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 / At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 7: Submitted.

In modern clinical practice, gamma camera is one of the most important imaging modalities for tumour diagnosis. The standard technique uses scintillator-based gamma cameras equipped with parallel-hole collimator to detect the planar position of γ photon interaction (scintillation). However, the positioning is of insufficient resolution and linearity for breast imaging. With the aim to improve spatial resolution and positioning linearity, a new gamma camera configuration was described specifically for breast-imaging. This breast-specific gamma camera was supposed to have the following technical features: variable angle slant-hole collimator; double SiPM arrays readout at the front and back sides of the scintillator; diffusive reflectors at the edges around the scintillator. Because slant-hole collimator was used, a new 3D scintillation positioning method was introduced and tested. The setup of the gamma detector was created in a Monte Carlo simulation toolkit, and a library of a number of light distributions from known positions was acquired through optical simulation. Two library-based positioning algorithms, similarity comparison and maximum likelihood, were developed to estimate the 3D scintillation position by comparing the responses from simulated gamma interactions and the responses from library. Results indicated that the planar spatial resolution and positioning linearity estimated with this gamma detector setup and positioning algorithm was higher than the conventional gamma detectors. The depth-of-interaction estimation was also of high linearity and resolution. With the results presented, the gamma detector setup and positioning method is promising in future breast cancer diagnosis.

<p>The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors.</p><p>The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects.</p><p>The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation.</p><p>The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction.</p><p>Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed.</p><p>From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.</p>

The major advantage of position sensitive radiation detector systems lies in their ability to non invasively map the regional distribution of the emitted radiation in real-time. Three of such detector systems were studied in this thesis, gamma-cameras, positron cameras and CMOS image sensors. A number of physical factors associated to these detectors degrade the qualitative and quantitative properties of the obtained images. These blurring factors could be divided into two groups. The first group consists of the general degrading factors inherent to the physical interaction processes of radiation with matter, such as scatter and attenuation processes which are common to all three detectors The second group consists of specific factors inherent to the particular radiation detection properties of the used detector which have to be separately studied for each detector system. Therefore, the aim of this thesis was devoted to the development of computational methods to enable quantitative molecular imaging in PET, SPET and in vivo patient dosimetry with CMOS image sensors. The first task was to develop a novel quantitative dual isotope method for simultaneous assessments of regional lung ventilation and perfusion using a SPET technique. This method included correction routines for photon scattering, non uniform attenuation at two different photon energies (140 and 392 keV) and organ outline. This quantitative method was validated both with phantom experiments and physiological studies on healthy subjects. The second task was to develop and clinically apply a quantitative method for tumour to background activity uptake measurements using planar mammo-scintigraphy, with partial volume compensation. The third stage was to produce several computational models to assess the spatial resolution limitations in PET from the positron range, the annihilation photon non-collineairy and the photon depth of interaction. Finally, a quantitative image processing method for a CMOS image sensor for applications in ion beam therapy dosimetry was developed. From the obtained phantom and physiological results it was concluded that the methodologies developed for the simultaneous measurement of the lung ventilation and perfusion and for the quantification of the tumour malignancy grade in breast carcinoma were both accurate. Further, the obtained models for the influence that the positron range in various human tissues, and the photon emission non-collinearity and depth of interaction have on PET image spatial resolution, could be used both to optimise future PET camera designs and spatial resolution recovery algorithms. Finally, it was shown that the proton fluence rate in a proton therapy beam could be monitored and visualised by using a simple and inexpensive CMOS image sensor.

Current positron emission mammography (PEM) depth of interaction (DOI) enabling detectors have low scintillator to photodetector encoding ratios, RE causing high system complexity and cost. The modularized dual-ended readout block (DERB) detector combines the Anger logic block detector with dual-ended readout to increase RE while measuring DOI. To investigate the trade-off between RE and spatial resolution, scalable DERB detectors with varying RE and light guide thickness were modelled with Monte- Carlo. Simulation showed RE can increase up to six-fold compared to the dual-ended readout design without significantly degrading spatial resolution. Experimental characterization of a RE = 9 : 8 DERB detector was found to achieve super-resolution <0.5 mm for resolving crystal indices, DOI resolution of ~5 mm FWHM, and mean energy resolution of 20% without recovering photons lost to neighbouring detector modules. The model was validated by agreement of simulation results adjusted for detector quantum efficiency with experimental results.

Current positron emission mammography (PEM) depth of interaction (DOI) enabling detectors have low scintillator to photodetector encoding ratios, RE causing high system complexity and cost. The modularized dual-ended readout block (DERB) detector combines the Anger logic block detector with dual-ended readout to increase RE while measuring DOI. To investigate the trade-off between RE and spatial resolution, scalable DERB detectors with varying RE and light guide thickness were modelled with Monte- Carlo. Simulation showed RE can increase up to six-fold compared to the dual-ended readout design without significantly degrading spatial resolution. Experimental characterization of a RE = 9 : 8 DERB detector was found to achieve super-resolution <0.5 mm for resolving crystal indices, DOI resolution of ~5 mm FWHM, and mean energy resolution of 20% without recovering photons lost to neighbouring detector modules. The model was validated by agreement of simulation results adjusted for detector quantum efficiency with experimental results.