Potential improvements of lung and prostate MLC tracking investigated by treatment simulations.

PURPOSE/OBJECTIVES: Intrafraction tumor motion during external radiotherapy is a challenge for the treatment accuracy. A novel technique to mitigate the impact of tumor motion is real-time adaptation of the multileaf collimator (MLC) aperture to the motion, also known as MLC tracking. Although MLC tracking improves the dosimetric accuracy, there are still residual errors. Here, we investigate and rank the performance of five prediction algorithms and seven improvements of an MLC tracking system by extensive tracking treatment simulations. MATERIALS AND METHODS: An in-house-developed MLC tracking simulator that has been experimentally validated against an electromagnetic-guided MLC tracking system was used to test the prediction algorithms and tracking system improvements. The simulator requires a Dicom treatment plan and a motion trajectory as input and outputs all motion of the accelerator during MLC tracking treatment delivery. For lung tumors, MLC tracking treatments were simulated with a low and a high modulation VMAT plan using 99 patient-measured lung tumor trajectories. For prostate, tracking was also simulated with a low and a high modulation VMAT plan, but with 695 prostate trajectories. For each simulated treatment, the tracking error was quantified as the mean MLC exposure error, which is the sum of the overexposed area (irradiated area that should have been shielded according to the treatment plan) and the underexposed area (shielded area that should have been irradiated). First, MLC tracking was simulated with the current MLC tracking system without prediction, with perfect prediction (Perfect), and with the following five prediction algorithms: linear Kalman filter (Kalman), kernel density estimation (KDE), linear adaptive filtering (LAF), wavelet-based multiscale autoregression (wLMS), and time variant seasonal autoregression (TVSAR). Next, MLC tracking was simulated using the best prediction algorithm and seven different tracking system improvements: no localization signal latency (a), doubled maximum MLC leaf speed (b), halved MLC leaf width (c), use of Y backup jaws to track motion perpendicular to the MLC leaves (d), dynamic collimator rotation for alignment of the MLC leaves with the dominant target motion direction (e), improvements 4 and 5 combined (f), and all improvements combined (g). RESULTS: All results are presented as the mean residual MLC exposure error compared to no tracking. In the prediction study, the residual MLC exposure error was 47.0% (no prediction), 45.1% (Kalman), 43.8% (KDE), 43.7% (LAF), 42.1% (wLMS), 40.1% (TVSAR), and 36.5% (Perfect) for lung MLC tracking. For prostate MLC tracking, it was 66.0% (no prediction), 66.9% (Kalman), and 63.4% (Perfect). For lung with TVSAR prediction, the residual MLC exposure error for the seven tracking system improvements was 37.2%(1), 38.3%(2), 37.4%(3), 34.2%(4), 30.6%(5), 27.7%(6), and 20.7%(7). For prostate with no prediction, the residual MLC exposure error was 61.7%(1), 61.4%(2), 55.4%(3), 57.2%(4), 47.5%(5), 43.7%(6), and 38.7%(7). CONCLUSION: For prostate, MLC tracking was slightly better without prediction than with linear Kalman filter prediction. For lung, the TVSAR prediction algorithm performed best. Dynamic alignment of the collimator with the dominant motion axis was the most efficient MLC tracking improvement except for lung tracking with the low modulation VMAT plan, where jaw tracking was slightly better

