Medical molecular imaging with positron emission tomography (PET) is sensitive to patient motion since PET scans last several minutes. Despite advancements in PET, such as improved photon-pair time-of-flight (TOF) difference resolution, motion deformations limit image resolution and quantification. Previous research of head motion tracking has produced the data-driven centroid-of-distribution (COD) algorithm. COD generates a 3D center-of-mass (COM) over time via raw list-mode PET data, which can guide motion correction such as gating and event rebinning in non-TOF PET. Knowledge gaps: COD could potentially benefit from sinogram corrections used in image reconstruction, while rebinning has not extended to TOF PET. Methods: This study develops COD with event mass (incorporating random correction and line-of-response (LOR) normalization) and a simplistic TOF rebinner. In scans of phantoms and moving heads with F11 flouro-deoxy-glucose (FDG) tracer, COD alternatives are evaluated with a signal-to-noise ratio (SNR) via linear fit to image COM, while rebinning is evaluated with mean squared error (MSE). Results: COD SNR did not benefit from a corrected event mass. The prototype TOF rebinning reduced MSE, although there were discretization errors and event loss at extreme bins for LOR and TOF due to the simplistic design, which introduced image artifacts. In conclusion, corrected event mass in COD is not promising, while TOF rebinning appears viable if techniques from state-of-the-art LOR rebinning are incorporated.

In this thesis, we develop a motion correction method to overcome the degradation of image quality introduced by respiratory motion in positron emission tomography (PET), so that diagnostic performance for lung cancer can be improved. Lung cancer is currently the most common cause of cancer death both in the UK and in the world. PET/CT, which is a combination of PET and CT, providing clinicians with both functional and anatomical information, is routinely used as a non-invasive imaging technique to diagnose and stage lung cancer. However, since a PET scan normally takes 15-30 minutes, respiration is inevitable in data acquisition. As a result, thoracic PET images are substantially degraded by respiratory motion, not only by being blurred, but also by being inaccurately attenuation corrected due to the mismatch between PET and CT. If these challenges are not addressed, the diagnosis of lung cancer may be misled. The main contribution of this thesis is to propose a novel process for respiratory motion correction, in which non-attenuation corrected PET images (PET-NAC) are registered to a reference position for motion correction and then multiplied by a voxel-wise attenuation correction factor (ACF) image for attenuation correction. The ACF image is derived from a CT image which matches the reference position, so that no attenuation correction artefacts would occur. In experiments, the motion corrected PET images show significant improvements over the uncorrected images, which represent the acquisitions typical of current clinical practice. The enhanced image quality means that our method has the potential to improve diagnostic performance for lung cancer. We also develop an automatic lesion detection method based on motion corrected images. A small lung lesion is only 2 or 3 voxels in diameter and of marginal contrast. It could easily be missed by human observers. Our method aims to provide radiologists with a map of potential lesions for decision so that diagnostic efficiency can be improved. It utilises both PET and CT images. The CT image provides a lung mask, to which lesion detection is confined, whereas the PET image provides distribution of glucose metabolism, according to which lung lesions are detected. Experimental results show that respiratory motion correction significantly increases the success of lesion detection, especially for small lesions, and most of the lung lesions can be detected by our method. The method can serve as a useful computer-aided image analysing tool to help radiologists read images and find malignant lung lesions. Finally, we explore the possibility of incorporating temporal information into respiratory motion correction. Conventionally, respiratory gated PET images are individually registered to the reference position. Temporal continuity across the respiratory period is not considered. We propose a spatio-temporal registration algorithm, which models temporally smooth deformation in order to improve the registration performance. However, we discover that the improvement introduced by temporal information is relatively small at the cost of a much longer computation time. Spatial registration with regularisation yields similar results but is superior in speed. Therefore, it is preferable for respiratory motion correction.

