Magnetic resonance imaging nowadays supplies a noninvasive method in clinical applications. For tetralogy of Fallot (TOF) patients, after undergoing clinical operation, their cardiac anatomy still cannot supply sufficient blood flow in the pulmonary arteries with respect to the normal. In this study, we use phase contrast MR imaging to evaluate of regurgitation and turbulence of flow in pulmonary arteries after repair of TOF. We use parameters such as coefficient of variance (CV), regurgitant fraction (RF), and normalized area variation (NAV) to analyze the difference between repaired patients and normal controls. Our result also shows that CV and regurgitant fraction have loose relation. This study may provide more information to help doctors in clinical diagnosis. In the meanwhile, another three parameters were used to evaluate patients and normal persons. We use windkessel volume to see the difference of flow volume between inlet and outlet in the pulmonary arteries. We use pulse wave velocity (PWV) to discuss the propagating velocity of pressure wave on the vascular wall. We use pulmonary vascular resistance (PVR) to analyze the resistance of blood wall. PWV and PVR may lose information by means of insufficient points in a cardiac cycle, but the result may still be a kind of reference.

QC 20100531

<p>Emotion is known to influence multiple aspects of memory formation, which may include the initial encoding of the memory trace, its consolidation over time, and the efficacy of its retrieval. However, prior investigations have tended to treat emotional modulation of episodic memory as a unitary construct, thus conflating the contributions of these different stages to emotion-mediated memory enhancements. The present thesis aims to disentangle the component processes of emotional memory formation and retrieval through a series of studies using cognitive behavioral and functional magnetic resonance imaging (fMRI) methods. In the first 2 studies, neural activity was evaluated during the initial viewing of emotionally arousing and neutral scenes and, in the 3rd study, neural activity during this initial viewing period was compared to that during a recognition memory task. The findings are compatible with the proposal that two distinct networks support successful emotional memory formation: an amygdala-medial temporal lobe (MTL) network that modulates the consolidation of memories over time and a prefrontal-MTL network that translates emotion effects on controlled elaboration into superior memory encoding. The superlative quality of emotional memories is furthermore marked by heightened similarity between neural states at encoding and retrieval, suggesting another line of evidence through which emotion effects can be observed. Taken together, the results presented here highlight the heterogeneity of processes that confer mnemonic advantages to emotionally significant information.</p> / Dissertation

Myocardial infarction (MI) causes high morbidity and mortality worldwide and for effective prevention and treatment MIs have to be adequately detected. The existence of clinically unrecognized MIs (UMIs) has been known for the past hundred years, but an ultimate tool for their detection has not yet been found. Using persistent Q waves on electrocardiography as a sign of MI, it has been estimated that UMIs constitute at least ¼ of all MIs and have mortality rates similar to those of recognized MIs (RMIs). These estimates are misleading, however, since persistent Q waves do not necessarily represent MIs. The late enhancement technique in magnetic resonance imaging (LE MRI) has been developed over the past decade and accurately determines myocardial viability. The aim of this research was to investigate the prevalence and impact of UMI and RMI in a population-based sample of 70-year-olds, assessed with MRI. Cardiac function and viability were examined with MRI in 259 randomly selected 70-year-old subjects (127 women, 132 men) participating in a larger population-based study (PIVUS). Information on other parameters of cardiovascular disease was obtained and related to the findings. Three methods for segmentation of the left ventricular mass were used in the first 100 subjects; these differed in accuracy and led to differences in systolic function values. In the subsequent 159 examinations one of the segmentation methods was used. The viability images were assessable in 248 subjects (123 women, 125 men). Among these, the prevalence of UMI, 19.8%, definitely exceeded the expectations and UMIs constituted 4/5 of all MIs. The prevalence of RMI was 4.4%. MRI-detected UMIs differed from RMIs in several respects; they were smaller, frequently located inferolaterally, did not appear to be associated with atherosclerosis, and displayed increased collagen turnover. The pathogenesis of these UMIs remains to be investigated, but our observations suggest that they are caused by ischemia. Subjects with UMI showed increased cardiac morbidity, a decreased ejection fraction and an increased left ventricular mass, indicating an increased cardiovascular risk. It is thus important to detect these UMIs, and this is adequately achieved by LE MRI. However, to decide upon prevention and treatment of these UMIs we need to know more about their pathogenesis and prognosis.

