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Novel Contrast Agents in Photon-Counting Computed Tomography

Amato, Carlo

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Recently, two innovations are being investigated for clinical CT applications: nanoparticle-based contrast agents and photon-counting (PC) detectors. Nanoparticles can be used to densely pack a highly attenuating element different than iodine and an engineered coating can be applied to the nanoparticles to create targeted agents and to enhance the biocompatibility of the contained high-Z element. This is particularly of interest for clinical applications since it may allow to exploit the physical properties of elements heavier than iodine, which, at the moment, is the only element allowed for intravenous injection for CT imaging. The PC detectors originally developed at CERN for particle tracking are being investigated for CT applications, and whole body PC scanners are already commercially available since November 2021. PC detectors have been already proven to provide better performance than conventional energy-integrating (EI) detectors concerning image noise, spatial resolution and iodine quantification. The main feature of the PC detector is the possibility to acquire spectral data thanks to the multiple and adjustable energy thresholds. This feature can be used in combination with high-Z materials which exhibit a K-edge in the energy interval of interest. In this thesis, the potential of high-Z elements for novel non-iodinated contrast agents was investigated in combination with the novel PC-CT technology. The topic was addressed both at a preclinical and clinical level. In preclinical imaging, contrast agents based on elements heavier than iodine are already commercially available and new ones are constantly developed. In this frame, a novel contrast agent based on bismuth was herein tested for the first time in-vivo. To do so, an experimental gantry equipped with a PC detector was assembled specifically for this application. The gantry geometry was modeled to fulfill the requirements of a micro-CT scanner. The bismuth agent was injected in four healthy black mice, which were then scanned at regular time intervals to quantify the biodistribution of the agent as a function of time. The results showed that right after the injection, the bismuth agent provides a contrast enhancement of about 1200 HU in the vasculature. Then the agent is slowly cleared from the system with a biological half-life of approximately 250 minutes and accumulates in the liver and in the spleen. Interestingly, the agent also accumulates slowly in the intestinal wall and provides 530 HU of contrast enhancement 5 h after the injection. This specific behavior of the novel agent is probably due to engineered coating applied to the nanoparticles, which is property of the manufacturer. Up to my knowledge, no other example of CT-agents accumulating in the intestinal walls are available in the literature, making the investigated bismuth agent an innovation with many possible application in abdominal diagnostic imaging, like polyps and intestinal ischemia detection or colon cancer imaging. Compared to an iodine-based nanoparticle agent, the bismuth agent provides about 80% more contrast than iodine at the same concentration and has a half-life more then twice longer. Furthermore, a protocol for multi contrast imaging was herein proposed and tested in-vivo on one mouse. The results showed that the novel bismuth agent can be used in combination with the Exitron Myoc (iodine-based) for the simultaneous imaging of the myocardium, brown adipose tissue and vasculature. In a clinical scenario, the potential of high-Z elements for contrast-enhanced PC-CT was thoroughly investigated in a wide variety of scenarios, both with phantom measurements and simulations. For each element, the contrast-to-noise ratio at unit concentration and at unit dose (CNRCD) was compared to the gold standard iodine for different patient sizes (infant, adult and obese), tube voltages (from 70 to 150 kV), filtration settings (with and without 0.4 mm Sn filter) and energy threshold values. Between the investigated elements, gadolinium provided the highest contrast enhancement in most scenarios. Compared to iodine, the usage of gadolinium lead to dose reductions up to 50% for adult and obese patients, and up to 30% for infant patient in combination with a 0.4 mm Sn filter. Since gadolinium is already used as a contrast agent for magnetic resonance imaging, its implementation as a CT contrast agent should be facilitated compared to other high-Z elements. Further dose reductions can be achieved by using two optimally combined bin images. The material decomposition performance of the high-Z elements were quantified using the measurements of the adult liver phantom with two energy thresholds and a tube voltage of 120 kV. The results confirmed again that gadolinium outperforms all the other investigated high-Z elements, but its material map showed contributions from other materials contained in the phantom, especially bone. For other elements with a K-edge at higher energies, like tungsten and bismuth, the CNRCD of the material decomposition resulted up to four times lower than for gadolinium, but no undesired contributions by other materials were present in the material decomposition. This will be particularly of interest for applications like calcified plaque detection, where it is essential to discern between the contrast-enhanced lumen of the vessels and the highly attenuating plaques.

Document type: Dissertation
Supervisor: Kachelrieß, Prof. Dr. Marc
Place of Publication: Heidelberg
Date of thesis defense: 17 October 2022
Date Deposited: 09 Sep 2022 08:30
Date: 2022
Faculties / Institutes: Medizinische Fakultät Heidelberg
Service facilities > German Cancer Research Center (DKFZ)
DDC-classification: 530 Physics
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