Development Of A Scintillation Detector And The Influence On Clinical Imaging

The detector is the functional unit within a Positron Emission Tomography (PET) scanner, serving to convert the energy of radiation emitted from a patient into positional information, and as such contributes significantly to the performance of the scanner. While modern whole-body scanners use detectors composed of very many (i.e., 20000-30000) small pixels, typically ~4x4x20mm3 in size, several groups are actively investigating the performance of continuous crystals coupled to position sensitive photodetectors as an alternative detector design with a number of potential advantages, including improved spatial resolution and position sampling. This work in particular focuses on thick (≥14mm) continuous crystals in order to maintain the sensitivity of modern scanners. Excellent spatial resolution in continuous detectors that are thick, however, has proven difficult to achieve using simple positioning algorithms, leading to research in the field to improve performance. This thesis aims to investigate the effect of modifications to the scintillation light spread within the bulk of the scintillator to improve performance, focusing on the use of laser induced optical barriers (LIOBs) etched within thick continuous crystals, and furthermore aims to translate the effect on detector performance to scanner quantitation in patient studies. The conventional continuous detector is first investigated by analyzing the various components of the detector as well as its limitations. It is seen that the performance of the detector is affected by a number of variables that either cannot be improved or may be improved only at the expense of greater complexity or computing time; these include the photodetector, the positioning algorithm, and Compton scatter in the detector. The performance of the detectors, however, is fundamentally determined by the light spread within the detector, and limited by the depth-dependence of the light spread and poor performance in the entrance region, motivating efforts to modify this aspect of the detector. The feasibility and potential of LIOBs to fine-tune this light spread and improve these limitations is then studied using both experiments and simulations. The behavior of the LIOBs in response to optical light is investigated, and the opacity of the etchings is shown to be dependent on the parameters of the etching procedure. Thick crystals were also etched with LIOBs in their entrance region in a grid pattern in order to improve the resolution in the entrance region. Measurements show an overall improvement in spatial resolution: the resolution in the etched region of the crystals is slightly improved (e.g., ~0.8mm for a 25mm thick crystal), though in the unetched region, it is slightly degraded (e.g., ~0.4mm for a 25mm thick crystal). While the depth-dependence of the response of the crystal is decreased, the depth-of-interaction (DOI) performance is degraded as well. Simulation studies informed by these measurements show that the properties of the LIOBs strongly affect the performance of the crystal, and ultimately further illustrate that trade-offs in spatial resolution, position sampling, and DOI resolution are inherent in varying the light spread using LIOBs in this manner; these may be used as a guide for future experiments. System Monte Carlo simulations were used to investigate the added benefit of improved detector spatial resolution and position sampling to the imaging performance of a whole-body scanner. These simulations compared the performance of scanners composed of conventional pixelated detectors to that of scanners using continuous crystals. Results showed that the improved performance (relative to that of 4-mm pixelated detectors) of continuous crystals with a 2-mm resolution, pertinent to both the etched 14mm thick crystal studied as well as potential designs with the etched 25mm thick crystal, increased the mean contrast recovery coefficient (CRC) of images by ~22% for 5.5mm spheres. Last, a set of experiments aimed to test the correspondence between quantification in phantom and patient images using a lesion embedding methodology, so that any improvements determined using phantom studies may be understood clinically. The results show that the average CRC values for lesions embedded in the lung and liver agree well with those for lesions embedded in the phantom for all lesion sizes. In addition, the relative changes in CRC resulting from application of post-filters on the subject and phantom images are consistent within measurement uncertainty. This study shows that the improvements in CRC resulting from improved spatial resolution, measured using phantom studies in the simulations, are representative of improvements in quantitative accuracy in patient studies. While unmodified thick continuous detectors hold promise for both improved image quality and quantitation in whole-body imaging, excellent performance requires intensive hardware and computational solutions. Laser induced optical barriers offer the ability to modify the light spread within the scintillator to improve the intrinsic performance of the detector: while measurements with crystals etched with relatively transmissive etchings show a slight improvement in resolution, simulations show that the LIOBs may be fine-tuned to result in improved performance using relatively simple positioning algorithms. For systems in which DOI information is less important, and transverse resolution and sensitivity are paramount, etching thick detectors with this design, fine-tuned to the particular thickness of the crystal and application, is an interesting alternative to the standard detector design

Apoptosome activation, an important molecular instigator in 6-mercaptopurine induced Leydig cell death.

