K-edge Subtraction Imaging Research Articles

Material decomposition with a prototype photon-counting detector CT system: expanding a stoichiometric dual-energy CT method via energy bin optimization and K-edge imaging

Objective. Computed tomography (CT) has advanced since its inception, with breakthroughs such as dual-energy CT (DECT), which extracts additional information by acquiring two sets of data at different energies. As high-flux photon-counting detectors (PCDs) become available, PCD-CT is also becoming a reality. PCD-CT can acquire multi-energy data sets in a single scan by spectrally binning the incident x-ray beam. With this, K-edge imaging becomes possible, allowing high atomic number (high-Z) contrast materials to be distinguished and quantified. In this study, we demonstrated that DECT methods can be converted to PCD-CT systems by extending the method of Bourque et al (2014). We optimized the energy bins of the PCD for this purpose and expanded the capabilities by employing K-edge subtraction imaging to separate a high-atomic number contrast material. Approach. The method decomposes materials into their effective atomic number (Z eff) and electron density relative to water (ρ e ). The model was calibrated and evaluated using tissue-equivalent materials from the RMI Gammex electron density phantom with known ρ e values and elemental compositions. Theoretical Z eff values were found for the appropriate energy ranges using the elemental composition of the materials. Z eff varied slightly with energy but was considered a systematic error. An ex vivo bovine tissue sample was decomposed to evaluate the model further and was injected with gold chloride to demonstrate the separation of a K-edge contrast agent. Main results. The mean root mean squared percent errors on the extracted Z eff and ρ e for PCD-CT were 0.76% and 0.72%, respectively and 1.77% and 1.98% for DECT. The tissue types in the ex vivo bovine tissue sample were also correctly identified after decomposition. Additionally, gold chloride was separated from the ex vivo tissue sample with K-edge imaging. Significance. PCD-CT offers the ability to employ DECT material decomposition methods, along with providing additional capabilities such as K-edge imaging.

Effect of the local energy distribution of x-ray beams generated through inverse Compton scattering in dual-energy imaging applications.

X-ray sources based on the inverse Compton interaction between a laser and a relativistic electron beam are emerging as a promising compact alternative to synchrotron for the production of intense monochromatic and tunable radiation. The emission characteristics enable several innovative imaging techniques, including dual-energy K-edge subtraction (KES) imaging. The performance of these techniques is optimal in the case of perfectly monochromatic x-ray beams, and the implementation of KES was proven to be very effective with synchrotron radiation. Nonetheless, the features of inverse Compton scattering (ICS) sources make them good candidates for a more compact implementation of KES techniques. The energy and intensity distribution of the emitted radiation is related to the emission direction, which means different beam qualities in different spatial positions. In fact, as the polar angle increases, the average energy decreases, while the local energy bandwidth increases and the emission intensity decreases. The scope of this work is to describe the impact of the local energy distribution variations on KES imaging performance. By means of analytical simulations, the reconstructed signal, signal-to-noise ratio, and background contamination were evaluated as a function of the position of each detector pixel. The results show that KES imaging is possible with ICS x-ray beams, even if the image quality slightly degrades at the detector borders for a fixed collimation angle and, in general, as the beam divergence increases. Finally, an approach for the optimization of specific imaging tasks is proposed by considering the characteristics of a given source.

High resolution propagation-based lung imaging at clinically relevant X-ray dose levels

