Modélisation de l’ablation radiofréquence pour la planification de la résection de tumeurs abdominales

The outcome of radiofrequency ablation (RFA) of abdominal tumors is challenged by the presence of blood vessels and time-varying thermal conductivity, which make patient-specific planning extremely difficult. By providing predictive tools, biophysical models may help clinicians to plan and guide the procedure for an effective treatment. We introduce a detailed computational model of the biophysical mechanisms involved in RFA of hepatic tumors such as heat diffusion and cellular necrosis. It simulates the extent of ablated tissue based on medical images, from which patient-specific models of the liver, visible vessels and tumors are segmented. In this thesis, a new approach for solving these partial differential equations based on the Lattice Boltzmann Method is introduced. The model is first evaluated against clinical data of patients who underwent RFA of liver tumors. Then, a comprehensive pre-clinical experiment that combines multi-modal, pre- and post-operative anatomical and functional images, as well as the interventional monitoring of the temperature and delivered power is presented. This enables an end-to-end validation framework that considers the most comprehensive data set for model validation. Then, we automatically estimate patient-specific parameters to better predict the ablated tissue. This personalization strategy has been validated on 7 ablations from 3 clinical cases. From the pre-clinical study, we can go further in the personalization by comparing the simulated temperature and delivered power with the actual measurements during the procedure. These contributions have led to promising results, and open new perspectives in RFA guidance and planning.L'ablation par radiofréquence (ARF) de tumeurs abdominales est rendue difficile par l’influence des vaisseaux sanguins et les variations de la conductivité thermique, compliquant la planification spécifique à un patient donné. En fournissant des outils prédictifs, les modèles biophysiques pourraient aider les cliniciens à planifier et guider efficacement la procédure. Nous introduisons un modèle mathématique détaillé des mécanismes impliqués dans l’ARF des tumeurs du foie comme la diffusion de la chaleur et la nécrose cellulaire. Il simule l’étendue de l’ablation à partir d’images médicales, d’après lesquelles des modèles personnalisés du foie, des vaisseaux visibles et des tumeurs sont segmentés. Dans cette thèse, une nouvelle approche pour résoudre ces équations basée sur la méthode de Lattice Boltzmann est introduite. Le modèle est d’abord évalué sur des données de patients qui ont subi une ARF de tumeurs du foie. Ensuite, un protocole expérimental combinant des images multi-modales, anatomiques et fonctionnelles pré- et post-opératoires, ainsi que le suivi de la température et de la puissance délivrée pendant l'intervention est présenté. Il permet une validation totale du modèle qui considère des données les plus complètes possibles. Enfin, nous estimons automatiquement des paramètres personnalisés pour mieux prédire l'étendu de l’ablation. Cette stratégie a été validée sur 7 ablations dans 3 cas cliniques. A partir de l'étude préclinique, la personnalisation est améliorée en comparant les simulations avec les mesures faites durant la procédure. Ces contributions ont abouti à des résultats prometteurs, et ouvrent de nouvelles perspectives pour planifier et guider l’ARF

Parameter Estimation for Personalization of Liver Tumor Radiofrequency Ablation

International audienceMathematical modeling has the potential to assist radiofrequency ablation (RFA) of tumors as it enables prediction of the extent of ablation. However, the accuracy of the simulation is challenged by the material properties since they are patient-specific, temperature and space dependent. In this paper, we present a framework for patient specific radiofrequency ablation modeling of multiple lesions in the case of metastatic diseases. The proposed forward model is based upon a computational model of heat diffusion, cellular necrosis and blood flow through vessels and liver which relies on patient images. We estimate the most sensitive material parameters, those need to be personalized from the available clinical imaging and data. The selected parameters are then estimated using inverse modeling such that the point to-mesh distance between the computed necrotic area and observed lesions is minimized. Based on the personalized parameters, the ablation of the remaining lesions are predicted. The framework is applied to a dataset of seven lesions from three patients including pre- and post-operative CT images. In each case, the parameters were estimated on one tumor and RFA is simulated on the other tumor(s) using these personalized parameters, assuming the parameters to be spatially invariant within the same patient. Results showed significantly good correlation between predicted and actual ablation extent (average point-to-mesh errors of 4.03 mm)

