Biomechanical Modeling for Lung Tumor Motion Prediction during Brachytherapy and Radiotherapy

A novel technique is proposed to develop a biomechanical model for estimating lung’s tumor position as a function of respiration cycle time. Continuous tumor motion is a major challenge in lung cancer treatment techniques where the tumor needs to be targeted; e.g. in external beam radiotherapy and brachytherapy. If not accounted for, this motion leads to areas of radiation over and/or under dosage for normal tissue and tumors. In this thesis, biomechanical models were developed for lung tumor motion predication in two distinct cases of lung brachytherapy and lung external beam radiotherapy. The lung and other relevant surrounding organs geometries, loading, boundary conditions and mechanical properties were considered and incorporated properly for each case. While using material model with constant incompressibility is sufficient to model the lung tissue in the brachytherapy case, in external beam radiation therapy the tissue incompressibility varies significantly due to normal breathing. One of the main issues tackled in this research is characterizing lung tissue incompressibility variations and measuring its corresponding parameters as a function of respiration cycle time. Results obtained from an ex-vivo porcine deflated lung indicated feasibility and reliability of using the developed biomechanical model to predict tumor motion during brachytherapy. For external beam radiotherapy, in-silico studies indicated very significant impact of considering the lung tissue incompressibility on the accuracy of predicting tumor motion. Furthermore, ex-vivo porcine lung experiments demonstrated the capability and reliability of the proposed approach for predicting tumor motion as a function of cyclic time. As such, the proposed models have a good potential to be incorporated effectively in computer assisted lung radiotherapy treatment systems

Inverse-Consistent Determination of Young\u27s Modulus of Human Lung

Human lung undergoes respiration-induced deformation due to sequential inhalation and exhalation. Accurate determination of lung deformation is crucial for tumor localization and targeted radiotherapy in patients with lung cancer. Numerical modeling of human lung dynamics based on underlying physics and physiology enables simulation and virtual visualization of lung deformation. Dynamical modeling is numerically complicated by the lack of information on lung elastic behavior, structural heterogeneity as well as boundary constrains. This study integrates physics-based modeling and image-based data acquisition to develop the patient-specific biomechanical model and consequently establish the first consistent Young\u27s modulus (YM) of human lung. This dissertation has four major components: (i) develop biomechanical model for computation of the flow and deformation characteristics that can utilize subject-specific, spatially-dependent lung material property; (ii) develop a fusion algorithm to integrate deformation results from a deformable image registration (DIR) and physics-based modeling using the theory of Tikhonov regularization; (iii) utilize fusion algorithm to establish unique and consistent patient specific Young\u27s modulus and; (iv) validate biomechanical model utilizing established patient-specific elastic property with imaging data. The simulation is performed on three dimensional lung geometry reconstructed from four-dimensional computed tomography (4DCT) dataset of human subjects. The heterogeneous Young\u27s modulus is estimated from a linear elastic deformation model with the same lung geometry and 4D lung DIR. The biomechanical model adequately predicts the spatio-temporal lung deformation, consistent with data obtained from imaging. The accuracy of the numerical solution is enhanced through fusion with the imaging data beyond the classical comparison of the two sets of data. Finally, the fused displacement results are used to establish unique and consistent patient-specific elastic property of the lung

A biomechanical approach for real-time tracking of lung tumors during External Beam Radiation Therapy (EBRT)

Lung cancer is the most common cause of cancer related death in both men and women. Radiation therapy is widely used for lung cancer treatment. However, this method can be challenging due to respiratory motion. Motion modeling is a popular method for respiratory motion compensation, while biomechanics-based motion models are believed to be more robust and accurate as they are based on the physics of motion. In this study, we aim to develop a biomechanics-based lung tumor tracking algorithm which can be used during External Beam Radiation Therapy (EBRT). An accelerated lung biomechanical model can be used during EBRT only if its boundary conditions (BCs) are defined in a way that they can be updated in real-time. As such, we have developed a lung finite element (FE) model in conjunction with a Neural Networks (NNs) based method for predicting the BCs of the lung model from chest surface motion data. To develop the lung FE model for tumor motion prediction, thoracic 4D CT images of lung cancer patients were processed to capture the lung and diaphragm geometry, trans-pulmonary pressure, and diaphragm motion. Next, the chest surface motion was obtained through tracking the motion of the ribcage in 4D CT images. This was performed to simulate surface motion data that can be acquired using optical tracking systems. Finally, two feedforward NNs were developed, one for estimating the trans-pulmonary pressure and another for estimating the diaphragm motion from chest surface motion data. The algorithm development consists of four steps of: 1) Automatic segmentation of the lungs and diaphragm, 2) diaphragm motion modelling using Principal Component Analysis (PCA), 3) Developing the lung FE model, and 4) Using two NNs to estimate the trans-pulmonary pressure values and diaphragm motion from chest surface motion data. The results indicate that the Dice similarity coefficient between actual and simulated tumor volumes ranges from 0.76±0.04 to 0.91±0.01, which is favorable. As such, real-time lung tumor tracking during EBRT using the proposed algorithm is feasible. Hence, further clinical studies involving lung cancer patients to assess the algorithm performance are justified

