) with their own detection circuits to simultaneously acquire MRI or localized spectroscopic signals. An example of parallel imaging technique that uses phased array coils is Sensitivy Enconding (SENSE). Sampled array is the name proposed in this work for a method in which each channel of a multichannel coil is responsible to acquire independently the signal from its sample so that each sample signal is addressed to its specific channel. In this work, we describe the development of a four-channel phased array coil for rat head anatomy using flexible printed circuit board (PCB), to operate on a 2T pre-clinical MRI scanner to validate the construction method and usage of flexible PCB as a receiver coil. We also developed a four-channel sample array coil to simultaneously perform the imaging of four seeds at the same scan, to validate the proposed method to improve image quality at the same time accelerating multiple seed imaging for agriculture studies. The results show that phased array PCB coil as compared to a regular wire winding coil provide good signal-to-noise ratio (SNR) imaging with more adequate geometry to the anatomy by being flexible. In addition, the coil manufacturing process is facilitated since the entire coil is constructed as a PCB prototype. The sample array imaging showed as a promising method for multiple sample increasing SNR and time to do experiments.

The brain ages, and with it come alterations in its micro- and macro-structure which reflect in its morphology and functioning. Changes in the brain structure and functional coupling between regions can be assessed with neuroimaging, and, more specifically, magnetic resonance imaging (MRI). Using MRI data from two stages (Pilot and Enhanced) of the Nathan Kline Institute Rockland Sample (NKI-RS), totalling 613, free of neurodegenerative diseases, and right-handed, participants aged 18 to 85 years old, we measured gray-matter parameters such as cortical volume, cortical thickness, and cortical surface area, and also volume of subcortical structures. We also measured cortico-cortical functional connectivity, defined either as the Pearson correlation coefficient and partial correlation coefficient, bivariate instantaneous Granger causality and Granger causality, and generalized partial directed coherence (GPDC). GPDC was evaluated in five frequencies between the four pairs of regions displaying the strongest evidence for linear thinning, measured by their associated t-statistic, and its alterations alongside aging were assessed using a multivariate approach based on Dirichlet Regression. We also studied spatial associations between patterns of morphometric and connectivity alterations. We reproduced generalized age-related atrophy reported in the literature in cortical volume (90% of the studied structures), surface area (68%) and thickness (90%), and volumetric atrophy of several subocortical structures. We observe a positive association in the joint distribution of the expected cortical thickness at 18 years old and the yearly percentage reduction in cortical thickness. We showed, projecting these two quantitities into their principal axes and analyzing the spatial distribution of the scores, that the first principal component correlates with neocortical granularity while the second principal component represents cortical type admixture. On functional connectivity, we gathered evidence for overall increased Pearson correlation coefficient (6% of the connections in the Pilot NKI-RS and 2% in the Enhanced NKI-RS), with proportionally smaller number of decreases (0.1% in the Pilot NKI-RS and 0.3% in the Enhanced NKI-RS). The Pearson partial correlation coefficient between 12 out of 65 homotopic region pairs shows a pattern of decline with age, suggesting inter-hemispheric disconnection. However, predictive causality, as measured by both Granger causalities, do not share the same degree of changes observed in the correlational metrics. We observe increased GPDC from several regions to themselves in many frequencies (25% out of a total of 40 self-connections), indicating a degree of disconnection to the other regions. Given seed regions, we uncovered spatially distributed significant patterns of association between the standardized effect of age on the connectivity to its targets and on their targets thicknesses. Regions with smaller evidence for age-related thinning, such as several occipital areas, tend to have fewer alterations in functional connectivity than regions with greater evidence for age-related thinning, like many frontal regions. We hypothesize that regions showing a negative association (5% of the seed regions) are part of compensatory systems, being increasingly correlated with regions displaying most atrophy. Regions showing a positive association (5%) do not have compensatory mechanisms available, and therefore are losing connectivity to atrophyc regions. Overall, we found evidence for brainwide alterations in connectivity and cortical and subcortical morphometry throughout the human adult lifespan. We also found a specifc pattern of associations between the atrophic trends and age-related alterations in connectivity in the brain / O cérebro envelhece, e com isso vêm à