Enhanced Molecular Sensitivity of Cisplatin Imaging by Time-of-Flight X-ray Fluorescence CT for Simultaneous Chemoradiation Therapy

Abstract

Image guidance in radiation therapy is established in modern treatment systems. Potential on-board molecular imaging devices are tempting as they would allow among others chemotherapy monitoring of cisplatin based drugs. In this contribution, the principle of time-of-flight (ToF) detection in combination with the molecular imaging modality x-ray fluorescence CT (XFCT) is studied. The addition of ToF information allows to reduce the scatter component in human examinations to levels comparable to those achieved in preclinical studies. The benefits of additional ToF information to standard XFCT is studied on the basis of Monte-Carlo simulations where the fluorescent Kβ photons of cisplatin with emission energies of 75.7 and 77.9 keV are examined. The detector geometry is set up in a scatter reduced back-orientation, given by a spherical detector with an acceptance angle of 120° in regard to the iso-center. The performance is compared for two different detector systems. One time with a 2 cm thick Si detector with an energy resolution of 400 eV FWHM and the other time with a 2 mm thick CdTe detector with a resolution of 1 keV. The molecular sensitivities for the described setup for XFCT imaging with and without ToF information are investigated for phantom diameters of 16, 26, and 36 cm. Each phantom contains six one centimeter diameter cylindrical target regions in the center of the phantom. The ToF precision of the pulsed x-ray source and the time resolution of the detector are both varied between 30 and 500 ps. The scatter reduction capability is analyzed by comparing the amount of reconstructed background photons in the central 5x5 cm2field of view. Image reconstruction with ToF kernels matching to the pulse length of the beam and the detector time resolution are utilized within a MLEM reconstruction framework. The additional time of flight information is able to substantially lower the scatter content in the reconstructed images where a scatter reduction of 94, 78, and 5% for the time resolution and beam pulse length of 30, 100, and 500 ps, respectively. The molecular sensitivity accessible in the center of the field of view is 60, 75, and 80 pM/L for the Si detector and 140, 150, and 165 pM/L for the CdTe detector for a time resolution of 30 ps and a target dose of 50 mGy. The incorporation of ToF information in XFCT imaging shows promising results for the imaging of high atomic number probes in human sized objects. Especially cisplatin imaging is interesting, for a combined radio-chemo therapy as existing on-board imaging systems could be upgraded with this new technology. It was shown that the majority of the scattered photons originate within the vicinity of the phantom surface and which makes the inclusion of ToF information extreme alluring for lesions in deep tissue and the concept achieves clinically relevant molecular sensitivities.