A Partial ring X-ray Fluorescence Computed Tomography Imaging Platform for In Vivo Imaging of Non-Radioactive Metal-based Therapeutic Agents in Small Animals.

318 Objectives: Metal elements can emit characteristic X-ray (X-ray Fluorescence) with significant energy under external X-ray irradiation, which allows for mapping nonradioactive interest element quantitively through X-ray Fluorescence Computed Tomography (XFCT) [1]. Metal-based antitumor drugs are widely used in cancer therapy [2-5]. For instance, cisplatin (Pt-based) plays major role in the treatment of bladder, head and neck, ovarian, testicular and non-small cell lung cancers; hafnium and gold are also being investigated for radioenhancement. Additionally, metal-based nanoparticles (NPs) have gained increasing interest as a novel carrier for investigating targeted drug delivery and therapeutic effect [6]. XFCT has great potential in exploring biomechanism of metal-based drug and NPs. However, XFCT is constrained seriously by the low Signal-to-Noise ratio, high dose and long acquisition time, resulting from the small part of source X-ray flux capable of stimulating X-ray fluorescence and high Compton background [7]. This work proposes a high-performance partial ring XFCT system with an aim of monitoring the delivery of high-Z metal elements contained in nanoparticle and anti-cancer drugs in vivo. With an aim to surpass Compton scattering, detectors are located at large scattering angles. Stimulating spectra will also be trimmed by selected filter-source configuration to increase useful X-ray flux fraction. Methods: This system contains one filterable 90kVp polychromatic source. The High Energy X-ray Imaging TEChnology (HEXITEC) CZT detector is selected to collect XF signal due to its high energy and spatial resolution and wide detecting range. Considering the anisotropy of Compton scattering photons, we put detectors at large scattering angles, from 90o to 150o. The scattering Compton photon will have lower energy and less count along with increasing scattering angle, which will reduce the interference with XF signal. Both our simulation and analytical result indicate the SNR (defined as ratio of XF signal and Compton background at K-alpha line) will be nearly 2 times at 120o and 6 times at 150o better than at 90o. For image formation, we use a collimated sheet beam to irradiate sample and collect photon traveling in given direction defined by parallel collimator (Fig.1 (C)) coupled with detectors. By summing and analyzing detected photon over each column of pixels and rotating sample, the corresponding sinogram can be obtained for each slice. One HEXITEC for transmission spectral CT will provide attenuation map of sample for quantitative XF image reconstruction. Results: Fig.1 shows the overview of our proposed system. Fig.2 and Fig.3 give the preliminary imaging study of our system based on previously used imaging method, X-ray Fluorescence Emission Tomography (XFET), whose detailed process can be found in our paper [8] and [9]. Spectral performance of HEXITEC is also tested by acquiring a multi-isotope spectrum (Fig.2(C)). Fig.2(A) and Fig.2(B) give the energy spectra obtained from 1-hour acquisition for 10mg/ml Gd solution and 10mg/ml Hf solution under irradiation of a 150kVp source, both with detectors located at 90o scattering angle.The corresponding reconstruction images are shown in Fig.2(D) and Fig.2(E). Our recent result also demonstrates that our preliminary system has the capacity to observe Pt Kα peak at concentration as low as 1mg/ml and Hf Kα line at 1mg/ml. Conclusions: We proposed a partial ring XFCT system working at large scattering angle to map the distribution of metal elements, which can be used for monitoring delivery and therapeutic effect of metal-based drugs as well as NPs. The modality’s potential for imaging interest element at extremely low concentration (