Prompt-gamma imaging (PGI) was proposed in the 2000s as a promising in vivo range-verification method to maintain the physical advantage of proton beams by reducing unwanted range-uncertainties. Recently, PGI with a slit camera has been successfully implemented in clinical application. Despite its high accuracy and sensitivity to range deviation being shown in several studies, the clinical benefits of PGI have not yet been investigated. Hence, to fully exploit the advantages of PGI, this thesis aims to investigate the feasibility of PGI-based range verification for the automatic classification of treatment deviations and differentiation of relevant from non-relevant changes in the treatment of head-and-neck (H&N) tumors. In the first part of this thesis, the four most common types of treatment deviations in proton therapy (PT) were investigated regarding their PGI signature and by considering clinically relevant and non-relevant scenarios. A heuristic decision tree (DT) model was iteratively developed. To gain understanding of the specific signature of the error sources, different levels of geometrical complexities were explored, from simple to complex. At the simplest level, a phantom with homogeneous density was used to distinguish range-prediction and setup errors. Next, in the intermediate complexity level, a phantom with heterogeneous density was used to inspect the additional error scenarios of anatomical changes. Finally, real patient CT scans were used to investigate the relevance of changes based on clinical constraints. In the final model, a five-step filtering approach was used during pre-processing to select reliable pencil-beam-scanning spots for range verification. In this study, five features extracted from the filtered PGI data were used to classify the treatment deviation. The model is able distinguish four introduced scenarios into six classes as follows: (1) overestimation of range prediction, (2) underestimation of range prediction, (3) setup error with larger air gap, (4) setup error with smaller air gap, (5) anatomical change, and (6) non-relevant change. To ensure the application was effective, independent patient CT datasets were used to test the model. The results yielded an excellent performance of the DT classifier, with high accuracy, sensitivity, and specificity of 96%, 100%, and 85.7%, respectively. According to these findings, this model can sensitively detect treatment deviations in PT based on simulated PGI data. In the second part of this work, an alternative approach based on machine learning (ML) was taken to automatically classify the error sources. In the first stage, the two approaches were compared, using the same features as well as the same training and test datasets. The results show that the ML approach was slightly better than the heuristic DT approach in terms of accuracy. However, the performance of both approaches was excellent for the individual scenarios. Thus, these results confirm that the PGI-based data classification with five features can be applied to detect individual sources of treatment deviation in PT. In the second stage, there was an investigation of more complex and more realistic combinations of error scenarios, which was out of the scope of the DT approach. The results demonstrated that the performance of the ML-based classifiers declined in general. Furthermore, the additional features of the PG shift did not substantially improve the performance of the classifiers. As a consequence, these findings mark important issues for future research. Potentially, usage of the spatial information from the spot-based PGI data and more complex techniques such as deep learning may improve the performance of classifiers with respect to scenarios with multiple error sources. However, regardless of this, it is recommended that these findings be confirmed and validated in simulations under measurement-like conditions or with real PG measurements of H&N patients themselves. Moreover, this classification model could eventually be tested with other body sites and entities in order to assess its compatibility and adaptation requirements. In summary, this study yielded promising results regarding the automatic classification of treatment-deviation sources and the differentiation of relevant and non-relevant changes in H&N-tumor treatment in PT with PGI data. This simulation study marks an important step towards fully automated PGI-based proton-range verification, which could contribute to closing the treatment-workflow loop of adaptive therapy by supporting clinical decision-making and, ultimately, improving clinical PT.:1 Introduction
2 Background
2.1 Proton therapy
2.1.1 Rationale for proton therapy
2.1.2 Uncertainties and their mitigation
2.2 In vivo range-verification techniques
2.2.1 Range probing
2.2.2 Proton tomography
2.2.3 Magnetic resonance imaging
2.2.4 Ionoacoustic detection
2.2.5 Treatment-activated positron-emission tomography imaging
2.2.6 Prompt-gamma based detection
3 Prompt-gamma imaging with a knife-edged slit camera
3.1 Current state-of-the-art
3.2 Prompt-gamma camera system
3.3 Data acquisition and analysis
4 Error-source classification using heuristic decision tree approach
4.1 Study design
4.1.1 Case selection
4.1.2 Investigated scenarios
4.1.3 Prompt-gamma simulation and range shift determination
4.2 Development of the model
4.2.1 First-generation model
4.2.2 Second-generation model
4.2.3 Third-generation model
4.3 Model testing
4.4 Discussion: decision-tree model
5 Error-source classification using a machine-learning approach
5.1 Machine learning for classification
5.1.1 Support-vector-machine algorithm
5.1.2 Ensemble algorithm – random forest
5.1.3 Logistic-regression algorithm
5.2 Study design
5.2.1 Case selection
5.2.2 Feature selection
5.3 Model generation
5.4 Model testing
5.5 Discussion
6 Summary/ Zusammenfassung
Bibliography
Appendix
List of Figures
List of Tables
List of Abbreviations
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:76058 |
| Date | 24 September 2021 |
| Creators | Khamfongkhruea, Chirasak |
| Contributors | Enghardt, Wolfgang, Richter, Christian, Thorwarth, Daniela, Technische Universität Dresden |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:doctoralThesis, info:eu-repo/semantics/doctoralThesis, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
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