Investigation of time-resolved volumetric MRI to enhance MR-guided radiotherapy of moving lung tumors

In photon radiotherapy of lung cancer, respiratory-induced motion introduces systematic and statistical uncertainties in treatment planning and dose delivery. By integrating magnetic resonance imaging (MRI) in the treatment planning process in MR-guided radiotherapy (MRgRT), uncertainties in target volume definition can be reduced with respect to state-of-the-art X-ray-based approaches. Furthermore, MR-guided linear accelerators (MR-Linacs) offer dose delivery with enhanced accuracy and precision through daily treatment plan adaptation and gated beam delivery based on real-time MRI. Today, the potential of MRgRT of moving targets is, however, not fully exploited due to the lack of time-resolved four-dimensional MRI (4D-MRI) in clinical practice. Therefore, the aim of this thesis was to develop and experimentally validate new methods for motion characterization and estimation with 4D-MRI for MRgRT of lung cancer. Different concepts were investigated for all phases of the clinical workflow - treatment planning, beam delivery, and post-treatment analysis. Firstly, a novel internal target volume (ITV) definition method based on the probability-of-presence of moving tumors derived from real-time 4D-MRI was developed. The ability of the ITVs to prospectively account for changes occurring over the course of several weeks was assessed in retrospective geometric analyses of lung cancer patient data. Higher robustness of the probabilistic 4D-MRI-based ITVs against interfractional changes was observed compared to conventional target volumes defined with four-dimensional computed tomography (4D-CT). The study demonstrated that motion characterization over extended times enabled by real-time 4D-MRI can reduce systematic and statistical uncertainties associated with today’s standard workflow. Secondly, experimental validation of a published motion estimation method - the propagation method - was conducted with a porcine lung phantom under realistic patient-like conditions. Estimated 4D-MRIs with a temporal resolution of 3.65 Hz were created based on orthogonal 2D cine MRI acquired at the scanner unit of an MR-Linac. A comparison of these datasets with ground truth respiratory-correlated 4D-MRIs in geometric analyses showed that the propagation method can generate geometrically accurate estimated 4D-MRIs. These could decrease target localization errors and enable 3D motion monitoring during beam delivery at the MR-Linac in the future. Lastly, the propagation method was extended to create continuous time-resolved estimated synthetic CTs (tresCTs). The proposed method was experimentally tested with the porcine lung phantom, successively imaged at a CT scanner and an MR-Linac. A high agreement of the images and corresponding dose distributions of the tresCTs and measured ground truth 4D-CTs was found in geometric and dosimetric analyses. The tresCTs could be used for post-treatment time-resolved reconstruction of the delivered dose to guide treatment adaptations in the future. These studies represent important steps towards a clinical application of time-resolved 4D-MRI methods for enhanced MRgRT of lung tumors in the near future

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task

Towards Closed-loop, Robot Assisted Percutaneous Interventions under MRI Guidance

Image guided therapy procedures under MRI guidance has been a focused research area over past decade. Also, over the last decade, various MRI guided robotic devices have been developed and used clinically for percutaneous interventions, such as prostate biopsy, brachytherapy, and tissue ablation. Though MRI provides better soft tissue contrast compared to Computed Tomography and Ultrasound, it poses various challenges like constrained space, less ergonomic patient access and limited material choices due to its high magnetic field. Even after, advancements in MRI compatible actuation methods and robotic devices using them, most MRI guided interventions are still open-loop in nature and relies on preoperative or intraoperative images. In this thesis, an intraoperative MRI guided robotic system for prostate biopsy comprising of an MRI compatible 4-DOF robotic manipulator, robot controller and control application with Clinical User Interface (CUI) and surgical planning applications (3DSlicer and RadVision) is presented. This system utilizes intraoperative images acquired after each full or partial needle insertion for needle tip localization. Presented system was approved by Institutional Review Board at Brigham and Women\u27s Hospital(BWH) and has been used in 30 patient trials. Successful translation of such a system utilizing intraoperative MR images motivated towards the development of a system architecture for close-loop, real-time MRI guided percutaneous interventions. Robot assisted, close-loop intervention could help in accurate positioning and localization of the therapy delivery instrument, improve physician and patient comfort and allow real-time therapy monitoring. Also, utilizing real-time MR images could allow correction of surgical instrument trajectory and controlled therapy delivery. Two of the applications validating the presented architecture; closed-loop needle steering and MRI guided brain tumor ablation are demonstrated under real-time MRI guidance

