Radiotherapy Treatment Assessment using DCE-MRI

Abstract

The goal of modern radiotherapy is to precisely deliver a prescribed radiation dose to delineated target volumes that contain a significant amount of tumor cells while sparing the surrounding healthy tissues/organs. Precise delineation of treatment and avoidance volumes is the key for the precision radiation therapy. In recent years, considerable clinical and research efforts have been devoted to integrate MRI into radiotherapy workflow motivated by the superior soft tissue contrast and functional imaging possibility. Dynamic contrast-enhanced MRI (DCE-MRI) is a noninvasive technique that measures properties of tissue microvasculature. Its sensitivity to radiation-induced vascular pharmacokinetic (PK) changes has been preliminary demonstrated. In spite of its great potential, two major challenges have limited DCE-MRI’s clinical application in radiotherapy assessment: the technical limitations of accurate DCE-MRI imaging implementation and the need of novel DCE-MRI data analysis methods for richer functional heterogeneity information.

This study aims at improving current DCE-MRI techniques and developing new DCE-MRI analysis methods for particular radiotherapy assessment. Thus, the study is naturally divided into two parts. The first part focuses on DCE-MRI temporal resolution as one of the key DCE-MRI technical factors, and some improvements regarding DCE-MRI temporal resolution are proposed; the second part explores the potential value of image heterogeneity analysis and multiple PK model combination for therapeutic response assessment, and several novel DCE-MRI data analysis methods are developed.

I. Improvement of DCE-MRI temporal resolution. First, the feasibility of improving DCE-MRI temporal resolution via image undersampling was studied. Specifically, a novel MR image iterative reconstruction algorithm was studied for DCE-MRI reconstruction. This algorithm was built on the recently developed compress sensing (CS) theory. By utilizing a limited k-space acquisition with shorter imaging time, images can be reconstructed in an iterative fashion under the regularization of a newly proposed total generalized variation (TGV) penalty term. In the retrospective study of brain radiosurgery patient DCE-MRI scans under IRB-approval, the clinically obtained image data was selected as reference data, and the simulated accelerated k-space acquisition was generated via undersampling the reference image full k-space with designed sampling grids. Two undersampling strategies were proposed: 1) a radial multi-ray grid with a special angular distribution was adopted to sample each slice of the full k-space; 2) a Cartesian random sampling grid series with spatiotemporal constraints from adjacent frames was adopted to sample the dynamic k-space series at a slice location. Two sets of PK parameters’ maps were generated from the undersampled data and from the fully-sampled data, respectively. Multiple quantitative measurements and statistical studies were performed to evaluate the accuracy of PK maps generated from the undersampled data in reference to the PK maps generated from the fully-sampled data. Results showed that at a simulated acceleration factor of four, PK maps could be faithfully calculated from the DCE images that were reconstructed using undersampled data, and no statistically significant differences were found between the regional PK mean values from undersampled and fully-sampled data sets. DCE-MRI acceleration using the investigated image reconstruction method has been suggested as feasible and promising.

Second, for high temporal resolution DCE-MRI, a new PK model fitting method was developed to solve PK parameters for better calculation accuracy and efficiency. This method is based on a derivative-based deformation of the commonly used Tofts PK model, which is presented as an integrative expression. This method also includes an advanced Kolmogorov-Zurbenko (KZ) filter to remove the potential noise effect in data and solve the PK parameter as a linear problem in matrix format. In the computer simulation study, PK parameters representing typical intracranial values were selected as references to simulated DCE-MRI data for different temporal resolution and different data noise level. Results showed that at both high temporal resolutions (<1s) and clinically feasible temporal resolution (~5s), this new method was able to calculate PK parameters more accurate than the current calculation methods at clinically relevant noise levels; at high temporal resolutions, the calculation efficiency of this new method was superior to current methods in an order of 102. In a retrospective of clinical brain DCE-MRI scans, the PK maps derived from the proposed method were comparable with the results from current methods. Based on these results, it can be concluded that this new method can be used for accurate and efficient PK model fitting for high temporal resolution DCE-MRI.

