Correction to: Towards clinical grating-interferometry mammography.

The article Towards clinical grating-interferometry mammography, written by Carolina Arboleda, Zhentian Wang, Konstantins Jefimovs, Thomas Koehler, Udo Van Stevendaal, Norbert Kuhn, Bernd David, Sven Prevrhal, Kristina Lång, Serafino Forte, Rahel Antonia Kubik-Huch, Cornelia Leo.

Towards clinical grating-interferometry mammography.

OBJECTIVES: Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, as several research works have demonstrated in a pre-clinical setting, since it is able to provide attenuation, differential phase contrast, and scattering images simultaneously. In order to translate this technique to the clinics, it has to be adapted to cover a large field-of-view within a clinically acceptable exposure time and radiation dose. METHODS: We set up a grating interferometer that fits into a standard mammography system and fulfilled the aforementioned conditions. Here, we present the first mastectomy images acquired with this experimental device. RESULTS AND CONCLUSION: Our system performs at a mean glandular dose of 1.6 mGy for a 5-cm-thick, 18%-dense breast, and a field-of-view of 26 × 21 cm2. It seems to be well-suited as basis for a clinical-environment device. Further, dark-field signals seem to support an improved lesion visualization. Evidently, the effective impact of such indications must be evaluated and quantified within the context of a proper reader study. KEY POINTS: • Grating-interferometry-based mammography (GIM) might facilitate breast cancer detection, since it is sensitive to refraction and scattering and thus provides additional tissue information. • The most straightforward way to do grating-interferometry in the clinics is to modify a standard mammography device. • In a first approximation, the doses given with this technique seem to be similar to those of conventional mammography.

Experimental feasibility of spectral photon-counting computed tomography with two contrast agents for the detection of endoleaks following endovascular aortic repair.

OBJECTIVES: After endovascular aortic repair (EVAR), discrimination of endoleaks and intra-aneurysmatic calcifications within the aneurysm often requires multiphase computed tomography (CT). Spectral photon-counting CT (SPCCT) in combination with a two-contrast agent injection protocol may provide reliable detection of endoleaks with a single CT acquisition. METHODS: To evaluate the feasibility of SPCCT, the stent-lined compartment of an abdominal aortic aneurysm phantom was filled with a mixture of iodine and gadolinium mimicking enhanced blood. To represent endoleaks of different flow rates, the adjacent compartments contained either one of the contrast agents or calcium chloride to mimic intra-aneurysmatic calcifications. After data acquisition with a SPCCT prototype scanner with multi-energy bins, material decomposition was performed to generate iodine, gadolinium and calcium maps. RESULTS: In a conventional CT slice, Hounsfield units (HU) of the compartments were similar ranging from 147 to 168 HU. Material-specific maps differentiate the distributions within the compartments filled with iodine, gadolinium or calcium. CONCLUSION: SPCCT may replace multiphase CT to detect endoleaks without sacrificing diagnostic accuracy. It is a unique feature of our method to capture endoleak dynamics and allow reliable distinction from intra-aneurysmatic calcifications in a single scan, thereby enabling a significant reduction of radiation exposure. KEY POINTS: • SPCCT might enable advanced endoleak detection. • Material maps derived from SPCCT can differentiate iodine, gadolinium and calcium. • SPCCT may potentially reduce radiation burden for EVAR patients under post-interventional surveillance.

Spectral Photon-counting CT: Initial Experience with Dual-Contrast Agent K-Edge Colonography.

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. © RSNA, 2016.

Sensitivity-based optimization for the design of a grating interferometer for clinical X-ray phase contrast mammography.

An X-ray grating interferometer (GI) suitable for clinical mammography must comply with quite strict dose, scanning time and geometry limitations, while being able to detect tumors, microcalcifications and other abnormalities. Such a design task is not straightforward, since obtaining optimal phase-contrast and dark-field signals with clinically compatible doses and geometrical constraints is remarkably challenging. In this work, we present a wave propagation based optimization that uses the phase and dark-field sensitivities as figures of merit. This method was used to calculate the optimal interferometer designs for a commercial mammography setup. Its accuracy was validated by measuring the visibility of polycarbonate samples of different thicknesses on a Talbot-Lau interferometer installed on this device and considering some of the most common grating imperfections to be able to reproduce the experimental values. The optimization method outcomes indicate that small grating pitches are required to boost sensitivity in such a constrained setup and that there is a different optimal scenario for each signal type.