Applied cancer research is heavily focused on the development of diagnostic tools with high sensitivity and specificity that are able to accurately detect the presence and anatomical location of neoplastic cells, as well as therapeutic strategies that are effective at curing or controlling the disease while being minimally invasive and having negligible side effects. Recently, much effort has been placed on the development of nanoparticles as diagnostic imaging and therapeutic agents, and several of these nanoplatforms have been successfully adopted in both the research and clinical arenas. This thesis describes the development of a nanoparticulate liposome system for use in a number of applications including multimodality imaging with computed tomography (CT) and magnetic resonance (MR), longitudinal vascular imaging, image-based biodistribution assessment, and CT detection of neoplastic and inflammatory lesions. Extensive in vitro and in vivo characterization was performed to determine the physico-chemical properties of the liposome agent, including its size, morphology, stability and agent loading, as well as its pharmacokinetics, biodistribution, tumor targeting and imaging performance. Emphasis was placed on the in vivo CT-based quantification of liposome accumulation and clearance from healthy and tumor tissues in a VX2 carcinoma rabbit model, gaining insight not only on the spatial but also the temporal biodistribution of the agent. The thesis concludes with a report that describes the performance of liposomes and CT imaging to detect and localize tumor and inflammatory lesions as compared to that of 18F-fluorodeoxyglucose (FDG) – positron emission tomography (PET). The outcome of the study suggests that liposome-CT could be employed as a competitive method for whole body image-based disease detection and localization. Overall, this work demonstrated that this liposome agent along with quantitative imaging systems and analysis tools, has the potential to positively impact cancer treatment outcome through improved diagnosis and staging, as well as enable personalization of treatment delivery via target delineation. However, in order to prove clinical benefit, steps must be taken to advance this agent through the regulatory stages and obtain approval for its use in humans. Ultimately, the clinical adoption of this multifunctional agent may offer improvements for disease detection, spatial delineation and therapy guidance.

Magnetic resonance imaging (MRI) is an imaging modality that noninvasively measures magnetic fields by selectively exciting the magnetization of protons inside the body. When combined with an understanding of electromagnetic theory, MRI can be used in a novel way to provide a powerful tool for measuring the electromagnetic fields and electrical properties of biological tissues. This thesis presents the analytical, numerical, processing and experimental components of a successful implementation of Low-Frequency Current Density Impedance Imaging (LF-CDII), an impedance imaging method based on MRI measurements. The accuracy, stability and noise tolerance of this technique are examined. The first in-vivo LF-CDII experiment was conducted with a clinical MRI scanner, and the conductivity distribution of the heart of a live piglet was obtained. Both the simulation and experimental results show that LF-CDII can be used as a reliable tool for accurate noninvasive, quantitative imaging of tissue conductivities. This thesis also presents new data processing algorithms, imaging procedures and hardware development for the measurement of electromagnetic fields at radio frequencies, based on Polar Decomposition Radio Frequency Current Density Imaging (PD-RFCDI). The method was tested on both numerical models and experiments on phantoms. The results show that the techniques presented here are able to successfully image current density fields without the strict restrictions on the direction and magnitude of the currents required in previous versions of RFCDI.

