Compact Synchrotron X-ray Source Research Articles

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.

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.

A proof of principle experiment for microbeam radiation therapy at the Munich compact light source.

Microbeam radiation therapy (MRT), a preclinical form of spatially fractionated radiotherapy, uses an array of microbeams of hard synchrotron X-ray radiation. Recently, compact synchrotron X-ray sources got more attention as they provide essential prerequisites for the translation of MRT into clinics while overcoming the limited access to synchrotron facilities. At the Munich compact light source (MuCLS), one of these novel compact X-ray facilities, a proof of principle experiment was conducted applying MRT to a xenograft tumor mouse model. First, subcutaneous tumors derived from the established squamous carcinoma cell line FaDu were irradiated at a conventional X-ray tube using broadbeam geometry to determine a suitable dose range for the tumor growth delay. For irradiations at the MuCLS, FaDu tumors were irradiated with broadbeam and microbeam irradiation at integral doses of either 3Gy or 5Gy and tumor growth delay was measured. Microbeams had a width of 50µm and a center-to-center distance of 350µm with peak doses of either 21Gy or 35Gy. A dose rate of up to 5Gy/min was delivered to the tumor. Both doses and modalities delayed the tumor growth compared to a sham-irradiated tumor. The irradiated area and microbeam pattern were verified by staining of the DNA double-strand break marker γH2AX. This study demonstrates for the first time that MRT can be successfully performed in vivo at compact inverse Compton sources.

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.

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.

The Munich Compact Light Source: Flux Doubling and Source Position Stabilization At a Compact Inverse-Compton Synchrotron X-ray Source.

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Increased cell survival and cytogenetic integrity by spatial dose redistribution at a compact synchrotron X-ray source.

X-ray microbeam radiotherapy can potentially widen the therapeutic window due to a geometrical redistribution of the dose. However, high requirements on photon flux, beam collimation, and system stability restrict its application mainly to large-scale, cost-intensive synchrotron facilities. With a unique laser-based Compact Light Source using inverse Compton scattering, we investigated the translation of this promising radiotherapy technique to a machine of future clinical relevance. We performed in vitro colony-forming assays and chromosome aberration tests in normal tissue cells after microbeam irradiation compared to homogeneous irradiation at the same mean dose using 25 keV X-rays. The microplanar pattern was achieved with a tungsten slit array of 50 μm slit size and a spacing of 350 μm. Applying microbeams significantly increased cell survival for a mean dose above 2 Gy, which indicates fewer normal tissue complications. The observation of significantly less chromosome aberrations suggests a lower risk of second cancer development. Our findings provide valuable insight into the mechanisms of microbeam radiotherapy and prove its applicability at a compact synchrotron, which contributes to its future clinical translation.

Diagnosing and Mapping Pulmonary Emphysema on X-Ray Projection Images: Incremental Value of Grating-Based X-Ray Dark-Field Imaging

PurposeTo assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution.Materials and MethodsLungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology.ResultsTransmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology.ConclusionIn a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections.

Diagnosing and mapping pulmonary emphysema on X-ray projection images

To assess whether grating-based X-ray dark-field imaging can increase the sensitivity of X-ray projection images in the diagnosis of pulmonary emphysema and allow for a more accurate assessment of emphysema distribution. Lungs from three mice with pulmonary emphysema and three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Median signal intensities of transmission (T), dark-field (V) and a combined parameter (normalized scatter) were compared between emphysema and control group. To determine the diagnostic value of each parameter in differentiating between healthy and emphysematous lung tissue, a receiver-operating-characteristic (ROC) curve analysis was performed both on a per-pixel and a per-individual basis. Parametric maps of emphysema distribution were generated using transmission, dark-field and normalized scatter signal and correlated with histopathology. Transmission values relative to water were higher for emphysematous lungs than for control lungs (1.11 vs. 1.06, p<0.001). There was no difference in median dark-field signal intensities between both groups (0.66 vs. 0.66). Median normalized scatter was significantly lower in the emphysematous lungs compared to controls (4.9 vs. 10.8, p<0.001), and was the best parameter for differentiation of healthy vs. emphysematous lung tissue. In a per-pixel analysis, the area under the ROC curve (AUC) for the normalized scatter value was significantly higher than for transmission (0.86 vs. 0.78, p<0.001) and dark-field value (0.86 vs. 0.52, p<0.001) alone. Normalized scatter showed very high sensitivity for a wide range of specificity values (94% sensitivity at 75% specificity). Using the normalized scatter signal to display the regional distribution of emphysema provides color-coded parametric maps, which show the best correlation with histopathology. In a murine model, the complementary information provided by X-ray transmission and dark-field images adds incremental diagnostic value in detecting pulmonary emphysema and visualizing its regional distribution as compared to conventional X-ray projections.

