Axel Thran

Atherosclerotic plaque composition: analysis with multicolor CT and targeted gold nanoparticles.

PURPOSE To investigate the potential of spectral computed tomography (CT) (popularly referred to as multicolor CT), used in combination with a gold high-density lipoprotein nanoparticle contrast agent (Au-HDL), for characterization of macrophage burden, calcification, and stenosis of atherosclerotic plaques. MATERIALS AND METHODS The local animal care committee approved all animal experiments. A preclinical spectral CT system in which incident x-rays are divided into six different energy bins was used for multicolor imaging. Au-HDL, an iodine-based contrast agent, and calcium phosphate were imaged in a variety of phantoms. Apolipoprotein E knockout (apo E-KO) mice were used as the model for atherosclerosis. Gold nanoparticles targeted to atherosclerosis (Au-HDL) were intravenously injected at a dose of 500 mg per kilogram of body weight. Iodine-based contrast material was injected 24 hours later, after which the mice were imaged. Wild-type mice were used as controls. Macrophage targeting by Au-HDL was further evaluated by using transmission electron microscopy and confocal microscopy of aorta sections. RESULTS Multicolor CT enabled differentiation of Au-HDL, iodine-based contrast material, and calcium phosphate in the phantoms. Accumulations of Au-HDL were detected in the aortas of the apo E-KO mice, while the iodine-based contrast agent and the calcium-rich tissue could also be detected and thus facilitated visualization of the vasculature and bones (skeleton), respectively, during a single scanning examination. Microscopy revealed Au-HDL to be primarily localized in the macrophages on the aorta sections; hence, the multicolor CT images provided information about the macrophage burden. CONCLUSION Spectral CT used with carefully chosen contrast agents may yield valuable information about atherosclerotic plaque composition.

Diffusion of metals in polymers

Abstract First information on metal diffusion in polymers resulted from surface spectroscopies which mainly provided insight into chemical interactions of metals at polymer surfaces and into their growth mode. Medium energy ion scattering, electron microscopy, atomic force microscopy, and second-harmonic generation revealed a strong tendency of metals of low and intermediate reactivity to form clusters when deposited onto polymers. The interplay of diffusion and aggregation was also studied by Monte Carlo simulations. Metal diffusivities were obtained from radiotracer and Rutherford backscattering measurements. The available results show that reactive metals do not have any long-range mobility and are effective diffusion barriers. In contrast, isolated atoms of less reactive metals diffuse deep into polymers at elevated temperatures. However, the very pronounced aggregation tendency of these metals effectively impedes diffusion unless they are deposited at rates of the order of monolayers per minute or lower. Nevertheless, traces of noble metals always diffuse into polymers during the early stages of metal deposition, whereas no significant diffusion occurs from a continuous metal film. Even noble metal diffusivities are many orders of magnitude smaller than diffusivities of non-reactive gas molecules and largely decoupled from polymer dynamics. This is attributed to a pronounced reduction in the local chain mobility near metal atoms, e.g., by temporary metal-atom-induced crosslinking.

Correlation between fractional free volume and diffusivity of gas molecules in glassy polymers

Despite its oversimplifications, the free-volume approach has proven to provide very useful correlative and even semipredictive capabilities. This article is concerned with the correlation between the diffusivity, D, of gas molecules in glassy polymers and the fractional free volume, FFV, determined by the Bondi method. The diffusivities were taken from a database, generated by the authors in connection with work on the new Landolt Bornstein series “Diffusion in Non-Metallic Solids”, which encompasses a very large variety of glassy polymers. For a given diffusant log D is a linear function of 1/FFV as predicted by the free volume theory. However, the deviations from this relationship are significant and strongly correlated between O2, N2, CO2, and CH4. The systematic deviations are opposite to the predicted effect of the polymer jumping unit size in the free-volume concept of Vrentas and Duda and are interpreted in terms of an increase in the activation energy with increasing chain stiffness. Correlation analysis further suggests that the diffusion mechanisms of H2 and particularly of He differ markedly from that of larger gas molecules. Furthermore the influence of the cohesive energy and the glass-transition temperature of the polymers is investigated.

