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In-beam positron emission tomography (in-beam PET) is currently the only method for an in-situ monitoring of highly tumor-conformed charged hadron therapy. In such therapy, the clinical effect of deviations from treatment planning is highly minimized by implementing safety margins around the tumor and selecting proper beam portals. Nevertheless, in-beam PET is able to detect eventual, undesirable range deviations and anatomical modifications during fractionated irradiation, to verify the accuracy of the beam portal delivered and to provide the radiotherapist with an estimation of the difference in dosage if the treatment delivered differs from the planned one. In a first study within this work, a set of simulation and fully-3D reconstruction routines shows that minimizing the opening angle of a cylindrical camera is determinant for an optimum quality of the in-beam PET images. The study yields two favorite detector geometries: a closed ring or a dual-head tomograph with narrow gaps. The implementation of either detector geometry onto an isocentric, ion beam delivery (gantry) is feasible by mounting the PET scanner at the beam nozzle. The implementation of an in-beam PET scanner with the mentioned detector geometries at therapeutic sites with a fixed, horizontal beam line is also feasible. Nevertheless, knowing that previous in-beam PET research in Berkeley was abandoned due to detector activation (Bismuth Germanate, BGO), arising most probably from passive beam shaping contaminations, the proposed detector configurations had to be tested in-beam. For that, BGO was substituted with a state-of-the-art scintillator (lutetium oxyorthosilicate, LSO) and two position sensitive detectors were built. Each detector contains 32 pixels, consisting of LSO finger-like crystals coupled to avalanche photodiode arrays (APDA). In order to readout the two detectors operated in coincidence, either in standalone mode or at the GSI medical beam line, a multi-channel, zero-suppressing free, list mode data acquisition system was built.The APDA were chosen for scintillation detection instead of photomultiplier tubes (PMT) due to their higher compactness and magnetic field resistance. A magnetic field resistant detector is necessary if the in-beam PET scanner is operated close to the last beam bending magnet, due to its fringe magnetic field. This is the case at the isocentric, ion beam delivery planned for the dedicated, heavy ion hospital facility under construction in Heidelberg, Germany. In-beam imaging with the LSO/APDA detectors positioned at small target angles, both upbeam and downbeam from the target, was successful. This proves that the detectors provide a solution for the proposed next-generation, improved in-beam PET scanners. Further confirming this result are germanium-detector-based, spectroscopic gamma-ray measurements: no scintillator activation is observed in patient irradiation conditions. Although a closed ring or a dual-head tomograph with narrow gaps is expected to provide improved in-beam PET images, low count rates in in-beam PET represent a second problem to image quality. More importantly, new accelerator developments will further enhance this problem to the point of making impossible in-beam PET data taking if the present acquisition system is used. For these reasons, two random-suppression methods allowing to collect in-beam PET events even during particle extraction were tested. Image counts raised almost twofold. This proves that the methods and associated data acquisition technique provide a solution for next-generation, in-beam positron emission tomographs installed at synchrotron or cyclotron radiotherapy facilities.

