Salim Si-Mohamed

Objective. Spectral photon counting computed tomography (SPCCT) represents a major advancement in diagnostic imaging, with the potential to significantly enhance image contrast and resolution by leveraging photon-counting detectors. The integration of high atomic number nanoparticles (NPs), such as gadolinium fluoride (GdF ₃ ), expands the scope of SPCCT by enabling combined high-resolution imaging and therapeutic strategies. This study investigates the interactions between SPCCT irradiation and acquisition parameters and surface-functionalized GdTbF ₃ NPs, with the goal of optimizing the x-ray-induced activation and imaging protocols. These optimizations are crucial toward in vivo application of x-ray induced photodynamic therapy (X-PDT). Approach. Nanoparticles, synthesized with and without surface modifications, were evaluated for their biocompatibility ( in vivo ) and imaging properties ( in vitro and in vivo ). SPCCT enabled K-edge imaging to achieve specific gadolinium NP distribution and quantification. Main results. In vitro experiments revealed a linear relationship between NP concentration and fluorescence intensity, confirming their potential as contrast agent for both K-edge imaging and fluorescence X-PDT. Optimization of emission activation conditions by varying tube voltage (kVp) and tube current (mA) demonstrated that fluorescence intensity increased proportionally with the tube current-time product (mAs). In vivo experiments in mice, following subcutaneous injections of functionalized GdTbF ₃ @PEG NPs, showed a clear concentration-dependent increase in fluorescence intensity. K-edge imaging further confirmed the specificity and distribution of the NPs. Significance. These findings demonstrate the dual capability of GdTbF ₃ NPs to act both as efficient contrast agents for x-ray-based imaging and as luminescent probes under x-ray excitation, highlighting their potential for multimodal imaging and X-PDT.

Applications cardiovasculaires en imagerie tomodensitométrique spectrale aux rayons X à comptage photonique: L'avènement de nouveaux détecteurs, dits à comptage photonique, appliqués à la tomodensitométrie aux rayons X permet l'analyse de la composition énergétique du spectre de rayons X transmis. En divisant le spectre en plusieurs fenêtres énergétiques, l’imagerie « multicouleur » spécifique et quantitative de matériaux (tels que le gadolinium et l'or), également appelée imagerie K-edge, est possible. Parallèlement, les nanoparticules d'or s'avèrent de bonnes candidates pour l'imagerie K-edge en raison de leur énergie K-edge élevée (~80.3 keV). De plus, elles ont le potentiel de circuler plus longtemps que les agents de contraste iodés pour une meilleure imagerie du compartiment vasculaire et d'être biocompatibles pour des applications in vivo. L'objectif principal de ce travail de thèse est d'évaluer l'imagerie K-edge in vitro et in vivo, permise par un prototype préclinique de tomodensitométrie spectrale à comptage photonique, en combinaison avec des nanoparticules d'or pégylées et des produits de contraste approuvés cliniquement à base d'iode et de gadolinium pour l'imagerie de la lumière et de la paroi artérielle chez le lapin sain et athéromateux. Notre principale contribution a été de démontrer que l'imagerie K-edge est réalisable in vivo en combinaison avec des nanoparticules d'or pour améliorer l'évaluation spécifique de la paroi artérielle athéromateuse en comparaison à l'imagerie conventionnelle via la quantification de sa charge macrophagique, ainsi que pour réaliser une imagerie spécifique « bicouleur » de la lumière artérielle marquée par un produit de contraste iodé et la plaque marquée par les nanoparticules d'or.

Combining dedicated X-ray imaging methods, such as K-edge subtraction (KES) or spectral photon-counting CT (SPCCT) imaging, with respiratory oscillometry offers a unique opportunity to investigate the relationship between regional heterogeneity and global lung mechanics with high precision in in vivo models of respiratory pathologies. However, with current technology, these techniques cannot be performed simultaneously during mechanical ventilation without disconnecting the subject from the ventilator. We developed and in vitro validated a mechanical ventilator capable of delivering common pressure-supported modes, estimating respiratory mechanics via oscillometry, and performing rapid gas-mixing switches for SPCCT ventilation imaging, while minimizing tracer (Xenon) gas waste. The system consists of a blower-based ventilator able to switch between open and closed-circuit architecture, enabling fast switching between configurations for Xenon wash-in and wash-out. Bench testing confirmed accurate pressure waveform delivery, precise FiO₂ control, and reliable measurement of respiratory mechanics. The rapid switch between open- and closed-circuit modes minimized Xenon consumption. in vitro tests in a ventilated rabbit model confirmed the capability of enabling oscillometry and clinical SPCCT during mechanical ventilation. This ventilator provides a powerful tool for studying the correlation between regional ventilation defects and global respiratory mechanics, advancing our understanding of pulmonary pathophysiology and supporting the development of personalized, physiology-driven ventilation strategies.

We report an original case of pulmonary hypertension with artery aneurysms due to the cell proliferation of a right atrial myxoma with multi-modality imaging. Only three cases have been reported in the literature. The description of endoluminal cells proliferation in pulmonary arteries is rare on imaging, and this observation could be very useful in demonstrating not only the usefulness of multi-modality imaging, but also the combined performance of the dual-energy scanner.