Effect of computed tomography scanning parameters on gold nanoparticle and iodine contrast

PurposeGold nanoparticles (gold-NPs) have lately been proposed as alternative contrast agents to iodine-based contrast agents (iodine-CA) for computed tomography (CT) angiography. The aims of this study were to confirm an appropriate environment in which to evaluate such novel contrast agents, to investigate the comparative contrast of iodine-CA versus gold-NP, and to determine optimal scanning parameters for gold-NP. Materials and MethodsThree different clinical scanners were used to acquire CT images. A range of concentrations (10 mM to 1.5 M) of gold-NP and iodine-CA were scanned with varying x-ray tube voltages and currents, reconstruction kernels, protocols, and scanner models. The different environments investigated were air, water, and water with a bone simulant (Ca3(PO4)2). Regression coefficients were derived from the attenuation values plotted against concentration and compared for statistical significance using t values. ResultsAs expected, contrast was linearly related to concentrations up to 500 to 1000 mM, depending on the conditions used, whereupon a plateau of 3000 Hounsfield units was reached. Attenuation was significantly different depending on the environment used (air, water, or water and bone simulant). Contrast is dependent on the x-ray tube voltage used, with the contrast produced from iodine-CA sharply declining with increasing voltage, whereas the contrast of gold-NP varied less with tube voltage but was maximal at 120 kV in water with bone simulant. Current, reconstruction kernels, protocols, and scanner model had less effect on contrast. ConclusionWater with a bone simulant is a preferable environment for evaluating novel cardiac CT contrast agents. Relative iodine-CA versus gold-NP contrast is dependent on the scanning conditions used. Optimal scanning conditions for gold-NP will likely use an x-ray tube voltage of 120 kV.

Sensitivity of Photon-Counting Based

The feasibility of K-edge imaging using energy-resolved, photon-counting transmission measurements in X-ray computed tomography (CT) has been demonstrated by simulations and experiments. The method is based on probing the discontinuities of the attenuation coefficient of heavy elements above and below the K-edge energy by using energy-sensitive, photon counting X-ray detectors. In this paper, we investigate the dependence of the sensitivity of K-edge imaging on the atomic number Z of the contrast material, on the object diameter D , on the spectral response of the X-ray detector and on the X-ray tube voltage. We assume a photon-counting detector equipped with six adjustable energy thresholds. Physical effects leading to a degradation of the energy resolution of the detector are taken into account using the concept of a spectral response function R(E,U) for which we assume four different models. As a validation of our analytical considerations and in order to investigate the influence of elliptically shaped phantoms, we provide CT simulations of an anthropomorphic Forbild-Abdomen phantom containing a gold-contrast agent. The dependence on the values of the energy thresholds is taken into account by optimizing the achievable signal-to-noise ratios (SNR) with respect to the threshold values. We find that for a given X-ray spectrum and object size the SNR in the heavy elements basis material image peaks for a certain atomic number Z. The dependence of the SNR in the high-Z basis-material image on the object diameter is the natural, exponential decrease with particularly deteriorating effects in the case where the attenuation from the object itself causes a total signal loss below the K-edge. The influence of the energy-response of the detector is very important. We observed that the optimal SNR values obtained with an ideal detector and with a CdTe pixel detector whose response, showing significant tailing, has been determined at a synchrotron differ by factors of about two to three. The potentially very important impact of scattered X-ray radiation and pulse pile-up occurring at high photon rates on the sensitivity of the technique is qualitatively discussed.

{\rm K}

The initial stages of growth of noble metals deposited onto untreated as well as Ar+ beam-treated polymer surfaces were investigated by means of X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), and radiotracer methods. Condensation coefficients C of the metals on the polymer surfaces were determined by comparison of the XPS signals of the metals with the nominal thicknesses measured by a quartz microbalance during deposition. These measurements were combined with radiotracer measurements, which allow to determine C independently with high accuracy and sensitivity. C was found to depend strongly on the chemical composition of the polymer surface, e.g., at room temperature, C varies between 0.95 for PMDA-ODA polyimide and 0.002 for Teflon AF. By ion beam treatment of the latter, C was raised considerably. During nucleation of the metal on the polymer surface, C increases strongly with metal coverage. C also depends on the deposition rate of the metal and decreases strongly at elevated temperatures.

