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.

Hepatic Responses of Juvenile Fundulus heteroclitus from Pollution-adapted and Nonadapted Populations Exposed to Elizabeth River Sediment Extract.

Atlantic killifish (Fundulus heteroclitus) inhabiting the Atlantic Wood Industries region of the Elizabeth River, Virginia, have passed polycyclic aromatic hydrocarbon (PAH) resistance to their offspring as evidenced by early life stage testing of developmental toxicity after exposure to specific PAHs. Our study focused on environmentally relevant PAH mixtures in the form of Elizabeth River sediment extract (ERSE). Juvenile (5 month) F1 progeny of pollution-adapted Atlantic Wood (AW) parents and of reference site (King's Creek [KC]) parents were exposed as embryos to ERSE. Liver alterations, including nonneoplastic lesions and microvesicular vacuolation, were observed in both populations. ERSE-exposed KC fish developed significantly more alterations than unexposed KC fish. Interestingly, unexposed AW killifish developed significantly more alterations than unexposed KC individuals, suggesting that AW juveniles are not fully protected from liver disease; rapid growth of juvenile fish may also be an accelerating factor for tumorigenesis. Because recent reports show hepatic tumor formation in adult AW fish, the differing responses from the 2 populations provided a way to determine whether embryo toxicity protection extends to juveniles. Future investigations will analyze older life stages of killifish to determine differences in responses related to chronic disease.

Ground and Electronic Excited States from Pairing Matrix Fluctuation and Particle-Particle Random Phase Approximation

The accurate description of ground and electronic excited states is an important and challenging topic in quantum chemistry. The pairing matrix fluctuation, as a counterpart of the density fluctuation, is applied to this topic. From the pairing matrix fluctuation, the exact electron correlation energy as well as two electron addition/removal energies can be extracted. Therefore, both ground state and excited states energies can be obtained and they are in principle exact with a complete knowledge of the pairing matrix fluctuation. In practice, considering the exact pairing matrix fluctuation is unknown, we adopt its simple approximation --- the particle-particle random phase approximation (pp-RPA) --- for ground and excited states calculations. The algorithms for accelerating the pp-RPA calculation, including spin separation, spin adaptation, as well as an iterative Davidson method, are developed. For ground states correlation descriptions, the results obtained from pp-RPA are usually comparable to and can be more accurate than those from traditional particle-hole random phase approximation (ph-RPA). For excited states, the pp-RPA is able to describe double, Rydberg, and charge transfer excitations, which are challenging for conventional time-dependent density functional theory (TDDFT). Although the pp-RPA intrinsically cannot describe those excitations excited from the orbitals below the highest occupied molecular orbital (HOMO), its performances on those single excitations that can be captured are comparable to TDDFT. The pp-RPA for excitation calculation is further applied to challenging diradical problems and is used to unveil the nature of the ground and electronic excited states of higher acenes. The pp-RPA and the corresponding Tamm-Dancoff approximation (pp-TDA) are also applied to conical intersections, an important concept in nonadiabatic dynamics. Their good description of the double-cone feature of conical intersections is in sharp contrast to the failure of TDDFT. All in all, the pairing matrix fluctuation opens up new channel of thinking for quantum chemistry, and the pp-RPA is a promising method in describing ground and electronic excited states.

Expérience précaire du monde et représentation de la poésie dans La fissure de la fiction et Désâmé de Patrice Desbiens

Diverses œuvres de poésie moderne et contemporaine mettent en scène le rapport à l’écriture d’un sujet lyrique. Une telle problématique trouve une incarnation particulièrement intéressante dans l’œuvre de Patrice Desbiens, notamment dans certains de ses textes des années 1990 et 2000, où elle apparaît avec plus d’acuité. Pourtant, sa pratique auto-réflexive a fait l’objet de très peu de recherches. Afin d’éclairer le rapport qu’entretient Patrice Desbiens avec l’écriture et avec la poésie, ce mémoire s’intéresse à deux de ses textes, soit La fissure de la fiction (1997) et Désâmé, (2005) en accordant davantage d’espace au premier, que je considère comme un texte-charnière dans la production poétique de Desbiens. Dans un premier temps, mon travail présente ainsi la précarité qui caractérise le protagoniste de La fissure de la fiction et, sous un autre angle, le sujet lyrique de Désâmé. Dans cette optique, la figure du poète est étudiée dans La fissure de la fiction à la lumière de la reprise ironique du mythe de la malédiction littéraire et du sens que la réactualisation de ce mythe confère au personnage dans ce récit poétique. Dans un second temps, ce mémoire s’attache à montrer que la cohérence et la vraisemblance des univers mis en scène dans La fissure de la fiction et Désâmé sont minées. C’est à l’aune de ces analyses que peut ensuite être envisagé le rôle d’une poésie qui, en dernière instance, comporte malgré tout un caractère consolateur, en dépit ou en raison de l’esthétique du grotesque, tantôt comique, tantôt tragique, dans laquelle elle s’inscrit et que nous tâcherons de mettre en lumière.