II. Development of DCE-MRI analysis methods for therapeutic response assessment. This part aims at methodology developments in two approaches. The first one is to develop model-free analysis method for DCE-MRI functional heterogeneity evaluation. This approach is inspired by the rationale that radiotherapy-induced functional change could be heterogeneous across the treatment area. The first effort was spent on a translational investigation of classic fractal dimension theory for DCE-MRI therapeutic response assessment. In a small-animal anti-angiogenesis drug therapy experiment, the randomly assigned treatment/control groups received multiple fraction treatments with one pre-treatment and multiple post-treatment high spatiotemporal DCE-MRI scans. In the post-treatment scan two weeks after the start, the investigated Rényi dimensions of the classic PK rate constant map demonstrated significant differences between the treatment and the control groups; when Rényi dimensions were adopted for treatment/control group classification, the achieved accuracy was higher than the accuracy from using conventional PK parameter statistics. Following this pilot work, two novel texture analysis methods were proposed. First, a new technique called Gray Level Local Power Matrix (GLLPM) was developed. It intends to solve the lack of temporal information and poor calculation efficiency of the commonly used Gray Level Co-Occurrence Matrix (GLCOM) techniques. In the same small animal experiment, the dynamic curves of Haralick texture features derived from the GLLPM had an overall better performance than the corresponding curves derived from current GLCOM techniques in treatment/control separation and classification. The second developed method is dynamic Fractal Signature Dissimilarity (FSD) analysis. Inspired by the classic fractal dimension theory, this method measures the dynamics of tumor heterogeneity during the contrast agent uptake in a quantitative fashion on DCE images. In the small animal experiment mentioned before, the selected parameters from dynamic FSD analysis showed significant differences between treatment/control groups as early as after 1 treatment fraction; in contrast, metrics from conventional PK analysis showed significant differences only after 3 treatment fractions. When using dynamic FSD parameters, the treatment/control group classification after 1st treatment fraction was improved than using conventional PK statistics. These results suggest the promising application of this novel method for capturing early therapeutic response.

The second approach of developing novel DCE-MRI methods is to combine PK information from multiple PK models. Currently, the classic Tofts model or its alternative version has been widely adopted for DCE-MRI analysis as a gold-standard approach for therapeutic response assessment. Previously, a shutter-speed (SS) model was proposed to incorporate transcytolemmal water exchange effect into contrast agent concentration quantification. In spite of richer biological assumption, its application in therapeutic response assessment is limited. It might be intriguing to combine the information from the SS model and from the classic Tofts model to explore potential new biological information for treatment assessment. The feasibility of this idea was investigated in the same small animal experiment. The SS model was compared against the Tofts model for therapeutic response assessment using PK parameter regional mean value comparison. Based on the modeled transcytolemmal water exchange rate, a biological subvolume was proposed and was automatically identified using histogram analysis. Within the biological subvolume, the PK rate constant derived from the SS model were proved to be superior to the one from Tofts model in treatment/control separation and classification. Furthermore, novel biomarkers were designed to integrate PK rate constants from these two models. When being evaluated in the biological subvolume, this biomarker was able to reflect significant treatment/control difference in both post-treatment evaluation. These results confirm the potential value of SS model as well as its combination with Tofts model for therapeutic response assessment.

In summary, this study addressed two problems of DCE-MRI application in radiotherapy assessment. In the first part, a method of accelerating DCE-MRI acquisition for better temporal resolution was investigated, and a novel PK model fitting algorithm was proposed for high temporal resolution DCE-MRI. In the second part, two model-free texture analysis methods and a multiple-model analysis method were developed for DCE-MRI therapeutic response assessment. The presented works could benefit the future DCE-MRI routine clinical application in radiotherapy assessment.

