Virtual clinical trials in medical imaging: a review

The accelerating complexity and variety of medical imaging devices and methods have outpaced the ability to evaluate and optimize their design and clinical use. This is a significant and increasing challenge for both scientific investigations and clinical applications. Evaluations would ideally be done using clinical imaging trials. These experiments, however, are often not practical due to ethical limitations, expense, time requirements, or lack of ground truth. Virtual clinical trials (VCTs) (also known as in silico imaging trials or virtual imaging trials) offer an alternative means to efficiently evaluate medical imaging technologies virtually. They do so by simulating the patients, imaging systems, and interpreters. The field of VCTs has been constantly advanced over the past decades in multiple areas. We summarize the major developments and current status of the field of VCTs in medical imaging. We review the core components of a VCT: computational phantoms, simulators of different imaging modalities, and interpretation models. We also highlight some of the applications of VCTs across various imaging modalities

A Novel Approach to Contamination Suppression in Transmission Detectors for Radiotherapy

The current trend in X-ray radiotherapy is to treat cancers that are in difficult locations in the body using beams with a complex intensity profile. Intensity Modulated Radiotherapy (IMRT) is a treatment which improves the dose distribution to the tumour whilst reducing the dose to healthy tissue. Such treatments administer a larger dose per treatment fraction and hence require more complex methods to verify the accuracy of the treatment delivery. Measuring beam intensity fluctuations is difficult as the beam is heavily distorted after leaving thepatient and transmission detectors will attenuate the beam and change the energy spectrum of the beam. Monolithic Active Pixel Sensors (MAPS) are ideal solid-state detectors to measure the 2D beam profile of a radiotherapy beam upstream of the patient. MAPS sensors can be made very thin (∼ 30 μm) with still very good signal-to-noise performance. This means that the beam would pass through the sensor virtually undisturbed(< 1% attenuation). Pixel pitches of between 2 μm to 100 μm are commercially available. Large area devices (∼ 15 × 15 cm 2 ) have been produced. MAPS can be made radiation hard enough to befully functional after a large number of fractions. All this makes MAPS a very realistic transmission detector candidate for beam monitoring upstream of the patient. A remaining challenge for thin, upstream sensors is that the detectors are sensitive to the signal of both therapeutic photons and electron contamination. Here a method is presented to distinguish between the signal due to electrons and photons and thus provide real-time dosimetric information in very thin sensors that does not require Monte Carlo simulation of each linear accelerator treatment head

DEVELOPMENT AND CLINICAL VALIDATION OF KNOWLEDGE-BASED PLANNING MODELS FOR STEREOTACTIC BODY RADIOTHERAPY OF EARLY-STAGE NON-SMALL-CELL LUNG CANCER PATIENTS

Lung stereotactic body radiotherapy (SBRT) is a viable alternative to surgical intervention for the treatment of early-stage non-small-cell lung cancer (NSCLC) patients. This therapy achieves strong local control rates by delivering ultra-high, conformal radioablative doses in typically one to five fractions. Historically, lung SBRT plans are manually generated using 3D conformal radiation therapy, dynamic conformal arcs (DCA), intensity-modulated radiation therapy, and more recently via volumetric modulated arc therapy (VMAT) on a C-arm linear accelerator (linac). Manually planned VMAT is an advanced technique to deliver high-quality lung SBRT due to its dosimetric capabilities and utilization of flattening-filter free beams to improve patient compliance. However, there are limitations in manual treatment planning as the final plan quality heavily depends on a planner’s skill and available planning time. This could subject the plan quality to inter-planner variability from a single institution with multiple planners. Generally, the standard lung SBRT patient ‘simulation-to-treatment’ time is 7 working days. This delays clinic workflow and degrades the quality of treatment by eliminating adaptive re-planning capabilities. There is an ongoing effort to automate treatment planning by creating a model library of previously treated, high-quality plans and using it to prospectively generate new plans termed model-based knowledge-based planning (KBP). KBP aims to mitigate the previously mentioned limitations of manual planning and improve clinic workflow. As part of this dissertation, lung SBRT KBP models were created using a commercially available KBP engine that was trained using non-coplanar VMAT lung SBRT plans with the final dose reported from an advanced Acuros-based algorithm. The dissertation begins with the development of a robust and adaptable lung SBRT KBP model for early-stage, centrally-located NSCLC tumors that is fully compliant with Radiation Therapy Oncology Group (RTOG)-0813 protocol’s requirements. This new model provided similar or better plan quality to clinical plans, however it significantly increased total monitor units and plan complexity. This prompted the development and validation of an automated KBP routine for SBRT of peripheral lung tumors via DCA-based VMAT per RTOG-0618 criteria. This planning routine helped incorporate a historical DCA-based treatment planning approach with a VMAT optimization automated KBP engine that helps reduce plan complexity. For both central and peripheral lung lesions, the validated models are able to generate high-quality, standardized plans in under 30 min with minimal planner effort compared to an estimated 129 ± 34 min of a dedicated SBRT planner’s time. In practice, planners are expected to meticulously work on multiple plans at once, significantly increasing manual planning time. Thus, these KBP models will shorten the ‘simulation-to-treatment’ time down to as few as 3 working days, reduce inter-planer variability and improve patient safety. This will help standardize clinics and enable offline adaptive re-planning of lung SBRT treatment to account for physiological changes errors resulting from improper patient set-up. Lastly, this dissertation sought to further expand these KBP models to support delivering lung SBRT treatments on a new O-ring linac that was recently introduced to support underserved areas and fast patient throughput. Despite learning from a C-arm modality training dataset, these KBP models helped the O-ring linac to become a viable treatment modality for lung SBRT by providing an excellent plan quality similar to a C-arm linac in under 30 min. These KBP models will facilitate the easy transfer of patients across these diverse modalities and will provide a solution to unintended treatment course disruption due to lengthy machine downtime. Moreover, they will relieve the burden on a single machine in a high-volume lung SBRT clinic. Further adaptation and validation of these KBP models for large lung tumors (\u3e 5 cm) with multi-level dosing scheme and synchronous multi-lesion lung SBRT is ongoing