Bubble Growth From First Principals

We consider the simplest relevant problem in the foaming of molten plastics, the growth of a single bubble in a sea of highly viscous Newtonian fluid, and without interference from other bubbles. This simplest problem has defied accurate solution from first principles. Despite plenty of research on foaming, classical approaches from first principles have neglected the temperature rise in the surrounding fluid, and we find that this oversimplification greatly accelerates bubble growth prediction. We use a transport phenomena approach to analyze the growth of a solitary bubble, expanding under its own pressure. We consider a bubble of ideal gas growing without the accelerating contribution from mass transfer into the bubble. We explore the roles of viscous forces, fluid inertia, and viscous dissipation. We find that bubble growth depends upon the nucleus radius and nucleus pressure. We begin with a detailed examination of the classical approaches (thermodynamics without viscous heating). Our failure to fit experimental data with these classical approaches, sets up the second part of our paper, a novel exploration of the essential decelerating role of viscous heating. We explore both isothermal and adiabatic bubble expansion, and also the decelerating role of surface tension. The adiabatic analysis accounts for the slight deceleration due to the cooling of the expanding gas, which depends on gas polyatomicity. We also explore the pressure profile, and the components of the extra stress tensor, in the fluid surrounding the growing bubble. These stresses can eventually be frozen into foamed plastics. We find that our new theory compares well with measured bubble behavior.

Cape Breton Provides Pointers for the Adjustment Programs Required by the Decline of the Old Economy (Working Paper 14)

The Cape Breton Development Corporation need not, should not, be dying in the way it is. “Devco” has been widely represented as a failure dragged out too long. In fact it had for a time considerable success in a role too difficult to be often attempted. The main failure was in the political will to stick to its purpose. This commentary is in three parts. The first, major section discusses the purpose of Devco and the policies that served the purpose quite well but were maintained for little more than a decade. It suggests that the benefits would have been greater if Devco had been started earlier in the period of postwar prosperity. The second section comments on the enfeeblement of Devco in the 1980s. The removal of its development function also weakened, and has eventually led to the abandonment of, Devco’s social purpose in the operation of coal mining. Third, a short epilogue pointing out that, while the Cape Breton case is extreme, there will be increasing need to moderate the socially disruptive consequences of accelerating economic change. There are lessons from the Devco experience: the longer remedial action is delayed, the more difficult and expensive it becomes, and the more necessary for its effectiveness is a steady political will.

Development of a knowledge sharing framework for improving the testing processes in global product development

As identified by Griffin (1997) and Kahn (2012), manufacturing organisations typically improve their market position by accelerating their product development (PD) cycles. One method for achieving this is to reduce the time taken to design, test and validate new products, so that they can reach the end customer before competition. This paper adds to existing research on PD testing procedures by reporting on an exploratory investigation carried out in a UK-based manufacturing plant. We explore the organisational and managerial factors that contribute to the time spent on testing of new products during development. The investigation consisted of three sections, viz. observations and process modelling, utilisation metrics and a questionnaire-based investigation, from which a proposed framework to improve and reduce the PD time cycle is presented. This research focuses specifically on the improvement of the utilisation of product testing facilities and the links to its main internal stakeholders - PD engineers.