When patients move during an MRI examination, severe artifacts arise in the reconstructed image and motion correction is therefore often desired. An in-plane motion correction algorithm suitable for PRESTO-CAN, a new 3D functional MRI method where sampling of k-space is radial in kx-direction and kz-direction and Cartesian in ky-direction, was implemented in this thesis work. Rotation and translation movements can be estimated and corrected for sepa- rately since the magnitude of the data is only affected by the rotation. The data were sampled in a radial pattern and the rotation was estimated by finding the translation in angular direction using circular correlation. Correlation was also used when finding the translation in x-direction and z-direction. The motion correction algorithm was evaluated on computer simulated data, the motion was detected and corrected for, and this resulted in images with greatly reduced artifacts due to patient movements. / När patienter rör sig under en MRI-undersökning uppstår artefakter i den rekonstruerande bilden och därför är det önskvärt med rörelsekorrigering. En 2D- rörelsekorrigeringsalgoritm som är anpassad för PRESTO-CAN har tagits fram. PRESTO-CAN är en ny fMRI-metod för 3D där samplingen av k-rummet är radiell i (kx,kz)-planet och kartesisk i ky-riktningen. Rotations- och translationsrörelser kan estimeras separat då magnituden av signalen bara påverkas av rotationsrörelser. Eftersom data är samplat radiellt kan rotationen estimeras genom att hitta translationen i vinkelled med hjälp av cirkulär korrelation. Korrelation används även för att hitta translationen i i x- och z-riktningen. Test på simulerat data visar att rörelsekorrigeringsalgoritmen både detekterar och korrigerar för rörelser vilket leder till bilder med mycket mindre rörelseartefakter.

<p>Diffusion tensor imaging (DTI) has emerged as a unique method to characterize brain tissue microstructure non-invasively. DTI typically provides the ability to study white matter structure with a standard voxel resolution of 8&mu;L over imaging field-of-views of the extent of the human brain. As such, it has long been recognized as a promising tool not only in clinical research for the diagnostic and monitoring of white matter diseases, but also for investigating the fundamental biological principles underlying the organization of long and short-range cortical networks. However, the complexity of brain structure within an MRI voxel makes it difficult to dissociate the tissue origins of the measured anisotropy. The tensor characterization is a composite result of proton pools in different tissue and cell structures with diverse diffusion properties. As such, partial volume effects introduce a strong bias which can lead to spurious measurements, especially in regions with a complex tissue structure such as interdigitating crossing fibers or in convoluted cortical folds near the grey/white matter interface.</p><p>This dissertation focuses on the design and development of acquisition and image reconstruction strategies to improve the spatial resolution of diffusion imaging. After a brief review of the theory of diffusion MRI and of the basic principles of streamline tractography in the human brain, the main challenges to increasing the spatial resolution are discussed. A comprehensive characterization of artifacts due to motion and field inhomogeneities is provided and novel corrective methods are proposed to enable the acquisition of diffusion weighted data with 2D mulitslice imaging techniques with full brain coverage, increased SNR and high spatial resolutions of 1.25&times;1.25&times;1.25 mm<super>3</super> within an acceptable scan time. The method is extended to a multishot k_{_z}-encoded 3D multislab spiral DTI and evaluated in normal human volunteers.</p><p>To demonstrate the increased SNR and enhanced resolution capability of the proposed methods and more generally to assess the value of high-spatial resolution in diffusion imaging, a study of cortical depth-dependence of fractional anisotropy was performed at an unprecedented <italic>in-vivo</italic> inplane resolution of 0.390&times;0.390&mu;m<super>2</super> and an investigation of the trade-offs between spatial resolution and cortical specificity was conducted within the connectome framework.</p> / Dissertation

