[X-Ray Dark-field radiography: Does this carry potential for diagnosing gout in exotic pets?] / Die Dunkelfeld-Radiografie ­ ein neuer Weg zur Diagnostik von Gichterkrankungen bei Vögeln und Reptilien?

OBJECTIVE: The aim of this study is to evaluate whether X-ray dark-field (DF) radiography is useful for the diagnosis of gout in birds and reptiles and whether this preclinical model could be helpful to establish this non-invasive imaging method in human medicine. MATERIAL AND METHODS: A total of 18 limbs originating from 11 birds (7 different species) and 7 reptiles (4 different species) with and without suspected joint gout were measured using a grating-based X-ray dark-field setup and conventional X-ray examination, respectively. Each image acquisition generated a dark-field and a conventional absorption x-ray image. The results of the individual scans were compared with the results of a pathological examination and arthrocentesis. RESULTS: In 5 of the birds and 4 of the reptiles examined, gout was detected by pathologic examination. In each group, uric acid crystals were found in the joints of 3 animals by means of arthrocentesis. The uric acid crystals were detectable in 2 bird and 2 reptile limbs in the dark-field image. CONCLUSION: The study demonstrated that the urate crystals evoke a clearly visible dark field signal, whereas this was not the case in the conventional radiographs. CLINICAL RELEVANCE: The results obtained show that uric acid crystal detection using less invasive imaging methods in an animal model with birds and reptiles may expand gout diagnostics not only in veterinary medicine but also in human medicine and possibly replace arthrocentesis if a DF signal is detectable. Preclinical scanners which use X-ray dark-field and phase-contrast radiography already exist for hands and mammography.

X-ray dark-field radiography for in situ gout diagnosis by means of an ex vivo animal study.

Gout is the most common form of inflammatory arthritis, caused by the deposition of monosodium urate (MSU) crystals in peripheral joints and tissue. Detection of MSU crystals is essential for definitive diagnosis, however the gold standard is an invasive process which is rarely utilized. In fact, most patients are diagnosed or even misdiagnosed based on manifested clinical signs, as indicated by the unchanged premature mortality among gout patients over the past decade, although effective treatment is now available. An alternative, non-invasive approach for the detection of MSU crystals is X-ray dark-field radiography. In our work, we demonstrate that dark-field X-ray radiography can detect naturally developed gout in animals with high diagnostic sensitivity and specificity based on the in situ measurement of MSU crystals. With the results of this study as a potential basis for further research, we believe that X-ray dark-field radiography has the potential to substantially improve gout diagnostics.

Quantitative X-ray phase contrast computed tomography with grating interferometry : Biomedical applications of quantitative X-ray grating-based phase contrast computed tomography.

The ability of biomedical imaging data to be of quantitative nature is getting increasingly important with the ongoing developments in data science. In contrast to conventional attenuation-based X-ray imaging, grating-based phase contrast computed tomography (GBPC-CT) is a phase contrast micro-CT imaging technique that can provide high soft tissue contrast at high spatial resolution. While there is a variety of different phase contrast imaging techniques, GBPC-CT can be applied with laboratory X-ray sources and enables quantitative determination of electron density and effective atomic number. In this review article, we present quantitative GBPC-CT with the focus on biomedical applications.

Single spectrum three-material decomposition with grating-based x-ray phase-contrast CT.