tona alterações em sua micro e macroestrutura que se refletem em sua morfologia e funcionamento. Mudanças na estrutura cerebral e acoplamento funcional entre suas regiões podem ser averiguadas através da neuroimagem, e, mais especificamente, imagem por ressonância magnética (IRM). Usando dados de IRM das duas etapas (Pilot and Enhanced) do Nathan Kline Institute Rockland Sample (NKI-RS), totalizando 613 participantes destros, livres de doenças neurodegenerativas, com idade entre 18 e 85 anos, medimos parâmetros de substância cinzenta como volume, espessura, e área de superfície corticais, e também volume de estruturas subcorticais. Também medimos conectividade funcional cortico-cortical, definida como o coeficiente de correlação de Pearson, coeficiente de correlação parcial de Pearson, causalidade instântanea de Granger e causalidade de Granger bivariadas, e coerência parcial direcionada generalizada (GPDC). A GPDC foi medida em cinco frequências entre quatro pares de regiões que demonstraram a mais forte evidência para diminuição da espessura cortical linearmente, medido pela estatística-t associada, e suas alterações ao longo do envelhecimento foram estudadas usando uma abordagem multivariada baseada na Regressão de Dirichlet. Também estudamos associações espaciais entre padrões de alterações morfométricas e na conectividade. Reproduzimos a atrofia generalizada devido à idade reportada na literatura no volume cortical (90% das estruturas estudadas), área de superfície (68%) e espessura (90%), e atrofia volumétrica de várias estruturas subcorticais. Observamos uma associação positiva na distribuição conjunta do valor esperado da espessura cortical aos 18 anos de idade e a redução percentual anual na espessura cortical. Mostramos, ao projetar ambos em seus eixos principais e analizar a distribuição espacial desses índices, que a primeira componente principal correlaciona-se com a granularidade neocortical enquanto que a segunda componente principal representa o tipo cortical. Sobre a conectividade funcional, colhemos evidências para um aumento geral no coeficiente de correlação de Pearson (6% das conexões no Pilot NKI-RS e 2% no Enhanced NKI-RS), com menor proporção de decréscimos (0.1% no Pilot NKI-RS e 0.3% no Enhanced NKI-RS). O coeficiente de correlação parcial de Pearson entre 12 de 65 pares de regiões homotópicas demonstra um padrão de declínio com a idade, sugerindo desconexão inter-hemisférica. No entanto, a causalidade preditiva, como medida através de ambas as métricas de causalidade de Granger, não aparenta o mesmo grau de mudanças observado nas medidas correlacionais. Observamos aumentos na GPDC de várias regiões para si próprias em muitas frequências (25% de um total de 40 auto-conexões), que indica um grau de disconexão às outras regiões. Dadas regiões semente, revelamos padrões significativos espacialmente distribuídos de associação entre efeitos padronizados da idade na conectividade para seus alvos e das espessuras dos alvos. Regiões com menor evidência para o desbastamento relacionado com a idade, como várias áreas occipitais, tendem a ter menos alterações em sua conectividade funcional que regiões com maior evidência suportando o desbastamento cortical relacionado à idade, como diversas regiões frontais. Hipotetizamos que regiões cuja associação é negativa (5% das regiões semente) são parte de sistemas compensatórios, estando correlacionadas com regiões que demonstram os maiores graus de atrofia de modo crescente. Regiões cuja associação é positiva (5%) não teriam mecanismos compensatórios à disposição, e portanto perdem conectividade para regiões atróficas. No geral, encontramos evidências para alterações na conectividade e na morfometria cortical e subcortical no cérebro todo ao longo da extensão da vida adulta humana. Também achamos um padrão específico de associações entre tendências atróficas e alterações na conectividade cerebral devido à idade

"This thesis presents the development of a magnetic resonance imaging (MRI) compatible pneumatic actuation test system regulated by piezoelectric valve for image guided robotic intervention. After comparing pneumatic, hydraulic and piezoelectric MRI-compatible actuation technologies, I present a piezoelectric valve regulated pneumatic actuation system consisted of PC, custom servo board driver, piezoelectric valves, sensors and pneumatic cylinder. This system was proposed to investigate the control schemes of a modular actuator, which provides fully MRI-compatible actuation; the initial goal is to control our MRI-compatible prostate biopsy robot, but the controller and system architecture are suited to a wide range of image guided surgical application. I present the mathematical modeling of the pressure regulating valve with time delay and the pneumatic cylinder. Three different sliding mode control (SMC) schemes are proposed to compare the system performance. Simulation results are presented to validate the control algorithm. Practical tests with parameters determined from simulation show that the system performance attained the goal. A novel MRI- compatible locking device for the pneumatic actuator was developed to provide safe lock function as the pneumatic actuator fully stopped."