Absorption-based clinical computed tomography (CT) is the current imaging method of choice in the diagnosis of lung diseases. Many pulmonary diseases are affecting microscopic structures of the lung, such as terminal bronchi, alveolar spaces, sublobular blood vessels or the pulmonary interstitial tissue. As spatial resolution in CT is limited by the clinically acceptable applied X-ray dose, a comprehensive diagnosis of conditions such as interstitial lung disease, idiopathic pulmonary fibrosis or the characterization of small pulmonary nodules is limited and may require additional validation by invasive lung biopsies. Propagation-based imaging (PBI) is a phase sensitive X-ray imaging technique capable of reaching high spatial resolutions at relatively low applied radiation dose levels. In this publication, we present technical refinements of PBI for the characterization of different artificial lung pathologies, mimicking clinically relevant patterns in ventilated fresh porcine lungs in a human-scale chest phantom. The combination of a very large propagation distance of 10.7 m and a photon counting detector with 100,upmu hbox {m} pixel size enabled high resolution PBI CT with significantly improved dose efficiency, measured by thermoluminescence detectors. Image quality was directly compared with state-of-the-art clinical CT. PBI with increased propagation distance was found to provide improved image quality at the same or even lower X-ray dose levels than clinical CT. By combining PBI with iodine k-edge subtraction imaging we further demonstrate that, the high quality of the calculated iodine concentration maps might be a potential tool for the analysis of lung perfusion in great detail. Our results indicate PBI to be of great value for accurate diagnosis of lung disease in patients as it allows to depict pathological lesions non-invasively at high resolution in 3D. This will especially benefit patients at high risk of complications from invasive lung biopsies such as in the setting of suspected idiopathic pulmonary fibrosis (IPF).

Fractal dimension of pulmonary gas and blood distribution assessed by synchrotron K-edge subtraction imaging: effect of bronchoconstriction.

We analyzed the fractal dimension (Df) of lung gas and blood distribution imaged with synchrotron radiation K-edge subtraction (KES), in six anesthetized adult New Zealand White rabbits. KES imaging was performed in upright position during stable Xe gas (64% in O2) inhalation and iodine infusion (Iomeron, 350 mg/mL), respectively, at baseline and after induced bronchoconstriction by aerosolized methacholine (125 mg/mL, 90 s) and bronchodilator (salbutamol, 10 mg/mL, 90 s) inhalation, at two axial image levels. Lung Xe and iodine images were segmented, and maps of regional lung gas and blood fractions were computed. The Df of lung gas (DfXe) and blood (DfIodine) distribution was computed based on a log-log plot of variation coefficient as a function of region volume. DfXe decreased significantly during bronchoconstriction (P < 0.0001), and remained low after salbutamol. DfIodine depended on the axial image level (P < 0.0001), but did not change with bronchoconstriction. DfXe was significantly associated with arterial [Formula: see text] (R = 0.67, P = 0.002), and negatively associated with [Formula: see text] (R = -0.62, P = 0.006), respiratory resistance (R = -0.58, P = 0.011), and elastance (R = -0.55, P = 0.023). These data demonstrate the reduced Df of gas distribution during acute bronchoconstriction, and the association of this parameter with physiologically meaningful variables. This finding suggests a decreased complexity and space-filling properties of lung ventilation during bronchoconstriction, and could serve as a functional imaging biomarker in obstructive airway diseases.NEW & NOTEWORTHY Here, we used an energy-subtractive imaging technique to assess the fractal dimension (Df) of lung gas and blood distribution and the effect of acute bronchoconstriction. We found that Df of gas significantly decreases in bronchoconstriction. Conversely, Df of blood exhibits gravity-dependent changes only, and is not affected by acute bronchoconstriction. Our data show that the fractal dimension of lung gas detects the emergence of clustered rather than scattered loss of ventilatory units during bronchoconstriction.

Optimal parameters estimation for K-edge subtraction imaging using PixiRad-2/PixieIII photon counting detector on a conventional laboratory X-ray micro-tomograph.

Photon Counting Detectors (PCDs) open new opportunities in X-ray imaging. Pixie III is a PCD using simultaneously two energy thresholds. This enables to acquire images using two distinct energy bins in a single exposure and allows to perform K-Edge Subtraction (KES) imaging with laboratory sources. In that context, one has however to deal with an energy bin optimization: narrow energy bins lead to high KES signal at the expense of higher noise, while wider energy bins lead to poor KES signal but better statistics. This work presents a model that aims at finding the optimal energy thresholds and source voltage in order to retrieve the best Contrast to Noise Ratio (CNR) for a given sample. The model also optimizes the parameters for conventional absorption modality and compares both modalities. Since the input flux and the energy difference between the thresholds influence image noise, this is included in the model using phenomenological laws. The model is then compared to empirical optimization by experimental screening of the parameters using model materials composed of barium, iodine and water. Finally, it is explained how to model the influence of sample composition on the predicted CNR values.

