Involuntary and voluntary patient motion has become a major obstacle for achieving high-precision radiation therapy of cancers especially in the thorax and upper abdomen. As the target is continuously moving, an additional margin has to be added to the clinical target volume to compensate for the uncertainty caused by the respiration-induced organ motion, causing toxicity to the normal tissue and limiting the dose delivered to the target. To account for the tumor motion, surrogate tracking methods are commonly used in clinics during radiotherapy. However, the relationship between the surrogate and tumor motion is hard to generalize as it depends on individual patients, tumor location, treatment fractions, and sometimes shows complex patterns or transient, unpredictable changes. Despite the lack of in-depth understanding of the underlying uncertainty, increasingly clinics are treating patients using surrogate delivery methods. Hence, there is an urgent need to better scrutinize our current surrogate-based motion management strategies. Moreover, the most robust motion management strategy for the given patient should be determined in the pre-treatment setting but we currently lack a sufficient imaging tool to provide this information.

Recent advances in 4D imaging technologies enable a growing movement toward 4D radiation therapy, aiming to track and compensate for target motion during the entire radiation treatment. A 4D-CT image is typically used to characterize the tumor motion over the course of the radiotherapy treatment. However, 4D-CT has significant limitations. 4D-CT is an oversimplified snapshot representation of a single-breathing cycle with low soft tissue contrast while imparting a considerable amount of radiation dose to the patient. Consequently, the limitations of 4D-CT prevent applicability in acquiring information over timescales that represent a treatment session, much less a course of radiotherapy.

MRI is highly advantageous as it is a non-ionizing imaging modality and provides excellent soft tissue contrast. Real-time 4D-MR imaging that produces dynamic 3D volumes at every phase of motion from a single acquisition is limited by low image quality and temporal resolution. On the other hand, fast 2D dynamic MR imaging techniques have high fidelity and spatio-temporal resolution requisite for real-time tracking of the moving target. Furthermore, a respiration-correlated 4D-MRI can be reconstructed from multi-slice 2D dynamic MR images, enabling volumetric image processing and analysis. Consequently, dynamic MRI has been used to observe the motion of multiple organs including the lung, liver, pancreas, diaphragm, breast and prostate. 4D-MRI is an attractive solution to address breathing motion and tumor tracking obstacles in radiotherapy.

The main goal of this research is to characterize patient-specific respiration-induced tumor and surrogate motion to evaluate the accuracy and effectiveness of the surrogate-based motion management strategies currently used in clinics. Specifically, we hypothesize that  dynamic MRI obtained over a temporal duration consistent with radiotherapy treatments will provide spatio-temporal information of both the tumor and surrogate, and therefore can serve as a means to assess the quality of the tumor motion tracking with the surrogate.

To test our hypothesis, we specifically propose to:

Aim 1: Track and characterize the tumor and surrogate motion with 4D-MRI. Multi-slice 2D dynamic MR images will be acquired in two orthogonal orientations over a prolonged imaging duration. A retrospective 4D-MRI encompassing the tumor and surrogate will be reconstructed using a respiration-based binning, averaging, and novel super-resolution reconstruction techniques. The reconstructed 4D-MRI will show the representative motion of the tumor and surrogate for a single breathing cycle and be used as a 3D template. In a successive scan, 2D dynamic MR image will be acquired only at mid-sagittal plane of the tumor and surrogate in an alternating fashion. The surrogate and target tumor will be tracked by volume-to-slice registration using the 3D template derived from the retrospective 4D-MRI.

Aim 2: Evaluate surrogate-based motion tracking in a cohort of patients with thoracic tumors. Thirty lung cancer patients with a surrogate marker attached to the skin will be scanned at pre-treatment and once during the course of treatment. Each imaging session will continue for approximately 20 minutes under different breathing scenarios; normal, shallow, deep, and coached breathing. The proposed approach will allow us to analyze the correlation between the surrogate and tumor motion in different breathing patterns, pre- and intra-treatment. The range and trajectory of motion, breathing phase dependent position uncertainties, sensitivity and specificity of the surrogate-based motion management will be analyzed.

4D-MRI is a promising tool to analyze complex breathing patterns in patients and, as such, will play an ever increasing role in the 4D radiation therapy and the management of mobile tumors. External and internal surrogate-based strategies commonly used in clinics have not been appropriately validated. With the increasing adaptation of these surrogate methods for motion management, the proposed research addresses these urgent issues in clinical radiotherapy while providing a means to achieve patient-specific motion management.