81 research outputs found
지연가역 신경수용체 결합 파라메트릭 영상화를 위한 동적 뇌 PET 기반 비침습적 이중도표분석법
No full text학위논문 (박사)-- 서울대학교 대학원 : 뇌인지과학과, 2016. 2. 이재성.Tracer kinetic modeling in dynamic positron emission tomography (PET) has been widely used to investigate characteristic distribution pattern or dysfunction of neuroreceptors in brain diseases, by offering a unique tool for generating images of quantitative parameters (or parametric imaging) of neuroreceptor binding. Graphical analysis (GA) is a major technique of parametric imaging, and is based on a simple linear regression model that is linearized and further simplified from a more complex general compartment model. Although each simple model of various GA methods enables very desirable parametric imaging, it depends on several assumptions that are commonly hard to satisfy simultaneously in parametric imaging for slow kinetic tracers, leading to error in parameter estimates. A combination of two GA methods, a bi-graphical analysis, may improve such intrinsic limitation of GA approaches by taking full advantage of spatiotemporal information captured in dynamic PET data and diverse strengths of individual GA methods.
This thesis focuses on a bi-graphical analysis for parametric imaging of reversible neuroreceptor binding. Firstly, I provide an overview of GA-based parametric image generation with dynamic neuroreceptor PET data. The associated basic concepts in tracer kinetic modeling are presented, including commonly used compartment models and major parameters of interest. Then, technical details of GA approaches for reversible and irreversible radioligands are described considering both arterial-plasma-input-based (invasive) and reference-region-input-based (noninvasive) modelstheir underlying assumptions and statistical properties are described in view of parametric imaging.
Next, I present a novel noninvasive bi-graphical analysis for the quantification of a reversible radiotracer binding that may be too slow to reach relative equilibrium (RE) state during PET scans. The proposed method indirectly implements the conventional noninvasive Logan plot, through arithmetic combination of the parameters of two other noninvasive GA methods and the apparent tissue-to-plasma efflux rate constant for the reference region (k_2^'). I investigate its validity and statistical properties, by performing a simulation study with various noise levels and k_2^' values, and also evaluate its feasibility for [18F]FP-CIT PET in human brain.
The results reveal that the proposed approach provides a binding-parameter estimation comparable to the Logan plot at low noise levels while improving underestimation caused by non-RE state differently depending on k_2^'. Furthermore, the proposed method is able to avoid noise-induced bias of the Logan plot at high noise levels, and the variability of its results is less dependent on k_2^' than the Logan plot. In sum, this approach, without issues related to arterial blood sampling if a pre-estimated k_2^' is given, could be useful in parametric image generation for slow kinetic tracers staying in a non-RE state within a PET scan.Chapter 1 Introduction 1
1.1 Tracer Kinetic Modeling in PET 1
1.2 Regional versus Voxel-wise Quantification 2
1.3 Requirements for Parametric Imaging 3
1.4 Graphical Analysis 4
1.5 Thesis Statement and Contributions 5
1.6 Organization of the Thesis 6
Chapter 2 Basic Theory in Tracer Kinetic Modeling 8
2.1 Dynamic PET Acquisition 8
2.2 Compartmental Models 11
2.3 Parameters of Interest in Neuroreceptor Study 14
2.4 Limitations in Parametric Image Generation 18
Chapter 3 Overview of Graphical Analysis 20
3.1 General Characteristics 20
3.2 Reversible Radioligand Models 25
3.2.1 Logan Plot 25
3.2.2 Relative Equilibrium-based Graphical Plot 31
3.2.3 Ito Plot 36
3.3 Irreversible Radioligand Models 39
3.3.1 Invasive Gjedde-Patlak Plot 39
3.3.2 Noninvasive Gjedde-Patlak Approaches 40
Chapter 4 Noninvasive Bi-graphical Analysis for the Quantification of Slowly Reversible Radioligand Binding 43
4.1 Background 43
4.2 Materials and Methods 45
4.2.1 Invasive RE-GP Plots 45
4.2.2 Noninvasive GA Approaches 47
4.2.3 Noninvasive RE-GP Plots 49
4.2.4 Computer Simulations 51
4.2.5 Human [18F]FP-CIT PET Data 52
4.3 Results 54
4.3.1 Regional Time-activity Curves and Graphical Plots 54
4.3.2 Simulation Results 59
4.3.3 Application to Human Data 60
4.4 Discussion 66
4.4.1 Characteristics of [18F]FP-CIT PET Data 67
4.4.2 Kinetic Methods for [18F]FP-CIT PET 67
4.4.3 Correction for NRE Effects 68
4.4.4 Linearity Condition 69
4.4.5 Advantages over the Noninvasive Logan plot 69
4.4.6 Comparison with the SRTM 71
4.4.7 Simulation Settings 72
4.4.8 Noninvasiveness 74
Chapter 5 Summary and Conclusion 76
Bibliography 77
초 록 97Docto
Presynaptic Dopamine Capacity in Patients with Treatment-Resistant Schizophrenia Taking Clozapine: An [18F]DOPA PET Study
No full textSome patients with schizophrenia show poor response to first-line antipsychotic treatments and this is termed treatment resistant schizophrenia. The differential response to first-line antipsychotic drugs may reflect a different underlying neurobiology. Indeed, a previous study found dopamine synthesis capacity was significantly lower in patients with treatment resistant schizophrenia. However, in this study, the treatment resistant patients were highly symptomatic whilst the responsive patients showed no or minimal symptoms. The study could not distinguish whether this was a trait effect or reflected the difference in symptom levels. Thus we aimed to test whether dopaminergic function is altered in patients with a history of treatment resistance to first-line drugs relative to treatment responders when both groups are matched for symptom severity levels by recruiting treatment resistant patients currently showed low symptom severity with the clozapine treatment. Healthy controls(n=12), patients treated with clozapine(n=12) who had not responded to first-line antipsychotics and patients who had responded to first-line antipsychotics(n=12) were recruited. Participants were matched for age and sex, and symptomatic severity level in patient groups. Participants' dopamine synthesis capacity was measured by using [(18)F]DOPA PET. We found that patients treated with clozapine show lower dopamine synthesis capacity than patients who have responded to first-line treatment(Cohen's d=0.9191(whole striatum), 0.7781(Associative striatum), 1.0344(Limbic striatum), 1.0189(Sensorimotor striatum) in line with the hypothesis that the dopaminergic function is linked to treatment response. This suggests that a different neurobiology may underlie treatment resistant schizophrenia and that dopamine synthesis capacity may be a useful biomarker to predict treatment responsiveness.Neuropsychopharmacology accepted article preview online, 18 November 2016. doi:10.1038/npp.2016.258