This thesis presented a microfluidic preparation of bubbles-templated micro-size materials. In particular, this thesis focused on the microfluidic formation and dissolution of CO2 bubbles. First, this thesis described pH-regulated behaviours of CO2 bubbles in the microfluidic channel. This method opened a new way to generate small (<10 µm in diameter) with a narrow size distribution (CV<5%). Second, the microfluidic dissolution of CO2 bubbles possessed the important feature: the local change of pH on the bubble surface. This allowed us to encapsulate the bubbles with various colloidal particles. The bubbles coated with particles showed a high stability against coalescences and Ostwald ripening. The dimensions and shapes of bubbles with a shell of colloidal particle were manipulated by the hydrodynamic and chemical means, respectively. Third, we proposed a microfluidic method for the generation of small and stable bubbles coated with a lysozyme-alginate shell. The local pH decrease at the periphery of CO2 bubbles led to the electrostatic attraction between lysozyme on the bubble surface and alginate in the continuous phase. This produced the bubbles with a shell of biopolymers, which gave a long-term stability (up to a month, at least) against the dissolution and coalescence. Fourth, we presented a single-step method to functionalize bubbles with a variety of nanoparticles. The bubbles showed the corresponding properties of nanoparticles on their surface. Further, we explored the potential applications of these bubbles as contrast agents in ultrasound and magnetic resonance imaging.

Biological tissues are generally conductive and knowing the current distribution in these tissues is of great importance in many biomedical applications. Radio frequency current density imaging (RF-CDI) is a technology that measures current density distributions at the Larmor frequency utilizing magnetic resonance imaging (MRI). RF-CDI computes the applied current density, J, from the non-invasively measured magnetic field, H, produced by J. The previously implemented RF-CDI techniques could only image a single slice at a time. The previous method for RF current density reconstruction only computed one component of J. Moreover, this reconstruction required an assumption about H, which may be easily violated. These technical constraints have limited the potential biomedical applications of RF-CDI. In this thesis, we address the limitations of RF-CDI mentioned above. First, we implement a multi-slice RF-CDI sequence with a clinical MRI system and characterize its sensitivity to MRI random noise. Second, we present a novel method to fully reconstruct all three components of J without relying on any assumption of H. The central idea of our approach is to rotate the sample by 180 degrees in the horizontal plane to collect adequate MR data from two opposite sample orientations to compute one component of J. Furthermore, this approach can be extended to reconstruct the other two components of J by adding one additional sample orientation in the horizontal plane. This method has been verified by simulations and electrolytic phantom experiments. We have therefore demonstrated for the first time the feasibility of imaging the magnitude and phase of all components of the RF current density vector. The work presented in this thesis is expected to significantly enhance RF-CDI to image biological subjects. The current density vector J or any component of J can be measured over multiple slices without the compromise of motions of organs and tissues caused by gravitational force, thanks to the method of horizontal rotations. In addition, the reconstruction of the complex conductivity of biological tissues becomes possible due to the current advance in RF-CDI presented here.

