Attenuation correction of myocardial perfusion scintigraphy images without transmission scanning

Attenuation correction is essential for reliable interpretation of emission tomography; however the use of transmission measurements to generate attenuation maps is limited by availability of equipment and potential mismatches between the transmission and emission measurements. This work investigates the possibility of estimating an attenuation map using measured scatter data without a transmission scan. A scatter model has been developed that predicts the distribution of photons which have been scattered once. The scatter model has been used as the basis of a maximum likelihood gradient ascent method (SMLGA) to estimate an attenuation map from measured scatter data. The SMLGA algorithm has been combined with an existing algorithm using photopeak data to estimate an attenuation map (MLAA) in order to obtain a more accurate attenuation map than using either algorithm alone. Iterations of the SMLGA-MLAA algorithm are alternated with iterations of the MLEM algorithm to estimate the activity distribution. Initial tests of the algorithm were performed in 2 dimensions using idealised data before extension to 3 dimensions. The basic algorithm has been tested in 3 dimensions using projection data simulated using a Monte Carlo simulator with software phantoms. All soft tissues within the body have similar attenuation characteristics and so only a small number of different values are normally present. A Level-Set technique to restrict the attenuation map to a piecewise constant function has therefore been investigated as a potential way to improve the quality of the reconstructed attenuation map. The basic SMLGA-MLAA algorithm contains a number of assumptions; the effect of these has been investigated and the model extended to include the effect of photons which are scattered more than once and scatter correction of the photopeak. The effect of different phantom shapes and activity distributions has been assessed and the final algorithm tested using data acquired using a physical phantom

Improving quantification in non-TOF 3D PET/MR by incorporating photon energy information

Hybrid PET/MR systems combine functional information obtained from positron emission tomography (PET) and anatomical information from magnetic resonance (MR) imaging. In spite of the advantages that such systems can offer, PET attenuation correction still represents one of the biggest challenges for imaging in the thorax. This is due to the fact that the MR signal is not directly correlated to gamma-photon attenuation. In current practice, pre-defined population-based attenuation values are used. However, this approach is prone to errors in tissues such as the lung where a variability of attenuation values can be found both within and between patients. A way to overcome this limitation is to exploit the fact that stand-alone PET emission data contain information on both the distribution of the radiotracer and photon attenuation. However, attempts to estimate the attenuation map from emission data only have shown limited success unless time-of-flight PET data is available. Several groups have investigated the possibility of using scattered data as an additional source of information to overcome re- construction ambiguities. This thesis presents work to extend the previous methods by using PET emission data acquired at multiple energy windows and incorporating prior information derived from MR. This thesis is organised as follows. We first cover both the literature and mathematical theory relevant to the framework. Then, we present and discuss results on the case of attenu- ation estimation from scattered data only, when the activity distribution is known. We then give an overview of several candidates for joint reconstruction, which reconstruct both the activity and attenuation from scattered and unscattered data. We present extensive results using simulated data and compare the proposed methods to state-of-the-art MLAA from a single energy window acquisition. We conclude with suggestions for future work to bring the proposed method into clinical practice

Quantitative Yttrium-90 Bremsstrahlung SPECT/CT and PET/CT Study for 3D Dosimetry in Radiomicrosphere Therapy

