Electronic Thesis and Dissertation Repository

Thesis Format

Integrated Article

Degree

Doctor of Philosophy

Program

Medical Biophysics

Supervisor

Gaede, Stewart

Affiliation

London Regional Cancer Progarm, University of Western Ontario

2nd Supervisor

Lee, Ting-Yim

Affiliation

Robarts Research Institute, Lawson Research Institute, University of Western Ontario

Co-Supervisor

Abstract

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. A significant challenge in treating NSCLC is balancing aggressive treatment with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges. 4-dimensional computed tomography (4D-CT) is an important part of motion management, but images often suffer from motion-induced artifacts. Volumetric CT scanners with wide axial field-of-view (aFOV) may reduce these artifacts and present an opportunity to advance CT-based functional lung imaging.

Chapter 2 presents a phantom imaging study to investigate the suitability of a 256-slice volumetric CT (vCT) scanner for radiotherapy treatment planning. The density of the highest density materials was under-estimated by the scanner, which can be addressed with the use of an appropriate relative electron density (RED) curve. An average RED curve for all aFOV settings may be used.

Chapter 3 presents a study of phantom and NSCLC patient 4D-CT images acquired on a clinical scanner and a vCT scanner. The v4D-CT images were re-sampled to simulate a conventional acquisition using a narrow aFOV clinical scanner. The phantom images demonstrated that target contouring variability decreased in v4D-CT imaging as compared to clinical 4D-CT. In the patient images, mean Hausdorff distance between organs at risk (OAR) contours was significantly correlated to respiratory phase, indicating that motion artifacts contribute to this variability.

Chapter 4 presents a novel acquisition and analysis pipeline to image lung ventilation (V), perfusion (Q) and V/Q ratio in a single volumetric CT scan. In a porcine study, these images of V and Q were significantly correlated to standard Xe-enhanced ventilation and PET perfusion images in voxel-wise analysis. In a NSCLC patient study, the images were sensitive to changes in V and Q between baseline imaging and follow-up 6 weeks after radiotherapy.

In this thesis, I demonstrate that volumetric CT scanners are suitable for use in radiation therapy simulation and treatment planning, and detail two scanning protocols which may reduce the challenges posed by respiratory motion and RILI risk in NSCLC.

Summary for Lay Audience

Non-small cell lung cancer (NSCLC) is one of the most diagnosed cancers in Canada, and the leading cause of cancer deaths. Most patients will undergo a combination of therapies which may include surgery, chemotherapy, radiation therapy, and recently, immunotherapy. Approximately one in three patients with NSCLC will undergo radiation therapy, which is the focus of this thesis. When treating this disease, a significant challenge is balancing aggressive treatment to kill the cancer with the potentially severe side effects. In radiation therapy, the management of respiratory motion and the risks of radiation-induced lung injury (RILI) pose significant challenges.

Respiratory motion presents a challenge because patients cannot hold their breath for an entire radiation therapy delivery, and the motion caused by breathing may cause their tumour to move during treatment. To give the maximum possible dose to the tumour and protect the surrounding healthy lungs, this motion must be measured and accounted for in treatment planning and delivery. 4-dimensional computed tomography (4D-CT) is an essential part of this process, in which CT images are acquired while the patient breathes freely. Current clinical CT scanners rely on very consistent patient breathing for this process, which is difficult for many NSCLC patients. Newer CT scanners with wider detectors may be able to improve these images.

In Chapter 2, many materials were scanned in the volumetric CT scanner to test its measurement accuracy. These results showed that the scanner is sufficiently accurate to be used in radiation treatment planning. In Chapter 3, a moving device was imaged using 4D-CT on a clinical and volumetric scanner, and four patients with NSCLC were imaged on both scanners. Analysis of these images showed that the volumetric 4D-CT images more accurately imaged the respiratory motion of organs in the thorax.

In Chapter 4, we developed and tested a method to image air flow (ventilation) and blood flow (perfusion) in the lungs using an injected contrast during one volumetric CT scan. The accuracy of these images was confirmed in an animal study and was demonstrated in two NSCLC patients before and after radiation therapy.

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