Iterative reconstruction for differential phase contrast imaging using spherically symmetric basis functions.

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.

A comparative study of a dual-energy-like imaging technique based on counting-integrating readout.

PURPOSE: The recent introduction of a specific electronic readout chip, designed for the processing of the same signal pulses from an x-ray sensor in one integrating and one counting channel in each pixel E. Kraft et al., [IEEE Trans. Nucl. Sci. 54, 383-390 (2007)]; E. Kraft, "Counting and integrating microelectronics development for direct conversion X-ray imaging," Ph.D. thesis, 2007; J. Fink, "Characterization of the imaging performance of the simultaneously counting and integrating X-ray detector CIX," Ph.D. thesis, 2010, enables an alternative to conventional dual-energy imaging methods. As shown in a previous paper, the proposed alternative benefits from positively correlated noise in the raw data, inherent to the counting-integrating readout (CIX), which results in a reduction of basis image noise after dual-energy decomposition. In the present paper, the authors compare the new approach to dual-energy imaging to two conventional dual-energy techniques, the dual-kV technique and the dual-crystal technique and to a photon-counting technique based on two energy windows. METHODS: The study is based on x-ray computed tomography (CT) simulations of an anthropomorphic head phantom, where the signal-to-noise ratios and the contrast-to-noise ratios in basis material images and quasi-monochromatic images at 60 keV are compared. Moreover, a simple pictorial illustration of the relevance of input noise correlations in the noise-propagation process during the dual-energy basis material decomposition are presented, as well as measurement data for the correlation obtained as a function of the x-ray flux rate. RESULTS: Under the idealized assumptions of the absence of scatter and detector imperfections like K-escape, crosstalk and detector noise, our comparison shows that among the dual-energy techniques investigated, the CIX concept together with the dual-kV technique performs best, confirming the mitigating effect of correlated measurement data on the dual-energy basis material decomposition. CONCLUSIONS: The novel concept of simultaneous counting of photons and integrating the x-ray energy flux has a large potential for dual-energy applications in both projection and tomographic x-ray imaging. Future work will have to focus on the sensitivity of the CIX dual-energy concept to scattered radiation, detector imperfections and high x-ray fluxes.

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.

Feasibility of improving vascular imaging in the presence of metallic stents using spectral photon counting CT and K-edge imaging.

Correct visualization of the vascular lumen is impaired in standard computed tomography (CT) because of blooming artifacts, increase of apparent size, induced by metallic stents and vascular calcifications. Recently, due to the introduction of photon-counting detectors in the X-ray imaging field, a new prototype spectral photon-counting CT (SPCCT) based on a modified clinical CT system has been tested in a feasibility study for improving vascular lumen delineation and visualization of coronary stent architecture. Coronary stents of different metal composition were deployed inside plastic tubes containing hydroxyapatite spheres to simulate vascular calcifications and in the abdominal aorta of one New Zealand White (NZW) rabbit. Imaging was performed with an SPCCT prototype, a dual-energy CT system, and a conventional 64-channel CT system (B64). We found the apparent widths of the stents significantly smaller on SPCCT than on the other two systems in vitro (p < 0.01), thus closer to the true size. Consequently, the intra-stent lumen was significantly larger on SPCCT (p < 0.01). In conclusion, owing to the increased spatial resolution of SPCCT, improved lumen visualization and delineation of stent metallic mesh is possible compared to dual-energy and conventional CT.

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.

Multicolour imaging with spectral photon-counting CT: a phantom study.