Since its inception around 1975, Positron Emission Tomography (PET) has proved to be an important tool in medical research as it allows imaging of the brain function in vivo with high sensitivity. It has been widely used in clinical dementia research with [18F]2-Fluoro-2-Deoxy-D-Glucose (FDG) and amyloid tracers as imaging biomarkers in Alzheimer's Disease (AD). The high resolution offered by modern scanner technology has the potential to provide new insight into the interaction of structural and functional changes in AD. However, the high resolution of PET is currently limited by movement and resolution (even for high resolution dedicated brain PET scanner) which results in partial volume effects, the undersampling of activity within small structures. A modified frame-by-frame (FBF) realignment algorithm has been developed that uses estimates of the centroid of activity within the brain to detect movement and subsequently reframe data to correct for intra-frame movement. The ability of the centroid to detect motion was assessed and the added benefit of reframing data for real clinical scans with patient motion was evaluated through comparison with existing FBF algorithms. Visual qualitative analysis on 6 FDG PET scans from 4 blinded observers demonstrated notable improvements (ANOVA with Tukey test, p < 0.001) and time-activity curves were found to deliver biologically more plausible activity concentrations. A new method for Partial Volume Correction (PVC) is also proposed, PARtially-Segmented Lucy-Richardson (PARSLR),that combines the strength of image based deconvolution approach of the Lucy-Richardson (LR) Iterative Deconvolution Algorithm with a partial segmentation of homogenous regions. Such an approach is of value where reliable segmentation is possible for part but not all of the image volume or sub-volume. Its superior performance with respect to region-based methods like Rousset or voxel-based methods like LR was successfully demonstrated via simulations and measured phantom data. The approach is of particular importance for studies with pathological abnormalities where complete and accurate segmentation across or with a sub-volume of the image volume is challenging and for regions of the brain containing heterogeneous structures which cannot be accurately segmented from co-registered images. The developed methods have been shown to recover radioactivity concentrations from small structures in the presence of motion and limited resolution with higher accuracy when compared to existing methods. It is expected that they will contribute significantly to future PET studies where accurate quantitation in small or atrophic brain structures is essential.

Positron emission tomography (PET) requires imaging times that last several minutes long. Therefore, when imaging areas that are prone to respiratory motion, blurring effects are often observed. This blurring can impair our ability to use these images for diagnostics purposes as well for treatment planning. While there are methods that are used to account for this effect, they often rely on adjustments to the imaging protocols in the form of longer scan times or subjecting the patient to higher doses of radiation. This dissertation explores an alternative approach that leverages state-of-the-art deep learning techniques to align the PET signal acquired at different points of the breathing motion. This method does not require adjustments to standard clinical protocols; and therefore, is more efficient and/or safer than the most widely adopted approach. To help validate this method, Monte Carlo (MC) simulations were conducted to emulate the PET imaging process, which represent the focus of our first experiment. The next experiment was the development and testing of our motion correction method. A clinical four-ring PET imaging system was modelled using GATE (v. 9.0). To validate the simulations, PET images were acquired of a cylindrical phantom, point source, and image quality phantom with the modeled system and the experimental procedures were also simulated. The simulations were compared against the measurements in terms of their count rates and sensitivity as well as their image uniformity, resolution, recovery coefficients, coefficients of variation, contrast, and background variability. When compared to the measured data, the number of true detections in the MC simulations was within 5%. The scatter fraction was found to be (31.1 ± 1.1)% and (29.8 ± 0.8)% in the measured and simulated scans, respectively. Analyzing the measured and simulated sinograms, the sensitivities were found to be 10.0 cps/kBq and 9.5 cps/kBq, respectively. The fraction of random coincidences were 19% in the measured data and 25% in the simulation. When calculating the image uniformity within the axial slices, the measured image exhibited a uniformity of (0.015 ± 0.005), while the simulated image had a uniformity of (0.029 ± 0.011). In the axial direction, the uniformity was measured to be (0.024 ± 0.006) and (0.040 ± 0.015) for the measured and