Near real time surface ocean velocity, Tyrrhenian Sea and Ligurian Sea in September 2016

The data set consists of maps of total velocity of the surface current in the North-Western Tyrrhenian Sea and Ligurian Sea averaged over a time interval of 1 hour around the cardinal hour. Surface ocean velocities estimated by HF Radar are representative of the upper 0.3-2.5 meters of the ocean. Total velocities are derived using least square fit that maps radial velocities measured from individual sites onto a cartesian grid. The final product is a map of the horizontal components of the ocean currents on a regular grid in the area of overlap of two or more radar stations.

Near real time surface ocean velocity in the Bay of Biscay - Basque Country from Mai to September 2016

The data set consists of maps of total velocity of the surface current in the Southeastern Bay of Biscay averaged over a time interval of 1 hour around the cardinal hour. Surface ocean velocities estimated by this HF Radar(4.65 MHz) are representative of the upper 2-3 meters of the ocean. The main objective of near real time processing is to produce the best product from available data at the time of processing. Total velocities are derived using least square fit that maps radial velocities measured from individual sites onto a cartesian grid. The final product is a map of the horizontal components of the ocean currents on a regular grid in the area of overlap of two or more radar stations.

Justificación y error en Descartes: un argumento pragmatista en la validación cartesiana del criterio de claridad y distinción

La percepción clara y distinta es el elemento sobre el que se asienta la certeza metafísica de Descartes. Con todo, el planteamiento de los argumentos escépticos referidos a la duda metódica cartesiana ha evidenciado la necesidad de hallar una justificación al propio criterio de la percepción clara y distinta. Frente a los intentos basados en la indubitabilidad de la percepción o en la garantía surgida de la bondad divina, se defenderá una justificación alternativa pragmatista.

In my ‘Mind’s Eye’: introspectionism, detectivism, and the basis of authoritative self-knowledge

It is widely accepted that knowledge of certain of one’s own mental states is authoritative in being epistemically more secure than knowledge of the mental states of others, and theories of self-knowledge have largely appealed to one or the other of two sources to explain this special epistemic status. The first, ‘detectivist’, position, appeals to an inner perception-like basis, whereas the second, ‘constitutivist’, one, appeals to the view that the special security awarded to certain self-knowledge is a conceptual matter. I argue that there is a fundamental class of cases of authoritative self-knowledge, ones in which subjects are consciously thinking about their current, conscious intentional states, that is best accounted for in terms of a theory that is,
broadly speaking, introspectionist and detectivist. The position developed has an intuitive plausibility that has inspired many who work in the Cartesian tradition, and the potential to yield a single treatment of the basis of authoritative self-knowledge for both intentional states and sensation states.

In My 'Mind's Eye': Introspectionism, Detectivism, and the Basis of Authoritative Self-Knowledge

It is widely accepted that knowledge of certain of one’s own mental states is authoritative in being epistemically more secure than knowledge of the mental states of others, and theories of self-knowledge have largely appealed to one or the other of two sources to explain this special epistemic status. The first, ‘detectivist’, position, appeals to an inner perception-like basis, whereas the second, ‘constitutivist’, one, appeals to the view that the special security awarded to certain self-knowledge is a conceptual matter. I argue that there is a fundamental class of cases of authoritative self-knowledge, ones in which subjects are consciously thinking about their current, conscious intentional states, that is best accounted for in terms of a theory that is, broadly speaking, introspectionist and detectivist. The position developed has an intuitive plausibility that has inspired many who work in the Cartesian tradition, and the potential to yield a single treatment of the basis of authoritative self-knowledge for both intentional states and sensation states.