BACKGROUND: To evaluate the feasibility of multicolour quantitative imaging with spectral photon-counting computed tomography (SPCCT) of different mixed contrast agents. METHODS: Phantoms containing eleven tubes with mixtures of varying proportions of two contrast agents (i.e. two selected from gadolinium, iodine or gold nanoparticles) were prepared so that the attenuation of each tube was about 280 HU. Scans were acquired at 120 kVp and 100 mAs using a five-bin preclinical SPCCT prototype, generating conventional, water, iodine, gadolinium and gold images. The correlation between prepared and measured concentrations was assessed using linear regression. The cross-contamination was measured for each material as the root mean square error (RMSE) of its concentration in the other material images, where no signal was expected. The contrast-to-noise ratio (CNR) relative to a phosphate buffered saline tube was calculated for each contrast agent. RESULTS: The solutions had similar attenuations (279 ± 10 HU, mean ± standard deviation) and could not be differentiated on conventional images. However, a distinction was observed in the material images within the same samples, and the measured and prepared concentrations were strongly correlated (R2 ≥ 0.97, 0.81 ≤ slope ≤ 0.95, -0.68 ≤ offset ≤ 0.89 mg/mL). Cross-contamination in the iodine images for the mixture of gold and gadolinium contrast agents (RMSE = 0.34 mg/mL) was observed. CNR for 1 mg/mL of contrast agent was better for the mixture of iodine and gadolinium (CNRiodine = 3.20, CNRgadolinium = 2.80) than gold and gadolinium (CNRgadolinium = 1.67, CNRgold = 1.37). CONCLUSIONS: SPCCT enables multicolour quantitative imaging. As a result, it should be possible to perform imaging of multiple uptake phases of a given tissue/organ within a single scan by injecting different contrast agents sequentially.

Evaluation of a preclinical photon-counting CT prototype for pulmonary imaging.

The purpose of this study was to investigate a preclinical spectral photon-counting CT (SPCCT) prototype compared to conventional CT for pulmonary imaging. A custom-made lung phantom, including nodules of different sizes and shapes, was scanned with a preclinical SPCCT and a conventional CT in standard and high-resolution (HR-CT) mode. Volume estimation was evaluated by linear regression. Shape similarity was evaluated with the Dice similarity coefficient. Spatial resolution was investigated via MTF for each imaging system. In-vivo rabbit lung images from the SPCCT system were subjectively reviewed. Evaluating the volume estimation, linear regression showed best results for the SPCCT compared to CT and HR-CT with a root mean squared error of 21.3 mm3, 28.5 mm3 and 26.4 mm3 for SPCCT, CT and HR-CT, respectively. The Dice similarity coefficient was superior for SPCCT throughout nodule shapes and all nodule sizes (mean, SPCCT: 0.90; CT: 0.85; HR-CT: 0.85). 10% MTF improved from 10.1 LP/cm for HR-CT to 21.7 LP/cm for SPCCT. Visual investigation of small pulmonary structures was superior for SPCCT in the animal study. In conclusion, the SPCCT prototype has the potential to improve the assessment of lung structures due to higher resolution compared to conventional CT.

On the influence of noise correlations in measurement data on basis image noise in dual-energylike x-ray imaging.

In conventional dual-energy systems, two transmission measurements with distinct spectral characteristics are performed. These measurements are used to obtain the line integrals of two basis material densities. Usually, the measurement process is such that the two measured signals can be treated as independent and therefore uncorrelated. Recently, however, a readout system for x-ray detectors has been introduced for which this is no longer the case. The readout electronics is designed to obtain simultaneous measurements of the total number of photons N and the total energy E they deposit in the sensor material. Practically, this is realized by a signal replication and separate counting and integrating processing units. Since the quantities N and E are (electronically) derived from one and the same physical sensor signal, they are statistically correlated. Nevertheless, the pair N and E can be used to perform a dual-energy processing following the well-known approach by Alvarez and Macovski. Formally, this means that N is to be identified with the first dual-energy measurement M1 and E with the second measurement M2. In the presence of input correlations between M1 = N and M2 = E, however, the corresponding analytic expressions for the basis image noise have to be modified. The main observation made in this paper is that for positively correlated data, as is the case for the simultaneous counting and integrating device mentioned above, the basis image noise is suppressed through the influence of the covariance between the two signals. We extend the previously published relations for the basis image noise to the case where the original measurements are not independent and illustrate the importance of the input correlations by comparing dual-energy basis image noise resulting from the device mentioned above and a device measuring the photon numbers and the deposited energies consecutively.