医学と環境における放射線防護線量に関する研究

Nowadays, with the development of modern radiation science, application of radiation exposure has been paid more and more attention in various fields. Although there are many benefits for human by the use of radiation in such as medical diagnose and treatment, utilization of nuclear power, more efforts should be made to radiation hazards and their control that are often neglected. The researches in this study were intended to meet the requirements with the center of radiation protection dose in a wide range which attracts the most attention and are involved, either directly or indirectly, with ionizing radiation, including diagnostic exposure doses in paediatric CT, radiation doses in normal tissues which surrounding the targets in radiotherapy, and environmental exposure doses in Fukushima nuclear accidental areas. In the researches about paediatric CT, the reference radiation dose and organ doses from chest CT studies of children were estimated by using the data of clinical practice of the National Center for Child Health and Development in Japan. In composing local diagnostic reference doses and organ doses, the aim of this research was to provide a reliable and accurate data on the exposures in X-ray CT examinations for paediatric patients, which could be useful for optimization of radiation protection. Moreover, to evaluate the changes of organ doses depending on the thickness of the soft tissue on body surface in paediatric abdomen CT, radiation doses were measured with radiophotoluminescence glass dosemeters set in various organ positions within a 6-year-old child anthropomorphic phantom with slices of soft tissue equivalent materials attached on the surface, and organ doses were evaluated from the measurement values. In the researches of radiation treatment, the characteristics of the hepatic tumor movement caused by respiration were evaluated by using fluoroscopy. To decrease exposure doses in healthy organs that surrounding targets in tumor tracking treatment, the feasibility of prospective tracking of respiratory caused tumor motion signal based on autoregressive model was also tested to compensate the retardation time that often exists between the acquisition of motion signal and the action execution. In the researches of environmental radiation exposure in Fukushima nuclear accidental areas, radiocesium contaminated soil was obtained from a polluted area in Fukushima and was remedied under strict control by use of electrokinetics, and to accurately measure surface radiation doses after depollution operations, a shield for environmental radiation dose survey meters in badly contaminated areas has been developed. According to the results of the researches, a set of CTDIs and organ doses in paediatric chest CT scan was compiled for the National Center for Child Health and Development based on children\u27s weights. Organ doses in paediatric abdomen CT were evaluated under different thicknesses of soft tissue on the surface of the same child anthropomorphic phantom. In the radiation therapy, thoracic and abdominal tumor motion has been verified to be pace with respiratory movement, and Burg\u27s method has been proved to be effective to predict tumor motion in real-time, and moreover, it could make a contribution to protection for normal organs. Radiocesium contaminated soil was laboratory depolluted effectively by use of electrokinetic remediation technology, and a new shield for survey meters was successfully developed to precisely measure the environmental radiation dose and evaluate decontamination work in the Fukushima.首都大学東京, 2013-09-30, 博士（放射線学）, 甲第452号首都大学東

Contrôle en temps réel de la précision du suivi indirect de tumeurs mobiles en radiothérapie