Heating the Early Universe : Numerical Methods and Their Analysis

During the epoch when the first collapsed structures formed (6<z<50) our Universe went through an extended period of changes. Some of the radiation from the first stars and accreting black holes in those structures escaped and changed the state of the Intergalactic Medium (IGM). The era of this global phase change in which the state of the IGM was transformed from cold and neutral to warm and ionized, is called the Epoch of Reionization.In this thesis we focus on numerical methods to calculate the effects of this escaping radiation. We start by considering the performance of the cosmological radiative transfer code C2-Ray. We find that although this code efficiently and accurately solves for the changes in the ionized fractions, it can yield inaccurate results for the temperature changes. We introduce two new elements to improve the code. The first element, an adaptive time step algorithm, quickly determines an optimal time step by only considering the computational cells relevant for this determination. The second element, asynchronous evolution, allows different cells to evolve with different time steps. An important constituent of methods to calculate the effects of ionizing radiation is the transport of photons through the computational domain or ``ray-tracing''. We devise a novel ray tracing method called PYRAMID which uses a new geometry - the pyramidal geometry. This geometry shares properties with both the standard Cartesian and spherical geometries. This makes it on the one hand easy to use in conjunction with a Cartesian grid and on the other hand ideally suited to trace radiation from a radially emitting source. A time-dependent photoionization calculation not only requires tracing the path of photons but also solving the coupled set of photoionization and thermal equations. Several different solvers for these equations are in use in cosmological radiative transfer codes. We conduct a detailed and quantitative comparison of four different standard solvers in which we evaluate how their accuracy depends on the choice of the time step. This comparison shows that their performance can be characterized by two simple parameters and that the C2-Ray generally performs best.

Michel Maffesoli y la razón sensible: una argumentación postmoderna

Se establecen algunas coordenadas de análisis para inscribir la obra de Michel Maffesoli, reconocido sociólogo francés, en el contexto de la reflexión postmoderna. Maffesoli, desde sus primeras obras, se ha interesado por construir una perspectiva en las ciencias sociales que vaya más allá del modernismo cartesiano y positivista. Su propuesta metodológica incorpora temáticas afines al pensamiento postmoderno, en particular, lo correspondiente a un nuevo concepto de razón y de conocimiento. Abstract There are some guidelines for inscribe the Michels Maffesioli writings in the postmodern context ; since his first works he has shown a great interest for build a theoretical perspective for social sciences that go beyond from the modernism and positivism cartesian thought. His method proposal incorporates close thematic areas with the posmodern thought, especially the themes related with a new concept of reason and knowledge.

ANOSOV MAPS, POLYCYCLIC GROUPS AND HOMOLOGY

Many manifolds that do not admit Anosov diffeomorphisms are constructed. For example: the Cartesian product of the Klein bottle and a torus.

Gestural communication of music structure during solo classical piano performance

The production and perception of music is a multimodal activity involving auditory, visual and conceptual processing, integrating these with prior knowledge and environmental experience. Musicians utilise expressive physical nuances to highlight salient features of the score. The question arises within the literature as to whether performers’ non-technical, non-sound-producing movements may be communicatively meaningful and convey important structural information to audience members and co-performers. In the light of previous performance research (Vines et al., 2006, Wanderley, 2002, Davidson, 1993), and considering findings within co-speech gestural research and auditory and audio-visual neuroscience, this thesis examines the nature of those movements not directly necessary for the production of sound, and their particular influence on audience perception. Within the current research 3D performance analysis is conducted using the Vicon 12- camera system and Nexus data-processing software. Performance gestures are identified as repeated patterns of motion relating to music structure, which not only express phrasing and structural hierarchy but are consistently and accurately interpreted as such by a perceiving audience. Gestural characteristics are analysed across performers and performance style using two Chopin preludes selected for their diverse yet comparable structures (Opus 28:7 and 6). Effects on perceptual judgements of presentation modes (visual-only, auditory-only, audiovisual, full- and point-light) and viewing conditions are explored. This thesis argues that while performance style is highly idiosyncratic, piano performers reliably generate structural gestures through repeated patterns of upper-body movement. The shapes and locations of phrasing motions are identified particular to the sample of performers investigated. Findings demonstrate that despite the personalised nature of the gestures, performers use increased velocity of movements to emphasise musical structure and that observers accurately and consistently locate phrasing junctures where these patterns and variation in motion magnitude, shape and velocity occur. By viewing performance motions in polar (spherical) rather than cartesian coordinate space it is possible to get mathematically closer to the movement generated by each of the nine performers, revealing distinct patterns of motion relating to phrasing structures, regardless of intended performance style. These patterns are highly individualised both to each performer and performed piece. Instantaneous velocity analysis indicates a right-directed bias of performance motion variation at salient structural features within individual performances. Perceptual analyses demonstrate that audience members are able to accurately and effectively detect phrasing structure from performance motion alone. This ability persists even for degraded point-light performances, where all extraneous environmental information has been removed. The relative contributions of audio, visual and audiovisual judgements demonstrate that the visual component of a performance does positively impact on the over- all accuracy of phrasing judgements, indicating that receivers are most effective in their recognition of structural segmentations when they can both see and hear a performance. Observers appear to make use of a rapid online judgement heuristics, adjusting response processes quickly to adapt and perform accurately across multiple modes of presentation and performance style. In line with existent theories within the literature, it is proposed that this processing ability may be related to cognitive and perceptual interpretation of syntax within gestural communication during social interaction and speech. Findings of this research may have future impact on performance pedagogy, computational analysis and performance research, as well as potentially influencing future investigations of the cognitive aspects of musical and gestural understanding.

