A New electronic image array: The Active pixel charge injection device

This is a Ph.D. thesis dissertation in which a new type of image sensor is investigated as possible successor to the charge coupled device (CCD) for scientific applications. As a result of the work described in this dissertation, the active pixel charge injection device (AP-CID) has been developed. This device retains most of the positive features of both the charge injection device (CJD) imager (random readout, non destructive readout, antiblooming, increased UV sensitivity, radiation tolerance, low power consumption, low manufacturing price) and the CCD imager (low noise, high dynamic range). The device lacks most of the drawbacks of the aforementioned devices. A functional array architecture was created. Based on this architecture several devices were fabricated. One of the arrays was fully measured, characterized and suggestions for improvement were formulated. Most of the characterizationalysis work described in this dissertation was centered on the following issues: temporal noise, linearity and FPN. The measured noise performance of the new device is excellent and comparable to the noise performance of the scientific CCD. The newly developed sensor is necessary for scientific imaging applications in space based operation. However due to its qualities, this device could be used in a much wider range of applications including commercial digital cameras, spectroscopy, biological, nuclear and other scientific applications

The Development of a Benchmark Tool for NoSQL Databases

The aim of this article is to describe a proposed benchmark methodology and software application targeted at measuring the performance of both SQL and NoSQL databases. These represent the results obtained during PhD research (being actually a part of a larger application intended for NoSQL database management). A reason for aiming at this particular subject is the complete lack of benchmarking tools for NoSQL databases, except for YCBS [1] and a benchmark tool made specifically to compare Redis to RavenDB. While there are several well-known benchmarking systems for classical relational databases (starting with the canon TPC-C, TPC-E and TPC-H), on the other side of databases world such tools are mostly missing and seriously needed

Photoacoustic imaging of lacZ gene expression in vivo

In the postgenomic era, imaging techniques are playing an important role in visualizing gene expression in vivo. This work represents the first demonstration of photoacoustic tomography (PAT) for reporter gene imaging. Rats inoculated with 9L/lacZ gliosarcoma tumor cells are imaged with PAT before and after injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme β β -galactosidase. Using far-red optical illumination, the genetically tagged tumors in rats are clearly visualized by PAT following the assay. The spatial resolution is quantified to be less than 400μm 400μm , while 500-nM-level sensitivity is demonstrated. With the future development of new absorption-based reporter gene systems, it is anticipated that photoacoustic technology will provide a valuable tool for molecular imaging research

In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion

Hypoxia is a critical event in tumor progression and angiogenesis. Hypoxia can be detected noninvasively by a novel spectroscopic photoacoustic tomography technology (SPAT) and this finding is supported by our molecular biology investigation aimed to elucidate the etiopathogenesis of SPAT detected hypoxia and angiogenesis. The present study provides an integrated approach to define oxygen status (hypoxia) of intracranial tumor xenografts using spectroscopic photoacoustic tomography. Brain tumors can be identified based on their distorted vascular architecture and oxygen saturation (SO2) images. Noninvasive in vivo tumor oxygenation imaging using SPAT is based on the spectroscopic absorption differences between oxyhemoglobin (O2Hb) and deoxyhemoblobin (HHb). Sprague-Dawley rats inoculated intracranially with ENU1564, a carcinogen-induced rat mammary adenocarcinoma cell line, were imaged with SPAT three weeks post inoculation. Proteins important for tumor angiogenesis and invasion were detected in hypoxic brain foci identified by SPAT and were elevated compared with control brain. Immunohistochemistry, Western blotting, and semi-quantitative RT-PCR showed that HIF-1 α, VEGF-A, and VEGFR2 (Flk-1) protein and mRNA expression levels were significantly higher (P<0.05) in brain tumor tissues compared to normal brain. Gelatin zymography and RT-PCR demonstrated the upregulation of MMP-9 in tumor foci compared with brain control. Together these results suggest the critical role of hypoxia in driving tumor angiogenesis and invasion through upregulation of target genes important for these functions. Moreover this report validates our hypothesis that a novel noninvasive technology (SPAT) developed in our laboratory is suitable for detection of tumors, hypoxia, and angiogenesis

European Union pharmacovigilance capabilities : potential for the new legislation

European Directives and Regulations introduced between late 2010 and 2012 have substantially overhauled pharmacovigilance processes across the European Union (EU). In this review, the implementation of the pharmacovigilance legislative framework by EU regulators is examined with the aim of mapping Directive 2010/84/EU and Regulation EC No. 1235/2010 against their aspired objectives of strengthening and rationalizing pharmacovigilance in the EU. A comprehensive review of the current state of affairs of the progress made by EU regulators is presented in this paper. Our review shows that intense efforts by regulators and industry to fulfil legislative obligations have resulted in major positive shifts in pharmacovigilance. Harmonized decision making, transparency in decision processes with patient involvement, information accessibility to the public, patient adverse drug reaction reporting, efforts in communication and enhanced cooperation between member states to maximize resource utilization and minimize duplication of efforts are observed.peer-reviewe

