Machine Learning Models to automate Radiotherapy Structure Name Standardization

Structure name standardization is a critical problem in Radiotherapy planning systems to correctly identify the various Organs-at-Risk, Planning Target Volumes and `Other\u27 organs for monitoring present and future medications. Physicians often label anatomical structure sets in Digital Imaging and Communications in Medicine (DICOM) images with nonstandard random names. Hence, the standardization of these names for the Organs at Risk (OARs), Planning Target Volumes (PTVs), and `Other\u27 organs is a vital problem. Prior works considered traditional machine learning approaches on structure sets with moderate success. We compare both traditional methods and deep neural network-based approaches on the multimodal vision-language prostate cancer patient data, compiled from the radiotherapy centers of the US Veterans Health Administration (VHA) and Virginia Commonwealth University (VCU) for structure name standardization. These de-identified data comprise 16,290 prostate structures. Our method integrates the multimodal textual and imaging data with Convolutional Neural Network (CNN)-based deep learning approaches such as CNN, Visual Geometry Group (VGG) network, and Residual Network (ResNet) and shows improved results in prostate radiotherapy structure name standardization. Our proposed deep neural network-based approach on the multimodal vision-language prostate cancer patient data provides state-of-the-art results for structure name standardization. Evaluation with macro-averaged F1 score shows that our CNN model with single-modal textual data usually performs better than previous studies. We also experimented with various combinations of multimodal data (masked images, masked dose) besides textual data. The models perform well on textual data alone, while the addition of imaging data shows that deep neural networks achieve better performance using information present in other modalities. Our pipeline can successfully standardize the Organs-at-Risk and the Planning Target Volumes, which are of utmost interest to the clinicians and simultaneously, performs very well on the `Other\u27 organs. We performed comprehensive experiments by varying input data modalities to show that using masked images and masked dose data with text outperforms the combination of other input modalities. We also undersampled the majority class, i.e., the `Other\u27 class, at different degrees and conducted extensive experiments to demonstrate that a small amount of majority class undersampling is essential for superior performance. Overall, our proposed integrated, deep neural network-based architecture for prostate structure name standardization can solve several challenges associated with multimodal data. The VGG network on the masked image-dose data combined with CNNs on the text data performs the best and presents the state-of-the-art in this domain

DATA SCIENCE METHODS FOR STANDARDIZATION, SAFETY, AND QUALITY ASSURANCE IN RADIATION ONCOLOGY

Radiation oncology is the field of medicine that deals with treating cancer patients through ionizing radiation. The clinical modality or technique used to treat the cancer patients in the radiation oncology domain is referred to as radiation therapy. Radiation therapy aims to deliver precisely measured dose irradiation to a defined tumor volume (target) with as minimal damage as possible to surrounding healthy tissue (organs-at-risk), resulting in eradication of the tumor, high quality of life, and prolongation of survival. A typical radiotherapy process requires the use of different clinical systems at various stages of the workflow. The data generated in these different stages of workflow is stored in an unstructured and non-standard format, which hinders interoperability and interconnectivity of data, thereby making it difficult to translate all of these datasets into knowledge that supports decision-making in routine clinical practice. In this dissertation, we present an enterprise-level informatics platform that can automatically extract and efficiently store clinical, treatment, imaging, and genomics data from radiation oncology patients. Additionally, we propose data science methods for data standardization, safety, and treatment quality analysis in radiation oncology. We demonstrate that our data standardization methods using word embeddings and machine learning are robust and highly generalizable on real-word clinical datasets collected from the nationwide radiation therapy centers administered by the US Veterans\u27 Health Administration. We also present different heterogeneous data integration approaches to enhance the data standardization process. For patient safety, we analyze the radiation oncology incident reports and propose an integrated natural language processing and machine learning based pipeline to automate the incident triage and prioritization process. We demonstrate that a deep learning based transfer learning approach helps in the automated incident triage process. Finally, we address the issue of treatment quality in terms of automated treatment planning in clinical decision support systems. We show that supervised machine learning methods can efficiently generate clinical hypotheses from radiation oncology treatment plans and demonstrate our framework\u27s data analytics capability

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 Learning Health System for Radiation Oncology

