Fluorescence lifetime sensing using time correlated single photon counting (TCSPC) is a key analytical tool for molecular and cell biology research, medical diagnosis and pharmacological development. However, commercially available TCSPC equipment is bulky, expensive and power hungry, typically requiring iterative software post-processing to calculate the fluorescence lifetime. Furthermore, the technique is restrictively slow due to a low photon throughput limit which is necessary to avoid distortions caused by TCSPC pile-up. An investigation into CMOS compatible multimodule architectures to miniaturise the standard TCSPC set up, allow an increase in photon throughput by overcoming the TCSPC pile-up limit, and provide fluorescence lifetime calculations in real-time is presented. The investigation verifies the operation of the architectures and leads to the selection of optimal parameters for the number of detectors and timing channels required to overcome the TCSPC pile-up limit by at least an order of magnitude. The parameters are used to implement a low power miniaturised sensor in a 130 nm CMOS process, combining single photon detection, multiple channel timing and embedded pre-processing of the fluorescence lifetime, all within a silicon area of < 2 mm2. Single photon detection is achieved using an array of single photon avalanche diodes (SPADs) arranged in a digital silicon photomultiplier (SiPM) architecture with a 10 % fill-factor and a compressed 250 ps output pulse, which provides a photon throughput of > 700 MHz. An array of time-interleaved time-to-digital converters (TI-TDCs) with 50 ps resolution and no processing dead-time records up to eight photon events during each excitation period, significantly reducing the effect of TCSPC pile-up. The TCSPC data is then processed using an embedded centre-of-mass method (CMM) pre-calculation to produce single exponential fluorescence lifetime estimations in real-time. The combination of high photon throughput and real-time calculation enables advances in applications such as fluorescence lifetime imaging microscopy (FLIM) and time domain fluorescence lifetime activated cell sorting. To demonstrate this, the device is validated in practical bulk sample fluorescence lifetime, FLIM and simulated flow based experiments. Photon throughputs in excess of the excitation frequency are demonstrated for a range of organic and inorganic fluorophores for minimal error in lifetime calculation by CMM (< 5 %).

A theoretical model with experimental verification is presented to enhance the quantum efficiency of a superconducting single-photon detector without increasing the length or thickness of the active element. The basic enhancement framework is based on: (1) Utilizing the plasmonic nature of a superconducting layer to increase the surface absorption of the input optical signal. (2) Enhancing the critical current of the nanowires by reducing the current crowding at the bend areas through optimally rounded-bend implementation. The experimental system quantum efficiency and fluctuation rates per second are assessed and compared to the proposed theoretical model. The model originated from an accurate description of the different liberation mechanisms of the nano-patterned superconducting films (vortex hopping and vortex-antivortex pairing). It is built complimentary to the existing, well-established models by considering the effects of quantum confinement on the singularities' energy states. The proposed model explains the dynamics of singularities for a wide range of temperatures and widths and describe an accurate count rate behavior for the structure. Furthermore, it explains the abnormal behaviors of the measured fluctuation rates occurring in wide nano-patterned superconducting structures below the critical temperature. In accordance to this model, it has been shown that for a typical strip width, not only is the vortex-antivortex liberation higher than the predicted rate, but also quantum tunneling is significant in certain conditions, and cannot be neglected as it has been in previous models. Also it is concluded that to satisfy both optical guiding and photon detection considerations of the design, the width and the thickness of the superconducting wires should be carefully determined in order to maintain the device sensitivity while crossing over from the current crowding to vortex-based detection mechanisms.

Thesis (Ph.D.)--University of Missouri-Columbia, 2005. / The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from title screen of research.pdf file viewed on (November 15, 2006) Vita. Includes bibliographical references.

The quantum properties of electromagnetic radiation at single photon level promise to offer what are classically inaccessible. Single photon sources and detectors are therefore on demand for exploiting these properties in practical applications, including but not limited to quantum information processing and communication. In this thesis, I advance Superconducting Nanowire Single Photon Detectors (SNSPD) both in terms of models describing their operation, and their performance. I report on characterization, semi-empirical modeling, quantum-optical modeling and detector tomography. The results provide more accurate methods and formulations to characterize and mathematically describe the detectors, valuable findings from both application and device points of views. I also introduce the concept of Gated SNSPDs, show how to implement and how to characterize them. Through series of theoretical and experimental investigations, I show performance advantages of Gated SNSPDs in terms of dead time and dark count rate, important figures for many applications like quantum key distribution. The ultimate limitations of gated operation are also explored by physical modeling and simulation steps.

