Ewald Roessl

Experimental feasibility of multi-energy photon-counting K-edge imaging in pre-clinical computed tomography

Theoretical considerations predicted the feasibility of K-edge x-ray computed tomography (CT) imaging using energy discriminating detectors with more than two energy bins. This technique enables material-specific imaging in CT, which in combination with high-Z element based contrast agents, opens up possibilities for new medical applications. In this paper, we present a CT system with energy detection capabilities, which was used to demonstrate the feasibility of quantitative K-edge CT imaging experimentally. A phantom was imaged containing PMMA, calcium-hydroxyapatite, water and two contrast agents based on iodine and gadolinium, respectively. Separate images of the attenuation by photoelectric absorption and Compton scattering were reconstructed from energy-resolved projection data using maximum-likelihood basis-component decomposition. The data analysis further enabled the display of images of the individual contrast agents and their concentrations, separated from the anatomical background. Measured concentrations of iodine and gadolinium were in good agreement with the actual concentrations. Prior to the tomographic measurements, the detector response functions for monochromatic illumination using synchrotron radiation were determined in the energy range 25 keV-60 keV. These data were used to calibrate the detector and derive a phenomenological model for the detector response and the energy bin sensitivities.

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.

The First Analysis and Clinical Evaluation of Native Breast Tissue Using Differential Phase-Contrast Mammography

Objectives:Phase-contrast and scattering-based x-ray imaging are known to provide additional and complementary information to conventional, absorption-based methods, and therefore have the potential to play a crucial role in medical diagnostics. We report on the first mammographic investigation of 5 native, that is, freshly dissected, breasts carried out with a grating interferometer and a conventional x-ray tube source. Four patients in this study had histopathologically proven invasive breast cancer. One male patient, without the presence of any malignant formations within the resected breast, was included as a control specimen. Materials and Methods:We used a Talbot-Lau grating setup installed on a conventional, low-brilliance x-ray source; the interferometer operated at the fifth Talbot distance, at a tube voltage of 40 kVp with mean energy of 28 keV, and at a current of 25 mA. The device simultaneously recorded absorption, differential phase and small-angle scattering signals from the native breast tissue. These quantities were then combined into novel color- and high-frequency-enhanced radiographic images. Presurgical images (conventional mammography, ultrasonography, and magnetic resonance imaging) supported the findings and clinical relevance was verified. Results:Our approach yields complementary and otherwise inaccessible information on the electron density distribution and the small-angle scattering power of the sample at the microscopic scale. This information can be used to potentially answer clinically relevant, yet unresolved questions such as unequivocally discerning between malignant and premalignant changes and postoperative scars and distinguishing cancer-invaded regions within healthy tissue. Conclusions:We present the first ex vivo images of fresh, native breast tissue obtained from mastectomy specimens using grating interferometry. This technique yields improved diagnostic capabilities when compared with conventional mammography, especially when discerning the type of malignant conversions and their breadth within normal breast tissue. These promising results advance us toward the ultimate goal, using grating interferometry in vivo on humans in a clinical setting.

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.

Computed tomography in color: NanoK-enhanced spectral CT molecular imaging.

New multidetector cardiac computed tomography (MDCT) can image the heart within the span of a few beats, and as such, it is the favored noninvasive approach to assess coronary anatomy rapidly. However, MDCT has proven to be more useful for excluding coronary disease than for making positive diagnoses. The inability to detect unstable cardiac disease arises from the confounding attenuating effects of calcium deposits within atherosclerotic plaques, which obscure lumen anatomy, and from the insensitivity of CT X-rays to image low attenuating intraluminal thrombus adhered to a disrupted plaque cap, the absolute condition of ruptured plaque and unstable disease.[1–6] It is now well understood that the sensitive detection and quantification of small intravascular thrombus in coronary arteries with molecular imaging techniques could provide a direct metric to diagnose and risk stratify patients presenting with chest pain.[7,8]

Cramér-Rao lower bound of basis image noise in multiple-energy x-ray imaging

We present an analytical method to compute the basis image noise in the context of multi-energy x-ray imaging based on the Cramér-Rao lower bound (CRLB). The proposed formalism extends the original idea of Alvarez and Macovski (1976 Phys. Med. Biol. 21 733) to estimate the noise in the photo-effect and Compton-effect basis images in the case of dual-energy imaging. It includes an arbitrary number of independent, spectrally distinct attenuation measurements and also goes beyond the two-dimensional decomposition of the attenuation, including, e.g., a contrast agent as a third basis material. To illustrate our method, we consider three simple applications. The first application is to study the influence of the exact values for the energy thresholds on the basis image noise for a binned photon-counting system. The second application relates to the same detector system as the first and is an investigation of the dependence of the basis image noise on the energy resolution of the detector system. Finally, the third application provides an example for the case of an energy-integrating detector: the aim is to optimize the front-scintillator layer thickness of a dual-crystal detector for dual-energy imaging. The CRLB is used to minimize the noise of a photo-effect/Compton-effect basis material decomposition.

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.

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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.

-Edge Imaging in X-ray Computed Tomography

PURPOSE The purpose of this work is to combine two areas of active research in tomographic x-ray imaging. The first one is the use of iterative reconstruction (IR) techniques. The second one is differential phase contrast imaging (DPCI). METHODS The authors derive a maximum likelihood (ML) reconstruction algorithm with regularization for DPCI. Forward and back-projection are implemented using spherically symmetric basis functions (blobs) and differential footprints, thus completely avoiding the need for numerical differentiation throughout the reconstruction process. The method is applied to the problem of reconstruction of an object from sparsely sampled projections. RESULTS The results show that the proposed method can handle the sparsely sampled data efficiently. In particular no streak artifacts are visible which are present in images obtained by filtered back-projection (FBP). CONCLUSIONS IR algorithms have a wide spectrum of proven advantages in the area of conventional computed tomography. The present work describes for the first time, how a matched forward and back-projection can be implemented for DPCI, which is furthermore free of any heuristics. The newly developed ML reconstruction algorithm for DPCI shows that for the case of sparsely sampled projection data, an improvement in image quality is obtained that is qualitatively comparable to a corresponding situation in conventional x-ray imaging. Based on the proposed operators for forward and back-projection, a large variety of IR algorithms is thus made available for DPCI.