-Edge Imaging in X-ray Computed Tomography

Photon-counting detector technology has enabled the first experimental investigations of energy-resolved computed tomography (CT) imaging and the potential use for K-edge imaging. However, limitations in regards to detecter technology have been imposing a limit to effective count rates. As a consequence, this has resulted in high noise levels in the obtained images given scan time limitations in CT imaging applications. It has been well recognized in the area of low-dose imaging with conventional CT that iterative image reconstruction provides a superior signal to noise ratio compared to traditional filtered backprojection techniques. Furthermore, iterative reconstruction methods also allow for incorporation of a roughness penalty function in order to make a trade-off between noise and spatial resolution in the reconstructed images. In this work, we investigate statistically-principled iterative image reconstruction from material-decomposed sinograms in spectral CT. The proposed reconstruction algorithm seeks to minimize a penalized likelihood-based cost functional, where the parameters of the likelihood function are estimated by computing the Fisher information matrix associated with the material decomposition step. The performance of the proposed reconstruction method is quantitatively investigated by use of computer-simulated and experimental phantom data. The potential for improved K-edge imaging is also demonstrated in an animal experiment.

Condensation coefficients and initial stages of growth for noble metals deposited onto chemically different polymer surfaces

Low-density lipoprotein (LDL) plays a critical role in cholesterol transport and is closely linked to the progression of several diseases. This motivates the development of methods to study LDL behavior from the microscopic to whole-body level. We have developed an approach to efficiently load LDL with a range of diagnostically active nanocrystals or hydrophobic agents. We performed focused experiments on LDL labeled with gold nanocrystals (Au-LDL). The labeling procedure had minimal effect on LDL size, morphology, or composition. Biological function was found to be maintained from both in vitro and in vivo experiments. Tumor-bearing mice were injected intravenously with LDL, DiR-LDL, Au-LDL, or a gold-loaded nanoemulsion. LDL accumulation in the tumors was detected with whole-body imaging methods, such as computed tomography (CT), spectral CT, and fluorescence imaging. Cellular localization was studied with transmission electron microscopy and fluorescence techniques. This LDL labeling procedure should permit the study of lipoprotein biointeractions in unprecedented detail.

Statistical Reconstruction of Material Decomposed Data in Spectral CT

Abstract Metal–polymer interfaces with different but well defined morphologies were prepared by evaporating noble metals (Au, Ag, Cu) onto chemically different polymers, i.e. bisphenol-trimethyl cyclohexane polycarbonate (TMC-PC), pyromellitic dianhydride-oxydianiline (PMDA-ODA) polyimide (PI), polystyrene (PS) and the low-k dielectric Teflon AF 1601. The interfaces were characterised using transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and atomic force microscopy (AFM). The combination of these techniques allowed one to determine morphological parameters such as concentration and distribution of metal clusters at the surface and in the near-surface region. In addition, radiotracer measurements yielded exact metal condensation coefficients C and was used to determine the extent of diffusion of metal atoms into the polymers. First experiments on the macroscopic adhesion of Cu on TMC-PC showed that the initially low peel strength can be increased substantially by subsequent annealing above the polymer glass transition temperature, T g .

Gold Nanocrystal Labeling Allows Low-Density Lipoprotein Imaging from the Subcellular to Macroscopic Level

Purpose To investigate the feasibility of using spectral photon-counting computed tomography (CT) to differentiate between gadolinium-based and nonionic iodine-based contrast material in a colon phantom by using the characteristic k edge of gadolinium. Materials and Methods A custom-made colon phantom was filled with nonionic iodine-based contrast material, and a gadolinium-filled capsule representing a contrast material-enhanced polyp was positioned on the colon wall. The colon phantom was scanned with a preclinical spectral photon-counting CT system to obtain spectral and conventional data. By fully using the multibin spectral information, material decomposition was performed to generate iodine and gadolinium maps. Quantitative measurements were performed within the lumen and polyp to quantitatively determine the absolute content of iodine and gadolinium. Results In a conventional CT section, absorption values of both contrast agents were similar at approximately 110 HU. Contrast material maps clearly differentiated the distributions, with gadolinium solely in the polyp and iodine in the lumen of the colon. Quantitative measurements of contrast material concentrations in the colon and polyp matched well with those of actual prepared mixtures. Conclusion Dual-contrast spectral photon-counting CT colonography with iodine-filled lumen and gadolinium-tagged polyps may enable ready differentiation between polyps and tagged fecal material.