Fuzzy-based Propagation of Prior Knowledge to Improve Large-Scale Image Analysis Pipelines

Many automatically analyzable scientific questions are well-posed and offer a variety of information about the expected outcome a priori. Although often being neglected, this prior knowledge can be systematically exploited to make automated analysis operations sensitive to a desired phenomenon or to evaluate extracted content with respect to this prior knowledge. For instance, the performance of processing operators can be greatly enhanced by a more focused detection strategy and the direct information about the ambiguity inherent in the extracted data. We present a new concept for the estimation and propagation of uncertainty involved in image analysis operators. This allows using simple processing operators that are suitable for analyzing large-scale 3D+t microscopy images without compromising the result quality. On the foundation of fuzzy set theory, we transform available prior knowledge into a mathematical representation and extensively use it enhance the result quality of various processing operators. All presented concepts are illustrated on a typical bioimage analysis pipeline comprised of seed point detection, segmentation, multiview fusion and tracking. Furthermore, the functionality of the proposed approach is validated on a comprehensive simulated 3D+t benchmark data set that mimics embryonic development and on large-scale light-sheet microscopy data of a zebrafish embryo. The general concept introduced in this contribution represents a new approach to efficiently exploit prior knowledge to improve the result quality of image analysis pipelines. Especially, the automated analysis of terabyte-scale microscopy data will benefit from sophisticated and efficient algorithms that enable a quantitative and fast readout. The generality of the concept, however, makes it also applicable to practically any other field with processing strategies that are arranged as linear pipelines.Comment: 39 pages, 12 figure

발달장애인을 위한 특수체육의 온라인 지식전환 평가

학위논문(석사) -- 서울대학교대학원 : 사범대학 체육교육과, 2023. 2. 이용호.Knowledge translation (KT) is an iterative process that translates research findings into practical information for users. Despite active knowledge production in adapted physical activity (APA), this knowledge is not delivered to people with developmental disabilities, causing a knowledge-to-action gap. This study aims to use a realistic evaluation (RE) of the online KT of APA in Korea to diagnose the gap. Fifteen pairs of a person with developmental disabilities and a primary caregiver participated in the study. Three websites were selected for evaluation using the web usability test, content quality evaluation rubric, and in-depth interviews. This study demonstrates context, enabling and constraining mechanisms, and the outcomes of web usability and content quality. The RE was conducted within the KT framework to define facilitators and barriers in the online KT of APA in Korea. The results of this study may contribute to the improvement of the online KT of APA.지식 전환은 학술적 연구를 통해 창출된 지식을 실용적인 정보로 전환하는 반복적인 과정이다. 특수체육 학계의 활발한 연구 활동 및 지식 생산에도 불구하고 학술적 결과물이 발달장애인이 접근 가능한 정보의 형태로 전달되지 않아 지식-실천 격차가 발생한다. 본 연구는 Realistic evaluation (RE) 방법을 활용하여 한국 내 특수체육의 온라인 지식 전환을 알아보고자 한다. 발달장애인 당사자와 주 양육자 15쌍이 연구에 참여했다. 웹 사용성 테스트, 콘텐츠 품질 평가, 그리고 2:1 인터뷰를 통해 3개의 발달장애인 정보 플랫폼을 평가했다. 이 연구는 웹 사용성과 콘텐츠 질에 있어 사용자 맥락, 촉진 및 방해 요인, 그리고 이에 따른 결과를 보여준다. RE는 특수체육의 온라인 지식전환에서의 촉진 및 방해 요인을 규명하기 위해 지식 전환 프레임워크 안에서 진행되었다. 본 연구의 결과는 특수체육의 온라인 지식 전환 개선에 기여하여 발달장애인의 특수체육지식-실천 격차를 줄이리라 기대된다.Chapter 1. Introduction 1 1.1 Background 1 1.2 Objectives 6 1.3 Literature Review 7 Chapter 2. Methods 10 2.1 Realistic Evaluation of Knowledge Translation 10 2.2 Research Participants 13 2.3 Web Usability Test 16 2.4 Two-on-one In-Depth Interviews 24 2.5 Content Quality Evaluation 25 2.6 Research Process 30 Chapter 3. Results 34 3.1 BODA 34 3.2 UPSG 38 3.3 DMOA 41 3.4 Analysis 44 Chapter 4. Discussion 48 References 53 Abstract in Korean 68석