Adaptive Radiotherapy Enabled by MRI Guidance.

Adaptive radiotherapy (ART) strategies systematically monitor variations in target and neighbouring structures to inform treatment-plan modification during radiotherapy. This is necessary because a single plan designed before treatment is insufficient to capture the actual dose delivered to the target and adjacent critical structures during the course of radiotherapy. Magnetic resonance imaging (MRI) provides superior soft-tissue image contrast over current standard X-ray-based technologies without additional radiation exposure. With integrated MRI and radiotherapy platforms permitting motion monitoring during treatment delivery, it is possible that adaption can be informed by real-time anatomical imaging. This allows greater treatment accuracy in terms of dose delivered to target with smaller, individualised treatment margins. The use of functional MRI sequences would permit ART to be informed by imaging biomarkers, so allowing both personalised geometric and biological adaption. In this review, we discuss ART solutions enabled by MRI guidance and its potential gains for our patients across tumour types

Optical Properties of Condensation Trails

Persistent condensation trails are clouds, induced by the exhaust of an aircraft engine in a cold and ice-supersaturated environment. These artificial ice clouds can both cool and heat the atmosphere by scattering solar radiation and absorbing terrestrial radiation, respectively. The influence of condensation trails on the Earth-atmosphere energy balance and therewith the answer to the question of the dominating process had been mostly approximated on a global scale by treating the condensation trail as plane parallel layer with constant optical properties. Individual condensation trails and the influence of the solar angle had been analyzed, always using a course spatial grid and never under consideration of the aircraft performance, generating the condensation trail. For a trajectory optimization, highly precise results of the impact of condensation trails on the radiation budget and the influence of the aircraft performance on this impact is needed, so that future air traffic may consider the main factors of flight performance on the environmental impact of condensation trails. That’s why, a model is developed in this thesis to continuously estimate the scattering and absorption properties and their dependence on the aircraft performance.:1 Introduction 3 1.1 Motivation 3 1.2 State of the art 5 1.3 Approach 6 2 Theoretical background 9 2.1 The Earth’s atmosphere 9 2.1.1 The mean vertical structure of the atmosphere 12 2.1.2 Standard atmospheres 14 2.2 Radiation 15 2.2.1 Nature of radiation 15 2.2.2 Important metrics describing radiation 17 2.2.3 Relevant spectra and principles of radiation 19 2.2.4 Solar radiation 20 2.2.5 Terrestrial radiation 21 2.2.6 Radiative transfer and extinction 22 2.2.7 Radiative transfer equation 30 2.2.8 Energy budget of the Earth-atmosphere system 32 2.3 Thermodynamics 33 2.3.1 Atmospheric stability 33 2.3.2 Turbulence 36 2.3.3 Conditions of contrail formation 41 3 Development of a radiative forcing model 45 3.1 Model atmosphere 45 3.2 Flight performance model 46 3.3 Atmospheric radiative transfer model 49 3.3.1 Two Stream Approximation 51 3.3.2 Discrete ordinate radiative transfer solver 52 3.3.3 Methods to calculate broadband radiances and irradiances 53 3.4 Contrail life cycle model 57 3.4.1 Dissipation regime 58 3.4.2 Diffusion regime 63 3.5 Contrail radiative forcing model 74 3.5.1 Consideration of multiple scattering using a Monte Carlo simulation 74 3.5.2 Geometry of the Monte Carlo simulation 75 3.5.3 Interpretation of Beer’s law 76 3.5.4 Procedure of the Monte Carlo simulation 79 3.5.5 The extinguished power per unit length contrail 87 3.5.6 Scattering and absorption efficiencies Qs, Qa and asymmetry parameters gHG 89 3.5.7 Calibration of the Monte Carlo simulation 94 4 Calculations 99 4.1 Contrail properties 99 4.1.1 Conditions of contrail formation 100 4.1.2 Initial dimensions at the end of the dissipation regime 101 4.1.3 Microphysical properties during the diffusion regime 103 4.2 Radiative transport up to the contrail 105 4.2.1 Solar direct and diffuse radiance 106 4.2.2 Terrestrial irradiance 107 4.3 Scattering and absorption properties of radiation within the contrail 109 4.3.1 Monte Carlo simulation for solar radiation 109 4.3.2 Monte Carlo simulation for terrestrial