O uso de agentes de contraste em técnicas de diagnóstico por imagem é uma prática médi-ca rotineira. Certos compostos, presentes em agentes de contraste, possuem propriedades paramagnéticas que podem afetar os sinais da tomografia por ressonância magnética, \"Mag-netic Resonance Imaging\"(MRI). Em estudos aplicados ao trato gastrintestinal (GI), os meios de contraste são amplamente utilizados por via endovenosa, mas também podem ser admi-nistrados oralmente. Porém, a adoção do uso oral é limitada, principalmente, porque os agentes convencionais são caros e causam, geralmente, efeitos colaterais. Desta forma, a-presentamos a caracterização e os resultados preliminares da implementação da polpa do fruto da Euterpe olerácea para um possível uso clínico como agente de contraste oral em MRI do trato GI. A polpa da Euterpe olerácea, conhecida como Açaí, de origem amazônica, apre-senta um aumento de sinal de MRI ponderado em T1 equivalente ao do Gd-DTPA e, tam-bém, um decréscimo de sinal em imagens ponderadas em T2. Investigamos propriedades intrínsecas que possam estar correlacionadas com o aumento de sinal em T1 e à opacidade em T2. O espectro de absorção atômica revelou a presença de íons Fe, Mn e Cu no Açaí, o que contribui para o valor susceptométrico encontrado de -4,83 . 10-6. Essa medida fomen-ta a hipótese de que as mudanças de contraste nas imagens são devido à presença de mate-rial paramagnético, revelando um contraste clinicamente satisfatório nas porções superiores do trato GI. Estudos preliminares indicaram que a homogeneidade e a intensidade do sinal da polpa do Açaí (Euterpe olerácea), no estômago, e duodeno, são próximos daquele encon-trado em agentes convencionais. Além disso, ele não apresentou efeito colateral algum. Devido ao aumento de contraste associado ao Açaí, podemos observar a parede gástrica de forma singular. Ainda, este agente contribuiu para o diagnóstico das vias pancreática e biliar em exames de colangiopancreatografia por ressonância magnética, Magnetic Resonance Colan-giopancreatography (MRCP), com seqüências ponderadas em T2, por reduzir o sinal das alças intestinais. / The use of contrast agents is a common practice in medical imaging protocols. Paramagnetic properties of certain compounds present in contrast agents can affect Magnetic Resonance Imaging (MRI) signals. For abdominal applications, they are usually injected, but may also be administered orally. However, their use as a routine technique is limited, mainly due to the lack of appropriate oral contrast agent. Standard agents are expensive and cause, generally, some kind of side effect. We herein present the preliminary characterization and results for implementation of Euterpe olerácea (popularly named Açaí) as a possible clinical oral contrast agent for MRI of the gastrointestinal (GI) tract. The pulp of Açaí, a fruit from the Amazon area, presented an increase in T1-weighted MRI signal, equivalent to that of Gd-DTPA, and a signal decrease in T2-weighted images. We looked for intrinsic properties that could be responsible for the T1 signal enhancement and T2 opacification. Atomic Absorption spectra revealed the presence of Fe, Mn and Cu ions in Açai. The presence of such ions contribute to the susceptometric value found of -4.83 x 10-6 . This finding assents with the hypothesis that image contrast changes were due to the presence of paramagnetic material. The first measurements in vivo demonstrate a clear increase of contrast due to signal intensity and homogeneity in stomach and bowel walls with the pulp of Açaí, which look like the effects related to standard agents. Consistently, the increase in T1-weighted and the opacification in a T2-weighted acquisition was evident, revealing a biphasic contrast on gastric tissues. Besides, the pulp does not present any side effect. It still has contributed to the diagnostic of pancreatobiliary system at Magnetic Resonance Cholangiopancreatography (MRCP), by reducing overlap of the surround tissues and those structures.

