An update on computational anthropomorphic anatomical models

The prevalent availability of high-performance computing coupled with validated computerized simulation platforms as open-source packages have motivated progress in the development of realistic anthropomorphic computational models of the human anatomy. The main application of these advanced tools focused on imaging physics and computational internal/external radiation dosimetry research. This paper provides an updated review of state-of-the-art developments and recent advances in the design of sophisticated computational models of the human anatomy with a particular focus on their use in radiation dosimetry calculations. The consolidation of flexible and realistic computational models with biological data and accurate radiation transport modeling tools enables the capability to produce dosimetric data reflecting actual setup in clinical setting. These simulation methodologies and results are helpful resources for the medical physics and medical imaging communities and are expected to impact the fields of medical imaging and dosimetry calculations profoundly.</p

Dosimétrie clinique en radiothérapie moléculaire

La radiothérapie moléculaire (RTM) est une radiothérapie systémique, où le produit radiopharmaceutique se lie spécifiquement sur les tumeurs pour détruire sélectivement les cibles cancéreuses tout en préservant les organes sains. Lutathera® (177Lu-DOTATATE) est un radiopharmaceutique récemment approuvé par la FDA/EMA pour le traitement des tumeurs neuroendocrines gastro-entéro-pancréatiques (GEP-NETs). Dans la pratique clinique, les patients reçoivent une activité fixe de Lutathera®, 4 cycles de 7,4 GBq, en supposant que la pharmacocinétique du radiopharmaceutique est même entre les patients. La dosimétrie spécifique au patient permet un changement de paradigme majeur dans l'administration de la RTM, passant d'une approche "taille unique" à une véritable médecine personnalisée où l'activité administrée est évaluée spécifiquement sur la base de l'irradiation délivrée à chaque patient. Pour ce faire, il faut généralement déterminer la distribution spatiale du radiopharmaceutique dans les organes par imagerie à différents moments (imagerie quantitative), estimer le nombre total de désintégrations radioactives en intégrant l'activité dans le temps (évaluation pharmacocinétique) et calculer la dose absorbée à partir des caractéristiques physiques du radionucléide et du transport de l'énergie dans les tissus du patient. Actuellement, il n'existe pas de procédures normalisées pour effectuer la dosimétrie clinique. En outre, l'évaluation des incertitudes associées à la procédure de dosimétrie n'est pas triviale. Le projet DosiTest a été lancé pour évaluer les incertitudes associées à chacune des étapes du flux de travail de la dosimétrie clinique, via une inter-comparaison multicentrique basée sur la modélisation de Monte Carlo (MC). La première phase de la thèse a consisté à comparer les analyses dosimétriques effectuées par différents centres utilisant le même logiciel et le même protocole sur le même ensemble de données de patients dans le cadre du projet IAEA-CRP E23005 afin d'évaluer la précision de la dosimétrie clinique. À notre connaissance, c'est la première fois qu'une comparaison dosimétrique multicentrique d'un seul ensemble de données cliniques sur un patient a été entreprise en utilisant le même protocole et le même logiciel par de nombreux centres dans le monde entier. Elle a mis en évidence le besoin crucial d'établir des points de contrôle et d'effectuer des vérifications de bon sens pour éliminer les disparités significatives entre les résultats et distinguer les pratiques erronées de la variabilité inter-opérateurs acceptable. Un résultat important de ce travail a été le manque d'assurance qualité en dosimétrie de médecine nucléaire clinique et la nécessité de développer des procédures de contrôle qualité. Alors que la dosimétrie gagne en popularité en médecine nucléaire, les meilleures pratiques doivent être adoptées pour garantir la fiabilité, la traçabilité et la reproductibilité des résultats. Cela met également en avant la nécessité de dispenser une formation suffisante après l'acquisition des progiciels relativement nouveaux, au-delà de quelques jours. Ceci est clairement insuffisant dans le contexte d'un domaine émergent où l'expérience professionnelle fait souvent défaut. Ensuite, l'étude de l'exactitude de la dosimétrie clinique nécessite de générer des ensembles de données de test, afin de définir la vérité de base par rapport à laquelle les