simulated data, respectively. Comparing the image resolution, an average percentage difference of 2.9% was found between the measurements and simulations. The recovery coefficients calculated in both the measured and simulated images were found to be within the EARL ranges, except for that of the simulation of the smallest sphere. The coefficients of variation for the measured and simulated images were found to be 12% and 13%, respectively. Lastly, the background variability was consistent between the measurements and simulations, while the average percentage difference in the sphere contrasts was found to be 8.8%. The code used to run the GATE simulations and evaluate the described metrics has been made available (https://github.com/teaghan/PET_MonteCarlo). Next, to correct for breathing motion in PET imaging, an interpretable and unsupervised deep learning technique, FlowNet-PET, was constructed. The network was trained to predict the optical flow between two PET frames from different breathing amplitude ranges. As a result, the trained model groups different retrospectively-gated PET images together into a motion-corrected single bin, providing a final image with similar counting statistics as a non-gated image, but without the blurring effects that were initially observed. As a proof-of-concept, FlowNet-PET was applied to anthropomorphic digital phantom data, which provided the possibility to design robust metrics to quantify the corrections. When comparing the predicted optical flows to the ground truths, the median absolute error was found to be smaller than the pixel and slice widths, even for the phantom with a diaphragm movement of 21 mm. The improvements were illustrated by comparing against images without motion and computing the intersection over union (IoU) of the tumors as well as the enclosed activity and coefficient of variation (CoV) within the no-motion tumor volume before and after the corrections were applied. The average relative improvements provided by the network were 54%, 90%, and 76% for the IoU, total activity, and CoV, respectively. The results were then compared against the conventional retrospective phase binning approach. FlowNet-PET achieved similar results as retrospective binning, but only required one sixth of the scan duration. The code and data used for training and analysis has been made publicly available (https://github.com/teaghan/FlowNet_PET). The encouraging results provided by our motion correction method present the opportunity for many possible future applications. For instance, this method can be transferred to clinical patient PET images or applied to alternative imaging modalities that would benefit from similar motion corrections. When applied to clinical PET images, FlowNet-PET would provide the capability of acquiring high quality images without the requirement for either longer scan times or subjecting the patients to higher doses of radiation. Accordingly, the imaging process would likely become more efficient and/or safer, which would be appreciated by both the health care institutions and their patients. / Graduate

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As a modern tomographic technique, Positron-Emission-Tomography (PET) enables non-invasive imaging of metabolic processes in living organisms. It allows the visualization of malfunctions which are characteristic for neurological, cardiological, and oncological diseases. Chemical tracers labeled with radioactive positron emitting isotopes are injected into the patient and the decay of the isotopes is then observed with the detectors of the tomograph. This information is used to compute the spatial distribution of the labeled tracers. Since the spatial resolution of PET devices increases steadily, the whole sensitive process of tomograph imaging requires minimizing not only the disturbing effects, which are specific for the PET measurement method, such as random or scattered coincidences, but also external effects like body movement of the patient. Methods to correct the influences of such patient movement have been developed in previous studies at the PET center, Rossendorf. These methods are based on the spatial correction of each registered coincidence. However, the large amount of data and the complexity of the correction algorithms limited the application to selected studies. The aim of this thesis is to optimize the correction algorithms in a way that allows movement correction in routinely performed PET examinations. The object-oriented development in C++ with support of the platform independent Qt framework enables the employment of multiprocessor systems. In addition, a graphical user interface