Multicolor spectral photon-counting computed tomography: in vivo dual contrast imaging with a high count rate scanner.

A new prototype spectral photon-counting computed tomography (SPCCT) based on a modified clinical CT system has been developed. SPCCT analysis of the energy composition of the transmitted x-ray spectrum potentially allows simultaneous dual contrast agent imaging, however, this has not yet been demonstrated with such a system. We investigated the feasibility of using this system to distinguish gold nanoparticles (AuNP) and an iodinated contrast agent. The contrast agents and calcium phosphate were imaged in phantoms. Conventional CT, gold K-edge, iodine and water images were produced and demonstrated accurate discrimination and quantification of gold and iodine concentrations in a phantom containing mixtures of the contrast agents. In vivo experiments were performed using New Zealand White rabbits at several times points after injections of AuNP and iodinated contrast agents. We found that the contrast material maps clearly differentiated the distributions of gold and iodine in the tissues allowing quantification of the contrast agents' concentrations, which matched their expected pharmacokinetics. Furthermore, rapid, repetitive scanning was done, which allowed measurement of contrast agent kinetics with high temporal resolution. In conclusion, a clinical scale, high count rate SPCCT system is able to discriminate gold and iodine contrast media in different organs in vivo.

Evaluation of spectral photon counting computed tomography K-edge imaging for determination of gold nanoparticle biodistribution in vivo.

Spectral photon counting computed tomography (SPCCT) is an emerging medical imaging technology. SPCCT scanners record the energy of incident photons, which allows specific detection of contrast agents due to measurement of their characteristic X-ray attenuation profiles. This approach is known as K-edge imaging. Nanoparticles formed from elements such as gold, bismuth or ytterbium have been reported as potential contrast agents for SPCCT imaging. Furthermore, gold nanoparticles have many applications in medicine, such as adjuvants for radiotherapy and photothermal ablation. In particular, longitudinal imaging of the biodistribution of nanoparticles would be highly attractive for their clinical translation. We therefore studied the capabilities of a novel SPCCT scanner to quantify the biodistribution of gold nanoparticles in vivo. PEGylated gold nanoparticles were used. Phantom imaging showed that concentrations measured on gold images correlated well with known concentrations (slope = 0.94, intercept = 0.18, RMSE = 0.18, R2 = 0.99). The SPCCT system allowed repetitive and quick acquisitions in vivo, and follow-up of changes in the AuNP biodistribution over time. Measurements performed on gold images correlated with the inductively coupled plasma-optical emission spectrometry (ICP-OES) measurements in the organs of interest (slope = 0.77, intercept = 0.47, RMSE = 0.72, R2 = 0.93). TEM results were in agreement with the imaging and ICP-OES in that much higher concentrations of AuNPs were observed in the liver, spleen, bone marrow and lymph nodes (mainly in macrophages). In conclusion, we found that SPCCT can be used for repetitive and non-invasive determination of the biodistribution of gold nanoparticles in vivo.

A Fourier approach to pulse pile-up in photon-counting x-ray detectors.

PURPOSE: An analytic Fourier approach to predict the expected number of counts registered in a photon-counting detector subject to pulse pile-up for arbitrary photon flux, detector response function, and pulse-shape is presented. The analysis provides a complete forward model for energy-sensitive, photon-counting x-ray detectors for spectral computed tomography. METHODS: The formalism of the stochastic theory of the expected frequency of level crossings of shot noise processes is applied to the pulse pile-up effect and build on a recently published analytic Fourier representation of the level crossing frequency of shot noise processes with piece-wise continuous kernels with jumps. RESULTS: The general analytic result is validated by a Monte Carlo simulation for pulses of the form g(t) = e(-t/τ) (t > 0) and a Gaussian detector response function. The Monte Carlo simulations are in excellent agreement with the analytic predictions of photon counts within the numerical accuracy of the calculations. CONCLUSIONS: The phenomenon of pulse pile-up is identified with the level-crossing problem of shot noise processes and an exact, analytic formula for the expected number of counts in energy-sensitive, photon-counting x-ray detectors for arbitrary photon flux, response function, and pulse-shapes is derived. The framework serves as a theoretical foundation for future works on pulse pile-up.