A COMPREHENSIVE ANALYTICAL MODEL FOR PNEUMATIC TIRES
No full textRights Copyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author. Downloaded 13-May-2016 02:28:16 Link to ite
Interpreting Romans 13 in Modern Korea
No full textThis essay introduced and examined the thesis “Politics of Romans 13” in which Korean historian Kang Seongho described the interpretations of Romans 13: 1-7 in Korea from the time beginning under Japan’s Imperial rule to the postwar era of the 1980s. The author evaluated Kang's long historical and self-critical analysis of Korean Protestantism, with an interesting examination relating to political confrontations of the time. At the same time, the author argued that Kang’s pioneer work would have more impact, if its theoretical framework was sophisticated and if it included “practical interpretations” of Romans 13.departmental bulletin pape
韓国におけるローマ書13章解釈史の試み ――カン・ソンホ「ロマ書13章の政治学」について
No full textThis essay introduced and examined the thesis “Politics of Romans 13” in which Korean historian Kang Seongho described the interpretations of Romans 13: 1-7 in Korea from the time beginning under Japan’s Imperial rule to the postwar era of the 1980s. The author evaluated Kang's long historical and self-critical analysis of Korean Protestantism, with an interesting examination relating to political confrontations of the time. At the same time, the author argued that Kang’s pioneer work would have more impact, if its theoretical framework was sophisticated and if it included “practical interpretations” of Romans 13
Nanoelectrokinetic Selective Preconcentration Based on Ion Concentration Polarization
No full textNanoscale electrokinetic phenomenon called ion concentration polarization (ICP) has opened a new era in bio- and chemical-analysis platform due to its high efficiency and easy sample handling. In this review, the most recent advancements of selective preconcentration process using ICP were introduced. The flux balances of charged analytes were theoretically analyzed so that the behavior and the shape of preconcentrated plug were categorized into stacking/propagating and dumbbell/plug, respectively. The experimental demonstrations of these features were also given to verify the modeling. Furthermore, promising applications based on the analysis were described in this review. Lastly, future research direction would be suggested by elucidating pros and cons of ICP process.Y
dCas9-mediated Nanoelectrokinetic Direct Detection of Target Gene for Liquid Biopsy
No full textThe-state-of-the-art
bio- and nanotechnology have opened up an
avenue to noninvasive liquid biopsy for identifying diseases from
biomolecules in bloodstream, especially DNA. In this work, we combined
sequence-specific-labeling scheme using mutated clustered regularly
interspaced short palindromic repeats associated protein 9 without
endonuclease activity (CRISPR/dCas9) and ion concentration polarization
(ICP) phenomenon as a mechanism to selectively preconcentrate targeted
DNA molecules for rapid and direct detection. Theoretical analysis
on ICP phenomenon figured out a critical mobility, elucidating two
distinguishable concentrating behaviors near a nanojunction, a stacking
and a propagating behavior. Through the modulation of the critical
mobility to shift those behaviors, the C–C chemokine receptor
type 5 (CCR5) sequences were optically detected without
PCR amplification. Conclusively, the proposed dCas9-mediated genetic
detection methodology based on ICP would provide rapid and accurate
micro/nanofluidic platform of liquid biopsies for disease diagnostics
Development and Initial Results of a Brain PET Insert for Simultaneous 7-Tesla PET/MRI Using an FPGA-Only Signal Digitization Method
No full textIn study, we developed a positron emission tomography (PET) insert for simultaneous brain imaging within 7-Tesla (7T) magnetic resonance (MR) imaging scanners. The PET insert has 18 sectors, and each sector is assembled with two-layer depth-of-interaction (DOI)-capable high-resolution block detectors. The PET scanner features a 16.7-cm-long axial field-of-view (FOV) to provide entire human brain images without bed movement. The PET scanner early digitizes a large number of block detector signals at a front-end data acquisition (DAQ) board using a novel field-programmable gate array (FPGA)-only signal digitization method. All the digitized PET data from the front-end DAQ boards are transferred using gigabit transceivers via non-magnetic high-definition multimedia interface (HDMI) cables. A back-end DAQ system provides a common clock and synchronization signal for FPGAs over the HDMI cables. An active cooling system using copper heat pipes is applied for thermal regulation. All the 2.17-mm-pitch crystals with two-layer DOI information were clearly identified in the block detectors, exhibiting a system-level energy resolution of 12.6%. The PET scanner yielded clear hot-rod and Hoffman brain phantom images and demonstrated 3D PET imaging capability without bed movement. We also performed a pilot simultaneous PET/MR imaging study of a brain phantom. The PET scanner achieved a spatial resolution of 2.5 mm at the center FOV (NU 4) and a sensitivity of 18.9 kcps/MBq (NU 2) and 6.19% (NU 4) in accordance with the National Electrical Manufacturers Association (NEMA) standards.
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