Le but de la radiothérapie est d’irradier les cellules cancéreuses tout en préservant au maximum les tissus sains environnants. Or, dans le cas du cancer du poumon, la respiration du patient engendre des mouvements de la tumeur pendant le traitement. Une solution possible est de repositionner continuellement le faisceau d’irradiation sur la cible tumorale en mouvement. L’e cacité et la sûreté de cette approche reposent sur la localisation précise en temps réel de la tumeur. Le suivi indirect consiste à inférer la position de la cible tumorale à partir de l’observation d’un signal substitut, visible en continu sans nécessiter de rayonnement ionisant. Un modèle de corrélation spatial doit donc être établi. Par ailleurs, pour compenser la latence du système, l’algorithme de suivi doit pouvoir également anticiper la position future de la cible. Parce que la respiration du patient varie dans le temps, les modèles de prédiction et de corrélation peuvent devenir imprécis. La prédiction de la position de la tumeur devrait alors idéalement être complétée par l’estimation des incertitudes associées aux prédictions. Dans la pratique clinique actuelle, ces incertitudes de positionnement en temps réel ne sont pas explicitement prédites. Cette thèse de doctorat s’intéresse au contrôle en temps réel de la précision du suivi indirect de tumeurs mobiles en radiothérapie. Dans un premier temps, une méthode bayésienne pour le suivi indirect en radiothérapie est développée. Cette approche, basée sur le filtre de Kalman, permet de prédire non seulement la position future de la tumeur à partir d’un signal substitut, mais aussi les incertitudes associées. Ce travail o re une première preuve de concept, et montre également le potentiel du foie comme substitut interne, qui apparait plus robuste et fiable que les marqueurs externes communément utilisés dans la pratique clinique. Dans un deuxième temps, une adaptation de la méthode est proposée afin d’améliorer sa robustesse face aux changements de respiration. Cette innovation permet de prédire des régions de confiance adaptatives, capables de détecter les erreurs de prédiction élevées, en se basant exclusivement sur l’observation du signal substitut. Les résultats révèlent qu’à sensibilité élevée (90%), une spécificité d’environ 50% est obtenue. Un processus de validation innovant basé sur ces régions de confiance adaptatives est ensuite évalué et comparé au processus conventionnel qui consiste en des mesures de la cible à intervalles de temps fixes et prédéterminés. Une version adaptative de la méthode bayésienne est donc développée afin d’intégrer des mesures occasionnelles de la position de la cible. Les résultats confirment que les incertitudes prédites par la méthode bayésienne permettent de détecter les erreurs de prédictions élevées, et démontrent que le processus de validation basé sur ces incertitudes a le potentiel d’être plus e cace que les validations régulières. Ces approches bayésiennes sont validées sur des séquences respiratoires de volontaires, acquises par imagerie par résonance magnétique (IRM) dynamique et interpolées à haute fréquence. Afin de compléter l’évaluation de la méthode bayésienne pour le suivi indirect, une validation expérimentale préliminaire est conduite sur des données cliniques de patients atteints de cancer du poumon. Les travaux de ce projet doctoral promettent une amélioration du contrôle en temps réel de la précision des prédictions lors des traitements de radiothérapie. Finalement, puisque l’imagerie ultrasonore pourrait être employée pour visualiser les substituts internes, une étude préliminaire sur l’évaluation automatique de la qualité des images ultrasonores est présentée. Ces résultats pourront être utilisés ultérieurement pour le suivi indirect en radiothérapie en vue d’optimiser les acquisitions ultrasonores pendant les traitements et faciliter l’extraction automatique du mouvement du substitut.The goal of radiotherapy is to irradiate cancer cells while maintaining a low dose of radiation to the surrounding healthy tissue. In the case of lung cancer, the patient’s breathing causes the tumor to move during treatment. One possible solution is to continuously reposition the irradiation beam on the moving target. The e ectiveness and safety of this approach rely on accurate real-time localization of the tumor. Indirect strategies derive the target positions from a correlation model with a surrogate signal, which is continuously monitored without the need for radiation-based imaging. In addition, to compensate for system latency, the tracking algorithm must also be able to anticipate the future position of the target. Because the patient’s breathing varies over time, prediction and correlation models can become inaccurate. Ideally, the prediction of the tumor location would also include an estimation of the uncertainty associated with the prediction. However, in current clinical practice, these real-time positioning uncertainties are not explicitly predicted. This doctoral thesis focuses on real-time control of the accuracy of indirect tracking of mobile tumors in radiotherapy. First, a Bayesian method is developed. This approach, based on Kalman filter theory, allows predicting both future target motion in real-time from a surrogate signal and associated uncertainty. This work o ers a first proof of concept, and also shows the potential of the liver as an internal substitute as it appears more robust and reliable than the external markers commonly used in clinical practice. Second, an adaptation of the method is proposed to improve its robustness against changes in breathing. This innovation enables the prediction of adaptive confidence regions that can be used to detect significant prediction errors, based exclusively on the observation of the surrogate signal. The results show that at high sensitivity (90%), a specificity of about 50% is obtained. A new validation process based on these adaptive confidence regions is then evaluated and compared to the conventional validation process (i.e., target measurements at fixed and predetermined time intervals). An adaptive version of the Bayesian method is therefore developed to valuably incorporate occasional measurements of the target position. The results confirm that the uncertainties predicted by the Bayesian method can detect high prediction errors, and demonstrate that the validation process based on these uncertainties has the potential to be more e cient and e ective than regular validations. For these studies, the proposed Bayesian methods are validated on respiratory sequences of volunteers, acquired by dynamic MRI and interpolated at high frequency. In order to complete the evaluation of the Bayesian method for indirect tracking, experimental validation is conducted on clinical data of patients with lung cancer. The work of this doctoral project promises to improve the real-time control of the accuracy of predictions during radiotherapy treatments. Finally, since ultrasound imaging could be used to visualize internal surrogates, a preliminary study on automatic ultrasound image quality assessment is presented. These results can later be used for indirect tracking in radiotherapy to optimize ultrasound acquisitions during treatments and facilitate the automatic estimation of surrogate motion

Multiparametric Magnetic Resonance Imaging Artificial Intelligence Pipeline for Oropharyngeal Cancer Radiotherapy Treatment Guidance