Development and validation of a simulation tool for K-edge Subtraction imaging with polychromatic spectra and X-ray photon counting detectors

In K-Edge Subtraction (KES) imaging the K-edge of a high-Z contrast medium is used to generate a differential image in which, in principle, only the contrast agent is visible, suppressing any background. A possible approach to KES imaging is by using polychromatic spectra and spectral X-ray photon counting detectors (XPCD). In this paper we present the development and validation of a simulation tool for KES imaging with spectral XPCD. In addition an analytical formula, based on theoretical considerations, is derived, that further supports the simulation results. The validation is made on experimental data obtained with an X-ray tube, an iodine-based contrast agent, and Pixirad-1/Pixie-III detection system.

Imaging Regional Lung Structure and Function in Small Animals Using Synchrotron Radiation Phase-Contrast and K-Edge Subtraction Computed Tomography.

Synchrotron radiation offers unique properties of coherence, utilized in phase-contrast imaging, and high flux as well as a wide energy spectrum which allow the selection of very narrow energy bands of radiation, used in K-edge subtraction imaging (KES) imaging. These properties extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and to map regional lung ventilation, perfusion, inflammation, aerosol particle distribution and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. These techniques have proven to be very useful for revealing the regional differences in both lung structure and function which is crucial for better understanding of disease mechanisms as well as for evaluating treatment in small animal models of lung diseases. Here, synchrotron radiation imaging methods are described and examples of their application to the study of disease mechanisms in preclinical animal models are presented.

Numerical evaluation of high-energy, laser-Compton x-ray sources for contrast enhancement and dose reduction in clinical imaging via gadolinium-based K-edge subtraction.

Conventional x-ray sources for medical imaging utilize bremsstrahlung radiation. These sources generate large bandwidth (BW) x-ray spectra with large fractions of photons that impart a dose, but do not contribute to image production. X-ray sources based on laser-Compton scattering can have inherently small energy BWs and can be tuned to low dose-imparting energies, allowing them to take advantage of atomic K-edge contrast enhancement. This paper investigates the use of gadolinium-based K-edge subtraction imaging in the context of mammography using a laser-Compton source through simulations quantifying contrast and dose in such imaging systems as a function of laser-Compton source parameters. Our simulations indicate that a K-edge subtraction image generated with a 0.5% BW (FWHM) laser-Compton x-ray source can obtain an equal contrast to a bremsstrahlung image with only 3% of the dose.

Spectroscopic imaging at compact inverse Compton X-ray sources.

While K-edge subtraction (KES) imaging is a commonly applied technique at synchrotron sources, the application of this imaging method in clinical imaging is limited although results have shown its superiority to conventional clinical subtraction imaging. Over the past decades, compact synchrotron X-ray sources, based on inverse Compton scattering, have been developed to fill the gap between conventional X-ray tubes and synchrotron facilities. These so called inverse Compton sources (ICSs) provide a tunable, quasi-monochromatic X-ray beam in a laboratory setting with reduced spatial and financial requirements. This allows for the transfer of imaging techniques that have been limited to synchrotrons until now, like KES imaging, into a laboratory environment. This review article presents the first studies that have successfully performed KES at ICSs. These have shown that KES provides improved image quality in comparison to conventional X-ray imaging. The results indicate that medical imaging could benefit from monochromatic imaging and KES techniques. Currently, the clinical application of KES is limited by the low K-edge energy of available iodine contrast agents. However, several ICSs are under development or already in commissioning which will provide monochromatic X-ray beams with higher X-ray energies and will enable KES using high-Z elements as contrast media. With these developments, KES at an ICS has the ability to become an important tool in pre-clinical research and potentially advancing existing clinical imaging techniques.

Functional lung imaging with synchrotron radiation: Methods and preclinical applications.

