3-D lung deformation and function from respiratory-gated 4-D x-ray CT images : application to radiation treatment planning.

Many lung diseases or injuries can cause biomechanical or material property changes that can alter lung function. While the mechanical changes associated with the change of the material properties originate at a regional level, they remain largely asymptomatic and are invisible to global measures of lung function until they have advanced significantly and have aggregated. In the realm of external beam radiation therapy of patients suffering from lung cancer, determination of patterns of pre- and post-treatment motion, and measures of regional and global lung elasticity and function are clinically relevant. In this dissertation, we demonstrate that 4-D CT derived ventilation images, including mechanical strain, provide an accurate and physiologically relevant assessment of regional pulmonary function which may be incorporated into the treatment planning process. Our contributions are as follows: (i) A new volumetric deformable image registration technique based on 3-D optical flow (MOFID) has been designed and implemented which permits the possibility of enforcing physical constraints on the numerical solutions for computing motion field from respiratory-gated 4-D CT thoracic images. The proposed optical flow framework is an accurate motion model for the thoracic CT registration problem. (ii) A large displacement landmark-base elastic registration method has been devised for thoracic CT volumetric image sets containing large deformations or changes, as encountered for example in registration of pre-treatment and post-treatment images or multi-modality registration. (iii) Based on deformation maps from MOFIO, a novel framework for regional quantification of mechanical strain as an index of lung functionality has been formulated for measurement of regional pulmonary function. (iv) In a cohort consisting of seven patients with non-small cell lung cancer, validation of physiologic accuracy of the 4-0 CT derived quantitative images including Jacobian metric of ventilation, Vjac, and principal strains, (V?1, V?2, V?3, has been performed through correlation of the derived measures with SPECT ventilation and perfusion scans. The statistical correlations with SPECT have shown that the maximum principal strain pulmonary function map derived from MOFIO, outperforms all previously established ventilation metrics from 40-CT. It is hypothesized that use of CT -derived ventilation images in the treatment planning process will help predict and prevent pulmonary toxicity due to radiation treatment. It is also hypothesized that measures of regional and global lung elasticity and function obtained during the course of treatment may be used to adapt radiation treatment. Having objective methods with which to assess pre-treatment global and regional lung function and biomechanical properties, the radiation treatment dose can potentially be escalated to improve tumor response and local control

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

A 3D discrete model of the diaphragm and human trunk

In this paper, a 3D discrete model is presented to model the movements of the trunk during breathing. In this model, objects are represented by physical particles on their contours. A simple notion of force generated by a linear actuator allows the model to create forces on each particle by way of a geometrical attractor. Tissue elasticity and contractility are modeled by local shape memory and muscular fibers attractors. A specific dynamic MRI study was used to build a simple trunk model comprised of by three compartments: lungs, diaphragm and abdomen. This model was registered on the real geometry. Simulation results were compared qualitatively as well as quantitatively to the experimental data, in terms of volume and geometry. A good correlation was obtained between the model and the real data. Thanks to this model, pathology such as hemidiaphragm paralysis can also be simulated.Comment: published in: "Lung Modelling", France (2006

Towards an optimal clinical protocol for the treatment of moving targets with pencil beam scanned proton therapy

At the University Medical Center Groningen (UMCG) Proton Therapy Center (GPTC), a novel and advantageous form of radiotherapy for the treatment of cancer is available. This treatment technique, referred as proton therapy, uses charged particles (protons) to irradiate, and consequently, damage the tumour. Due to the physical properties of protons, proton therapy allows to successfully kill the tumour, while sparing the adjacent healthy tissue from any damaging radiation. The tumours within liver, lung, and oesophageal cancer patients move due to the patients’ respiration. These moving tumours are surrounded by organs (heart, lung, spinal cord, and oesophagus), which need to be spared from radiation. This is why proton therapy is particularly valuable for these patients. However, the interference of the movement of these tumours with the highly precise proton therapy machine, brings a challenge for the execution of their treatments at the GPTC, and other proton centres. The work performed throughout this thesis focuses on achieving optimal and safe proton treatments for moving tumours. To complete this, we performed comprehensive and representative analysis with clinical patient data and proton machine specific information of our department. The tools developed and the results obtained contributed to the start of the treatment of moving tumours at the GPTC, and therefore we believe they will play an important role for the proton therapy community in general. We aim to extend our gained experience to all proton centres worldwide, so that moving tumours can take advantage of the clinical benefits expected from proton therapy

2012 Activity Report of the Regional Research Programme on Hadrontherapy for the ETOILE Center

2012 is the penultimate year of financial support by the CPER 2007-2013 for ETOILE's research program, sustained by the PRRH at the University Claude Bernard. As with each edition we make the annual review of the research in this group, so active for over 12 years now. Over the difficulties in the decision-making process for the implementation of the ETOILE Center, towards which all our efforts are focussed, some "themes" (work packages) were strengthened, others have progressed, or have been dropped. This is the case of the eighth theme (technological developments), centered around the technology for rotative beam distribution heads (gantries) and, after being synchronized with the developments of ULICE's WP6, remained so by ceasing its activities, coinciding also with the retirement of its historic leader at IPNL, Marcel Bajard. Topic number 5 ("In silico simulations") has suffered the departure of its leader, Benjamin Ribba, although the work has still been provided by Branka Bernard, a former postdoctoral fellow in Lyon Sud, and now back home in Croatia, still in contract with UCBL for the ULICE project. Aside from these two issues (and the fact that the theme "Medico-economical simulations" is now directly linked to the first one ("Medical Project"), the rest of the teams are growing, as evidenced by the publication statistics at the beginning of this report. This is obviously due to the financial support of our always faithful regional institutions, but also to the synergy that the previous years, the European projects, the arrival of the PRIMES LabEx, and the national France Hadron infrastructure have managed to impulse. The Rhone-Alpes hadron team, which naturally includes the researchers of LPC at Clermont, should also see its influence result in a strong presence in France Hadron's regional node, which is being organized. The future of this regional research is not yet fully guaranteed, especially in the still uncertain context of ETOILE, but the tracks are beginning to emerge to allow past and present efforts translate into a long future that we all want to see established. Each of the researchers in PRRH is aware that 2013 will be (and already is) the year of great challenge : for ETOILE, for the PRRH, for hadron therapy in France, for French hadrontherapy in Europe (after the opening and beginning of treatments in the German [HIT Heidelberg, Marburg], Italian [CNAO, Pavia] and Austrian [MedAustron, Wien Neuerstadt]) centers. Let us meet again in early 2014 for a comprehensive review of the past and a perspective for the future ..