Dual energy CT for simultaneous and quantitative imaging of iodinated contrast agent and gadolinium nanoparticles: A perspective for increasing the therapeutic efficacy of nanoparticles

Abstract

Introduction Tumoral radiosensitivity enhanced by nanoparticles (NPs) has widely been described in vitro (Butterworth) (Brun). In vivo, results are more reserved and strongly depend on the NPs distribution within the tumor. Dual energy CT has been developed at the European synchrotron medical beamline in order to study this distribution. The method allows mapping and separating three mixed elements (Vinegar). The practical application presented here, aims at characterizing the distribution of gadolinium NPs (GdNPs) directly injected in a brain tumor and comparing it to the tumor volume (imaged through iodinated contrast agent (CA)). This characterization would allow optimizing the treatment planning combining NPs and external irradiation. Material and methods GdNPs are directly injected in a rat bearing glioma, followed by the intravenous injection of iodine CA. The brain is then simultaneously scanned by two monochromatic X-rays beams, with mean energies bracketing the iodine K-edge (33.17 keV). Images are then reconstructed by filtered back-projection method. The three searched elements (healthy tissues, tumor (iodine) and Gd) are separated using Granton et al. formalism. Finally, the volumes are segmented for measuring the overlap of the tumor with GdNPs. The elements concentrations and elimination constants are also calculated. Results Dual energy CT allows simultaneous imaging of GdNPs and iodine CA in brain tumors. Simultaneous images acquisition at both energies allows measuring the tumor overlap by GdNPs, avoiding complex non-rigid image registration and movement artifacts. Direct injection was efficient for increasing the NPs concentration in the brain tumor (compared to intravenous injection) and for slowing down their elimination (3 times less compared to CA). Moreover, the method has been shown to be relevant for optimizing direct injection parameters of radiosensitizing drugs. Conclusion The optimization of the tumor covering by radiosensitizing NPs is possible with dual energy CT. This appears as an encouraging perspective for increasing their therapeutic efficacy in vivo. Tumoral radiosensitivity enhanced by nanoparticles (NPs) has widely been described in vitro (Butterworth) (Brun). In vivo, results are more reserved and strongly depend on the NPs distribution within the tumor. Dual energy CT has been developed at the European synchrotron medical beamline in order to study this distribution. The method allows mapping and separating three mixed elements (Vinegar). The practical application presented here, aims at characterizing the distribution of gadolinium NPs (GdNPs) directly injected in a brain tumor and comparing it to the tumor volume (imaged through iodinated contrast agent (CA)). This characterization would allow optimizing the treatment planning combining NPs and external irradiation. GdNPs are directly injected in a rat bearing glioma, followed by the intravenous injection of iodine CA. The brain is then simultaneously scanned by two monochromatic X-rays beams, with mean energies bracketing the iodine K-edge (33.17 keV). Images are then reconstructed by filtered back-projection method. The three searched elements (healthy tissues, tumor (iodine) and Gd) are separated using Granton et al. formalism. Finally, the volumes are segmented for measuring the overlap of the tumor with GdNPs. The elements concentrations and elimination constants are also calculated. Dual energy CT allows simultaneous imaging of GdNPs and iodine CA in brain tumors. Simultaneous images acquisition at both energies allows measuring the tumor overlap by GdNPs, avoiding complex non-rigid image registration and movement artifacts. Direct injection was efficient for increasing the NPs concentration in the brain tumor (compared to intravenous injection) and for slowing down their elimination (3 times less compared to CA). Moreover, the method has been shown to be relevant for optimizing direct injection parameters of radiosensitizing drugs. The optimization of the tumor covering by radiosensitizing NPs is possible with dual energy CT. This appears as an encouraging perspective for increasing their therapeutic efficacy in vivo.