irradiances 112 4.3.3 Relevance of multiple scattering 116 4.4 Radiative extinction 116 4.4.1 Solar zenith and azimuthal angle 118 4.4.2 Flightpath 120 4.4.3 Contrail evolution 122 4.4.4 Turbulence 126 4.4.5 Wavelength specific extinction 129 4.5 Terrestrial energy forcing of a contrail 133 4.6 Verification 135 5 Conclusion and outlook 141 5.1 Conclusion 141 5.2 Outlook 144 List of Figures 147 List of Tables 151 Abbreviations and Symbols 153 Glossary 161 Bibliography 169 Acknowledgements 183Langlebige Kondensstreifen sind Eiswolken, welche durch Kondensation von Wasserdampf an Rußpartikeln in einer eisübersättigten Atmosphäre entstehen. Der Wasserdampf entstammt einerseits aus dem Triebwerkabgas und andererseits aus der Atmosphäre. Kondensstreifen können die Atmosphäre durch Rückstreuung solarer Strahlung kühlen und durch Rückstreuung und Absorption terrestrischer Strahlung erwärmen. Der Einfluss von Kondensstreifen auf den Wärmehaushalt der Atmosphäre und damit die Antwort auf die Frage nach dem dominierenden Effekt wurde bisher zumeist auf globaler Ebene ermittelt, wobei der Kondensstreifen als planparallele Schicht mit konstanten optischen Eigenschaften angenähert wurde. Individuelle Kondensstreifen und der Einfluss des Sonnenstandes wurden bisher nur mithilfe eines groben Rasters betrachtet und niemals unter Berücksichtigung der Flugleistung des Luftfahrzeuges, welches den Kondensstreifen generiert hat. Für eine Trajektorienoptimierung sind jedoch präzise Berechnungen des Strahlungseinflusses und eine gewissenhafte Berücksichtigung der Flugleistung notwendig. Nur so kann der zukünftige Luftverkehr die Haupteinflussfaktoren der Flugeigenschaften auf den Strahlungseinfluss der Kondensstreifen berücksichtigen. Aus diesem Grund wurde in dieser Arbeit ein Modell entwickelt, welches die Eigenschaften des Strahlungstransfers durch den Kondensstreifen kontinuierlich bestimmt und die aus der Flugleistung resultierenden Parameter berücksichtigt.:1 Introduction 3 1.1 Motivation 3 1.2 State of the art 5 1.3 Approach 6 2 Theoretical background 9 2.1 The Earth’s atmosphere 9 2.1.1 The mean vertical structure of the atmosphere 12 2.1.2 Standard atmospheres 14 2.2 Radiation 15 2.2.1 Nature of radiation 15 2.2.2 Important metrics describing radiation 17 2.2.3 Relevant spectra and principles of radiation 19 2.2.4 Solar radiation 20 2.2.5 Terrestrial radiation 21 2.2.6 Radiative transfer and extinction 22 2.2.7 Radiative transfer equation 30 2.2.8 Energy budget of the Earth-atmosphere system 32 2.3 Thermodynamics 33 2.3.1 Atmospheric stability 33 2.3.2 Turbulence 36 2.3.3 Conditions of contrail formation 41 3 Development of a radiative forcing model 45 3.1 Model atmosphere 45 3.2 Flight performance model 46 3.3 Atmospheric radiative transfer model 49 3.3.1 Two Stream Approximation 51 3.3.2 Discrete ordinate radiative transfer solver 52 3.3.3 Methods to calculate broadband radiances and irradiances 53 3.4 Contrail life cycle model 57 3.4.1 Dissipation regime 58 3.4.2 Diffusion regime 63 3.5 Contrail radiative forcing model 74 3.5.1 Consideration of multiple scattering using a Monte Carlo simulation 74 3.5.2 Geometry of the Monte Carlo simulation 75 3.5.3 Interpretation of Beer’s law 76 3.5.4 Procedure of the Monte Carlo simulation 79 3.5.5 The extinguished power per unit length contrail 87 3.5.6 Scattering and absorption efficiencies Qs, Qa and asymmetry parameters gHG 89 3.5.7 Calibration of the Monte Carlo simulation 94 4 Calculations 99 4.1 Contrail properties 99 4.1.1 Conditions of contrail formation 100 4.1.2 Initial dimensions at the end of the dissipation regime 101 4.1.3 Microphysical properties during the diffusion regime 103 4.2 Radiative transport up to the contrail 105 4.2.1 Solar direct and diffuse radiance 106 4.2.2 Terrestrial irradiance 107 4.3 Scattering and absorption properties of radiation within the contrail 109 4.3.1 Monte Carlo simulation for solar radiation 109 4.3.2 Monte Carlo simulation for terrestrial irradiances 112 4.3.3 Relevance of multiple scattering 116 4.4 Radiative extinction 116 4.4.1 Solar zenith and azimuthal angle 118 4.4.2 Flightpath 120 4.4.3 Contrail evolution 122 4.4.4 Turbulence 126 4.4.5 Wavelength specific extinction 129 4.5 Terrestrial energy forcing of a contrail 133 4.6 Verification 135 5 Conclusion and outlook 141 5.1 Conclusion 141 5.2 Outlook 144 List of Figures 147 List of Tables 151 Abbreviations and Symbols 153 Glossary 161 Bibliography 169 Acknowledgements 18