The quantum properties of electromagnetic radiation at single photon level promise to offer what are classically inaccessible. Single photon sources and detectors are therefore on demand for exploiting these properties in practical applications, including but not limited to quantum information processing and communication. In this thesis, I advance Superconducting Nanowire Single Photon Detectors (SNSPD) both in terms of models describing their operation, and their performance. I report on characterization, semi-empirical modeling, quantum-optical modeling and detector tomography. The results provide more accurate methods and formulations to characterize and mathematically describe the detectors, valuable findings from both application and device points of views. I also introduce the concept of Gated SNSPDs, show how to implement and how to characterize them. Through series of theoretical and experimental investigations, I show performance advantages of Gated SNSPDs in terms of dead time and dark count rate, important figures for many applications like quantum key distribution. The ultimate limitations of gated operation are also explored by physical modeling and simulation steps.

This dissertation presents the results of an investigation into the performance characteristics of a unique hemispherical SPECT (single-photon emission computed tomography) imaging system capable of producing three-dimensional (3D) tomographic images of the human brain. The system is completely stationary and collects all necessary views of the patient simultaneously, with no system motion. The imager consists of twenty small (10cm x 10cm crystal area), digital gamma cameras arranged in a hemispherical pattern around the patient's head and a hemispherical lead aperture. The hemispherical aperture is positioned between the cameras and the head and contains a large number of pinholes; in this way each camera sees a number of overlapping pinhole projections of the radioactive distribution within the patient's brain. The initial investigation of the performance characteristics of a 3D SPECT system of this design were carried out using a computer simulation in which effects due to radiometry, finite pinhole size, finite detector resolution, photon noise, and object attenuation were included. We used a digital 3D brain phantom as the test object and an iterative search algorithm to perform the reconstructions. The simulations were used to compare the performance of a variety of system configurations. Based upon the results of the simulation study, we constructed a laboratory prototype of the 3D SPECT system, which we used to further characterize the expected performance of a clinical imaging system of the same design. Prior to collecting SPECT data we calibrated the imaging system, which required that we efficiently measure and store the spatially variant system response function. These calibration data were then included in the reconstructions of the SPECT phantoms that we imaged. A number of different SPECT phantoms were imaged to demonstrate the system performance. We measured a reconstructed spatial resolution of 4.8mm full-width at half-maximum and a full-system sensitivity of 36cps/μCi, where both values were measured for a point source in air located at the center of the field of view. We also describe an analysis that we performed to determine the equivalent, non-multiplexed system sensitivity; using this method, we found that the equivalent sensitivity was 79% of the measured value for the system configuration and the particular task that we investigated.

A short report submitted to the Faculty of Medicine, University of the Witwatersrand in partial fulfilment of the requirements for the degree of Master of Medicine in Nuclear Medicine / 19 patients were selected, from the patients screened, for investigation within 48 hours of the onset of an ischaemic cerebrovascular accident. Clinical neurulogical scoring, computerized tomography lCT) scans and single photon emission computed tomography (SPECT) scans were performed on day 1, day 10 and day 30. SPECT scan data was analysed by 5 semi-quantitative methods, and findings were compared with neuroloyical clinical scores on each respective day. It was found that day 1 SPECT scans are of value for early localization of the acute ischaemic infarction. A multiple regression model was developed using both the day 30 Defect Volume index and segmental analysis score which related to the day 30 clinical scores. The day 1 model was unsatisfactory and no such model was found relating day 10 SPECT semi-quantitative methods to day 10 clinical scoring. Changes in semi-quantitative scores from day 1 to day 30 did not correlate with clinical changes. Longer follow up may be required for there to be value in performing SPECT scans in stroke trials. A prognostic equation was derived by multiple regression analysis of day 1 SPECT scan scores and day 30 clinical scores. / Andrew Chakane 2019