Grating-based x-ray phase-contrast imaging provides three simultaneous image channels originating from a single image acquisition. While the phase signal provides direct access to the electron density in tomography, there is additional information on sub-resolutional structural information which is called dark-field signal in analogy to optical microscopy. The additional availability of the conventional attenuation image qualifies the method for implementation into existing diagnostic routines. The simultaneous access to the attenuation coefficient and the electron density allows for quantitative two-material discrimination as demonstrated lately for measurements at a quasi-monochromatic compact synchrotron source. Here, we investigate the transfer of the method to conventional polychromatic x-ray sources and the additional inclusion of the dark-field signal for three-material decomposition. We evaluate the future potential of grating-based x-ray phase-contrast CT for quantitative three-material discrimination for the specific case of early stroke diagnosis at conventional polychromatic x-ray sources. Compared to conventional CT, the method has the potential to discriminate coagulated blood directly from contrast agent extravasation within a single CT acquisition. Additionally, the dark-field information allows for the clear identification of hydroxyapatite clusters due to their micro-structure despite a similar attenuation as the applied contrast agent. This information on materials with sub-resolutional microstructures is considered to comprise advantages relevant for various pathologies.

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.

X-ray Dark-Field Radiography: Potential for Visualization of Monosodium Urate Deposition.

OBJECTIVE: The aim of this study was to evaluate the potential of x-ray dark-field radiography for the noninvasive detection of monosodium urate (MSU) crystals as a novel diagnostic tool for gout. MATERIALS AND METHODS: Contrast-to-noise ratios of MSU crystals in conventional radiography and dark-field radiography have been compared in a proof of principle measurement. Monosodium urate crystals have been injected into mouse legs in an ex vivo experimental gout setup. Three radiologists independently evaluated the images for the occurrence of crystal deposits in a blinded study for attenuation images only, dark-field images only, and with both images available for a comprehensive diagnosis. All imaging experiments have been performed at an experimental x-ray dark-field setup with a 3-grating interferometer, a rotating anode tube (50 kVp), and a photon-counting detector (effective pixel size, 166 µm). RESULTS: X-ray dark-field radiography provided a strong signal increase for MSU crystals in a physiological buffer solution compared with conventional attenuation radiography with a contrast-to-noise ratio increase from 0.8 to 19.3. Based on conventional attenuation images only, the reader study revealed insufficient diagnostic performance (sensitivity, 11%; specificity, 92%) with poor interrater agreement (Cohen's coefficient κ = 0.031). Based on dark-field images, the sensitivity increased to 100%, specificity remained at 92%, and the interrater agreement increased to κ = 0.904. Combined diagnosis based on both image modalities maximized both sensitivity and specificity to 100% with absolute interrater agreement (κ = 1.000). CONCLUSIONS: X-ray dark-field radiography enables the detection of MSU crystals in a mouse-based gout model. The simultaneous avaliability of a conventional attenuation image together with the dark-field image provides excellent detection rates of gout deposits with high specificity.

Publisher Correction: Direct quantitative material decomposition employing grating-based X-ray phase-contrast CT.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has not been fixed in the paper.

K-edge subtraction imaging for coronary angiography with a compact synchrotron X-ray source.

About one third of all deaths worldwide can be traced back to cardiovascular diseases. An interventional radiology procedure for their diagnosis 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 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 feasibility in clinical routine. Compact synchrotron X-ray sources based on inverse Compton scattering, which have been evolving substantially over the past decade, provide X-rays with sufficient brilliance that meet spatial and financial requirements affordable in laboratory settings or for university hospitals. In this work, we demonstrate a first proof-of-principle K-edge subtraction imaging experiment using the Munich Compact Light Source (MuCLS), the first user-dedicated installation of a compact synchrotron X-ray source worldwide. It is shown experimentally that the technique of KES increases the visibility of small blood vessels overlaid by bone structures.

Direct quantitative material decomposition employing grating-based X-ray phase-contrast CT.

