Dual-contrast photon-counting micro-CT using iodine and a novel bismuth-based contrast agent.

Objectives.To characterize for the first timein vivoa novel bismuth-based nanoparticular contrast agent developed for preclinical applications. Then, to design and testin vivoa multi-contrast protocol for functional cardiac imaging using the new bismuth nanoparticles and a well-established iodine-based contrast agent.Approach.A micro-computed tomography scanner was assembled and equipped with a photon-counting detector. Five mice were administered with the bismuth-based contrast agent and systematically scanned over 5 h to quantify the contrast enhancement in relevant organs of interest. Subsequently, the multi-contrast agent protocol was tested on three mice. Material decomposition was performed on the acquired spectral data to quantify the concentration of bismuth and iodine in multiple structures, e.g. the myocardium and vasculature.Main results.In the vasculature, the bismuth agent provides a peak enhancement of 1100 HU and a half-life of about 260 min. After the injection, it accumulates in the liver, spleen and intestinal wall reaching a CT value of 440 HU about 5 h post injection. Phantom measurements showed that the bismuth provides more contrast enhancement than iodine for a variety of tube voltages. The multi-contrast protocol for cardiac imaging successfully allowed the simultaneous decomposition of the vasculature, the brown adipose tissue and the myocardium.Significance.The new bismuth-based contrast agent was proven to have a long circulation time suitable for preclinical applications and to provide more contrast than iodine agents. The proposed multi-contrast protocol resulted in a new tool for cardiac functional imaging. Furthermore, thanks to the contrast enhancement provided in the intestinal wall, the novel contrast agent may be used to develop further multi contrast agent protocols for abdominal and oncological imaging.

Toward molecular imaging using spectral photon-counting computed tomography?

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.

Potential of contrast agents based on high-Z elements for contrast-enhanced photon-counting computed tomography.

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.

Coronary micro-computed tomography angiography in mice.

Coronary computed tomography angiography is an established technique in clinical practice and a valuable tool in the diagnosis of coronary artery disease in humans. Imaging of coronaries in preclinical research, i.e. in small animals, is very difficult due to the high demands on spatial and temporal resolution. Mice exhibit heart rates of up to 600 beats per minute motivating the need for highest detector framerates while the coronaries show diameters below 100 µm indicating the requirement for highest spatial resolution. We herein use a custom built micro-CT equipped with dedicated reconstruction algorithms to illustrate that coronary imaging in mice is possible. The scanner provides a spatial and temporal resolution sufficient for imaging of smallest, moving anatomical structures and the dedicated reconstruction algorithms reduced radiation dose to less than 1 Gy but do not yet allow for longitudinal studies. Imaging studies were performed in ten mice administered with a blood-pool contrast agent. Results show that the course of the left coronary artery can be visualized in all mice and all major branches can be identified for the first time using micro-CT. This reduces the gap in cardiac imaging between clinical practice and preclinical research.

Effects of Detector Sampling on Noise Reduction in Clinical Photon-Counting Whole-Body Computed Tomography.

OBJECTIVES: Reconstructing images from measurements with small pixels below the system's resolution limit theoretically results in image noise reduction compared with measurements with larger pixels. We evaluate and quantify this effect using data acquired with the small pixels of a photon-counting (PC) computed tomography scanner that can be operated in different detector pixel binning modes and with a conventional energy-integrating (EI) detector. MATERIALS AND METHODS: An anthropomorphic abdominal phantom that can be extended to 3 sizes by adding fat extension rings, equipped with iodine inserts as well as human cadavers, was measured at tube voltages ranging from 80 to 140 kV. The images were acquired with the EI detector (0.6 mm pixel size at isocenter) and the PC detector operating in Macro mode (0.5 mm pixel size at iso) and ultrahigh-resolution (UHR) mode (0.25 mm pixel size at iso). Both detectors are components of the same dual-source prototype computed tomography system. During reconstruction, the modulation transfer functions were matched to the one of the EI detector. The dose-normalized contrast-to-noise ratio (CNRD) values are evaluated as a figure of merit. RESULTS: Images acquired in UHR mode achieve on average approximately 6% higher CNRD compared with Macro mode at the same spatial resolution for a quantitative D40f kernel. Using a sharper B70f kernel, the improvement increases to 21% on average. In addition, the better performance of PC detectors compared with EI detectors with regard to iodine imaging has been evaluated by comparing CNRD values for Macro and EI. Combining both of these effects, a CNRD improvement of up to 34%, corresponding to a potential dose reduction of up to 43%, can be achieved for D40f. CONCLUSIONS: Reconstruction of UHR data with a modulation transfer function below the system's resolution limit reduces image noise for all patient sizes and tube voltages compared with standard acquisitions. Thus, a relevant dose reduction may be clinically possible while maintaining image quality.