This thesis introduces the linear and nonlinear properties of photonic crystal fibre (PCF), describes the fabrication and characterisation of different PCFs, and demonstrates their applications to supercontinuum (SC) generation and single-photon sources. The linear properties of PCF include endlessly single-mode transmission, highly controllable dispersion and birefringence. These unique properties have made PCFs the best media to demonstrate all kinds of nonlinear effects such as self-phase modulation (SPM), cross-phase modulation (XPM), Raman effects, four-wave mixing and modulation instability (FWM and MI), and soliton effects. The combination of these nonlinear effects has led to impressive spectral broadening known as SC generation in PCFs. The intrinsic correlation of signal and idler photons from FWM has brought PCF to the application of single-photon generation. Four projects about SC generation were demonstrated. The first was visible continuum generation in a monolithic PCF device, which gave a compact, bright (-20 dBm/nm), flat and single-mode visible continuum source extending to short wavelength at 400 nm. The second was polarised SC generation in a highly bire-fringent PCF. A well linearly polarised continuum source spanning 450-1750 nm was achieved with >99% power kept in a single linear polarisation. This polarised continuum source was then applied to tuneable visible/UV generation in a BIBO crystal. The third was residual pump peak removal for SC generation in PCFs. The fourth was to design an all-fibre dual-wavelength pumping for spectrally localised continuum generation. Two projects about photon pair generation using FWM were then demonstrated. One was an all-fibre photon pair source designed in the telecom band for quantum communication. This source achieved >50% heralding efficiency which is the highest in fibre photon pair sources reported so far. Another one was to design birefringent PCFs for naturally narrow band photon pair generation in the Si SPAD high detection efficiency range. 0.122 nm bandwidth signal photons at 596.8 nm were generated through cross polarisation phase matched FWM in a weakly birefringent PCF pumped by a picosecond Ti:Sapphire laser at 705 nm in the normal dispersion regime.

Seizures are thought to arise primarily from the cerebral cortex. However, the propagation and behavioral manifestations of seizures involve a network of both cortical and subcortical structures. The medial thalamus and upper brainstem reticular formation are crucial areas for the maintenance of normal consciousness. Bilateral involvement of these structures may be responsible for loss of consciousness during partial seizures. Therefore, we sought to investigate the role of the medial thalamus and brainstem in seizures. We performed SPECT ictal-interictal difference imaging co-registered with high-resolution MRI scans to localize regions of cerebral blood flow changes in patients undergoing inpatient monitoring for epilepsy. Ictal-interictal SPECT scans from 43 seizures in 40 patients were analyzed. The medial thalami showed SPECT difference imaging changes of >20% in 18 patients. Of patients with medial thalamic changes, the majority (13 of 18) had seizure onset in the temporal lobe, while only 1 had confirmed onset in extratemporal structures, and the remainder were non-localized. In contrast, in the 22 patients without >20% SPECT changes in the medial thalami, 6 had extratemporal onset, 6 had temporal onset, and the remainder were non-localized. In patients with temporal lobe seizures, the side of greater medial thalamic and brainstem reticular formation involvement was strongly related to SPECT injection timing such that there was a sequential pattern of ipsilateral followed by contralateral changes. Brainstem structures showed >20% SPECT changes in 27 of 43 seizures with no clear relation to temporal or extratemporal onset. We conclude that the medial thalamus is preferentially involved in seizures arising from the temporal lobes, possibly reflecting the strong connections between limbic temporal structures and the medial thalamus. Sequential involvement of ipsilateral followed by contralateral structures in the medial thalamus and upper brainstem may explain how seizures produce peri-ictal loss of consciousness despite incomplete involvement of the cerebral cortex.

Quantum mechanics allows us to use nonclassical states of light to make measurements with a greater precision than comparable classical states. Here an experiment is presented that squeezes the polarization state of three photons. We demonstrate the deep connection that exists between squeezing and entanglement, unifying the squeezed state and multi-photon entangled state approaches to quantum metrology. For the first time we observe the phenomenon of over-squeezing where a system is squeezed to the point that further squeezing leads to a counter-intuitive increase in measurement uncertainty. Quasi-probability distributions on the surface of a Poincaré sphere are the most natural way to represent the topology of our polarization states. Using this representation it is easy to observe the squeezing and over-squeezing behaviour of our photon states. Work is also presented on two different technologies for generating nonclassical states of light. The first is based on the nonlinear process of spontaneous parametric downconversion to produce pairs of photons. With this source up to 200,000 pairs of photons/s have been collected into single-mode fibre, and over 100 double pairs/s have been detected. This downconversion source is suitable for use in a wide variety of multi-qubit quantum information applications. The second source presented is a single-photon source based on semiconductor quantum dots. The single-photon character of the source is verified using a Hanbury Brown-Twiss interferometer.