Osteoarthritis (OA) is one of the leading causes of disability world-wide. It affects 12% of all Americans ages 25-74 [1]. One of the challenges with OA, is that there are currently no clinically viable methods to measure the health of the cartilage before cartilage loss. There are no ways to replace or heal the cartilage after it has been lost. It is known that the early stages of OA involve a decrease in the amount of glycosaminoglycans (GAG), one of the main molecules in cartilage. This decrease in GAG leads to a change in the fixed charge density of the cartilage and a higher water content with higher diffusivity. The development of techniques to measure the PG content in the cartilage could lead to early diagnosis and the development of effective preventative treatments.One of the suggested methods for measuring the PG content is through quantitative magnetic resonance imaging (MRI). MRI is a non-invasive medical imaging technique known for it's ability to image soft tissue. MRI measures the reaction of the nuclear spin in a magnetic field to a radio frequency (RF) pulse. These spins, and the signal they produce, are sensitive to magnetic fields. This makes it possible to measure small changes in anatomical structure, like a decrease in PG content, because the magnetic spins are sensitive to the local magnetic environment. There are several MRI techniques that are able to measure the PG content in the cartilage.The behavior of the MR signal can be affected by changes in the molecular environment. This effect can by measured through changes in the MR signal parameters T1r and T2. More complex MRI techniques such as chemical exchange saturation transfer (CEST) can be used to directly measure the amount of GAG by taking advantage of the transfer of proton magnetization between the GAG molecules and the surrounding fluids. There are even MRI techniques such as balanced steady state free precession (bSSFP) which makes it possible to measure high resolution morphological images, making it easier to interpret the quantitative scans.This thesis will describe methods employed to improve MRI imaging of cartilage. One method is the developing and testing a new technique for creating maps of the local magnetic field. These field maps can help scans that are particularly sensitive to non-homogeneities in the field. Another method is improving the parameter estimation algorithms which make it easier to more accurately predict values of signal parameters like T1r and T2. This thesis will also describe ongoing efforts to create, and optimize a clinically viable whole-joint cartilage imaging protocol that can be used for early OA detection and diagnosis.