In-beam positron emission tomography (in-beam PET) is currently the only method for an in-situ monitoring of highly tumor-conformed charged hadron therapy. In such therapy, the clinical effect of deviations from treatment planning is highly minimized by implementing safety margins around the tumor and selecting proper beam portals. Nevertheless, in-beam PET is able to detect eventual, undesirable range deviations and anatomical modifications during fractionated irradiation, to verify the accuracy of the beam portal delivered and to provide the radiotherapist with an estimation of the difference in dosage if the treatment delivered differs from the planned one. In a first study within this work, a set of simulation and fully-3D reconstruction routines shows that minimizing the opening angle of a cylindrical camera is determinant for an optimum quality of the in-beam PET images. The study yields two favorite detector geometries: a closed ring or a dual-head tomograph with narrow gaps. The implementation of either detector geometry onto an isocentric, ion beam delivery (gantry) is feasible by mounting the PET scanner at the beam nozzle. The implementation of an in-beam PET scanner with the mentioned detector geometries at therapeutic sites with a fixed, horizontal beam line is also feasible. Nevertheless, knowing that previous in-beam PET research in Berkeley was abandoned due to detector activation (Bismuth Germanate, BGO), arising most probably from passive beam shaping contaminations, the proposed detector configurations had to be tested in-beam. For that, BGO was substituted with a state-of-the-art scintillator (lutetium oxyorthosilicate, LSO) and two position sensitive detectors were built. Each detector contains 32 pixels, consisting of LSO finger-like crystals coupled to avalanche photodiode arrays (APDA). In order to readout the two detectors operated in coincidence, either in standalone mode or at the GSI medical beam line, a multi-channel, zero-suppressing free, list mode data acquisition system was built.The APDA were chosen for scintillation detection instead of photomultiplier tubes (PMT) due to their higher compactness and magnetic field resistance. A magnetic field resistant detector is necessary if the in-beam PET scanner is operated close to the last beam bending magnet, due to its fringe magnetic field. This is the case at the isocentric, ion beam delivery planned for the dedicated, heavy ion hospital facility under construction in Heidelberg, Germany. In-beam imaging with the LSO/APDA detectors positioned at small target angles, both upbeam and downbeam from the target, was successful. This proves that the detectors provide a solution for the proposed next-generation, improved in-beam PET scanners. Further confirming this result are germanium-detector-based, spectroscopic gamma-ray measurements: no scintillator activation is observed in patient irradiation conditions. Although a closed ring or a dual-head tomograph with narrow gaps is expected to provide improved in-beam PET images, low count rates in in-beam PET represent a second problem to image quality. More importantly, new accelerator developments will further enhance this problem to the point of making impossible in-beam PET data taking if the present acquisition system is used. For these reasons, two random-suppression methods allowing to collect in-beam PET events even during particle extraction were tested. Image counts raised almost twofold. This proves that the methods and associated data acquisition technique provide a solution for next-generation, in-beam positron emission tomographs installed at synchrotron or cyclotron radiotherapy facilities.

Normal-hearing listeners can locate sound sources, using binaural cues for azimuth angle. These binaural differences in the timing and intensity of sound arriving at the two ears, interaural time differences (ITDs) and interaural intensity differences (IIDs), also support selective listening in multi-talker environments. Auditory-brainstem neurons of the medial superior olive (MSO) and lateral superior olive (LSO) encode ITD in the envelope of sound (ITDENV) and in the temporal fine structure of low-frequency sound (ITDTFS); LSO neurons encode IID. Bilateral-cochlear-implant (bCI) listeners generally receive only IID and ITDENV. Experimental bCI pulse-bursts overcome adaptation, and convey electrical ITDTFS. Improving the understanding of mechanisms for ITD sensitivity can help bCI developers convey acoustic ITDTFS. In this dissertation, models for auditory-brainstem neurons are developed that explain human ability to detect small differences in ITD, as neuronal and MSO population mechanisms. Promoting binaural-coincidence detection and limiting backpropagation, model MSO ion-channels set resting potentials that reproduce dendritic and somatic KLT activation, somatic Na+ inactivation, and a lower amount of axonal Na+ inactivation. Sensitivity to ITDTFS in moderately fast and very fast model MSO neurons collectively match physiological data from 150 to 2000 Hz. The best-ITD (the ITD of highest spike rate) can be made contralateral-leading, by contralateral inhibition of moderate speed, or by asymmetric axon location, leveraging dendritic filtering. Leveraging standard binaural-display models, neuronal populations based on these model MSO neurons match normal-hearing human discrimination thresholds for ITDTFS in sine tones from 39 to 1500 Hz. Adaptation before binaural interaction helps model MSO neurons glimpse the ITDTFS of sound direct from a source, before reflected sound arrives from different directions. With inputs from adapting model spherical bushy cells, a moderately fast model MSO neuron reproduces in vivo responses to amplitude-modulated binaural beats, with a frequency-dependent emphasis of rising vs. peak sound-pressure for ITDTFS encoding, which reflects human ITD detection and reverberation times in outdoor environments. Distinct populations of model LSO neurons, spanning the range of electrical membrane impedance as a function of frequency in LSO neurons, collectively reflect discrimination thresholds for ITDENV in transposed tones across carrier frequency (4-10 kHz) and modulation rate (32-800 Hz). / 2022-09-28T00:00:00Z