Oropharyngeal cancer (OPC) is a widespread disease and one of the few domestic cancers that is rising in incidence. Radiographic images are crucial for assessment of OPC and aid in radiotherapy (RT) treatment. However, RT planning with conventional imaging approaches requires operator-dependent tumor segmentation, which is the primary source of treatment error. Further, OPC expresses differential tumor/node mid-RT response (rapid response) rates, resulting in significant differences between planned and delivered RT dose. Finally, clinical outcomes for OPC patients can also be variable, which warrants the investigation of prognostic models. Multiparametric MRI (mpMRI) techniques that incorporate simultaneous anatomical and functional information coupled to artificial intelligence (AI) approaches could improve clinical decision support for OPC by providing immediately actionable clinical rationale for adaptive RT planning. If tumors could be reproducibly segmented, rapid response could be classified, and prognosis could be reliably determined, overall patient outcomes would be optimized to improve the therapeutic index as a function of more risk-adapted RT volumes. Consequently, there is an unmet need for automated and reproducible imaging which can simultaneously segment tumors and provide predictive value for actionable RT adaptation. This dissertation primarily seeks to explore and optimize image processing, tumor segmentation, and patient outcomes in OPC through a combination of advanced imaging techniques and AI algorithms. In the first specific aim of this dissertation, we develop and evaluate mpMRI pre-processing techniques for use in downstream segmentation, response prediction, and outcome prediction pipelines. Various MRI intensity standardization and registration approaches were systematically compared and benchmarked. Moreover, synthetic image algorithms were developed to decrease MRI scan time in an effort to optimize our AI pipelines. We demonstrated that proper intensity standardization and image registration can improve mpMRI quality for use in AI algorithms, and developed a novel method to decrease mpMRI acquisition time. Subsequently, in the second specific aim of this dissertation, we investigated underlying questions regarding the implementation of RT-related auto-segmentation. Firstly, we quantified interobserver variability for an unprecedented large number of observers for various radiotherapy structures in several disease sites (with a particular emphasis on OPC) using a novel crowdsourcing platform. We then trained an AI algorithm on a series of extant matched mpMRI datasets to segment OPC primary tumors. Moreover, we validated and compared our best model\u27s performance to clinical expert observers. We demonstrated that AI-based mpMRI OPC tumor auto-segmentation offers decreased variability and comparable accuracy to clinical experts, and certain mpMRI input channel combinations could further improve performance. Finally, in the third specific aim of this dissertation, we predicted OPC primary tumor mid-therapy (rapid) treatment response and prognostic outcomes. Using co-registered pre-therapy and mid-therapy primary tumor manual segmentations of OPC patients, we generated and characterized treatment sensitive and treatment resistant pre-RT sub-volumes. These sub-volumes were used to train an AI algorithm to predict individual voxel-wise treatment resistance. Additionally, we developed an AI algorithm to predict OPC patient progression free survival using pre-therapy imaging from an international data science competition (ranking 1st place), and then translated these approaches to mpMRI data. We demonstrated AI models could be used to predict rapid response and prognostic outcomes using pre-therapy imaging, which could help guide treatment adaptation, though further work is needed. In summary, the completion of these aims facilitates the development of an image-guided fully automated OPC clinical decision support tool. The resultant deliverables from this project will positively impact patients by enabling optimized therapeutic interventions in OPC. Future work should consider investigating additional imaging timepoints, imaging modalities, uncertainty quantification, perceptual and ethical considerations, and prospective studies for eventual clinical implementation. A dynamic version of this dissertation is publicly available and assigned a digital object identifier through Figshare (doi: 10.6084/m9.figshare.22141871)

A comparison of the CAR and DAGAR spatial random effects models with an application to diabetics rate estimation in Belgium

When hierarchically modelling an epidemiological phenomenon on a finite collection of sites in space, one must always take a latent spatial effect into account in order to capture the correlation structure that links the phenomenon to the territory. In this work, we compare two autoregressive spatial models that can be used for this purpose: the classical CAR model and the more recent DAGAR model. Differently from the former, the latter has a desirable property: its ρ parameter can be naturally interpreted as the average neighbor pair correlation and, in addition, this parameter can be directly estimated when the effect is modelled using a DAGAR rather than a CAR structure. As an application, we model the diabetics rate in Belgium in 2014 and show the adequacy of these models in predicting the response variable when no covariates are available

A Statistical Approach to the Alignment of fMRI Data

Multi-subject functional Magnetic Resonance Image studies are critical. The anatomical and functional structure varies across subjects, so the image alignment is necessary. We define a probabilistic model to describe functional alignment. Imposing a prior distribution, as the matrix Fisher Von Mises distribution, of the orthogonal transformation parameter, the anatomical information is embedded in the estimation of the parameters, i.e., penalizing the combination of spatially distant voxels. Real applications show an improvement in the classification and interpretability of the results compared to various functional alignment methods