Teolog fundamentalny wobec ataku Przypadku, Nieokreśloności, Prawdopodobieństwa, Dwuznaczności, Wieloznaczności?

Postmodernizm prezentuje postawę akceptacji Nieładu, Chaosu i Przypadku. Czy istnieje moż- liwość dialogu z taką postawą? Postmodernizm powstaje jako bunt na pograniczu filozofii i estetyki. Kontestuje zastany Ład. Sprzeciwia się kartezjańskiemu Cogito ergo sum oraz podziałowi na res cogitans i res extensa. Jest to ruch kulturowy, który nie ma jeszcze swojego ostatecznego wyrazu. Jest on ciągle postrzegany jako proces przechodzenia od starego do nowego Ładu. Taki brak dookreślenia budzi niepokój i sprzeciw. Teologia fundamentalna jest badaniem granic i dialogu. Stoi na progu, więc ma obowiązek rozeznać ludzki niepokój w akceptacji otaczającego świata. Musimy zapytać, dlaczego człowiek akceptuje ten Nieład?

Wave impedance selection for passivity-based bilateral teleoperation

When a task must be executed in a remote or dangerous environment, teleoperation systems may be employed to extend the influence of the human operator. In the case of manipulation tasks, haptic feedback of the forces experienced by the remote (slave) system is often highly useful in improving an operator's ability to perform effectively. In many of these cases (especially teleoperation over the internet and ground-to-space teleoperation), substantial communication latency exists in the control loop and has the strong tendency to cause instability of the system. The first viable solution to this problem in the literature was based on a scattering/wave transformation from transmission line theory. This wave transformation requires the designer to select a wave impedance parameter appropriate to the teleoperation system. It is widely recognized that a small value of wave impedance is well suited to free motion and a large value is preferable for contact tasks. Beyond this basic observation, however, very little guidance exists in the literature regarding the selection of an appropriate value. Moreover, prior research on impedance selection generally fails to account for the fact that in any realistic contact task there will simultaneously exist contact considerations (perpendicular to the surface of contact) and quasi-free-motion considerations (parallel to the surface of contact). The primary contribution of the present work is to introduce an approximate linearized optimum for the choice of wave impedance and to apply this quasi-optimal choice to the Cartesian reality of such a contact task, in which it cannot be expected that a given joint will be either perfectly normal to or perfectly parallel to the motion constraint. The proposed scheme selects a wave impedance matrix that is appropriate to the conditions encountered by the manipulator. This choice may be implemented as a static wave impedance value or as a time-varying choice updated according to the instantaneous conditions encountered. A Lyapunov-like analysis is presented demonstrating that time variation in wave impedance will not violate the passivity of the system. Experimental trials, both in simulation and on a haptic feedback device, are presented validating the technique. Consideration is also given to the case of an uncertain environment, in which an a priori impedance choice may not be possible.