procédures de dosimétrie clinique peuvent être comparées. La deuxième section de la thèse traite de la simulation de l'imagerie TEMP scintigraphique tridimensionnelle en implémentant le mouvement du détecteur d'auto-contournement dans la boîte à outils Monte Carlo GATE. Après la validation des projections TEMP/TDM sur des modèles anthropomorphes, une série d'images réalistes de patients cliniques a été générée. La dernière partie de la thèse a établi la preuve de concept du projet DosiTest, en utilisant un ensemble de données TEMP/TDM virtuelles (simulées) à différents moments, avec différentes gamma-caméras, permettant de comparer différentes techniques dosimétriques et d'évaluer la faisabilité clinique du projet dans certains départements de médecine nucléaire.Molecular radiotherapy (MRT) is a systemic radiotherapy where the radiopharmaceutical binds specifically to tumours to selectively destroy cancer targets while sparing healthy organs. Lutathera® (177Lu-DOTATATE) is a radiopharmaceutical that was recently FDA/EMA approved for the treatment of the GastroEnteroPancreatic NeuroEndocrine Tumours (GEP-NETs). In clinical practice, patients are administered with a fixed activity of Lutathera®, assuming that radiopharmaceutical distribution is the same for all patients. Patient-specific dosimetry allows for a major paradigm shift in the administration of MRT from "one-size-fits-all" approach, to real personalised medicine where administered activity is assessed specifically on the base of the irradiation delivered to each patient. This usually requires determining the spatial distribution of the radiopharmaceutical in various organs via imaging at different times (quantitative imaging), estimating the total number of radioactive decays by integrating activity over time (pharmacokinetic assessment) and calculating the absorbed dose using the physical characteristics of the radionuclide and implementing radiation transport in patient's tissues. Currently, there are no standardised procedures to perform clinical dosimetry. In addition, the assessment of the uncertainties associated with the dosimetry procedure is not trivial. The DosiTest project (http://www.dositest.org/) was initiated to evaluate uncertainties associated with each of the steps of the clinical dosimetry workflow, via a multicentric inter-comparison based on Monte Carlo (MC) modelling. The first phase of the thesis compared dosimetry analysis performed by various centres using the same software and protocol on the same patient dataset as a part of IAEA-CRP E23005 project in order to appraise the precision of clinical dosimetry. To our knowledge, this is the first time that a multi-centric dosimetry comparison of a single clinical patient dataset has been undertaken using the same protocol and software by many centres worldwide. It highlighted the critical need to establish checkpoints and conduct sanity checks to eliminate significant disparities among results, and distinguish erroneous practice with acceptable inter-operator variability. A significant outcome of this work was the lack of quality assurance in clinical nuclear medicine dosimetry and the need for the development of quality control procedures. While dosimetry is gaining popularity in nuclear medicine, best practices should be adopted to ensure that results are reliable, traceable, and reproducible. It also brings forward the need to deliver sufficient training after the acquisition of the relatively new software packages beyond a couple of days. This is clearly insufficient in a context of an emerging field where the professional experience is quite often lacking. Next, the study of clinical dosimetry accuracy requires generating test datasets, to define the ground truth against which clinical dosimetry procedures can be benchmarked. The second section of the thesis addressed the simulation of three-dimensional scintigraphic SPECT imaging by implementing auto-contouring detector motion in the GATE Monte Carlo toolkit. Following the validation of SPECT/CT projections on anthropomorphic models, a series of realistic clinical patient images were generated. The last part of the thesis established the proof of concept of the DosiTest project, using a virtual (simulated) SPECT/CT dataset at various time points, with various gamma cameras, enabling comparison of various dosimetric techniques and to assess the clinical feasibility of the project in selected nuclear medicine departments

Advantages of MCNPX-based lattice tally over mesh tally in high-speed Monte Carlo dose reconstruction for proton radiotherapy