Comparison of Contrast-to-Noise Ratios of Transmission and Dark-Field Signal in Grating-Based X-ray Imaging for Healthy Murine Lung Tissue

PurposeAn experimental comparison of the contrast-to-noise ratio (CNR) between transmission and dark-field signals in grating-based X-ray imaging for ex-vivo murine lung tissue. Materials and MethodsLungs from three healthy mice were imaged ex vivo using a laser-driven compact synchrotron X-ray source. Background noise of transmission and dark-field signal was quantified by measuring the standard deviation in a region of interest (ROI) placed in a homogeneous area outside the specimen. Image contrast was quantified by measuring the signal range in rectangular ROIs placed in central and peripheral lung parenchyma. The relative contrast gain (RCG) of dark-field over transmission images was calculated as CNRDF / CNRT. ResultsIn all images, there was a trend for contrast-to-noise ratios of dark-field images (CNRDF) to be higher than for transmission images (CNRT) for all ROIs (median 61 vs. 38, p=0.10), but the difference was statistically significant only for peripheral ROIs (61 vs. 32, p=0.03). Median RCG was >1 for all ROIs (1.84). RCG values were significantly smaller for central ROIs than for peripheral ROIs (1.34 vs. 2.43, p=0.03). ConclusionThe contrast-to-noise ratio of dark-field images compares more favorably to the contrast-to-noise ratio of transmission images for peripheral lung regions as compared to central regions. For any specific specimen, a calculation of the RCG allows comparing which X-ray modality (dark-field or transmission imaging) produces better contrast-to-noise characteristics in a well-defined ROI.

The HELIOS series of advanced, synchrotron based, X-ray sources

The compact synchrotron X-ray source, HELIOS built by Oxford Instruments, was commissioned at IBM's Advanced Lithography Facility at Fishkill New York in 1991. Key features and specifications for HELIOS are described, emphasising the unique features of this storage ring X-ray source. The performance of the first machine is outlined, based on almost two years'routine operation, identifying key factors such as output flux, beam lifetime and reliability. A description of the second HELIOS and enhancements to its performance is included

Performance of the IBM synchrotron X-ray source for lithography

The compact superconducting synchrotron X-ray source at the IBM Advanced Lithography Facility in East Fishkill, New York has been in service to customers since the start of 1992. Its availability during scheduled time is greater than 90%, with recent months frequently surpassing 95%. Data on the long-term behavior of the X-ray source properties and subsystem performance are now available. The full system continues to meet all specifications and even to surpass them in key areas. Measured electron beam properties such as beam size, short- and long-term positional stability, and beam lifetime are presented. Lifetimes greater than 20 hours for typical stored beams have significantly simplified operations and increased availability compared to projections. This paper also describes some unique features of this X-ray source and goes beyond a discussion of downtime to describe the efforts behind the scenes to maintain and operate it.

Early operating experience with the helios compact synchrotron x-ray source

The Helios compact synchrotron installed at IBM's Advanced Lithography Facility provides a unique opportunity to obtain compact synchrotron reliability data in an industrial environment. This paper presents data from the first eight months of user oriented operation of the machine. Running and uptime statistics are tabulated, as well as achieved performance parameters. Unscheduled downtime in the various subsystems is described.

Installation and early operating experience with the Helios compact synchrotron x-ray source

During 1991 the Oxford Instruments’ compact synchrotron x-ray source Helios was installed at IBM’s Advanced Lithography Facility, following factory tests in Oxford during 1990. The machine has met or exceeded all performance specifications at the East Fishkill site. Since January, 1992 it has been run routinely for lithography development work. Running and reliability statistics are being generated, and the results for the first five months are presented here.

High-energy lithography illumination by Oxford’s synchrotron: A compact superconducting synchrotron x-ray source

Successful results on a development scale have demonstrated the benefits of x-ray lithography for producing fine features with broad process latitude. This paper is concerned with design of an x-ray source appropriate for production scale utilization of this technology. General considerations of throughput required show that, regardless of type, the source must provide several kilowatts of continuous x-ray power. At present, only synchrotrons can achieve this level. Conventional synchrotrons are too large for installation in a wafer fabrication facility, but superconducting synchrotrons can be relatively compact. Oxford Instruments Ltd. are presently building high-energy lithography illumination by Oxford’s synchrotron (HELIOS), a compact superconducting synchrotron, for installation in the IBM Advanced Lithography Facility at East Fishkill, New York. HELIOS will produce over 8 kW of continuous x-ray power with a characteristic critical wavelength of 0.84 nm. The design and performance of HELIOS are described, together with a discussion of the design choices which lead to the key features of HELIOS.