Lattice Boltzmann Method For Fast Patient-Specific Simulation of Liver Tumor Ablation from CT Images

International audienceRadio-frequency ablation (RFA), the most widely used minimally invasive ablative therapy of liver cancer, is challenged by a lack of patient-specifi c planning. In particular, the presence of blood vessels and time varying thermal di ffusivity makes the prediction of the extent of the ablated tissue diffi cult. This may result in incomplete treatments and increased risk of recurrence. We propose a new model of the physical mechanisms involved in RFA of abdominal tumors based on Lattice Boltzmann Method to predict the extent of ablation given the probe location and the biological parameters. Our method relies on patient images, from which level set representations of liver geometry, tumor shape and vessels are extracted. Then a computational model of heat diff usion, cellular necrosis and blood flow through vessels and liver is solved to estimate the extent of ablated tissue. After quantitative verifi cations against an analytical solution, we apply our framework to 5 patients datasets which include pre- and post-operative CT images, yielding promising correlation between predicted and actual ablation extent (mean point to mesh errors of 8.7 mm). Implemented on graphics processing units, our method may enable RFA planning in clinical settings as it leads to near real-time computation: 1 minute of ablation is simulated in 1.14 minutes,which is almost 60 faster than standard fi nite element method

Challenges to Validate Multi-physics Model of Liver Tumor Radiofrequency Ablation from Pre-clinical Data

International audienceThe planning and interventional guidance of liver tumor ra-diofrequency ablation (RFA) is difficult due to the cooling effect of large vessels and the large variability of tissue parameters. Subject-specific modeling of RFA is challenging as it requires the knowledge of model geometry and hemodynamics as well as the simulation of heat transfer and cell death mechanisms. In this paper, we propose to validate such a model from pre-operative multi-modal images and intra-operative signals (temperature and power) measured by the ablation device itself. In particular , the RFA computation becomes subject-specific after three levels of personalization: anatomical, heat transfer and a novel cellular necro-sis model. We propose an end-to-end pre-clinical validation framework that considers the most comprehensive dataset for model validation. This framework can also be used for parameter estimation and we evaluate its predictive power in order to fully assess the possibility to personalize our model in the future. Such a framework would therefore not require any necrosis information, thus better suited for clinical applications. We evaluated our approach on seven ablations from three healthy pigs. The predictive power of the model was tested: a mean point to mesh error between predicted and actual ablation extent of 3.5 mm was achieved

Comprehensive Pre-Clinical Evaluation of a Multi-physics Model of Liver Tumor Radiofrequency Ablation

International audiencePurpose: We aim at developing a framework for the validation of a subject-specific multi-physics model of liver tumor radiofrequency ablation (RFA). Methods: The RFA computation becomes subject-specific after several levels of personalization: geometrical and biophysical (hemodynamics, heat transfer and an extended cellular necrosis model). We present a comprehensive experimental setup combining multi-modal, pre-and post-operative anatomical and functional images, as well as the interventional monitoring of intra-operative signals: the temperature and delivered power. Results: To exploit this data set, an efficient processing pipeline is introduced, which copes with image noise, variable resolution and anisotropy. The validation study includes twelve ablations from five healthy pig livers: a mean point-to-mesh error between predicted and actual ablation extent of 5.3 ± 3.6 mm is achieved. Conclusion: This enables an end-to-end pre-clinical validation framework that considers the available data set

Thermal ablation of biological tissues in disease treatment: A review of computational models and future directions

Percutaneous thermal ablation has proved to be an effective modality for treating both benign and malignant tumors in various tissues. Among these modalities, radiofrequency ablation (RFA) is the most promising and widely adopted approach that has been extensively studied in the past decades. Microwave ablation (MWA) is a newly emerging modality that is gaining rapid momentum due to its capability of inducing rapid heating and attaining larger ablation volumes, and its lesser susceptibility to the heat sink effects as compared to RFA. Although the goal of both these therapies is to attain cell death in the target tissue by virtue of heating above 50 oC, their underlying mechanism of action and principles greatly differs. Computational modelling is a powerful tool for studying the effect of electromagnetic interactions within the biological tissues and predicting the treatment outcomes during thermal ablative therapies. Such a priori estimation can assist the clinical practitioners during treatment planning with the goal of attaining successful tumor destruction and preservation of the surrounding healthy tissue and critical structures. This review provides current state-of- the-art developments and associated challenges in the computational modelling of thermal ablative techniques, viz., RFA and MWA, as well as touch upon several promising avenues in the modelling of laser ablation, nanoparticles assisted magnetic hyperthermia and non- invasive RFA. The application of RFA in pain relief has been extensively reviewed from modelling point of view. Additionally, future directions have also been provided to improve these models for their successful translation and integration into the hospital work flow