The proposed research aims to address the challenges faced by clinical data science researchers in radiation oncology accessing, integrating, and analyzing heterogeneous data from various sources. The research presents a scalable intelligent infrastructure, called the Health Information Gateway and Exchange (HINGE), which captures and structures data from multiple sources into a knowledge base with semantically interlinked entities. This infrastructure enables researchers to mine novel associations and gather relevant knowledge for personalized clinical outcomes. The dissertation discusses the design framework and implementation of HINGE, which abstracts structured data from treatment planning systems, treatment management systems, and electronic health records. It utilizes disease-specific smart templates for capturing clinical information in a discrete manner. HINGE performs data extraction, aggregation, and quality and outcome assessment functions automatically, connecting seamlessly with local IT/medical infrastructure. Furthermore, the research presents a knowledge graph-based approach to map radiotherapy data to an ontology-based data repository using FAIR (Findable, Accessible, Interoperable, Reusable) concepts. This approach ensures that the data is easily discoverable and accessible for clinical decision support systems. The dissertation explores the ETL (Extract, Transform, Load) process, data model frameworks, ontologies, and provides a real-world clinical use case for this data mapping. To improve the efficiency of retrieving information from large clinical datasets, a search engine based on ontology-based keyword searching and synonym-based term matching tool was developed. The hierarchical nature of ontologies is leveraged to retrieve patient records based on parent and children classes. Additionally, patient similarity analysis is conducted using vector embedding models (Word2Vec, Doc2Vec, GloVe, and FastText) to identify similar patients based on text corpus creation methods. Results from the analysis using these models are presented. The implementation of a learning health system for predicting radiation pneumonitis following stereotactic body radiotherapy is also discussed. 3D convolutional neural networks (CNNs) are utilized with radiographic and dosimetric datasets to predict the likelihood of radiation pneumonitis. DenseNet-121 and ResNet-50 models are employed for this study, along with integrated gradient techniques to identify salient regions within the input 3D image dataset. The predictive performance of the 3D CNN models is evaluated based on clinical outcomes. Overall, the proposed Learning Health System provides a comprehensive solution for capturing, integrating, and analyzing heterogeneous data in a knowledge base. It offers researchers the ability to extract valuable insights and associations from diverse sources, ultimately leading to improved clinical outcomes. This work can serve as a model for implementing LHS in other medical specialties, advancing personalized and data-driven medicine

Learning from Multi-Class Imbalanced Big Data with Apache Spark

With data becoming a new form of currency, its analysis has become a top priority in both academia and industry, furthering advancements in high-performance computing and machine learning. However, these large, real-world datasets come with additional complications such as noise and class overlap. Problems are magnified when with multi-class data is presented, especially since many of the popular algorithms were originally designed for binary data. Another challenge arises when the number of examples are not evenly distributed across all classes in a dataset. This often causes classifiers to favor the majority class over the minority classes, leading to undesirable results as learning from the rare cases may be the primary goal. Many of the classic machine learning algorithms were not designed for multi-class, imbalanced data or parallelism, and so their effectiveness has been hindered. This dissertation addresses some of these challenges with in-depth experimentation using novel implementations of machine learning algorithms using Apache Spark, a distributed computing framework based on the MapReduce model designed to handle very large datasets. Experimentation showed that many of the traditional classifier algorithms do not translate well to a distributed computing environment, indicating the need for a new generation of algorithms targeting modern high-performance computing. A collection of popular oversampling methods, originally designed for small binary class datasets, have been implemented using Apache Spark for the first time to improve parallelism and add multi-class support. An extensive study on how instance level difficulty affects the learning from large datasets was also performed

Artificial General Intelligence for Radiation Oncology

The emergence of artificial general intelligence (AGI) is transforming radiation oncology. As prominent vanguards of AGI, large language models (LLMs) such as GPT-4 and PaLM 2 can process extensive texts and large vision models (LVMs) such as the Segment Anything Model (SAM) can process extensive imaging data to enhance the efficiency and precision of radiation therapy. This paper explores full-spectrum applications of AGI across radiation oncology including initial consultation, simulation, treatment planning, treatment delivery, treatment verification, and patient follow-up. The fusion of vision data with LLMs also creates powerful multimodal models that elucidate nuanced clinical patterns. Together, AGI promises to catalyze a shift towards data-driven, personalized radiation therapy. However, these models should complement human expertise and care. This paper provides an overview of how AGI can transform radiation oncology to elevate the standard of patient care in radiation oncology, with the key insight being AGI's ability to exploit multimodal clinical data at scale