This dissertation presents results of a medical image analysis project leading towards development of a comprehensive set of methods and tools for computational image analysis of dynamic contrast-enhanced (DCE) breast magnetic resonance image (MRI), with the aim to aid the physician in interpreting DCE breast MRI examinations. Toward this goal, we developed image analysis methods that would be needed in a breast MRI computer aided diagnosis (CADx) system. A novel contribution of this dissertation is the performance evaluation for each of the major algorithm components developed in this dissertation project. This dissertation begins with reviewing breast imaging techniques, including routinely used modalities in current clinical practice and emerging techniques still in development. We discuss at length the principles of DCE breast MRI, a very sensitive breast imaging modality that has been increasingly used in clinical practice. Then we review the diagnostic guidelines for interpreting DCE breast MRI, and explain the needs and challenges that arise in developing computational image analysis system for breast MRI applications. In this dissertation project, both the morphological and kinetic features of the lesion are automatically extracted for diagnostic purpose. In order to extract morphological features from the segmented lesions, the lesion needs to be accurately segmented out from its surrounding tissues. We utilized a probabilistic method to obtain an optimal segmentation map based on several algorithmic segmentation outputs. In evaluating the performance of segmentation algorithms, we compared the algorithmic segmentation results against manually segmented lesions, and further assessed the segmentation impact on subsequent classification stage. In order to extract accurate kinetic information, the motion needs to be compensated across image volumes acquired sequentially. In this dissertation, we comparatively assessed the similarity metric in registering DCE breast MR images. The performance of cross correlation(CC) coefficient, and mutual information (MI) were studied in both rigid and non-rigid registration schemes. Numerical results and statistical properties were reported. The resultant image quality after registration is discussed both qualitatively and quantitatively. In this dissertation we implemented a classification system based upon quantitative morphological and kinetic features in improving the specificity of breast MRI. Morphological and kinetic features of the lesion were extracted automatically, and then the feature selection step was utilized to select the most relevant features to maximize the classifier performance. In our study, the area under the receiver operating curve (AUC) is used as the performance metric of the classifier, and our results are competitive with those of previous studies. The dissertation concludes by summarizing the contribution of this project and suggesting the future directions of quantitative and highly automated approaches to breast MR image analysis. / text

Introduction Two current major research topics in nuclear medicine are in the development of long-lived positron-emitting nuclides for imaging tracers with long biological half-lives and in theranostics, imaging nuclides which have a chemically analogous therapy isotope. As shown in TABLE 1, the radioisotopes of arsenic (As) are well suited for both of these tasks with several imaging and therapy isotopes of a variety of biologically relevant half-lives accessible through the use of small medical cyclotrons. The five naturally abundant isotopes of germanium are both a boon and challenge for the medical nuclear chemist. They are beneficial in that they facilitate a wide array of producible radioarsenic isotopes. They are a challenge as monoisotopic radioarsenic production requires isotopically-enriched targets that are expensive and of limited availability. This makes it highly desirable that the germanium target material is reclaimed from arsenic isolation chemistry. One major factor which has limited the development of radioarsenic has been difficulties in its incorporation into biologically relevant targeting vectors. Previous studies have labeled antibodies and polymers through covalent bonding of arsenite (As(III)) with the sulfydryl group1,2,3. Recent work in our group has shown the facile synthesis and utility of superparamagnetic iron oxide nanoparticle- (SPION-)bound radioarsenic as a dual modality positron emission tomography (PET)/magnetic resonance imaging (MRI) agent4. Presently, we have built upon previous studies producing, isolating, and labeling untargeted SPION with radioarsenic4,5. We have incorp-rated the use of isotopically-enriched 72GeO2 for the production of radioisotopically pure 72As. The bulk of the 72GeO2 target material was re-claimed from the arsenic isolation chemical procedure for reuse in future irradiations. The 72As was used for ongoing development toward the synthesis of targeted, As-SPION-based, dual-modality PET/MRI agents. Material and Methods Targets of ~100 mg of