RFA Guardian: Comprehensive Simulation of Radiofrequency Ablation Treatment of Liver Tumors

The RFA Guardian is a comprehensive application for high-performance patient-specific simulation of radiofrequency ablation of liver tumors. We address a wide range of usage scenarios. These include pre-interventional planning, sampling of the parameter space for uncertainty estimation, treatment evaluation and, in the worst case, failure analysis. The RFA Guardian is the first of its kind that exhibits sufficient performance for simulating treatment outcomes during the intervention. We achieve this by combining a large number of high-performance image processing, biomechanical simulation and visualization techniques into a generalized technical workflow. Further, we wrap the feature set into a single, integrated application, which exploits all available resources of standard consumer hardware, including massively parallel computing on graphics processing units. This allows us to predict or reproduce treatment outcomes on a single personal computer with high computational performance and high accuracy. The resulting low demand for infrastructure enables easy and cost-efficient integration into the clinical routine. We present a number of evaluation cases from the clinical practice where users performed the whole technical workflow from patient-specific modeling to final validation and highlight the opportunities arising from our fast, accurate prediction techniques

The Effect of Hyperthermia on Doxorubicin Therapy and Nanoparticle Penetration in Multicellular Ovarian Cancer Spheroids

The efficient treatment of cancer with chemotherapy is challenged by the limited penetration of drugs into the tumor. Nanoparticles (10 – 100 nanometers) have emerged as a logical choice to specifically deliver chemotherapeutics to tumors, however, their transport into the tumor is also impeded owing to their bigger size compared to free drug moieties. Currently, monolayer cell cultures, as models for drug testing, cannot recapitulate the structural and functional complexity of in-vivo tumors. Furthermore, strategies to improve drug distribution in tumor tissues are also required. In this study, we hypothesized that hyperthermia (43°C) will improve the distribution of silica nanoparticles in three-dimensional multicellular tumor spheroids. Tumor spheroids mimic the functional and histomorphological complexity of in-vivo avascular tumors and are therefore valuable tools to study drug distribution. Ovarian cancer (Skov3) and uterine sarcoma (MES-SA/Dx5) spheroids were generated using the liquid overlay method. The growth ratio and cytotoxicity assays showed that the application of adjuvant hyperthermia with Doxorubicin (DOX) did not yield higher cell killing compared to DOX therapy alone. These results illustrated the role of spheroids in resistance to heat and DOX. In order to study the cellular uptake kinetics of nanoparticles under hyperthermia conditions, the experimental measurements of silica nanoparticle uptake by cells were fitted using a novel inverse estimation method based on Bayesian estimation. This was coupled with advection reaction transport to model nanoparticle transport in spheroids. The model predicted an increase in Area Under the Curve (AUC) and penetration distance (W1/2) that were validated with in-vitro experiments in spheroids. Based on these observations, a novel multifunctional theranostic nanoparticle probe was created for generating highly localized hyperthermia by encapsulating a Near Infrared (NIR) dye, IR820 (for imaging and hyperthermia) and DOX in Organically modified silica nanoparticles (Ormosil). Pegylated Ormosil nanoparticles had an average diameter of 58.2±3.1 nm, zeta potential of -6.9 ± 0.1 mV and high colloidal stability in physiological buffers. Exposure of the IR820 within the nanoparticles to NIR laser led to the generation of hyperthermia as well as release of DOX which translated to higher cell killing in Skov3 cells, deeper penetration of DOX into spheroids and complete destruction of the spheroids. In-vivo bio-distribution studies showed higher fluorescence from organs and increased plasma elimination life of IR820 compared to free IR820. However, possible aggregation of particles on laser exposure and accumulation in lungs still remain a concern