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Background: The introduction of energy-selective photon-counting detectors into clinical practice represents the next milestone in computed tomography (CT). In addition to significantly higher resolution, these detectors allow the implicit acquisition of dual or multispectral data in a single measurement through the use of typically freely selectable thresholds. This capability reignited the interest in new contrast agents based on heavy elements, so-called high‑z elements, for clinical CT., Objective: The present article aims to investigate the potential suitability of different chemical elements as contrast agents and to discuss possible clinical applications, for example, K‑edge imaging or simultaneous application of different contrast agents., Conclusion: First preclinical experiments as well as experiments in large animals could demonstrate potential advantages of contrast agents based on heavy elements. For example, such contrast agents promise a significant increase in image contrast compared to conventional iodine-based agents., (© 2023. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Molecular imaging is a valuable tool in drug discovery and development, early screening and diagnosis of diseases, and therapy assessment among others. Although many different imaging modalities are in use today, molecular imaging with computed tomography (CT) is still challenging owing to its low sensitivity and soft tissue contrast compared with other modalities. Recent technical advances, particularly the introduction of spectral photon-counting detectors, might allow overcoming these challenges. Herein, the fundamentals and recent advances in CT relevant to molecular imaging are reviewed and potential future preclinical and clinical applications are highlighted. The review concludes with a discussion of potential future advancements of CT for molecular imaging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: In clinics, only iodine- and barium-based contrast agents are currently used for contrast-enhanced x-ray computed tomography (CT). Recently, the introduction of new photon-counting (PC) detectors increased the interest in developing new contrast agents based on heavier elements. These elements may provide more contrast and spectral information compared to iodine and barium thanks to their k-edges at higher energies. In this paper, the potential of high-Z elements in contrast-enhanced CT was evaluated for different patient sizes and x-ray spectra using a PC detector., Methods: An adult liver phantom with five high-Z element solutions (iodine, gadolinium, ytterbium, tungsten, and bismuth) was scanned with a whole-body photon-counting computed tomography (PCCT) prototype. For each element, the contrast-to-noise ratio at unit concentration and at unit dose (CNRCD) was evaluated in low threshold images ( T 0 = 20 keV ) as function of the tube voltage (80, 100, 120, and 140 kV) and in bin images (tube voltage = 120 kV) as function of the higher threshold ( T 0 = 20 keV and T 1 ∈ [ 50 , 90 ] keV ). Simulations were performed for validation with measurements and to investigate more elements (cerium and gold), different patient sizes (infant, adult, and obese), and spectrum filtration (with and without 0.4-mm tin filter). The dose reductions associated with the CNRCD improvements over iodine were quantified as well., Results: CNRCD improvements and dose reductions depend on the investigated scenario. For the infant phantom, dose reductions around 30% were reached using cerium or gadolinium in combination with the tin filter. For the adult and obese phantom, reductions around 50% were provided by gadolinium or ytterbium in combination with the tin filter. Independently of the high-Z element, the CNRCD of two optimally combined bin images was higher than the CNRCD of the low threshold image. Good agreement was found between measurements and simulations., Conclusions: Between the investigated elements, gadolinium resulted to have the highest potential as novel contrast agent in PCCT, providing significant dose reductions for all patient sizes. Compared to the other elements, the implementation of gadolinium as CT contrast agent may be facilitated since it is already deployed as contrast agents for magnetic resonance imaging., (© 2020 The Authors. Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.)

Purpose: To assess the dose-normalized iodine contrast-to-noise-ratio (CNRD) improvement and contrast media reduction potential obtained with photon-counting (PC) CT compared to conventional energy-integrating (EI) CT as a function of patient size and tube voltage., Method: Images of a semi-anthropomorphic phantom of different sizes (small, medium, large) equipped with vials containing different iodine concentrations were acquired at the SOMATOM CounT prototype CT system using tube voltages of 80 kV-140 kV. CNRD is evaluated in reconstructions obtained using the EI detector, the PC detector using a single bin, and in reconstructions obtained by statistically optimally weighting acquisitions with two bins. Iodine CNRD improvements, potential dose reduction and the potential contrast media volume reduction are reported., Results: In general, iodine CNRD improvement increases with increasing tube voltage for all patient sizes. In particular, if only one energy bin is used, the CNRD improvement is up to 30 % (small: 10 %, medium: 18 %, large: 30 %) and up to 37 % if an optimal weighting of two bins is performed (small: 13 %, medium: 25 %, large: 37 %) which is equivalent to the potential contrast media volume reduction. The improved iodine CNRD of PC compared to EI may allow for a potential radiation dose reduction of up to 46 %., Conclusions: All patients' iodine contrast at given x-ray dose, and particularly medium and large sized patients acquired at higher tube voltages, may benefit from photon-counting CT. The iodine contrast improvement can be used to reduce patient dose or to reduce the amount of contrast agent that is administered., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to report., (Copyright © 2020. Published by Elsevier B.V.)

We herein developed a micro-CT method using the innovative contrast agent ExiTron™ MyoC 8000 to longitudinally monitor cardiac processes in vivo in small animals. Experiments were performed on healthy mice and mice with myocardial infarction inflicted by ligation of the left anterior descending artery. Time-dependent signal enhancement in different tissues of healthy mice was measured and various contrast agent doses were investigated so as to determine the minimum required dose for imaging of the myocardium. Due to its ability to be taken up by healthy myocardium but not by infarct tissue, ExiTron MyoC 8000 enables detection of myocardial infarction even at a very low dose. The signal enhancement in the myocardium of infarcted mice after contrast agent injection was exploited for quantification of infarct size. The values of infarct size obtained from the imaging method were compared with those obtained from histology and showed a significant correlation ( R 2 = 0.98). Thus, the developed micro-CT method allows for monitoring of a variety of processes such as cardiac remodeling in longitudinal studies.

Cardiac perfusion studies using computed tomography are a common tool in clinical practice. Recent technical advances and the availability of dedicated small animal scanners allow the transfer of these techniques to the preclinical sector in general and to mouse models of cardiac diseases in particular. This necessitates new requirements for contrast injection techniques as a rapid transport of contrast media from the intravenous access to the animal heart. Clinical contrast agents containing high iodine concentrations are used within small animal studies although they exhibit a high viscosity which might limit their transport within the vasculature. The authors provide a comparison of the transport of contrast media following an injection into the lateral tail vein and an injection into the retrobulbar sinus and discuss the anatomy involved. The temporal evolution of a contrast bolus and its in vivo distribution is visualized. It is demonstrated that injecting contrast agents into the lateral tail vein of mice results in a retrograde blood flow to the liver veins and therefore does not deliver a detectable contrast bolus to the heart, and thus it cannot be used for cardiac perfusion studies. By contrast, boli injected into the retrobulbar sinus are rapidly transported to the heart and provide ventricular contrast enabling perfusion studies similar to those in human patients. The results demonstrate that an injection into the retrobulbar sinus is superior to an injection into the lateral tail vein for the delivery of contrast boli to the animal heart, while all drawbacks of an injection into the lateral tail vein are overcome.