Monte Carlo simulations are increasingly used to reconstruct dose distributions in radiotherapy research studies. Many studies have used the MCNPX Monte Carlo code with a mesh tally for dose reconstructions. However, when the number of voxels in the simulated patient anatomy is large, the computation time for a mesh tally can become prohibitively long. The purpose of this work was to test the feasibility of using lattice tally instead of mesh tally for whole-body dose reconstructions. We did this by comparing the dosimetric accuracy and computation time of lattice tallies with those of mesh tallies for craniospinal proton irradiation. The two tally methods generated nearly identical dosimetric results, within 1% in dose and within 1 mm distance-to-agreementfor 99% of the voxels. For a typical craniospinal proton treatment field, simulation speed was 4 to 17 times faster using the lattice tally than using the mesh tally, depending on the numbers of proton histories and voxels. We conclude that the lattice tally is an acceptable substitute for the mesh tally in dose reconstruction, making it a suitable potential candidate for clinical treatment planning

S-values for Holmium-166, Lutetium-177 and Yttrium-90 for the ICRP 110 voxel phantom and ICRP 145 mesh phantom using the Geant4/GATE Monte Carlo tool

In Molecular Radiation Therapy, the estimation of energy absorbed within tissue is critical for the assessment of the e cacy of radiopharmaceuticals. Computational phantoms are a valuable tool to estimate radiation dose and to ensure that radiation dose to healthy tissue is minimised whilst still achieving a therapeutic level of radiation dose to disease cells. The International Commission on Radiological Protection (ICRP) has published several computational phantoms for the radiation protection of the population, amongst these are female and male adult voxelised phantoms (ICRP Publication 110) and adult mesh reference phantoms (ICRP Publication 145). The ICRP 110 voxelised phantoms have been widely used for the investigation of radiation dose from internalization of radionuclides. The ICRP 145 mesh phantom has multiple advantages compared to the voxel phantom, with the ability to morph the phantom, as well as create more accurate organ shapes with the availability of rendering software. The aim of this study was to implement the latter in the Geant4/GATE Monte Carlo tool and assess its performance when compared to the ICRP 110 phantom, of which it is an adaptation

Fast Monte Carlo Simulations for Quality Assurance in Radiation Therapy

Monte Carlo (MC) simulation is generally considered to be the most accurate method for dose calculation in radiation therapy. However, it suffers from the low simulation efficiency (hours to days) and complex configuration, which impede its applications in clinical studies. The recent rise of MRI-guided radiation platform (e.g. ViewRay’s MRIdian system) brings urgent need of fast MC algorithms because the introduced strong magnetic field may cause big errors to other algorithms. My dissertation focuses on resolving the conflict between accuracy and efficiency of MC simulations through 4 different approaches: (1) GPU parallel computation, (2) Transport mechanism simplification, (3) Variance reduction, (4) DVH constraint. Accordingly, we took several steps to thoroughly study the performance and accuracy influence of these methods. As a result, three Monte Carlo simulation packages named gPENELOPE, gDPMvr and gDVH were developed for subtle balance between performance and accuracy in different application scenarios. For example, the most accurate gPENELOPE is usually used as golden standard for radiation meter model, while the fastest gDVH is usually used for quick in-patient dose calculation, which significantly reduces the calculation time from 5 hours to 1.2 minutes (250 times faster) with only 1% error introduced. In addition, a cross-platform GUI integrating simulation kernels and 3D visualization was developed to make the toolkit more user-friendly. After the fast MC infrastructure was established, we successfully applied it to four radiotherapy scenarios: (1) Validate the vender provided Co60 radiation head model by comparing the dose calculated by gPENELOPE to experiment data; (2) Quantitatively study the effect of magnetic field to dose distribution and proposed a strategy to improve treatment planning efficiency; (3) Evaluate the accuracy of the build-in MC algorithm of MRIdian’s treatment planning system. (4) Perform quick quality assurance (QA) for the “online adaptive radiation therapy” that doesn’t permit enough time to perform experiment QA. Many other time-sensitive applications (e.g. motional dose accumulation) will also benefit a lot from our fast MC infrastructure