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.

Focal cystic high-attenuation lesions: characterization in renal phantom by using photon-counting spectral CT--improved differentiation of lesion composition.

PURPOSE: To evaluate the capability of spectral computed tomography (CT) to improve the characterization of cystic high-attenuation lesions in a renal phantom and to test the hypothesis that spectral CT will improve the differentiation of cystic renal lesions with high protein content and those that have undergone hemorrhage or malignant contrast-enhancing transformation. MATERIALS AND METHODS: A renal phantom that contained cystic lesions grouped in nonenhancing cyst and hemorrhage series and an iodine-enhancing series was developed. Spectral CT is based on new detector designs that may possess energy-sensitive photon-counting abilities, thereby facilitating the assessment of quantitative information about the elemental and molecular composition of tissue or contrast materials. Imaging of the renal phantom was performed with a prototype scanner at 20 mAs and 70 keV, allowing characterization of x-ray photons at 25-34, 34-39, 39-44, 44-49, 49-55, and more than 55 keV. Region of interest analysis was used to determine lesion attenuation values at various x-ray energies. Statistical analysis was performed to assess attenuation patterns and identify distinct levels of attenuation on the basis of curve regression analysis with analysis of variance tables. RESULTS: Spectral CT depicted linear clusters for the cyst (P < .001, R(2) > 0.940) and hemorrhage (P < .001, R(2) > 0.962) series without spectral overlap. A distinct linear attenuation profile without spectral overlap was also detected for the iodine-enhancing series (P < .001, R(2) > 0.964), with attenuation values attained in the 34-39-keV energy bin statistically identified as outliers (mean slope variation, >37%), corresponding with iodine k-edge effects at 33.2 keV. CONCLUSION: Spectral CT has the potential to enable distinct characterization of hyperattenuating fluids in a renal phantom by helping identify proteinaceous and hemorrhagic lesions through assessment of their distinct levels of attenuation as well as by revealing iodine-containing lesions through analysis of their specific k-edge discontinuities.

Multienergy photon-counting K-edge imaging: potential for improved luminal depiction in vascular imaging.

The purpose of this study was to investigate whether spectral computed tomography (CT) has the potential to improve luminal depiction by differentiating among intravascular gadolinium-based contrast agent, calcified plaque, and stent material by using the characteristic k edge of gadolinium. A preclinical spectral CT scanner with a photon-counting detector and six energy threshold levels was used to scan a phantom vessel. A partially occluded stent was simulated by using a calcified plaque isoattenuated to a surrounding gadolinium chelate solution. The reconstructed images showed an effective isolation of the gadolinium with subsequent clear depiction of the perfused vessel lumen. The calcified plaque and the stent material are suppressed.

Sensitivity of photon-counting based K-edge imaging in X-ray computed tomography.

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 element's 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.