Medical physics challenges in clinical MR-guided radiotherapy

The integration of magnetic resonance imaging (MRI) for guidance in external beam radiotherapy has faced significant research and development efforts in recent years. The current availability of linear accelerators with an embedded MRI unit, providing volumetric imaging at excellent soft tissue contrast, is expected to provide novel possibilities in the implementation of image-guided adaptive radiotherapy (IGART) protocols. This study reviews open medical physics issues in MR-guided radiotherapy (MRgRT) implementation, with a focus on current approaches and on the potential for innovation in IGART.Daily imaging in MRgRT provides the ability to visualize the static anatomy, to capture internal tumor motion and to extract quantitative image features for treatment verification and monitoring. Those capabilities enable the use of treatment adaptation, with potential benefits in terms of personalized medicine. The use of online MRI requires dedicated efforts to perform accurate dose measurements and calculations, due to the presence of magnetic fields. Likewise, MRgRT requires dedicated quality assurance (QA) protocols for safe clinical implementation.Reaction to anatomical changes in MRgRT, as visualized on daily images, demands for treatment adaptation concepts, with stringent requirements in terms of fast and accurate validation before the treatment fraction can be delivered. This entails specific challenges in terms of treatment workflow optimization, QA, and verification of the expected delivered dose while the patient is in treatment position. Those challenges require specialized medical physics developments towards the aim of fully exploiting MRI capabilities. Conversely, the use of MRgRT allows for higher confidence in tumor targeting and organs-at-risk (OAR) sparing.The systematic use of MRgRT brings the possibility of leveraging IGART methods for the optimization of tumor targeting and quantitative treatment verification. Although several challenges exist, the intrinsic benefits of MRgRT will provide a deeper understanding of dose delivery effects on an individual basis, with the potential for further treatment personalization

Development and validation of real-time simulation of X-ray imaging with respiratory motion

International audienceWe present a framework that combines evolutionary optimisation, soft tissue modelling and ray tracing on GPU to simultaneously compute the respiratory motion and X-ray imaging in real-time. Our aim is to provide validated building blocks with high fidelity to closely match both the human physiology and the physics of X-rays. A CPU-based set of algorithms is presented to model organ behaviours during respiration. Soft tissue deformation is computed with an extension of the Chain Mail method. Rigid elements move according to kinematic laws. A GPU-based surface rendering method is proposed to compute the X-ray image using the Beer-Lambert law. It is provided as an open-source library. A quantitative validation study is provided to objectively assess the accuracy of both components: i) the respiration against anatomical data, and ii) the X-ray against the Beer-Lambert law and the results of Monte Carlo simulations. Our implementation can be used in various applications, such as interactive medical virtual environment to train percutaneous transhepatic cholangiography in interventional radiology, 2D/3D registration, computation of digitally reconstructed radiograph, simulation of 4D sinograms to test tomography reconstruction tools

Reducing Uncertainty in Head and Neck Radiotherapy with Plastic Robotics

One of the greatest challenges in achieving accurate positioning in head and neck radiotherapy is that the anatomy at and above the cervical spine does not act as a single, mechanically rigid body. Current immobilization techniques contain residual uncertainties that are especially present in the lower neck that cannot be reduced by setting up to any single landmark. The work presented describes the development of a radiotherapy friendly mostly-plastic 6D robotic platform for positioning independent landmarks, (i.e., allowing remote, independent positioning of the skull relative to landmarks in the thorax), including analysis of kinematics, stress, radiographic compatibility, trajectory planning, physical construction, and phantom measurements of correction accuracy. No major component of the system within the field of imaging or treatment had a measured attenuation value greater than 250 HU, showing compatibility with x-ray-based imaging techniques. Relative to arbitrary overall setup errors of the head (min = 1.1 mm, max = 5.2 mm vector error) the robotic platform corrected the position down to a residual overall error of 0.75 mm +/- 0.33 mm over 15 cases as measured with optical tracking. This device shows the potential for providing reductions to dose margins in head and neck therapy cases, while also reducing setup time and effort