Modeling and Simulation in Engineering

This book provides an open platform to establish and share knowledge developed by scholars, scientists, and engineers from all over the world, about various applications of the modeling and simulation in the design process of products, in various engineering fields. The book consists of 12 chapters arranged in two sections (3D Modeling and Virtual Prototyping), reflecting the multidimensionality of applications related to modeling and simulation. Some of the most recent modeling and simulation techniques, as well as some of the most accurate and sophisticated software in treating complex systems, are applied. All the original contributions in this book are jointed by the basic principle of a successful modeling and simulation process: as complex as necessary, and as simple as possible. The idea is to manipulate the simplifying assumptions in a way that reduces the complexity of the model (in order to make a real-time simulation), but without altering the precision of the results

Focal Spot, Summer/Fall 2005

https://digitalcommons.wustl.edu/focal_spot_archives/1100/thumbnail.jp

Methodology for complex dataflow application development

This thesis addresses problems inherent to the development of complex applications for reconfig- urable systems. Many projects fail to complete or take much longer than originally estimated by relying on traditional iterative software development processes typically used with conventional computers. Even though designer productivity can be increased by abstract programming and execution models, e.g., dataflow, development methodologies considering the specific properties of reconfigurable systems do not exist. The first contribution of this thesis is a design methodology to facilitate systematic develop- ment of complex applications using reconfigurable hardware in the context of High-Performance Computing (HPC). The proposed methodology is built upon a careful analysis of the original application, a software model of the intended hardware system, an analytical prediction of performance and on-chip area usage, and an iterative architectural refinement to resolve identi- fied bottlenecks before writing a single line of code targeting the reconfigurable hardware. It is successfully validated using two real applications and both achieve state-of-the-art performance. The second contribution extends this methodology to provide portability between devices in two steps. First, additional tool support for contemporary multi-die Field-Programmable Gate Arrays (FPGAs) is developed. An algorithm to automatically map logical memories to hetero- geneous physical memories with special attention to die boundaries is proposed. As a result, only the proposed algorithm managed to successfully place and route all designs used in the evaluation while the second-best algorithm failed on one third of all large applications. Second, best practices for performance portability between different FPGA devices are collected and evaluated on a financial use case, showing efficient resource usage on five different platforms. The third contribution applies the extended methodology to a real, highly demanding emerging application from the radiotherapy domain. A Monte-Carlo based simulation of dose accumu- lation in human tissue is accelerated using the proposed methodology to meet the real time requirements of adaptive radiotherapy.Open Acces