Multiple Particle Positron Emission Particle Tracking and its Application to Flows in Porous Media

Positron emission particle tracking (PEPT) is a method for flow interrogation capable of measurement in opaque systems. In this work a novel method for PEPT is introduced that allows for simultaneous tracking of multiple tracers. This method (M-PEPT) is adapted from optical particle tracking techniques and is designed to track an arbitrary number of positron-emitting tracer-particles entering and leaving the field of view of a detector array. M-PEPT is described, and its applicability is demonstrated for a number of measurements ranging from turbulent shear flow interrogation to cell migration. It is found that this method can locate over 80 particles simultaneously with spatial resolution of order 0.2 mm at tracking frequency of 10 Hz and, at lower particle number densities, can achieve similar spatial resolution at tracking frequency 1000 Hz. The method is limited in its ability to resolve particles approaching close to one another, and suggestions for future improvements are made.M-PEPT is used to study flow in porous media constructed from packing of glass beads of different diameters. Anomalous (i.e. non-Fickian) dispersion of tracers is studied in these systems under the continuous time random walk (CTRW) paradigm. Pore-length transition time distributions are measured, and it is found that in all cases, these distributions indicate the presence of long waiting times between transitions, confirming the central assumption of the CTRW model. All systems demonstrate non-Fickian spreading of tracers at early and intermediate times with a late time recovery of Fickian dispersion, but a clear link between transition time distributions and tracer spreading is not made. Velocity increment statistics are examined, and it is found that temporal velocity increments in the mean-flow direction show a universal scaling. Spatial velocity increments also appear to collapse to a similar form, but there is insufficient data to determine the presence of universal scaling

Novel PET Systems and Image Reconstruction with Actively Controlled Geometry

Positron Emission Tomography (PET) provides in vivo measurement of imaging ligands that are labeled with positron emitting radionuclide. Since its invention, most PET scanners have been designed to have a group of gamma ray detectors arranged in a ring geometry, accommodating the whole patient body. Virtual Pinhole PET incorporates higher resolution detectors being placed close to the Region-of-Interest (ROI) within the imaging Field-of-View (FOV) of the whole-body scanner, providing better image resolution and contrast recover. To further adapt this technology to a wider range of diseases, we proposed a second generation of virtual pinhole PET using actively controlled high resolution detectors integrated on a robotic arm. When the whole system is integrated to a commercial PET scanner, we achieved positioning repeatability within 0.5 mm. Monte Carlo simulation shows that by focusing the high-resolution detectors to a specific organ of interest, we can achieve better resolution, sensitivity and contrast recovery. In another direction, we proposed a portable, versatile and low cost PET imaging system for Point-of-Care (POC) applications. It consists of one or more movable detectors in coincidence with a detector array behind a patient. The movable detectors make it possible for the operator to control the scanning trajectory freely to achieve optimal coverage and sensitivity for patient specific imaging tasks. Since this system does not require a conventional full ring geometry, it can be built portable and low cost for bed-side or intraoperative use. We developed a proof-of-principle prototype that consists of a compact high resolution silicon photomultiplier detector mounted on a hand-held probe and a half ring of conventional detectors. The probe is attached to a MicroScribe device, which tracks the location and orientation of the probe as it moves. We also performed Monte Carlo simulations for two POC PET geometries with Time-of-Flight (TOF) capability. To support the development of such PET systems with unconventional geometries, a fully 3D image reconstruction framework has been developed for PET systems with arbitrary geometry. For POC PET and the second generation robotic Virtual Pinhole PET, new challenges emerge and our targeted applications require more efficiently image reconstruction that provides imaging results in near real time. Inspired by the previous work, we developed a list mode GPU-based image reconstruction framework with the capability to model dynamically changing geometry. Ordered-Subset MAP-EM algorithm is implemented on multi-GPU platform to achieve fast reconstruction in the order of seconds per iteration, under practical data rate. We tested this using both experimental and simulation data, for whole body PET scanner and unconventional PET scanners. Future application of adaptive imaging requires near real time performance for large statistics, which requires additional acceleration of this framework

