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.
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.
The complexity of lung diseases makes pre-clinical in vivo respiratory research in mouse lungs of great importance for a better understanding of physiology and therapeutic effects. Synchrotron-based imaging has been successfully applied to lung research studies, however longitudinal studies can be difficult to perform due to limited facility access. Laboratory-based x-ray sources, such as inverse Compton x-ray sources, remove this access limitation and open up new possibilities for pre-clinical small-animal lung research at high spatial and temporal resolution. The in vivo visualization of drug deposition in mouse lungs is of interest, particularly in longitudinal research, because the therapeutic outcome is not only dependent on the delivered dose of the drug, but also on the spatial distribution of the drug. An additional advantage of this approach, when compared to other imaging techniques, is that anatomic and dynamic information is collected simultaneously. Here we report the use of dynamic x-ray phase-contrast imaging to observe pulmonary drug delivery via liquid instillation, and by inhalation of micro-droplets. Different liquid volumes (4 l , 20 l , 50 l ) were tested and a range of localized and global distributions were observed with a temporal resolution of up to 1.5 fps. The in vivo imaging results were confirmed by ex vivo x-ray and fluorescence imaging. This ability to visualize pulmonary substance deposition in live small animals has provided a better understanding of the two key methods of delivery; instillation and nebulization.
We describe the first dynamic and the first in vivo X-ray imaging studies successfully performed at a laser-undulator-based compact synchrotron light source. The X-ray properties of this source enable time-sequence propagation-based X-ray phase-contrast imaging. We focus here on non-invasive imaging for respiratory treatment development and physiological understanding. In small animals, we capture the regional delivery of respiratory treatment, and two measures of respiratory health that can reveal the effectiveness of a treatment; lung motion and mucociliary clearance. The results demonstrate the ability of this set-up to perform laboratory-based dynamic imaging, specifically in small animal models, and with the possibility of longitudinal studies.
We demonstrate the applicability of propagation-based X-ray phase-contrast imaging at a laser-assisted compact light source with known phantoms and the lungs and airways of a mouse. The Munich Compact Light Source provides a quasi-monochromatic beam with partial spatial coherence, and high flux relative to other non-synchrotron sources (up to 1010 ph/s). In our study we observe significant edge-enhancement and quantitative phase-retrieval is successfully performed on the known phantom. Furthermore the images of a small animal show the potential for live bio-imaging research studies that capture biological function using short exposures.
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.
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.X-ray imaging is an invaluable diagnostic tool in clinical practice. While conventional x-ray tubes are well established and reliable in clinical x-ray imaging, their broad bremsstrahlung spectra impose a number of drawbacks with respect to image quality. The polychromatic spectrum can introduce beam hardening artifacts or impede the aim to optimize both the dose level and the image quality, as the x-ray energy cannot be tuned directly to the desired range. On the other hand, 3rd generation synchrotron sources offer highly brilliant and monochromatic x-ray beams, but their high spatial and financial demands make their clinical use impracticable. To close this performance gap, new types of x-ray sources have been investigated throughout the last decades. One possibility are compact light sources (CLS) based on inverse Compton scattering 1 , which provide a quasi-mono-energetic, tunable and partially coherent x-ray beam. The first commercially sold system has only recently been installed in Munich, Germany 2 .One of the clinical applications that could benefit significantly from a mono-energetic x-ray beam is coronary angiography, as it relies on contrast media application. A mono-energetic x-ray beam could thoroughly exploit the sudden increase of the absorption coefficient of a contrast medium at its K-edge.Coronary angiography is an invaluable tool for the diagnosis of coronary disease. Complications are frequently associated with the high amount of iodine-based contrast media that are injected during the catheterization procedure. Especially for patients presenting with pre-existing renal insufficiency, there is a high risk to suffer from renal failure due to nephrotoxic effects of iodine-based contrast agents, resulting in severe renal dysfunction and a high risk of subsequent dialysis treatment 3-6 . In addition, several patients show allergic reactions following iodine injection, with the life-threatening risk of anaphylaxis 6 . A high amount of iodine c...
Targeted delivery of nanomedicine/nanoparticles (NM/NPs) to the site of disease (e.g., the tumor or lung injury) is of vital importance for improved therapeutic efficacy. Multimodal imaging platforms provide powerful tools for monitoring delivery and tissue distribution of drugs and NM/NPs. This study introduces a preclinical imaging platform combining X-ray (two modes) and fluorescence imaging (three modes) techniques for timeresolved in vivo and spatially resolved ex vivo visualization of mouse lungs during pulmonary NP delivery. Liquid mixtures of iodine (contrast agent for X-ray) and/or (nano)particles (X-ray absorbing and/or fluorescent) are delivered to different regions of the lung via intratracheal instillation, nasal aspiration, and ventilator-assisted aerosol inhalation. It is demonstrated that in vivo propagation-based phase-contrast X-ray imaging elucidates the dynamic process of pulmonary NP delivery, while ex vivo fluorescence imaging (e.g., tissue-cleared light sheet fluorescence microscopy) reveals the quantitative 3D drug/particle distribution throughout the entire lung with cellular resolution. The novel and complementary information from this imaging platform unveils the dynamics and mechanisms of pulmonary NM/NP delivery and deposition for each of the delivery routes, which provides guidance on optimizing pulmonary delivery techniques and noveldesigned NM for targeting and efficacy.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.
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