Audiovisual Storytelling and Ideological Horizons : Audiences, Cultural Contexts and Extra-textual Meaning Making

Abstract: Audiovisual Storytelling and Ideological Horizons: Audiences, Cultural Contexts and Extra-textual Meaning Making In a society characterized by mediatization people are to an increasing degree dependent on mediated narratives as a primary means by which we make sense of our experience through time and our place in society (Hoover 2006, Lynch 2007, Hjarvard 2008, Hjarvard & Lövheim 2012). American media scholar Stewart Hoover points to symbols and scripts available in the media environment, what he call the “symbolic inventory” out of which individuals make religious or spiritual meaning (Hoover 2006: 55). Vernacular meaning-making embedded in everyday life among viewers’ dealing with fiction narratives in films and tv-series highlight a need for a more nuanced understanding of complex audiovisual storytelling. Moving images provide individuals with stories by which reality is maintained and by which humans construct ordered micro-universes for themselves using film as a resource for moral assessment and ideological judgments about life (Plantinga 2009, Johnston 2010, Axelson 2015). Important in this theoretical context are perspectives on viewers’ moral frameworks (Zillman 2005, Andersson & Andersson 2005, Frampton 2006, Avila 2007).This paper presentation will focus on ideological contested meaning making where audiences of different cultural background engage emotionally with filmic narratives, possibly eliciting ideological and spiritual meaning-making related to viewers’ personal world views. Through the example of the Homeland tv-series I want to discuss how spectators’ cultural, religious, political and ideological identities could be understood playing a role in the interpretative process of decoding content. Is it possible to trace patterns of different receptions of the multilayered and ambiguous story depicted in Homeland by religiously engaged Christians and Moslems as well as non-believers, in America, Europe and Middle East? How is the fiction narrative dealt with by spectators in the audience in different cultural contexts and how is it interpreted through the process of extra-text evaluation and real world2understanding in a global era preoccupied with war on terror? The presentation will also discuss methodological considerations about how to reach out to audiences anchored in different cultural context.

The Good Liberal and the Scoundrel Author: Fantasy, Dissent, and neoliberal subjectivity in Philip Pullman’s His Dark Materials

Philip Pullman, author of the His Dark Materials trilogy, has acquired an impressive critical reputation and acquired a favored role in British culture as a social commentator. This essay attempts to link the pleasures associated with the trilogy with the politics inscribed in them, and consider both in the context of Pullman’s role in the civil society. The essay suggests that The Northern Lights offers pleasures in fantastical and metaphysical possibilities, and social confederacies that potentially offset the affective privations of neoliberalism. These possibilities are set in the context of recent theories of the “enterprise society.” The essay draws attention to a number of discontinuities that unfold as the trilogy progresses, and suggests that these undermine the possibilities inherent in the first novel. These disconti - nuities throw the role of fantasy and alternative universes into question, and reveal the limitations of Pullman’s fiction. The essay considers the limit and scope of Pullman’s political vision, both as a function of his fiction and his public engagement with social issues, and suggests that he exemplifies Raymond Williams’s concept of “bourgeois dissent” in which political critique and a continuing investment in traditional institutions and class hierarchy can be mutually reinforcing.

Aposição da lateralidade prática e simbólica: contributos do design

A presente dissertação foca-se na análise do dualismo esquerda-direita tanto em termos de motricidade humana, como em relação ao universo material e simbólico criado pelo homem. Para além do contraste simbólico entre a esquerda, com carácter negativo, e a direita, com carácter positivo, o mundo artificial está claramente orientado para promover a preferência de utilização da mão direita. Esta condição acentua uma maior assimetria na preferência e desempenho manuais dos destros, mas, em contrapartida, incentiva involuntariamente a que a generalidade dos esquerdinos apresente uma maior ambivalência motora entre as duas mãos. Neste documento são analisadas as vantagens desta estimulação psicomotora tanto com o objectivo de compensar o desequilíbrio motor entre esquerda e direita, como na consequente acepção simbólica e psicológica dos termos. A investigação resulta na aplicação prática da concepção de um jogo / brinquedo que, sob a forma de uma luva calçada pela mão preferida, permitirá o desenvolvimento de exercícios de motricidade fina realizados pela mão preterida. Com este projecto julgamos poder contribuir para uma sociedade mais inclusiva e desenvolvimento do potencial humano.