Liver cancer ranks the third most common cause of cancer related mortality worldwide. Radiomicrosphere therapy (RMT), a form of radiation therapy, involves administration of Yttrium-90 (90Y) microspheres to the liver via the hepatic artery. 90Y microspheres bremsstrahlung SPECT/CT or PET/CT imaging could potentially identify an extrahepatic uptake. An early detection of such an uptake, thus, could initiate preventative measures early on. However, the quantitative accuracy of bremsstrahlung SPECT/CT images is limited by the wide and continuous energy spectrum of 90Y bremsstrahlung photons. 90Y PET/CT imaging is also possible but limited by the extremely small internal pair production decay. These limitation lead to inaccurate quantitation of microsphere biodistribution especially in small tumors. SPECT/CT and PET/CT acquisition of a Jasczak phantom with eight spherical inserts filled with 90Y3Cl solution were performed to measure the quantitative accuracy of the two imaging modalities. 90Y microsphere SPECT/CT data of 17 patients who underwent RMT for primary or metastatic liver cancer were acquired. Technetium-99m macroaggregated albumin (99mTc-MAA) SPECT/CT scans were also collected, but available for only twelve of the patients. SPECT/CT images from phantoms were used to determine the optimal iteration number for the iterative spatial resolution recovery algorithm. Methods for image based calculation of calibration factors for activity estimation from the patient and phantom 90Y bremsstrahlung SPECT/CT images were developed. Tumor areas were segmented using an active contour method. The 99mTc-MAA and 90Y microsphere SPECT/CT images were co-registered a priori for correlation analysis. Comparison of uptake on 99mTc-MAA and 90Y microsphere SPECT/CT images was assessed using tumor to healthy liver ratios. Furthermore, a three dimensional absorbed dose estimation algorithm was developed using the voxel S-value method. Absorbed doses within the tumor and healthy part of the liver were investigated for correlation with administered activity. Improvement in contrast to noise ratio and contrast recovery coefficients (QH) on patient and phantom 90Y bremsstrahlung SPECT/CT images as well as PET/CT images were achieved. Total activity estimations in liver and phantom gave mean percent errors of -4 ± 12% and -23 ± 41% for patient and phantom SPECT/CT studies. The pre and post-treatment images showed significant correlation (r = 0.9, p \u3c 0.05) with mean TLR of 9.2 ± 9.4 and 5.0 ± 2.2 on 99mTc-MAA and 90Y microspheres SPECT/CT respectively. The correlation between the administered activity and tumor absorbed dose was weak (r = 0.5, p \u3e 0.05), however, healthy liver absorbed dose increased with administered activity (r = 0.8, p \u3c 0.05)

Joint Activity and Attenuation Reconstruction from Multiple Energy Window Data with Photopeak Scatter Re-Estimation in non-TOF 3D PET

Estimation of attenuation from PET data only is of interest for PET-MR and systems where CT is not available or recommended. However, when using data from a single energy window, emission-based non-TOF PET AC methods suffer from ‘cross-talk’ artefacts. Based on earlier work, this manuscript explores the hypothesis that cross-talk can be reduced by using more than one energy window. We propose an algorithm for the simultaneous estimation of both activity and attenuation images as well as the scatter component of the measured data from a PET acquisition, using multiple energy windows. The model for the measurements is 3D and accounts for the finite energy resolution of PET detectors; it is restricted to single scatter. The proposed MLAA-EB-S algorithm is compared with simultaneous estimation from a single energy window (MLAA-S). The evaluation is based on simulations using the characteristics of the Siemens mMR scanner. Phantoms of different complexity were investigated. In particular, a 3D XCAT torso phantom was used to assess the inpainting of attenuation values within the lung region. Results show that the cross-talk present in non-TOF MLAA reconstructions is significantly reduced when using multiple energy windows and indicate that the proposed approach warrants further investigation

Personalized Dosimetry for 188Re Radionuclide Therapies Based on Post-Treatment SPECT/CT Scans

Over the last three decades, Rhenium-188 (188Re) applications in Nuclear Medicine therapies have gathered a lot of interest thanks to the favorable physical and chemical characteristics of this isotope. In order to optimize 188Re therapies, the accurate knowledge of the activity distribution within the patient body is required. To this end, the nuclear medicine images must yield accurate quantitative measurements. However, the decay of 188Re results in a large variety of emissions such as β-particles, γ-particles and Bremsstrahlung, making quantitative measurements of 188Re activity a very difficult task. In this paper, we discuss the imaging protocols, data acquisitions, techniques used in image reconstruction and processing, and dose estimation methods required for accurate, image-based, personalized dosimetry for molecular therapies with 188Re

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