Multivariate Statistical Techniques for Accurately and Noninvasively Localizing Tumors Subject to Respiration-Induced Motion

Tumors in the lung, liver, and pancreas can move considerably with normal respiration. The tumor motion extent, path, and baseline position change over time. This creates a complex "moving target" for external beam radiation and is a major obstacle to treating cancer. Real-time tumor motion compensation systems have emerged, but device performance is limited by tumor localization accuracy. Direct tumor tracking is not feasible for these tumors, but tumor displacement can be predicted from surrogate measurements of respiration. In this dissertation, we have developed a series of multivariate statistical techniques for reliably and accurately localizing tumors from respiratory surrogate markers affixed to the torso surface. Our studies utilized radiographic tumor localizations measured concurrently with optically tracked respiratory surrogates during 176 lung, liver, and pancreas radiation treatment and dynamic MR imaging sessions. We identified measurement precision, tumor-surrogate correlation, training data selection, inter-patient variations, and algorithm design as factors impacting localization accuracy. Training data timing was particularly important, as tumor localization errors increased over time in 63% of 30-min treatments. This was a result of the changing relationship between surrogate signals and tumor motion. To account for these changes, we developed a method for detecting and correcting large localization errors. By monitoring the surrogate-to-surrogate and surrogate-to-model relationships, tumor localization errors exceeding 3 mm could be detected at a sensitivity of 95%. The method that we have proposed and validated in this dissertation leads to 69% fewer treatment interruptions than conventional respiratory surrogate model monitoring techniques. Finally, we extended respiratory surrogate-based tumor motion prediction to the otherwise time-consuming process of contouring respiratory-correlated computed tomography scans. This dissertation clarifies the scope and significance of problems underlying existing surrogate-based tumor localization models. Furthermore, it presents novel solutions that make it possible to improve radiation delivery to tumors without increasing the time required to plan and deliver radiation treatments

PREDICTION OF RESPIRATORY MOTION

Radiation therapy is a cancer treatment method that employs high-energy radiation beams to destroy cancer cells by damaging the ability of these cells to reproduce. Thoracic and abdominal tumors may change their positions during respiration by as much as three centimeters during radiation treatment. The prediction of respiratory motion has become an important research area because respiratory motion severely affects precise radiation dose delivery. This study describes recent radiotherapy technologies including tools for measuring target position during radiotherapy and tracking-based delivery systems. In the first part of our study we review three prediction approaches of respiratory motion, i.e., model-based methods, model-free heuristic learning algorithms, and hybrid methods. In the second part of our work we propose respiratory motion estimation with hybrid implementation of extended Kalman filter. The proposed method uses the recurrent neural network as the role of the predictor and the extended Kalman filter as the role of the corrector. In the third part of our work we further extend our research work to present customized prediction of respiratory motion with clustering from multiple patient interactions. For the customized prediction we construct the clustering based on breathing patterns of multiple patients using the feature selection metrics that are composed of a variety of breathing features. In the fourth part of our work we retrospectively categorize breathing data into several classes and propose a new approach to detect irregular breathing patterns using neural networks. We have evaluated the proposed new algorithm by comparing the prediction overshoot and the tracking estimation value. The experimental results of 448 patients’ breathing patterns validated the proposed irregular breathing classifier