SURGICAL NAVIGATION AND AUGMENTED REALITY FOR MARGINS CONTROL IN HEAD AND NECK CANCER

I tumori maligni del distretto testa-collo rappresentano un insieme di lesioni dalle diverse caratteristiche patologiche, epidemiologiche e prognostiche. Per una porzione considerevole di tali patologie, l’intervento chirurgico finalizzato all’asportazione completa del tumore rappresenta l’elemento chiave del trattamento, quand’anche esso includa altre modalità quali la radioterapia e la terapia sistemica. La qualità dell’atto chirurgico ablativo è pertanto essenziale al fine di garantire le massime chance di cura al paziente. Nell’ambito della chirurgia oncologica, la qualità delle ablazioni viene misurata attraverso l’analisi dello stato dei margini di resezione. Oltre a rappresentare un surrogato della qualità della resezione chirurgica, lo stato dei margini di resezione ha notevoli implicazioni da un punto di vista clinico e prognostico. Infatti, il coinvolgimento dei margini di resezione da parte della neoplasia rappresenta invariabilmente un fattore prognostico sfavorevole, oltre che implicare la necessità di intensificare i trattamenti postchirurgici (e.g., ponendo indicazione alla chemioradioterapia adiuvante), comportando una maggiore tossicità per il paziente. La proporzione di resezioni con margini positivi (i.e., coinvolti dalla neoplasia) nel distretto testa-collo è tra le più elevate in ambito di chirurgia oncologica. In tale contesto si pone l’obiettivo del dottorato di cui questa tesi riporta i risultati. Le due tecnologie di cui si è analizzata l’utilità in termini di ottimizzazione dello stato dei margini di resezione sono la navigazione chirurgica con rendering tridimensionale e la realtà aumentata basata sulla videoproiezione di immagini. Le sperimentazioni sono state svolte parzialmente presso l’Università degli Studi di Brescia, parzialmente presso l’Azienda Ospedale Università di Padova e parzialmente presso l’University Health Network (Toronto, Ontario, Canada). I risultati delle sperimentazioni incluse in questo elaborato dimostrano che l'impiego della navigazione chirurgica con rendering tridimensionale nel contesto di procedure oncologiche ablative cervico-cefaliche risulta associata ad un vantaggio significativo in termini di riduzione della frequenza di margini positivi. Al contrario, le tecniche di realtà aumentata basata sulla videoproiezione, nell'ambito della sperimentazione preclinica effettuata, non sono risultate associate a vantaggi sufficienti per poter considerare tale tecnologia per la traslazione clinica.Head and neck malignancies are an heterogeneous group of tumors. Surgery represents the mainstay of treatment for the large majority of head and neck cancers, with ablation being aimed at removing completely the tumor. Radiotherapy and systemic therapy have also a substantial role in the multidisciplinary management of head and neck cancers. The quality of surgical ablation is intimately related to margin status evaluated at a microscopic level. Indeed, margin involvement has a remarkably negative effect on prognosis of patients and mandates the escalation of postoperative treatment by adding concomitant chemotherapy to radiotherapy and accordingly increasing the toxicity of overall treatment. The rate of margin involvement in the head and neck is among the highest in the entire field of surgical oncology. In this context, the present PhD project was aimed at testing the utility of 2 technologies, namely surgical navigation with 3-dimensional rendering and pico projector-based augmented reality, in decreasing the rate of involved margins during oncologic surgical ablations in the craniofacial area. Experiments were performed in the University of Brescia, University of Padua, and University Health Network (Toronto, Ontario, Canada). The research activities completed in the context of this PhD course demonstrated that surgical navigation with 3-dimensional rendering confers a higher quality to oncologic ablations in the head and neck, irrespective of the open or endoscopic surgical technique. The benefits deriving from this implementation come with no relevant drawbacks from a logistical and practical standpoint, nor were major adverse events observed. Thus, implementation of this technology into the standard care is the logical proposed step forward. However, the genuine presence of a prognostic advantage needs longer and larger study to be formally addressed. On the other hand, pico projector-based augmented reality showed no sufficient advantages to encourage translation into the clinical setting. Although observing a clear practical advantage deriving from the projection of osteotomy lines onto the surgical field, no substantial benefits were measured when comparing this technology with surgical navigation with 3-dimensional rendering. Yet recognizing a potential value of this technology from an educational standpoint, the performance displayed in the preclinical setting in terms of surgical margins optimization is not in favor of a clinical translation with this specific aim

The role of turbulence on the bubble-particle collision – An experimental study with particle tracking methods