Algoritmos construtivos para treino de redes neuronais b-spline

Dissertação de mest. em Engenharia de Sistemas e Computação - Área de Sistemas de Controlo, Faculdade de Ciências e Tecnologia, Univ.do Algarve, 2001

Análise de viabilidade de injeção de fluidos alternativos ao vapor em reservatórios de óleo pesado

Many of hydrocarbon reserves existing in the world are formed by heavy oils (°API between 10 and 20). Moreover, several heavy oil fields are mature and, thus, offer great challenges for oil industry. Among the thermal methods used to recover these resources, steamflooding has been the main economically viable alternative. Latent heat carried by steam heats the reservoir, reducing oil viscosity and facilitating the production. This method has many variations and has been studied both theoretically and experimentally (in pilot projects and in full field applications). In order to increase oil recovery and reduce steam injection costs, the injection of alternative fluid has been used on three main ways: alternately, co-injected with steam and after steam injection interruption. The main objective of these injection systems is to reduce the amount of heat supplied to the reservoir, using cheaper fluids and maintaining the same oil production levels. This works discusses the use of carbon dioxide, nitrogen, methane and water as an alternative fluid to the steam. The analyzed parameters were oil recoveries and net cumulative oil productions. The reservoir simulation model corresponds to an oil reservoir of 100 m x 100 m x 28 m size, on a Cartesian coordinates system (x, y and z directions). It is a semi synthetic model with some reservoir data similar to those found in Brazilian Potiguar Basin. All studied cases were done using the simulator STARS from CMG (Computer Modelling Group, version 2009.10). It was found that waterflood after steam injection interruption achieved the highest net cumulative oil compared to other fluids injection. Moreover, it was observed that steam and alternative fluids, co-injected and alternately, did not present increase on profitability project compared with steamflooding

A PHENOMENOLOGY OF MIMETIC LEARNING AND MULTIMODAL COGNITION: INTEGRATING EXPERIENTIAL KNOWLEDGE INTO PROGRAMS IN RHETORIC, COMPOSITION, AND TECHNICAL COMMUNICATION

My dissertation emphasizes a cognitive account of multimodality that explicitly integrates experiential knowledge work into the rhetorical pedagogy that informs so many composition and technical communication programs. In these disciplines, multimodality is widely conceived in terms of what Gunther Kress calls “socialsemiotic” modes of communication shaped primarily by culture. In the cognitive and neurolinguistic theories of Vittorio Gallese and George Lakoff, however, multimodality is described as a key characteristic of our bodies’ sensory-motor systems which link perception to action and action to meaning, grounding all communicative acts in knowledge shaped through body-engaged experience. I argue that this “situated” account of cognition – which closely approximates Maurice Merleau-Ponty’s phenomenology of perception, a major framework for my study – has pedagogical precedence in the mimetic pedagogy that informed ancient Sophistic rhetorical training, and I reveal that training’s multimodal dimensions through a phenomenological exegesis of the concept mimesis. Plato’s denigration of the mimetic tradition and his elevation of conceptual contemplation through reason, out of which developed the classic Cartesian separation of mind from body, resulted in a general degradation of experiential knowledge in Western education. But with the recent introduction into college classrooms of digital technologies and multimedia communication tools, renewed emphasis is being placed on the “hands-on” nature of inventive and productive praxis, necessitating a revision of methods of instruction and assessment that have traditionally privileged the acquisition of conceptual over experiential knowledge. The model of multimodality I construct from Merleau-Ponty’s phenomenology, ancient Sophistic rhetorical pedagogy, and current neuroscientific accounts of situated cognition insists on recognizing the significant role knowledges we acquire experientially play in our reading and writing, speaking and listening, discerning and designing practices.