Slit-scanning differential x-ray phase-contrast mammography: proof-of-concept experimental studies.

PURPOSE: The purpose of this work is to investigate the feasibility of grating-based, differential phase-contrast, full-field digital mammography (FFDM) in terms of the requirements for field-of-view (FOV), mechanical stability, and scan time. METHODS: A rigid, actuator-free Talbot interferometric unit was designed and integrated into a state-of-the-art x-ray slit-scanning mammography system, namely, the Philips MicroDose L30 FFDM system. A dedicated phase-acquisition and phase retrieval method was developed and implemented that exploits the redundancy of the data acquisition inherent to the slit-scanning approach to image generation of the system. No modifications to the scan arm motion control were implemented. RESULTS: The authors achieve a FOV of 160 × 196 mm consisting of two disjoint areas measuring 77 × 196 mm with a gap of 6 mm between them. Typical scanning times vary between 10 and 15 s and dose levels are lower than typical FFDM doses for conventional scans with identical acquisition parameters due to the presence of the source-grating G0. Only minor to moderate artifacts are observed in the three reconstructed images, indicating that mechanical vibrations induced by other system components do not prevent the use of the platform for phase contrast imaging. CONCLUSIONS: To the best of our knowledge, this is the first attempt to integrate x-ray gratings hardware into a clinical mammography unit. The results demonstrate that a scanning differential phase contrast FFDM system that meets the requirements of FOV, stability, scan time, and dose can be build.

Quantitative spectral K-edge imaging in preclinical photon-counting x-ray computed tomography.

OBJECTIVES: The objective of this study was to investigate the feasibility and the accuracy of spectral computed tomography (spectral CT) to determine the tissue concentrations and localization of high-attenuation, iodine-based contrast agents in mice. Iodine tissue concentrations determined with spectral CT are compared with concentrations measured with single-photon emission computed tomography (SPECT) and inductively coupled plasma mass spectrometry (ICP-MS). MATERIALS AND METHODS: All animal procedures were performed according to the US National Institutes of Health principles of laboratory animal care and were approved by the ethical review committee of Maastricht, The Netherlands. Healthy Swiss mice (n = 4) were injected with an iodinated emulsion radiolabeled with indium as multimodal contrast agent for CT and SPECT. The CT and SPECT scans were acquired using a dedicated small-animal SPECT/CT system. Subsequently, scans were performed with a preclinical spectral CT scanner equipped with a photon-counting detector and 6 energy threshold levels. Quantitative data analysis of SPECT and spectral CT scans were obtained using 3-dimensional volumes-of-interest drawing methods. The ICP-MS on dissected organs was performed to determine iodine uptake per organ and was compared with the amounts determined from spectral CT and SPECT. RESULTS: Iodine concentrations obtained with image-processed spectral CT data correlated well with data obtained either with noninvasive SPECT imaging (slope = 0.96, r = 0.75) or with ICP-MS (slope = 0.99, r = 0.89) in tissue samples. CONCLUSIONS: This preclinical proof-of-concept study shows the in vivo quantification of iodine concentrations in tissues using spectral CT. Our multimodal imaging approach with spectral CT and SPECT using radiolabeled iodinated emulsions together with ICP-based quantification allows a direct comparison of all methods. Benchmarked against ICP-MS data, spectral CT in the present implementation shows a slight underestimation of organ iodine concentrations compared with SPECT but with a more narrow distribution. This slight deviation is most likely caused by experimental rather than technical issues.