isotopically-enriched 72GeO2 (96.6% 72Ge, 2.86% 73Ge, 0.35% 70Ge, 0.2% 74Ge, 0.01% 76Ge, Isoflex USA) were pressed into a niobium beam stop at 225 MPa, covered with a 25 µm HAVAR containment foil, attached to a water-cooling target port, and irradiated with 3 µA of 16.1 MeV protons for 2–3 hours using a GE PETtrace cyclotron. After irradiation, the target and beam stop were assembled into a PTFE dissolution apparatus, where the 72GeO2 target material was dissolved with the addition of 2 mL of 4 M NaOH and subsequent stirring. After dissolution was completed, the clear, colorless solution was transferred to a fritted glass column and the bulk 72GeO2 was reprecipitated by neutralizing the solution with the addition of 630 µL [HCl]conc, filtered, and rinsed with 1 mL [HCl]conc. To the combined 72As-containing filtrates, 100 µL 30% H2O2 was added to ensure that 72As was in the nonvolatile As(V) oxidation state. The ~3 mL solution was then evaporated at 115 ˚C while the vessel was purged with argon, followed by a second addition of 100 µL H2O2 after the volume was reduced to 1 mL. When the filtrate volume was ~0.3 mL, the vessel was removed from heat, allowed to cool with argon flow, and the arsenic reconstituted in 1 mL [HCl]conc and loaded onto a 1.5 mL bed volume Bio-Rad AG 1×8, 200–400 mesh anion exchange column preconditioned with 10 M HCl. The radioarsenic was eluted in 10 M HCl in the next ~10 mL, with 90% of the activity eluting in a 4 mL fraction. The column was then eluted with 5 mL 1 M HCl. The 72As-rich 10 M HCl fraction was reduced to As(III) with the addition of ~100 mg CuCl, and heating to 60 ˚C for 1 hour. The resulting AsCl3 was then extracted twice into 4 mL cyclohexane, which were combined and back extracted into 500 µL of water as As(OH)3. This solution of 72As in H2O was then used directly to label SPION and for subsequent experiments conjugating 72As-SPION with TRC105, an angiogenesis-marking monoclonal antibody (MAb) targeting endoglin/CD105. Several methods were initially attempted involving directly conjugating the surface-modified SPION to the MAb through a polyethylene glycol (PEG) linker. More recent studies have investigated the radioarsenic labeling of SPION encapsulated in hollow mesoporous silica nanoparticles (SPION@HMSN) and its subsequent conjugation to TRC105. Results and Conclusion Irradiation of pressed, isotopically-enriched 72GeO2 resulted in a production yield for 72As of 17 ± 2 mCi/(µA·hr·g) and for 71As of 0.37 ± 0.04 mCi/(µA·hr·g), which are 64 % and 33 %, of those predicted from literature6, respectively. However, these production yields are in agreement with those scaled from observed production yields using analagous natGeO2 targets. The end-of-bombardment 72As radionuclidic purity can be improved by minimizing the 72Ge(p,2n)71As reaction by degrading the beam energy. A 125 µm Nb containment foil would degrade impinging protons to 14.1 MeV and is predicted to reduce 71As yield by a factor of three, while only reducing 72As yield by 1 %6, improving end-of-bombardment radionuclidic purity from 98 % to greater than 99 %. Overall decay-corrected radiochemical yield of the 72As isolation procedure from 72GeO2 were 51 ± 2 % (n = 3) in agreement with those observed with natGeO2 57 ± 7 % (n = 14). The beam current was limited to 3 µA as higher cur-rents 4–5 µA exhibited inconsistent dissolution and reprecipitation steps, resulting in an overall yield of 44 ± 21 % (n = 6). Dissolution time also played an important role in overall yield with at least one hour necessary to minimize losses in these first two steps. The separation procedure effectively removed all radiochemical contaminants and resulted in 72As(OH)3 isolated in a small volume, pH~4.5 water solution. Over the course of minutes to hours after back extraction, rapid auto-oxidation to 72AsO4H3 was observed. The bulk 72GeO2 target material, which was reclaimed from the isolation procedure, is being collected for future use. The synthesis of a targeted PET/MRI agent based on the functionalization of 72As-SPION has proved to be a difficult task. Experiments conjugating 72As-SPION to TRC105 through a PEG linker were unsuccessful, despite the investigation of a variety bioconjugation procedures. Current work is investigating the use of SPION@HMSN, which have a similar affinity for 72As as unencapsulated SPION. This new class of 72As-labeled SPION@HMSN has a hollow cavity for potential anti-cancer drug loading, as well as the mesoporous silica surface, which may facilitate the efficient conjugation of TRC105 using a well-developed bioconjugation technique. In summary, radioarsenic holds potential in the field of diagnostic and therapeutic nuclear medicine. However, this potential remains locked behind challenges related to its production and useful in vivo targeting. The present work strives to address several of these challenges through the use of enriched 72GeO2 target material, a chemical isolation procedure that reclaims the bulk of the target material, and the investigation of new targeted nanoparticle-based PET/MRI agents.