Dual-energy CT has opened up a new level of quantitative X-ray imaging for many diagnostic applications. The energy dependence of the X-ray attenuation is the key to quantitative material decomposition of the volume under investigation. This material decomposition allows the calculation of virtual native images in contrast enhanced angiography, virtual monoenergetic images for beam-hardening artifact reduction and quantitative material maps, among others. These visualizations have been proven beneficial for various diagnostic questions. Here, we demonstrate a new method of 'virtual dual-energy CT' employing grating-based phase-contrast for quantitative material decomposition. Analogue to the measurement at two different energies, the applied phase-contrast measurement approach yields dual information in form of a phase-shift and an attenuation image. Based on these two image channels, all known dual-energy applications can be demonstrated with our technique. While still in a preclinical state, the method features the important advantages of direct access to the electron density via the phase image, simultaneous availability of the conventional attenuation image at the full energy spectrum and therefore inherently registered image channels. The transfer of this signal extraction approach to phase-contrast data multiplies the diagnostic information gained within a single CT acquisition. The method is demonstrated with a phantom consisting of exemplary solid and fluid materials as well as a chicken heart with an iodine filled tube simulating a vessel. For this first demonstration all measurements have been conducted at a compact laser-undulator synchrotron X-ray source with a tunable X-ray energy and a narrow spectral bandwidth, to validate the quantitativeness of the processing approach.

Spectral Angiography Material Decomposition Using an Empirical Forward Model and a Dictionary-Based Regularization.

By resolving the energy of the incident X-ray photons, spectral X-ray imaging with photon counting detectors offers additional material-specific information compared to conventional X-ray imaging. This additional information can be used to improve clinical diagnosis for various applications. However, spectral imaging still faces several challenges. Amplified noise and a reduced signal-to-noise ratio on the decomposed basis material images remain a major problem, especially for low-dose applications. Furthermore, it is challenging to construct an accurate model of the spectral measurement acquisition process. In this paper, we present a novel algorithm for projection-based material decomposition. It uses an empirical polynomial model that is tuned by calibration measurements. We combine this method with a statistical model of the measured photon counts and a dictionary-based joint regularization approach. We focused on spectral coronary angiography as a potential clinical application of projection-based material decomposition with photon counting detectors. Numerical and real experiments show that spectral angiography with realistic dose levels and gadolinium contrast agent concentrations are feasible using the proposed decomposition algorithm and currently available photon-counting detector technology.

Simultaneous wood and metal particle detection on dark-field radiography.

BACKGROUND: Currently, the detection of retained wood is a frequent but challenging task in emergency care. The purpose of this study is to demonstrate improved foreign-body detection with the novel approach of preclinical X-ray dark-field radiography. METHODS: At a preclinical dark-field x-ray radiography, setup resolution and sensitivity for simultaneous detection of wooden and metallic particles have been evaluated in a phantom study. A clinical setting has been simulated with a formalin fixated human hand where different typical foreign-body materials have been inserted. Signal-to-noise ratios (SNR) have been determined for all test objects. RESULTS: On the phantom, the SNR value for wood in the dark-field channel was strongly improved by a factor 6 compared to conventional radiography and even compared to the SNR of an aluminium structure of the same size in conventional radiography. Splinters of wood < 300 µm in diameter were clearly detected on the dark-field radiography. Dark-field radiography of the formalin-fixated human hand showed a clear signal for wooden particles that could not be identified on conventional radiography. CONCLUSIONS: x-ray dark-field radiography enables the simultaneous detection of wooden and metallic particles in the extremities. It has the potential to improve and simplify the current state-of-the-art foreign-body detection.

Joint Statistical Iterative Material Image Reconstruction for Spectral Computed Tomography Using a Semi-Empirical Forward Model.

By acquiring tomographic measurements with several distinct photon energy spectra, spectral computed tomography (spectral CT) is able to provide additional material-specific information compared with conventional CT. This information enables the generation of material selective images, which have found various applications in medical imaging. However, material decomposition typically leads to noise amplification and a degradation of the signal-to-noise ratio. This is still a fundamental problem of spectral CT, especially for low-dose medical applications. Inspired by the success for low-dose conventional CT, several statistical iterative reconstruction algorithms for spectral CT have been developed. These algorithms typically rely on detailed knowledge about the spectrum and the detector response. Obtaining this knowledge is often difficult in practice, especially if photon counting detectors are used to acquire the energy specific information. In this paper, a new algorithm for joint statistical iterative material image reconstruction is presented. It relies on a semi-empirical forward model which is tuned by calibration measurements. This strategy allows to model spatially varying properties of the imaging system without requiring detailed prior knowledge of the system parameters. We employ an efficient optimization algorithm based on separable surrogate functions to accelerate convergence and reduce the reconstruction time. Numerical as well as real experiments show that our new algorithm leads to reduced statistical bias and improved image quality compared with projection-based material decomposition followed by analytical or iterative image reconstruction.