Embolada e outras coisas do folclore tulusano: a experiência da Associação Escambiar em Toulouse - França

Since the middle 80 s from the 20th century, some musical genres associated to the Brazilian Northeastern region notably the forró, coco de embolada and repente de viola have been gradually incorporated to the musical production of south France linked to the occitanista trend, currently linking many musicians and groups from those regions in both countries. This paper is engaged in reflecting on the particular experience of the groups formed by the Escambiar Association, located on the city of Toulouse, and specially the duet Fabulous Trobadors, whose compositions are mostly made in the coco de embolada form. Watching the motivations and the processes that led to the creation of the groups from this association and it s current operation, this study investigates the transcultural phenomenon, that allow to cross two symbolic universes through rationalizing speeches about music, considering the locality s production in the midst of a political debate that involve questions about cultural identity and tradition

Solar coronal jets: observations, theory, and modeling

Coronal jets represent important manifestations of ubiquitous solar transients, which may be the source of significant mass and energy input to the upper solar atmosphere and the solar wind. While the energy involved in a jet-like event is smaller than that of “nominal” solar flares and coronal mass ejections (CMEs), jets share many common properties with these phenomena, in particular, the explosive magnetically driven dynamics. Studies of jets could, therefore, provide critical insight for understanding the larger, more complex drivers of the solar activity. On the other side of the size-spectrum, the study of jets could also supply important clues on the physics of transients close or at the limit of the current spatial resolution such as spicules. Furthermore, jet phenomena may hint to basic process for heating the corona and accelerating the solar wind; consequently their study gives us the opportunity to attack a broad range of solar-heliospheric problems.

A NAIRU assessment: an applied case to Colombia’s labor markets

Given the discrepancy over the optimum levels of employment for Colombia, this research targets both, the national and urban, Non-Accelerating Inflation Rate of Unemployment (NAIRU) for the Colombian markets -- In doing so, there is a strong pertinence in estimating the constant NAIRU through raw and minimally altered data and providing the reader with a complete brief of the theory in which the model is founded -- The introduction of supply shocks is considered to attain improved estimations and a more reliable assessment of the NAIRU to those that have previously been attempted -- The backbone of the analysis is conducted through the relationship established by the Phillips curve from 2001 until 2015

Meta-cinematic cultism: between high and low culture

ABSTRACT - Meta-cinema can depict film viewers’ attitudes towards cinema and their type of devotion for films. One subcategory of viewers - which I call meta-spectators - is highly specialized in its type of consumption, bordering on obsession. I contend that there are two main varieties of meta-cinematic reception, not altogether incompatible with one another, despite their apparent differences. As both of them are depicted on meta-cinematic products, the films themselves are the best evidence of my typology. My categories of film viewers are the ‘cinephile’, an elite prone to artistic militancy and the adoration of filmic masters; and the ‘fan’, a low culture consumer keen on certain filmic universes and their respective figures and motifs. I will base my rationale on four films that portray such reception practices: Travelling Avant (Jean-Charles Tacchella, 1987, FRA), The Dreamers (Bernardo Bertolucci, 2003, UK/FRA/ITA); Free Enterprise (Robert Mayer Burnett, 1998, USA); Fanboys (2009, Kyle Newman, USA).

Creating Common Ground: Architecture For Tactical Learning and Creative Convergence

Certain environments can inhibit learning and stifle enthusiasm, while others enhance learning or stimulate curiosity. Furthermore, in a world where technological change is accelerating we could ask how might architecture connect resource abundant and resource scarce innovation environments? Innovation environments developed out of necessity within urban villages and those developed with high intention and expectation within more institutionalized settings share a framework of opportunity for addressing change through learning and education. This thesis investigates formal and informal learning environments and how architecture can stimulate curiosity, enrich learning, create common ground, and expand access to education. The reason for this thesis exploration is to better understand how architects might design inclusive environments that bring people together to build sustainable infrastructure encouraging innovation and adaptation to change for years to come. The context of this thesis is largely based on Colin McFarlane’s theory that the “city is an assemblage for learning” The socio-spatial perspective in urbanism, considers how built infrastructure and society interact. Through the urban realm, inhabitants learn to negotiate people, space, politics, and resources affecting their daily lives. The city is therefore a dynamic field of emergent possibility. This thesis uses the city as a lens through which the boundaries between informal and formal logics as well as the public and private might be blurred. Through analytical processes I have examined the environmental devices and assemblage of factors that consistently provide conditions through which learning may thrive. These parameters that make a creative space significant can help suggest the design of common ground environments through which innovation is catalyzed.