Superior material discrimination provided by photon counting detector (PCD) technology promises to transform X-ray CT into a functional and molecular imaging modality while maintaining its high spatial resolution, fast scanning times, and relatively low cost. Our group has developed pre-clinical photon-counting CT (PCCT) prototype systems and applied them, in combination with nanoparticle contrast agents, for cancer and cardiac imaging. This work aims to compare the PCCT imaging performance using a gallium arsenide (GaAs) and a cadmium telluride (CdTe) based PCD, both with 150- μm pixels and 4 energy thresholds. The two PCDs were integrated in the same PCCT system. Phantoms containing elemental solutions of Iodine, Gadolinium, Tantalum, Hafnium, Bismuth and Calcium were imaged with each detector to establish the spectral separation capabilities for PCCT. Moreover, combined dual detectors PCCT imaging was also tested. A joint iterative reconstruction followed by image-based material decomposition was used to provide material maps of different elements. The accuracy of the estimated concentrations within the material decompositions were compared. Our results have shown that GaAs-based PCCT imaging has an overall higher sensitivity (by ~15%) to Iodine than CdTe when using identical acquisition parameters. The CdTe imaging, has higher quantum efficiency at high keVs, supporting higher source kVps and energy threshold settings for imaging the K-edges of Bismuth or other high-Z NPs (such as Gold). Based on the average vial measurements, hybrid GaAs-CdTe PCCT decompositions have the most accurate decompositions for nearly all materials except for Bismuth. The combination of CdTe and GaAs PCDs into a dual source PCCT system will provide high sensitivity in separating multi-element contrast agents from intrinsic tissues.
Developing novel contrast agents for multi-energy photon-counting (PC)CT will require a clear translation pathway from preclinical validation to clinical applications. To begin this development, we have used a clinical PCCT scanner (Siemens NAEOTOM Alpha) to study the spectral separation of a few contrast elements (Iodine, I; Gadolinium, Gd; Hafnium, Hf; Tantalum, Ta; Bismuth, Bi; Calcium, Ca) with currently available scanning protocols (fixed: 120 kVp, 20 and 65 keV thresholds). We also explored the capabilities of clinical and preclinical PCCT to image mice with sarcoma tumors injected with nanoparticles (NP). Our results indicate that Ta or Hf are complementary to I or Gd, providing excellent spectral separation for future multi-agent studies. Based on preclinical PCCT with four energy thresholds, we also conclude that additional energy thresholds will benefit clinical PCCT. Furthermore, we demonstrate the role that multi-channel denoising and reconstruction algorithms will play in pushing the bounds of spatial and spectral resolution with clinical PCCT. Performing co-clinical research will facilitate the translation of novel imaging algorithms and NP contrast agents for PCCT
High-Z based nanoparticles (NP) are emerging as promising agents for both cancer radiotherapy (RT) and CT imaging. NPs can be delivered to tumors via the enhanced permeability and retention (EPR) effect and they preferentially accumulate in tumor’s perivascular region. Both gold and iodine NPs produce low-energy, short-range photoelectrons during RT, boosting radiation dose. Using spectral CT imaging, we sought to investigate (1) if iodine nanoparticles augmentation of RT increases vascular permeability in solid tumors, and (2) if iodine-RT induced changes in tumor vascular permeability improves delivery of nanoparticle-based chemotherapeutics. In vivo studies were performed in a carcinogen-induced and genetically engineered primary mouse model of soft tissue sarcoma. Tumor-bearing mice in test group were intravenously injected with liposomal-iodine (Lip-I) (1.32 g I/kg) on day 0. On day 1, both test (with Lip-I) and control (without Lip-I) mice received RT (single dose, 10 Gy). One day post-RT (day 2), all mice were intravenously injected with liposomal gadolinium (Lip-Gd) (0.32 g Gd/kg), a surrogate of nanoparticle chemotherapeutic agent. Three days later (day 5) mice were imaged on our hybrid spectral micro-CT system. A dual source pre-clinical CT prototype system that combines a photon counting detector (PCD) and an energy integrating detector (EID) in a single hybrid system served as our imaging device. The results demonstrate that Lip-I augmented RT, resulting in increased tumor vascular permeability compared to control mice treated with RT alone. Consequently, Lip-I +RT treated mice demonstrated a 4- fold higher intra-tumoral accumulation of Lip-Gd compared to RT alone treated mice. In conclusion, our work suggests that Lip-I augments RT-induced effects on tumor vasculature, resulting in increased vascular permeability and higher intratumoral deposition of chemotherapeutic nanoparticles.
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