Positron-Emission-Tomography (PET) is a modern imaging technique in nuclear medicine providing quantitative 3D distribution of a radioactive tracer substance in the human body. The gamma-detector is the first link in the chain of components that constitutes a PET. It converts incoming radiation into optical light pulses, which are detected by photo multiplier tubes. Here the light is converted into electric pulses, to be further processed by the acquisition electronics. Improving detector sensitivity and resolution is of great value in research and in clinical practice. The focus of this work is to improve the detector to give it time-of-flight (TOF) capabilities, in order to further improve sensitivity, which in turn leads to increased image quality, faster scan time and/or reduced dose exposure for the patient. Image quality has improved over the years, but losses in image quality have been reported for heavy patients, due to increased attenuation, and more dispersed counts over a larger volume. Instrumentation limits are still significant in heavy patient images, but the incorporation of TOF information promises to alleviate some of the limitations. In order to improve the timing resolution of the detector fast photo-multipliers and a novel scheme to extract the event timing trigger from a detector by using the summed dynode signal were investigated. When designing new PET detectors, it is important to have detailed understanding and control of the light sharing mechanisms in the crystal arrays. Therefore it was necessary to perform optical simulations and single crystal light output measurements to derive a model for an LSO block detector. Another way to improve the image quality is to use the depth-of-interaction (DOI) of the gamma ray within the detector. It is shown that a multi-layer phoswich detector comprised of LSO with different decay times and TOF capability, combines the benefits of TOF and DOI in one detector, maximizing the effective sensitivity gain. / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 7: Submitted.

This thesis presents a distributed power-management architecture for concentrating photovoltaic (CPV) systems. Specifically, the Δ-conversion scheme with voltage equalization is analyzed and verified for the CPV system from Morgan Solar, Inc. This architecture uses inverting buck-boost converters, denoted Δ-converters, which equalize the voltages of neighbouring CPV cells in a series-connected string of cells and improve the systems tolerance to parameter variations. The power benefits of Δ-conversion and the Δ-converter current distributions are investigated using statistical simulations. The effectiveness of Δ-conversion in the presence of randomly distributed mismatches is demonstrated, and current cascading is identified as the main design challenge. The Δ-converter is modelled and compensated using Middlebrook's Extra Element Theorem. Analysis of measured data from a six-cell CPV system demonstrate the benefits of Δ-conversion under realistic scenarios. Experimental results from prototype systems show up to 31% power benefits in the presence of mismatches.

This thesis presents a distributed power-management architecture for concentrating photovoltaic (CPV) systems. Specifically, the Δ-conversion scheme with voltage equalization is analyzed and verified for the CPV system from Morgan Solar, Inc. This architecture uses inverting buck-boost converters, denoted Δ-converters, which equalize the voltages of neighbouring CPV cells in a series-connected string of cells and improve the systems tolerance to parameter variations. The power benefits of Δ-conversion and the Δ-converter current distributions are investigated using statistical simulations. The effectiveness of Δ-conversion in the presence of randomly distributed mismatches is demonstrated, and current cascading is identified as the main design challenge. The Δ-converter is modelled and compensated using Middlebrook's Extra Element Theorem. Analysis of measured data from a six-cell CPV system demonstrate the benefits of Δ-conversion under realistic scenarios. Experimental results from prototype systems show up to 31% power benefits in the presence of mismatches.

Sound localization is a vital aspect of hearing for safe navigation of everyday environments. It is also an important factor in speech intelligibility. This ability is facilitated by the interaural level difference (ILD) cue, which arises from binaural hearing: a sound will be more intense at the nearer ear than the farther. In a hearing-impaired listener, this binaural cue may not be available for use and localization may be diminished. While conventional, bilateral, wide dynamic range compression (WDRC) hearing aids distort the interaural level difference by independently altering sound intensities in each ear, wirelessly-linked devices have been suggested to benefit this task by matching amplification in order to preserve ILD. However, this technology has been shown to have varying degrees of success in aiding speech intelligibility and sound localization. As hearing impairment has wide-ranging adverse impacts to physical and mental health, social activity, and cognition, the task of localization improvement must be urgently addressed. Toward this end, neural modelling techniques are used to determine neural representations of ILD cues for linked and unlinked bilateral WDRC hearing aids. Findings suggest that wirelessly-linked WDRC is preferable over unlinked hearing aids or unaided, hearing-impaired listening, although parameters for optimal benefit are dependent on sound level, frequency content, and preceding sounds. / Thesis / Master of Applied Science (MASc)