Simultaneous Molecular and Hypoxia Imaging of Brain Tumors In Vivo Using Spectroscopic Photoacoustic Tomography

Noninvasive molecular and functional imaging in vivo is promising for detecting and monitoring various physiological conditions in animals and ultimately humans. To this end, we present a novel noninvasive technology, spectroscopic photoacoustic tomography (SPAT), which offers both strong optical absorption contrast and high ultrasonic spatial resolution. Optical contrast allows spectroscopic separation of signal contributions from multiple optical absorbers (e.g., oxyhemoglobin, deoxyhemoglobin, and a molecular contrast agent), thus enabling simultaneous molecular and functional imaging. SPAT successfully imaged with high resolution the distribution of a molecular contrast agent targeting integrin overexpressed in human U87 glioblastomas in nude mouse brains. Simultaneously, SPAT also imaged the hemoglobin oxygen saturation and the total hemoglobin concentration of the vasculature, which revealed hypoxia in tumor neovasculature. Therefore, SPAT can potentially lead to better understanding of the interrelationships between hemodynamics and specific biomarkers associated with tumor progression

Photoacoustic molecular imaging of small animals in vivo

Molecular imaging is a newly emerging field in which the modern tools of molecular and cell biology have been married to state-of-the-art technologies for noninvasive imaging. The study of molecular imaging will lead to better methods for understanding biological processes as well as diagnosing and managing disease. Here we present noninvasive in vivo spectroscopic photoacoustic tomography (PAT)-based molecular imaging of αvβ3 integrin in a nude mouse U87 brain tumor. PAT combines high optical absorption contrast and high ultrasonic resolution by employing short laser pulses to generate acoustic waves in biological tissues through thermoelastic expansion. Spectroscopic PAT-based molecular imaging offers the separation of the contributions from different absorbers based on the differences in optical absorption spectra among those absorbers. In our case, in the near infrared (NIR) range, oxy-heamoglobin (O2Hb), deoxy-heamoglobin (HHb) and the injected αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent are the three main absorbers. Therefore, with the excitation by multiple wavelength laser pulses, spectroscopic PAT-based molecular imaging not only provides the level of the contrast agent accumulation in the U87 glioblastoma tumor, which is related to the metabolism and angiogenesis of the tumor, but also offers the information on tumor angiogenesis and tumor hypoxia

Photoacoustic imaging of lacZ gene expression in vivo

In the postgenomic era, imaging techniques are playing an important role in visualizing gene expression in vivo. This work represents the first demonstration of photoacoustic tomography (PAT) for reporter gene imaging. Rats inoculated with 9L/lacZ gliosarcoma tumor cells are imaged with PAT before and after injection of X-gal, a colorimetric assay for the lacZ-encoded enzyme β β -galactosidase. Using far-red optical illumination, the genetically tagged tumors in rats are clearly visualized by PAT following the assay. The spatial resolution is quantified to be less than 400μm 400μm , while 500-nM-level sensitivity is demonstrated. With the future development of new absorption-based reporter gene systems, it is anticipated that photoacoustic technology will provide a valuable tool for molecular imaging research

Photoacoustic molecular imaging of small animals in vivo

Molecular imaging is a newly emerging field in which the modern tools of molecular and cell biology have been married to state-of-the-art technologies for noninvasive imaging. The study of molecular imaging will lead to better methods for understanding biological processes as well as diagnosing and managing disease. Here we present noninvasive in vivo spectroscopic photoacoustic tomography (PAT)-based molecular imaging of αvβ3 integrin in a nude mouse U87 brain tumor. PAT combines high optical absorption contrast and high ultrasonic resolution by employing short laser pulses to generate acoustic waves in biological tissues through thermoelastic expansion. Spectroscopic PAT-based molecular imaging offers the separation of the contributions from different absorbers based on the differences in optical absorption spectra among those absorbers. In our case, in the near infrared (NIR) range, oxy-heamoglobin (O2Hb), deoxy-heamoglobin (HHb) and the injected αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent are the three main absorbers. Therefore, with the excitation by multiple wavelength laser pulses, spectroscopic PAT-based molecular imaging not only provides the level of the contrast agent accumulation in the U87 glioblastoma tumor, which is related to the metabolism and angiogenesis of the tumor, but also offers the information on tumor angiogenesis and tumor hypoxia