Many lung disease processes are characterized by structural and functional heterogeneity that is not directly appreciable with traditional physiological measurements. Experimental methods and lung function modeling to study regional lung function are crucial for better understanding of disease mechanisms and for targeting treatment. Synchrotron radiation offers useful properties to this end: coherence, utilized in phase-contrast imaging, and high flux and a wide energy spectrum which allow the selection of very narrow energy bands of radiation, thus allowing imaging at very specific energies. K-edge subtraction imaging (KES) has thus been developed at synchrotrons for both human and small animal imaging. The unique properties of synchrotron radiation extend X-ray computed tomography (CT) capabilities to quantitatively assess lung morphology, and also to map regional lung ventilation, perfusion, inflammation and biomechanical properties, with microscopic spatial resolution. Four-dimensional imaging, allows the investigation of the dynamics of regional lung functional parameters simultaneously with structural deformation of the lung as a function of time. This review summarizes synchrotron radiation imaging methods and overviews examples of its application in the study of disease mechanisms in preclinical animal models, as well as the potential for clinical translation both through the knowledge gained using these techniques and transfer of imaging technology to laboratory X-ray sources.

X-ray Spectral Imaging Program: XSIP.

Spectral K-edge subtraction imaging and wide-field energy-dispersive X-ray absorption spectroscopy imaging are novel, related, synchrotron imaging techniques for element absorption contrast imaging and element speciation imaging, respectively. These two techniques serve different goals but share the same X-ray optics principles with a bent Laue type monochromator and the same data processing algorithms. As there is a growing interest to implement these novel techniques in synchrotron facilities, Python-based software has been developed to automate the data processing procedures for both techniques. In this paper, the concept of the essential data processing algorithms are explained, the workflow of the software is described, and the main features and some related utilities are introduced.

BriXS, a new X-ray inverse Compton source for medical applications.

MariX is a research infrastructure conceived for multi-disciplinary studies, based on a cutting-edge system of combined electron accelerators at the forefront of the world-wide scenario of X-ray sources. The generation of X-rays over a large photon energy range will be enabled by two unique X-ray sources: a Free Electron Laser and an inverse Compton source, called BriXS (Bright compact X-ray Source). The X-ray beam provided by BriXS is expected to have an average energy tunable in the range 20-180keV and intensities between 1011 and 1013 photon/s within a relative bandwidth ΔE/E=1-10%. These characteristics, together with a very small source size (~20μm) and a good transverse coherence, will enable a wide range of applications in the bio-medical field. An additional unique feature of BriXS will be the possibility to make a quick switch of the X-ray energy between two values for dual-energy and K-edge subtraction imaging. In this paper, the expected characteristics of BriXS will be presented, with a particular focus on the features of interest to its possible medical applications.

The versatile X-ray beamline of the Munich Compact Light Source: design, instrumentation and applications.

Inverse Compton scattering provides means to generate low-divergence partially coherent quasi-monochromatic, i.e. synchrotron-like, X-ray radiation on a laboratory scale. This enables the transfer of synchrotron techniques into university or industrial environments. Here, the Munich Compact Light Source is presented, which is such a compact synchrotron radiation facility based on an inverse Compton X-ray source (ICS). The recent improvements of the ICS are reported first and then the various experimental techniques which are most suited to the ICS installed at the Technical University of Munich are reviewed. For the latter, a multipurpose X-ray application beamline with two end-stations was designed. The beamline's design and geometry are presented in detail including the different set-ups as well as the available detector options. Application examples of the classes of experiments that can be performed are summarized afterwards. Among them are dynamic in vivo respiratory imaging, propagation-based phase-contrast imaging, grating-based phase-contrast imaging, X-ray microtomography, K-edge subtraction imaging and X-ray spectroscopy. Finally, plans to upgrade the beamline in order to enhance its capabilities are discussed.