Virtual Reality Simulation of Liver Biopsy with a Respiratory Component

International audienceThe field of computer-based simulators has grown exponentially in the last few decades, especially in Medicine. Advantages of medical simulators include: (1) provision of a platform where trainees can practice procedures without risk of harm to patients; (2) anatomical fidelity; (3) the ability to train in an environment wherein physiological behaviour is observed, something that is not permitted where in-vitro phantoms are used; (4) flexibility regarding anatomical and pathological variation of test cases that is valuable in the acquisition of experience; (5) quantification of metrics relating to task performance that can be used to monitor trainee performance throughout the learning curve; and (6) cost effectiveness. In this chapter, we will focus on the current state of the art of medical simulators, the relevant parameters required to design a medical simulator, the basic framework of the simulator, methods to produce a computer-based model of patient respiration and finally a description of a simulator for ultrasound guided for liver biopsy. The model that is discussed presents a framework that accurately simulates respiratory motion, allowing for the fine tuning of relevant parameters in order to produce a patient-specific breathing pattern that can then be incorporated into a simulation with real-rime haptic interaction. Thus work was conducted as part CRaIVE collaboration [1], whose aim is to develop simulators specific to interventional radiology

A Heterogeneous Patient-Specific Biomechanical Model of the Lung for Tumor Motion Compensation and Effective Lung Radiation Therapy Planning

Radiation therapy is a main component of treatment for many lung cancer patients. However, the respiratory motion can cause inaccuracies in radiation delivery that can lead to treatment complications. In addition, the radiation-induced damage to healthy tissue limits the effectiveness of radiation treatment. Motion management methods have been developed to increase the accuracy of radiation delivery, and functional avoidance treatment planning has emerged to help reduce the chances of radiation-induced toxicity. In this work, we have developed biomechanical model-based techniques for tumor motion estimation, as well as lung functional imaging. The proposed biomechanical model accurately estimates lung and tumor motion/deformation by mimicking the physiology of respiration, while accounting for heterogeneous changes in the lung mechanics caused by COPD, a common lung cancer comorbidity. A biomechanics-based image registration algorithm is developed and is combined with an air segmentation algorithm to develop a 4DCT-based ventilation imaging technique, with potential applications in functional avoidance therapies

Determining the Biomechanical Behavior of the Liver Using Medical Image Analysis and Evolutionary Computation

Modeling the liver deformation forms the basis for the development of new clinical applications that improve the diagnosis, planning and guidance in liver surgery. However, the patient-specific modeling of this organ and its validation are still a challenge in Biomechanics. The reason is the difficulty to measure the mechanical response of the in vivo liver tissue. The current approach consist of performing minimally invasive or open surgery aimed at estimating the elastic constant of the proposed biomechanical models. This dissertation presents how the use of medical image analysis and evolutionary computation allows the characterization of the biomechanical behavior of the liver, avoiding the use of these minimally invasive techniques. In particular, the use of similarity coefficients commonly used in medical image analysis has permitted, on one hand, to estimate the patient-specific biomechanical model of the liver avoiding the invasive measurement of its mechanical response. On the other hand, these coefficients have also permitted to validate the proposed biomechanical models. Jaccard coefficient and Hausdorff distance have been used to validate the models proposed to simulate the behavior of ex vivo lamb livers, calculating the error between the volume of the experimentally deformed samples of the livers and the volume from biomechanical simulations of these deformations. These coefficients has provided information, such as the shape of the samples and the error distribution along their volume. For this reason, both coefficients have also been used to formulate a novel function, the Geometric Similarity Function (GSF). This function has permitted to establish a methodology to estimate the elastic constants of the models proposed for the human liver using evolutionary computation. Several optimization strategies, using GSF as cost function, have been developed aimed at estimating the patient-specific elastic constants of the biomechanical models proposed for the human liver. Finally, this methodology has been used to define and validate a biomechanical model proposed for an in vitro human liver.Martínez Martínez, F. (2014). Determining the Biomechanical Behavior of the Liver Using Medical Image Analysis and Evolutionary Computation [Tesis doctoral no publicada]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/39337TESI