Magnetic resonance imaging (MRI) is an imaging technique to visualize internal structures of the body. Diffusion MRI is an MRI modality that measures overall diffusion effect of molecules in vivo and non-invasively. Diffusion tensor imaging (DTI) is an extended technique of diffusion MRI. The major application of DTI is to measure the location, orientation and anisotropy of fiber tracts in white matter. It enables non-invasive investigation of major neural pathways of human brain, namely tractography. As spatial resolution of MRI is limited, it is possible that there are multiple fiber bundles within the same voxel. However, diffusion tensor model is only capable of resolving a single direction. The goal of this dissertation is to investigate complex anatomical structures using high angular resolution diffusion imaging (HARDI) data without any assumption on the parameters. The dissertation starts with a study of the noise distribution of truncated MRI data. The noise is often not an issue in diffusion tensor model. However, in HARDI studies, with many more gradient directions being scanned, the number of repetitions of each gradient direction is often small to restrict total acquisition time, making signal-to-noise ratio (SNR) lower. Fitting complex diffusion models to data with reduced SNR is a major interest of this study. We focus on fitting diffusion models to data using maximum likelihood estimation (MLE) method, in which the noise distribution is used to maximize the likelihood. In addition to the parameters being estimated, we use likelihood values for model selection when multiple models are fit to the same data. The advantage of carrying out model selection after fitting the models is that both the quality of data and the quality of fitting results are taken into account. When it comes to tractography, we extend streamline method by using covariance of the estimated parameters to generate probabilistic tracts according to the uncertainty of local tract orientations.

Diffusion MRI (dMRI) measurements allow us to infer the microstructural properties of white matter and to reconstruct fiber pathways in-vivo. High angular diffusion imaging (HARDI) allows for the creation of more and more complex local models connecting the microstructure to the measured signal. One of the challenges is the derivation of meaningful metrics describing the underlying structure from the local models. The aim hereby is to increase the specificity of the widely used metric fractional anisotropy (FA) by using the additional information contained within the HARDI data. A local model which is connected directly to the underlying microstructure through the model of a single fiber population is spherical deconvolution. It produces a fiber orientation density function (fODF), which can often be interpreted as superposition of multiple peaks, each associated to one relatively coherent fiber population (bundle). Parameterizing these peaks one is able to disentangle and characterize these bundles. In this work, the fODF peaks are approximated by Bingham distributions, capturing first and second order statistics of the fiber orientations, from which metrics for the parametric quantification of fiber bundles are derived. Meaningful relationships between these measures and the underlying microstructural properties are proposed. The focus lies on metrics derived directly from properties of the Bingham distribution, such as peak length, peak direction, peak spread, integral over the peak, as well as a metric derived from the comparison of the largest peaks, which probes the complexity of the underlying microstructure. These metrics are compared to the conventionally used fractional anisotropy (FA) and it is shown how they may help to increase the specificity of the characterization of microstructural properties. Visualization of the micro-structural arrangement is another application of dMRI. This is done by using tractography to propagate the fiber layout, extracted from the local model, in each voxel. In practice most tractography algorithms use little of the additional information gained from HARDI based local models aside from the reconstructed fiber bundle directions. In this work an approach to tractography based on the Bingham parameterization of the fODF is introduced. For each of the fiber populations present in a voxel the diffusion signal and tensor are computed. Then tensor deflection tractography is performed. This allows incorporating the complete bundle information, performing local interpolation as well as using multiple directions per voxel for generating tracts. Another aspect of this work is the investigation of the spherical harmonic representation which is used most commonly for the fODF by means of the parameters derived from the Bingham distribution fit. Here a strong connection between the approximation errors in the spherical representation of the Dirac delta function and the distribution of crossing angles recovered from the fODF was discovered. The final aspect of this work is the application of the metrics derived from the Bingham fit to a number of fetal datasets for quantifying the brain’s development. This is done by introducing the Gini-coefficient as a metric describing the brain’s age.