Dynamic K-edge Subtraction Fluoroscopy at a Compact Inverse-Compton Synchrotron X-ray Source

X-ray fluoroscopy is a commonly applied diagnostic tool for morphological and functional evaluation of the intestine in clinical routine. Acquisition of repetitive X-ray images following oral or rectal application of iodine contrast agent visualizes the time dependent distribution of the contrast medium, and helps to detect for example leakages, tumors or functional disorders. However, movements of the intestine and air trapped inside usually prevent temporal subtraction imaging to be applied to fluoroscopy of the gastrointestinal tract. K-edge subtraction (KES) imaging would enable subtraction fluoroscopy because it allows for imaging of moving organs with little artefacts. Although KES imaging is a well established technique at synchrotron sources, this imaging method is not applied in clinical routine as it relies on brilliant synchrotron radiation. Recently emerging compact synchrotron X-ray sources could provide a quasi-monochromatic, high-flux X-ray beam and allow for the application of KES in a laboratory environment. Here, we present a filter-based dynamic KES approach at the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron X-ray source worldwide. Compared to conventional temporal subtraction X-ray radiography, our approach increases the contrast while reducing the generated image artefacts.

K-edge subtraction imaging for iodine and calcium separation at a compact synchrotron x-ray source.

Purpose: About one third of all deaths worldwide can be traced to some form of cardiovascular disease. The gold standard for the diagnosis and interventional treatment of blood vessels is digital subtraction angiography (DSA). An alternative to DSA is K-edge subtraction (KES) imaging, which has been shown to be advantageous for moving organs and for eliminating image artifacts caused by patient movement. As highly brilliant, monochromatic x-rays are required for this method, it has been limited to synchrotron facilities so far, restraining the applicability in the clinical routine. Over the past decades, compact synchrotron x-ray sources based on inverse Compton scattering have been evolving; these provide x-rays with sufficient brilliance and meet spatial and financial requirements for laboratory settings or university hospitals. Approach: We demonstrate a proof-of-principle KES imaging experiment using the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron x-ray source worldwide. A series of experiments were performed both on a phantom and an excised human carotid to demonstrate the ability of the proposed KES technique to separate the iodine contrast agent and calcifications. Results: It is shown that the proposed filter-based KES method allows for the iodine-contrast agent and calcium to be clearly separated, thereby providing x-ray images only showing one of the two materials. Conclusions: The results show that the quasimonochromatic spectrum of the MuCLS enables filter-based KES imaging and can become an important tool in preclinical research and possible future clinical diagnostics.

Single-shot K-edge subtraction x-ray discrete computed tomography with a polychromatic source and the Pixie-III detector

K-edge subtraction (KES) imaging is a technique able to map a specific element such as e.g. a contrast agent within the tissues, by exploiting the sharp rise of its absorption coefficient at the K-edge energy. Whereas mainly explored at synchrotron radiation sources, the energy discrimination properties of modern x-ray photon counting detectors (XPCDs) pave the way for an implementation of single-shot KES imaging with conventional polychromatic sources. In this work we present an x-ray CT imaging system based on the innovative Pixie-III detector and discrete reconstruction. The results reported here show that a reliable automatic localization of Barium (above a certain concentration) is possible with a few dozens of tomographic projections for a volume having an axial slice of 512 512 pixels. The final application is a routine high-fidelity 3D mapping of a specific element ready for further morphological quantification by means of x-ray CT with potential promising applications in vivo.

Determining elemental strontium distribution in rat bones treated with strontium ranelate and strontium citrate using 2D micro‐XRF and 3D dual energy K‐edge subtraction synchrotron imaging