Trabecular bone anisotropy imaging with a compact laser-undulator synchrotron x-ray source.

Conventional x-ray radiography is a well-established standard in diagnostic imaging of human bones. It reveals typical bony anatomy with a strong surrounding cortical bone and trabecular structure of the inner part. However, due to limited spatial resolution, x-ray radiography cannot provide information on the microstructure of the trabecular bone. Thus, microfractures without dislocation are often missed in initial radiographs, resulting in a lack or delay of adequate therapy. Here we show that x-ray vector radiography (XVR) can overcome this limitation and allows for a deeper insight into the microstructure with a radiation exposure comparable to standard radiography. XVR senses x-ray ultrasmall-angle scattering in addition to the attenuation contrast and thereby reveals the mean scattering strength, its degree of anisotropy and the orientation of scattering structures. Corresponding to the structural characteristics of bones, there is a homogenous mean scattering signal of the trabecular bone but the degree of anisotropy is strongly affected by variations in the trabecular structure providing more detailed information on the bone microstructure. The measurements were performed at the Munich Compact Light Source, a novel type of x-ray source based on inverse Compton scattering. This laboratory-sized source produces highly brilliant quasi-monochromatic x-rays with a tunable energy.

Mono-Energy Coronary Angiography with a Compact Synchrotron Source.

X-ray coronary angiography is an invaluable tool for the diagnosis of coronary artery disease. However, the use of iodine-based contrast media can be contraindicated for patients who present with chronic renal insufficiency or with severe iodine allergy. These patients could benefit from a reduced contrast agent concentration, possibly achieved through application of a mono-energetic x-ray beam. While large-scale synchrotrons are impractical for daily clinical use, the technology of compact synchrotron sources strongly advanced during the last decade. Here we present a quantitative analysis of the benefits a compact synchrotron source can offer in coronary angiography. Simulated projection data from quasi-mono-energetic and conventional x-ray tube spectra is used for a CNR comparison. Results show that compact synchrotron spectra would allow for a significant reduction of contrast media. Experimentally, we demonstrate the feasibility of coronary angiography at the Munich Compact Light Source, the first commercial installation of a compact synchrotron source.

Advanced Non-Destructive Ocular Visualization Methods by Improved X-Ray Imaging Techniques.

Due to limited X-ray contrast, the use of micro-CT in histology is so far not as widespread as predicted. While specific staining procedures-mostly using iodine-address this shortcoming, long diffusion times restrict its use in the often time-constrained daily routine. Recently, a novel staining protocol has been proposed using a biochemical preconditioning step, which increases the permeability of the cells for the staining agent. This could enable the imaging of entire organs of small mammals at a yet unmatched image quality with reasonable preparation and scan times. We here propose an adaptation of this technique for virtual ophthalmology and histology by volumetrically assessing both human and porcine eyes. Hereby, we demonstrate that (contrast-enhanced) micro-CT can outperform conventional histology in the assessment of tumor entities, as well as functioning as a supplementary tool for surgeons in the positioning of intraocular implants in-vitro and as a general assessment tool for ophthalmologic specimens.

Improved Diagnostics by Assessing the Micromorphology of Breast Calcifications via X-Ray Dark-Field Radiography.