Zielsetzung: Die diffusionsgewichtete Bildgebung ist wesentlicher Bestandteil der Magnetresonanz-tomographie des Prostatakarzinoms (PCa). Aus entsprechenden Rohdaten, aufgenommen bei verschie-denen b-Werten (Diffusionswichtungsfaktoren), kann der Diffusionskoeffizient (apparent diffusion coefficient - ADC) abgeschätzt werden, der ein sensitiver Indikator für maligne Veränderungen der Gewebearchitektur ist. Die absoluten ADC-Werte sind allerdings stark von der Wahl der zugrundeliegenden b-Werte abhängig und darüber hinaus gibt es Hinweise, dass die Wahl der b-Werte einen signifikanten Einfluss auf die visuelle Analyse, insbesondere auf die Abgrenzbarkeit der Läsion von der Umgebung und auf den Kontrast hat. Es wurde daher untersucht, inwieweit die Wahl der b-Werte den diagnostischen Wert des ADC im Hinblick auf die Detektion und Beurteilung des PCa hat. Methodik: 41 konsekutive Patienten mit gesichertem PCa erhielten eine multiparametrische, endorektale MR-Bildgebung bei 3 Tesla. Die ADC-Karten wurden retrospektiv auf Basis vier verschiedener Kombinationen von b-Werten (0-800 s/mm2) berechnet. Drei Untersucher bestimmten die „führende“ Läsion und beurteilten dann den diagnostischen Wert der jeweiligen ADC-Karten (Visual Score - VS) mit sehr gut (2), befriedigend (1) oder schlecht (0). Für die quantitative Auswertung wurden der mittlere ADC für gesundes und für Tumorgewebe bestimmt. Unterschiede in Abhängigkeit von den gewählten b-Werten wurden mittels statistischer Tests (einseitige ANOVA, Faktor Methode, Signifikanzniveau 5 %) ausgewertet. Ergebnisse: 85 % der Tumoren wurden von den Auswertern richtig erkannt. Die Wahl der b-Werte hatte hochgradig signifikanten (P<0,001) Einfluss auf die absoluten ADC-Werte in gesundem und verändertem Gewebe. ADC-Karten auf Basis von b=[50, 800] und [0, 800] wurden am besten (VS=1,6±0,3) und zweitbesten (VS=1,1±0,3; P<0,001) bewertet. Insbesondere für niedrig-gradige Karzinome (Gleason Score ≤ 6, 13/41 Patienten), wurde nur die Kombination [50, 800] besser als befriedigend (VS=1,4±0,3) bewertet. Der mittlere Tumor-ADC zeigte eine moderate aber signifikant negative Korrelation (Spearman ρ: -0,38 bis -0,46; P<0,05) mit dem Gleason Score. Schlussfolgerung: Absolute ADC-Werte sind stark von der Wahl der zugrundeliegenden b-Werte abhängig und eignen sich daher nicht zur allgemeingültigen Charakterisierung von Prostatakarzinomen. Ein minimaler b-Wert > 0 s/mm2 wird für die Berechnung der ADC-Karten im Hinblick auf eine nachweislich verbesserte visuelle Auswertbarkeit empfohlen.

An acute demyelinating syndrome (ADS) in a child may be a monophasic illness or may represent the incident attack of multiple sclerosis (MS) – an inflammatory demyelinating neurodegenerative disorder affecting the brain, spinal cord and optic nerves. The central objective of this dissertation was to identify MRI parameters present at ADS that predict MS diagnosis. A scoring tool was first created containing 14 parameters identified from the literature and demonstrating substantial inter-rater agreement (Cohen’s kappa values ≥0.6). Children aged <16 years were enrolled at incident ADS and are currently followed for five years at 23 Canadian centers. Standardized MRI scans were acquired at onset and serially. MS was defined based on the occurrence of a second demyelinating attack or MRI evidence of new lesions in accordance with McDonald criteria for dissemination in time. Multivariable Cox proportional hazards regression models were used to identify MRI parameters that predicted MS diagnosis. Over 1100 MRI scans in 284 children with ADS were evaluated. To date, 57(20%) children have been diagnosed with MS. For those that developed MS, the median (IQR) time from incident attack to diagnosis was 6.2 (4.7-11.1) months. The presence of ≥1 T1-hypointense lesion (HR 20.6, 95% CI 5.5-78.0) and ≥1 T2 periventricular lesion (3.3, 1.3-8.8) were associated with an increased likelihood for MS diagnosis (sensitivity 84%, specificity 93%, PPV 76%, NPV 96%). The predictive parameters were validated in an independent Dutch cohort of 45 children with ADS (n=15, 33% MS): sensitivity 93%, specificity 87%, PPV 78%, NPV 96%. Finally, it was determined that the 2010 McDonald criteria are applicable for diagnosis of pediatric-onset MS diagnosis in older children with non-ADEM presentations. The work embodied herein emphasizes the value of MRI in predicting MS diagnosis in children with incident ADS. Early identification of children with MS is important for planning clinical care and will be valuable in future pediatric MS treatment trials.