Strontium‐based medications, such as strontium ranelate, have been suggested to have therapeutic effects in patients with osteoporosis. Strontium salts available off‐shelf in stores across North America are assumed to provide similar effects as strontium ranelate and thus should lead to similar distributions of elemental strontium incorporated in bone. The objective of this study was to compare the spatial distribution of strontium in animal bones following the administration of strontium ranelate and strontium citrate. Seventeen‐week‐old Sprague–Dawley rats were split into three groups over 10 weeks and given 625 mg/kg/day of strontium ranelate and 676 mg/kg/day of strontium citrate; the control group received no additional supplementary strontium. The humeri were collected from all animals, and strontium distribution was mapped using 2D micro‐XRF and 3D dual energy K‐edge subtraction (KES) imaging. 2D and 3D elemental mapping methods demonstrated that strontium delivered during treatment by both salts had the same spatial distribution. 3D elemental strontium maps of treated animal bones showed that strontium was largely observed in the trabecular regions under the epiphyseal (growth) plate. The thickness of the strontium layers in both the strontium ranelate and strontium citrate sample was not significantly different (p = .9201). 2D micro‐XRF and 3D dual‐energy KES images effectively elucidated the spatial distribution of elemental strontium in calcified tissue. These methods provide a novel approach to evaluating the potential efficacy of strontium supplements in the treatment of osteoporosis.

Wide field imaging energy dispersive X-ray absorption spectroscopy

A new energy dispersive X-ray absorption spectroscopy (EDXAS) method is presented for simultaneous wide-field imaging and transmission X-ray absorption spectroscopy (XAS) to enable rapid imaging and speciation of elements. Based on spectral K-Edge Subtraction imaging (sKES), a bent Laue imaging system diffracting in the vertical plane was developed on a bend magnet beamline for selenium speciation. The high flux and small vertical focus, forming a wide horizontal line beam for projection imaging and computed tomography applications, is achieved by precise matching of lattice plane orientation and crystal surface (asymmetry angle). The condition generating a small vertical focus for imaging also provides good energy dispersion. Details for achieving sufficient energy and spatial resolution are demonstrated for both full field imaging and computed tomography in quantifying selenium chemical species. While this system has lower sensitivity as it uses transmission and may lack the flux and spatial resolution of a dedicated focused beamline system, it has significant potential in rapid screening of heterogeneous biomedical or environmental systems to correlate metal speciation with function.

Contrast-enhanced spectral mammography with a compact synchrotron source.

For early breast cancer detection, mammography is nowadays the commonly used standard imaging approach, offering a valuable clinical tool for visualization of suspicious findings like microcalcifications and tumors within the breast. However, due to the superposition of anatomical structures, the sensitivity of mammography screening is limited. Within the last couple of years, the implementation of contrast-enhanced spectral mammography (CESM) based on K-edge subtraction (KES) imaging helped to improve the identification and classification of uncertain findings. In this study, we introduce another approach for CESM based on a two-material decomposition, with which we expect fundamental improvements compared to the clinical procedure. We demonstrate the potential of our proposed method using the quasi-monochromatic radiation of a compact synchrotron source—the Munich Compact Light Source (MuCLS)—and a modified mammographic accreditation phantom. For direct comparison with the clinical CESM approach, we also performed a standard dual-energy KES at the MuCLS, which outperformed the clinical CESM images in terms of contrast-to-noise ratio (CNR) and spatial resolution. However, the dual-energy-based two-material decomposition approach achieved even higher CNR values. Our experimental results with quasi-monochromatic radiation show a significant improvement of the image quality at lower mean glandular dose (MGD) than the clinical CESM. At the same time, our study indicates the great potential for the material-decomposition instead of clinically used KES to improve the quantitative outcome of CESM.

K-edge Subtraction Computed Tomography with a Compact Synchrotron X-ray Source

In clinical diagnosis, X-ray computed tomography (CT) is one of the most important imaging techniques. Yet, this method lacks the ability to differentiate similarly absorbing substances like commonly used iodine contrast agent and calcium which is typically seen in calcifications, kidney stones and bones. K-edge subtraction (KES) imaging can help distinguish these materials by subtracting two CT scans recorded at different X-ray energies. So far, this method mostly relies on monochromatic X-rays produced at large synchrotron facilities. Here, we present the first proof-of-principle experiment of a filter-based KES CT method performed at a compact synchrotron X-ray source based on inverse-Compton scattering, the Munich Compact Light Source (MuCLS). It is shown that iodine contrast agent and calcium can be clearly separated to provide CT volumes only showing one of the two materials. These results demonstrate that KES CT at a compact synchrotron source can become an important tool in pre-clinical research.