Leydig cells are crucial to the production of testosterone in males. It is unknown if the cancer chemotherapeutic drug, 6-mercaptopurine (6 MP), produces Leydig cell failure among adult survivors of childhood acute lymphoblastic leukemia. Moreover, it is not known whether Leydig cell failure is due to either a loss of cells or an impairment in their function. Herein, we show, in a subset of childhood cancer survivors, that Leydig cell failure is related to the dose of 6 MP. This was extended, in a murine model, to demonstrate that 6 MP exposure induced caspase 3 activation, and the loss of Leydig cells was independent of Bak and Bax activation. The death of these non-proliferating cells was triggered by 6 MP metabolism, requiring formation of both cytosolic reactive oxygen species and thiopurine nucleotide triphosphates. The thiopurine nucleotide triphosphates (with physiological amounts of dATP) uniquely activated the apoptosome. An ABC transporter (Abcc4/Mrp4) reduced the amount of thiopurines, thereby providing protection for Leydig cells. The studies reported here demonstrate that the apoptosome is uniquely activated by thiopurine nucleotides and suggest that 6 MP induced Leydig cell death is likely a cause of Leydig cell failure in some survivors of childhood cancer

On the Stratospheric Aerosol and Gas Experiment III on the International Space Station

The Stratospheric Aerosol and Gas Experiment III on International Space Station (SAGE3/ISS) is anticipated to be delivered to Cape Canaveral in the spring of 2015. This is the fourth generation, fifth instrument, of visible/near-IR solar occultation instruments operated by the National Aeronautics and Space Agency (NASA) to investigate the Earth's upper atmosphere. The instrument is a moderate resolution spectrometer covering wavelengths from 290 nm to 1550 nm. The nominal science products include vertical profiles of trace gases, such as ozone, nitrogen dioxide and water vapor, along with multi-wavelength aerosol extinction. The SAGE3/ISS validation program will be based upon internal consistency of the measurements, detailed analysis of the retrieval algorithm, and comparisons with independent correlative measurements. The Instrument Payload (IP), mission architecture, and major challenges are also discussed

Role of eddy forcing in the dynamics of multiple zonal jets in a model of the North Atlantic

Author Posting. © American Meteorological Society, 2009. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Journal of Physical Oceanography 39 (2009): 1361-1379, doi:10.1175/2008JPO4096.1.Multiple zonal jets are observed in satellite data–based estimates of oceanic velocities, float measurements, and high-resolution numerical simulations of the ocean circulation. This study makes a step toward understanding the dynamics of these jets in the real ocean by analyzing the vertical structure and dynamical balances within multiple zonal jets simulated in an eddy-resolving primitive equation model of the North Atlantic. In particular, the authors focus on the role of eddy flux convergences (“eddy forcing”) in supporting the buoyancy and relative/potential vorticity (PV) anomalies associated with the jets. The results suggest a central role of baroclinic eddies in the barotropic and baroclinic dynamics of the jets, and significant differences in the effects of eddy forcing between the subtropical and subpolar gyres. Additionally, diabatic potential vorticity sources and sinks, associated with vertical diffusion, are shown to play an important role in supporting the potential vorticity anomalies. The resulting potential vorticity profile does not resemble a “PV staircase”—a distinct meridional structure observed in some idealized studies of geostrophic turbulence.Funding for IK was provided by NSF Grants OCE 0346178 and 0749722. Funding for PB was provided by NSF Grants OCE 0344094 and OCE 0725796 and by the research grant from the Newton Trust of the University of Cambridge. For JP the acknowledgement is to NSF OCE-0451086

Quantifying expert opinion with discrete choice models: Invasive elodea's influence on Alaska salmonids

Scientific evidence should inform environmental policy, but rapid environmental change brings high ecological uncertainty and associated barriers to the science-management dialogue. Biological invasions of aquatic plants are a worldwide problem with uncertain ecological and economic consequences. We demonstrate that the discrete choice method (DCM) can serve as a structured expert elicitation alternative to quantify expert opinion across a range of possible but uncertain environmental outcomes. DCM is widely applied in the social sciences to better understand and predict human preferences and trade-offs. Here we apply it to Alaska's first submersed invasive aquatic freshwater plant, Elodea spp. (elodea), and its unknown effects on salmonids. While little is known about interactions between elodea and salmonids, ecological research suggests that aquatic plant invasions can have positive and negative, as well as direct and indirect, effects on fish. We use DCM to design hypothetical salmonid habitat scenarios describing elodea's possible effect on critical environmental conditions for salmonids: prey abundance, dissolved oxygen, and vegetation cover. We then observe how experts choose between scenarios that they believe could support persistent salmonid populations in elodea-invaded salmonid habitat. We quantify the relative importance of habitat characteristics that influence expert choice and investigate how experts trade off between habitat characteristics. We take advantage of Bayesian techniques to estimate discrete choice models for individual experts and to simulate expert opinion for specific environmental management situations. We discuss possible applications and advantages of the DCM approach for expert elicitation in the ecological context. We end with methodological questions for future research

Testing control of radiationinduced diarrhea with a psyllium bulking agent: A pilot study

Sixty cancer patients who were undergoing radiation therapy to the pelvis of at least 4,000 cGy in 20 fractions over four weeks were randomized to take or not take Metamucil®. Results were analyzed for the presence of radiation-induced diarrhea in two groups: patients taking Metamucil (n=30) or not taking Metamucil (n=30). The Murphy Diarrhea Scale was developed to assist in the synthesis of data collected in daily patient-reported diaries. Results were analyzed using ANOVA F-tests. Metamucil significantly decreased the incidence (p=0.049) and severity (p=0.030) of diarrhea and showed a strong trend in reducing the use of anti-diarrhea medication (p=0.062). According to this pilot study, Metamucil was an effective method of controlling radiation-induced diarrhea. Results of this pilot study have implications for clinical practice and nursing research