Heiner Daerr

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

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.

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.

Clinical boundary conditions for grating-based differential phase-contrast mammography

Research in grating-based differential phase-contrast imaging (DPCI) has gained increasing momentum in the past couple of years. The first results on the potential clinical benefits of the technique for X-ray mammography are becoming available and indicate improvements in terms of general image quality, the delineation of lesions versus the background tissue and the visibility of microcalcifications. In this paper, we investigate some aspects related to the technical feasibility of DPCI for human X-ray mammography. After a short introduction to state-of-the-art full-field digital mammography in terms of technical aspects as well as clinical aspects, we put together boundary conditions for DPCI. We then discuss the implications for system design in a comparative manner for systems with two-dimensional detectors versus slit-scanning systems, stating advantages and disadvantages of the two designs. Finally, focusing on a slit-scanning system, we outline a possible concept for phase acquisition.

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.

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.

Combined effects of pulse pile-up and energy response in energy-resolved, photon-counting computed tomography

The very high x-ray flux rates employed in todays human computed tomography (CT) scanners in order to keep scanning times at a conveniently low level constitute the most challenging obstacle to the advent of clinical, photon-counting (spectral) CT. Even with most sophisticated, application-specific, energy-discriminating, photon-counting readout electronics, designed for room-temperature semi-conductor sensors like CdTe or CZT, the effects of spectral degradation due to pulse pile-up, i.e., count rate losses and gains will have to be taken into account in a clinical setting. The energy registered in a first-order pile-up event (superposition of two pulses) depends strongly on the energies of the two primaries involved, the difference in their arrival times and the spectral detector response behavior. We present an analytic model for the number of expected counts in binned photon-counting detectors, which is based on work by Wielopolski and Gardner and takes into account the combined effects of a spectral detector response function and 1st order pulse pile-up. The analytic model is validated by means of Monte-Carlo simulations and is applied to a simulation of a clinical spectral CT scenario in the context of K-edge imaging of a high-atomic number element as a contrast material. The artifacts in the reconstructed single-bin images and their manifestation in material-decomposed images are discussed and interpreted in terms of gains and losses of counts due to pile-up. Finally, we discuss the shortcomings of the model like the limitation to 1st order pile-up and the inherent restriction of the Wielopolski-Gardner model to peak pile-up.

Slit-scanning differential phase-contrast mammography: first experimental results

The demands for a large field-of-view (FOV) and the stringent requirements for a stable acquisition geometry rank among the major obstacles for the translation of grating-based, differential phase-contrast techniques from the laboratory to clinical applications. While for state-of-the-art Full-Field-Digital Mammography (FFDM) FOVs of 24 cm x 30 cm are common practice, the specifications for mechanical stability are naturally derived from the detector pixel size which ranges between 50 and 100 μm. However, in grating-based, phasecontrast imaging, the relative placement of the gratings in the interferometer must be guaranteed to within micro-meter precision. In this work we report on first experimental results on a phase-contrast x-ray imaging system based on the Philips MicroDose L30 mammography unit. With the proposed approach we achieve a FOV of about 65 mm x 175 mm by the use of the slit-scanning technique. The demand for mechanical stability on a micrometer scale was relaxed by the specific interferometer design, i.e., a rigid, actuator-free mount of the phase-grating G1 with respect to the analyzer-grating G2 onto a common steel frame. The image acquisition and formation processes are described and first phase-contrast images of a test object are presented. A brief discussion of the shortcomings of the current approach is given, including the level of remaining image artifacts and the relatively inefficient usage of the total available x-ray source output.

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

ObjectivesAfter 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.MethodsTo 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.ResultsIn 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.ConclusionSPCCT 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.

Simultaneous dual-contrast multi-phase liver imaging using spectral photon-counting computed tomography: a proof-of-concept study

BackgroundTo assess the feasibility of dual-contrast spectral photon-counting computed tomography (SPCCT) for liver imaging.MethodsWe present an SPCCT in-silico study for simultaneous mapping of the complementary distribution in the liver of two contrast agents (CAs) subsequently intravenously injected: a gadolinium-based contrast agent and an iodine-based contrast agent. Four types of simulated liver lesions with a characteristic arterial and portal venous pattern (haemangioma, hepatocellular carcinoma, cyst, and metastasis) are presented. A material decomposition was performed to reconstruct quantitative iodine and gadolinium maps. Finally, a multi-dimensional classification algorithm for automatic lesion detection is presented.ResultsOur simulations showed that with a single-scan SPCCT and an adapted contrast injection protocol, it was possible to reconstruct contrast-enhanced images of the liver with arterial distribution of the iodine-based CA and portal venous phase of the gadolinium-based CA. The characteristic patterns of contrast enhancement were visible in all liver lesions. The approach allowed for an automatic detection and classification of liver lesions using a multi-dimensional analysis.ConclusionsDual-contrast SPCCT should be able to visualise the characteristic arterial and portal venous enhancement with a single scan, allowing for an automatic lesion detection and characterisation, with a reduced radiation exposure.

Towards in-vivo K-edge imaging using a new semi-analytical calibration method

Flat field calibration methods are commonly used in computed tomography (CT) to correct for system imperfections. Unfortunately, they cannot be applied in energy-resolving CT when using bow-tie filters owing to spectral distortions imprinted by the filter. This work presents a novel semi-analytical calibration method for photon-counting spectral CT systems, which is applicable with a bow-tie filter in place and efficiently compensates pile-up effects at fourfold increased photon flux compared to a previously published method without degradation of image quality. The achieved reduction of the scan time enabled the first K-edge imaging in-vivo. The method employs a calibration measurement with a set of flat sheets of only a single absorber material and utilizes an analytical model to predict the expected photon counts, taking into account factors such as x-ray spectrum and detector response. From the ratios of the measured x-ray intensities and the corresponding simulated photon counts, a look-up table is generated. By use of this look-up table, measured photon-counts can be corrected yielding data in line with the analytical model. The corrected data show low pixel-to-pixel variations and pile-up effects are mitigated. Consequently, operations like material decomposition based on the same analytical model yield accurate results. The method was validated on a experimental spectral CT system equipped with a bow-tie filter in a phantom experiment and an in-vivo animal study. The level of artifacts in the resulting images is considerably lower than in images generated with a previously published method. First in-vivo K-edge images of a rabbit selectively depict vessel occlusion by an ytterbium-based thermoresponsive polymer.