allows the use of the application by the medical assistant technicians of the PET center. Furthermore, the application provides methods to acquire and administrate movement information directly from the motion tracking system via network communication. Due to the parallelization the performance of the new implementation demonstrates a significant improvement. The parallel optimizations and the implementation of an intuitive usable graphical interface finally enables the PET center Rossendorf to use movement correction in routine patient investigations, thus providing patients an improved tomograph imaging. / Die Positronen-Emissions-Tomographie (PET) ist ein modernes medizinisches Diagnoseverfahren, das nichtinvasive Einblicke in den Stoffwechsel lebender Organismen ermöglicht. Es erfasst Funktionsstörungen, die für neurologische, kardiologische und onkologische Erkrankungen charakteristisch sind. Hierzu werden dem Patienten radioaktive, positronen emittierende Tracer injiziert. Der radioaktive Zerfall der Isotope wird dabei von den umgebenden Detektoren gemessen und die Aktivitätsverteilung durch Rekonstruktionsverfahren bildlich darstellbar gemacht. Da sich die Auflösung solcher Tomographen stetig verbessert und somit sich der Einfluss von qualitätsmindernden Faktoren wie z.B. das Auftreten von zufälligen oder gestreuten Koinzidenzen erhöht, gewinnt die Korrektur dieser Einflüsse immer mehr an Bedeutung. Hierzu zählt unter anderem auch die Korrektur der Einflüsse eventueller Patientenbewegungen während der tomographischen Untersuchung. In vorangegangenen Studien wurde daher am PET Zentrum Rossendorf ein Verfahren entwickelt, um die nachträgliche listmode-basierte Korrektur dieser Bewegungen durch computergestützte Verfahren zu ermöglichen. Bisher schränkte der hohe Rechenaufwand den Einsatz dieser Methoden jedoch ein. Diese Arbeit befasst sich daher mit der Aufgabe, durch geeignete Parallelisierung der Korrekturalgorithmen eine Optimierung dieses Verfahrens in dem Maße zu ermöglichen, der einen routinemässigen Einsatz während PET Untersuchungen erlaubt. Hierbei lässt die durchgeführte objektorientierte Softwareentwicklung in C++ , unter Zuhilfenahme des plattformübergreifenden Qt Frameworks, eine Nutzung von Mehrprozessorsystemen zu. Zusätzlich ermöglicht eine graphische Oberfläche die Bedienung einer solchen Bewegungskorrektur durch die medizinisch technischen Assistenten des PET Zentrums. Um darüber hinaus die Administration und Datenakquisition der Bewegungsdaten zu ermöglichen, stellt die entwickelte Anwendung Funktionen bereit, die die direkte Kommunikation mit dem Bewegungstrackingsystem erlauben. Es zeigte sich, dass durch die Parallelisierung die Geschwindigkeit wesentlich gesteigert wurde. Die parallelen Optimierungen und die Implementation einer intuitiv nutzbaren graphischen Oberfläche erlaubt es dem PET Zentrum nunmehr Bewegungskorrekturen innerhalb von Routineuntersuchungen durchzuführen, um somit den Patienten ein verbessertes Bildgebungsverfahren bereitzustellen.

Respiratory motion during PET acquisition degrades image quality. It is mainly the area around the thorax and abdomen which is affected. External devices do provide respiratory gating solutions but are time-consuming to set up on patients and may not always be available. A data-driven gating (DDG) method based on principal component analysis (PCA) was found to provide a reliable respiratory gating signal, discriminating the need for external gating systems with FDG, but it remains to be investigated how well it performs with other PET tracers. The HER2-targeting radiotracer 68Ga-ABY-025 is currently in phase 3 development and is aimed to develop methods to select breast cancer patients that benefit from HER2-targeted treatment. Hence, absolute quantification is important. Respiratory motion correction will be important for improved quantitative accuracy since many patients have metastases in the lower part of the lungs or the liver.  DDG was applied to PET/CT list mode data retrospectively using quiescent period gating. Gated images were then compared to reconstructions without gating with a matched number of coincidences. Two iterative reconstructions were evaluated, TOF OSEM (3 iterations, 16 subsets, and a 5 mm gaussian postprocessing filter) and TOF BSREM β 400. Images were evaluated for standardized uptake value (SUV) changes for well-defined lesions in thorax and abdomen where respiratory motion is prevalent. Respiratory motion was detected in a mean 2.1 bed positions per examination. DDG application resulted in a mean increase of 12.7% in SUVmax for TOF OSEM reconstruction (p=0.0156).

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