Breast microcalcifications play an essential role in the detection and evaluation of early breast cancer in clinical diagnostics. However, in digital mammography, microcalcifications are merely graded with respect to their global appearance within the mammogram, while their interior microstructure remains spatially unresolved and therefore not considered in cancer risk stratification. In this article, we exploit the sub-pixel resolution sensitivity of X-ray dark-field contrast for clinical microcalcification assessment. We demonstrate that the micromorphology, rather than chemical composition of microcalcification clusters (as hypothesised by recent literature), determines their absorption and small-angle scattering characteristics. We show that a quantitative classification of the inherent microstructure as ultra-fine, fine, pleomorphic and coarse textured is possible. Insights underlying the micromorphological nature of breast calcifications are verified by comprehensive high-resolution micro-CT measurements. We test the determined microtexture of microcalcifications as an indicator for malignancy and demonstrate its potential to improve breast cancer diagnosis, by providing a non-invasive tool for sub-resolution microcalcification assessment. Our results indicate that dark-field imaging of microcalcifications may enhance the diagnostic validity of current microcalcification analysis and reduce the number of invasive procedures.

The Munich Compact Light Source: initial performance measures.

While large-scale synchrotron sources provide a highly brilliant monochromatic X-ray beam, these X-ray sources are expensive in terms of installation and maintenance, and require large amounts of space due to the size of storage rings for GeV electrons. On the other hand, laboratory X-ray tube sources can easily be implemented in laboratories or hospitals with comparatively little cost, but their performance features a lower brilliance and a polychromatic spectrum creates problems with beam hardening artifacts for imaging experiments. Over the last decade, compact synchrotron sources based on inverse Compton scattering have evolved as one of the most promising types of laboratory-scale X-ray sources: they provide a performance and brilliance that lie in between those of large-scale synchrotron sources and X-ray tube sources, with significantly reduced financial and spatial requirements. These sources produce X-rays through the collision of relativistic electrons with infrared laser photons. In this study, an analysis of the performance, such as X-ray flux, source size and spectra, of the first commercially sold compact light source, the Munich Compact Light Source, is presented.

Toward Clinically Compatible Phase-Contrast Mammography.

Phase-contrast mammography using laboratory X-ray sources is a promising approach to overcome the relatively low sensitivity and specificity of clinical, absorption-based screening. Current research is mostly centered on identifying potential diagnostic benefits arising from phase-contrast and dark-field mammography and benchmarking the latter with conventional state-of-the-art imaging methods. So far, little effort has been made to adjust this novel imaging technique to clinical needs. In this article, we address the key points for a successful implementation to a clinical routine in the near future and present the very first dose-compatible and rapid scan-time phase-contrast mammograms of both a freshly dissected, cancer-bearing mastectomy specimen and a mammographic accreditation phantom.

Non-invasive differentiation of kidney stone types using X-ray dark-field radiography.

Treatment of renal calculi is highly dependent on the chemical composition of the stone in question, which is difficult to determine using standard imaging techniques. The objective of this study is to evaluate the potential of scatter-sensitive X-ray dark-field radiography to differentiate between the most common types of kidney stones in clinical practice. Here, we examine the absorption-to-scattering ratio of 118 extracted kidney stones with a laboratory Talbot-Lau Interferometer. Depending on their chemical composition, microscopic growth structure and morphology the various types of kidney stones show strongly varying, partially opposite contrasts in absorption and dark-field imaging. By assessing the microscopic calculi morphology with high resolution micro-computed tomography measurements, we illustrate the dependence of dark-field signal strength on the respective stone type. Finally, we utilize X-ray dark-field radiography as a non-invasive, highly sensitive (100%) and specific (97%) tool for the differentiation of calcium oxalate, uric acid and mixed types of stones, while additionally improving the detectability of radio-lucent calculi. We prove clinical feasibility of the here proposed method by accurately classifying renal stones, embedded within a fresh pig kidney, using dose-compatible measurements and a quick and simple visual inspection.