Die Analyse von Kollisionen zwischen Partikeln und Blasen in einer turbulenten Strömung ist ein grundlegendes Problem von hoher technologischer Relevanz, z. B. für die Abtrennung wertvoller Mineralpartikel durch Schaumflotation. Dieser Relevanz steht ein Defizit an experimentellen Daten und Erkenntnissen über den Kollisionsprozess gegenüber. Ein Hauptproblem ist die geringe Anzahl der verfügbaren Messtechniken zur direkten Beobachtung der Kollisionen zwischen Partikeln und Blasen. Daher besteht das Ziel dieser Dissertation darin, neue Methoden zu entwickeln, um die Wechselwirkung zwischen Blasen und Partikeln unter definierten hydrodynamischen Bedingungen zu messen. Diese Methoden beruhen auf der Verfolgung von einzelnen Partikeln mit 4D Particle Tracking Velocimetry (PTV) und Positron Emission Particle Tracking (PEPT), um die Lagrangeschen Partikeltrajektorien in der Nähe einer Blase zu bestimmen und die kollidierenden Partikel zu klassifizieren. In zwei Versuchsaufbauten werden diese Messmethoden angewandt, um die Wechselwirkung zwischen Blasen und Partikeln in turbulenten Strömungen zu untersuchen. In einer Blasensäule wird die Turbulenz im Nachlauf einer frei aufsteigenden Blasenkette erzeugt, während in einem Wasserkanal die Turbulenz durch die Umströmung eines Gitters produziert wird. In beiden Fällen wird das vorhandene turbulente Strömungsfeld um die Blasen mittels Tomographic Particle Image Velocimetry (TPIV) charakterisiert. Zunächst wird der Einfluss des Blasennachlaufs auf die Blasen-Partikel-Kollision für beide Versuchsaufbauten mit dem 4D-PTV-Verfahren analysiert. Es wird gezeigt, dass in beiden Versuchsanordnungen die Kollision von feinen Partikeln nicht nur an der Vorderseite, sondern auch an der Hinterseite der Blase stattfindet. Diese Ergebnisse werden mit der gemessenen turbulenten kinetischen Energie und der Dissipationsrate um die Blase korreliert. Anschließend werden die experimentell ermittelte turbulente kinetische Energie und Dissipationsrate genutzt, um die Kollisionsfrequenz vorherzusagen. Dafür werden bestehende Modelle angewendet und deren Vorhersagen den experimentellen Ergebnissen gegenübergestellt. Weiterhin wird der Wasserkanal genutzt, um den Einfluss der turbulenten Flüssigkeitsströmung auf die Kollision zwischen einer stagnierenden Blase und den Modellpartikeln zu verdeutlichen. Neben der Untersuchung in einer verdünnten Feststoffsuspension wird auch die Blasen-Partikel-Wechselwirkung in einer dichten Strömung mit dem PEPT-Verfahren untersucht. Das PEPT-Verfahren hat das Potenzial, Suspensionen mit einem hohen Feststoffanteil zu messen, was mit optischen Trackingverfahren, wie 4D-PTV, nicht möglich ist. Für den Nachweis einzelner Partikel mit dem PEPT-Verfahren wurden radioaktive Tracerpartikel entwickelt, welche repräsentativ für die Modellpartikeln sind. Die Trajektorien der markierten Partikel werden verwendet, um die durchschnittliche Partikelverteilung im turbulenten Feld zu bestimmen und die Blasen-Partikel-Wechselwirkung zu beschreiben. Insgesamt bieten die entwickelten Methoden eine Möglichkeit die Kollision zwischen Partikeln und Blasen in einer turbulenten Strömung direkt zu untersuchen. Die gewonnenen experimentellen Daten ermöglichen es, bestehende Kollisionsmodelle zu überprüfen und das Verständnis über die Rolle von Turbulenzen in der Schaumflotation zu verbessern.The analysis of collisions between particles and bubbles in a turbulent flow is a fundamental problem of high technological relevance, e.g. for the separation of valuable mineral particles by froth flotation. That relevance contrasts with an apparent lack of experimental data and insights into this collision process. A major issue is the limitation of available measurement techniques to directly observe the collisions between particles and bubbles. In this dissertation, novel methodologies are developed to measure the interaction between bubbles and particles under defined hydrodynamic conditions. These methodologies comprise particle tracking techniques such as 4D PTV and PEPT to triangulate the Lagrangian particle trajectories in the vicinity of a bubble and classify those which are colliding. In two experimental setups, these techniques are applied to investigate the bubble-particle interaction in turbulent flows. In a bubble column, turbulence is generated in the wake of a freely rising bubble chain, whereas in a water channel, a fluid passing through grid produces a turbulent flow upstream of a stagnant bubble. Accordingly, the turbulent flow field around these bubbles is characterized by TPIV. Firstly, the influence of the bubble wake on the bubble-particle collision is analyzed for both experimental setups with 4D PTV. It is shown that the collision of fluorescent fine particles take place not only at the leading edge but also at the trailing edge of the bubble, independently of the experimental setup. These findings are correlated with the measured TKE and dissipation rates around the bubble and in the bubble wake. Subsequently, the experimental TKE and dissipation rates are applied to existing models for collision frequency, and their predictions are discussed. Secondly, the impact of the turbulent liquid flow on the collision between a stagnant bubble and model particles is studied for a range of turbulent length scales. Besides the investigation in a dilute solid suspension, the bubble-particle interaction is also examined in a dense flow with PEPT. PEPT has the potential to measure suspensions with a high solid fraction, which could not be achieved with optical particle tracking methods. For the detection of individual particles with PEPT, radioactive tracer particles were designed to represent the bulk particles. The trajectories of the labeled particles are used to determine the average particle distribution in the turbulent field and describe the bubble-particle interactions. Overall, the developed methodologies in this dissertation provide a framework to investigate directly the collision between particles and bubble in a turbulent flow. The gained experimental validation data allows to verify existing collision models and to advance our understanding of the role of turbulence in froth flotation