6TH INTERNATIONAL CONFERENCE ON MEDICAL APPLICATIONS OF SYNCHROTRON RADIATION
1266(2010); http://dx.doi.org/10.1063/1.3478195View Description Hide Description
As a result of the enthusiastic support from the Australian biomedical, medical and clinical communities, the Australian Synchrotron is constructing a world‐class facility for medical research, the ‘Imaging and Medical Beamline’. The IMBL began phased commissioning in late 2008 and is scheduled to commence the first clinical research programs with patients in 2011. It will provide unrivalled x‐ray facilities for imaging and radiotherapy for a wide range of research applications in diseases, treatments and understanding of physiological processes. The main clinical research drivers are currently high resolution and sensitivity cardiac and breast imaging, cell tracking applied to regenerative and stem cell medicine and cancer therapies. The beam line has a maximum source to sample distance of 136 m and will deliver a 60 cm by 4 cm x‐ray beam1—monochromatic and white—to a three storey satellite building fully equipped for pre‐clinical and clinical research. Currently operating with a 1.4 Tesla multi‐pole wiggler, it will upgrade to a 4.2 Tesla device which requires the ability to handle up to 21 kW of x‐ray power at any point along the beam line. The applications envisaged for this facility include imaging thick objects encompassing materials, humans and animals. Imaging can be performed in the range 15–150 keV. Radiotherapy research typically requires energies between 30 and 120 keV, for both monochromatic and broad beam.
1266(2010); http://dx.doi.org/10.1063/1.3478187View Description Hide Description
A dedicated micro‐tomography beamline is proposed for the Australian Synchrotron. It will enable high‐resolution micro‐tomography with resolution below a micron and supporting phase‐contrast imaging modes. A key feature of the beamline will be high‐throughput/high‐speed operation enabling near real‐time micro‐tomography.
1266(2010); http://dx.doi.org/10.1063/1.3478189View Description Hide Description
This article illustrates the phase contrast instrumentation installed at the Tomographic Microscopy and Coherent Radiology beamline (TOMCAT) of the Swiss Light Source. Our experimental framework has been designed to extract phase information at spatial resolutions covering three orders of magnitude. For moderate (5–10 microns) resolutions we implemented a two‐gratings interferometer, operated at energies between 14 and 40 keV. For high resolution (1–5 microns) we obtain phase information thanks to a modified transport of intensity approach. For very high‐resolutions (0.1–0.5 microns) we developed a broadband hard X‐ray full‐field microscope operated in Zernike‐phase contrast.
1266(2010); http://dx.doi.org/10.1063/1.3478190View Description Hide Description
At the SYnchrotron Radiation for MEdical Physics (SYRMEP) beamline of Elettra Synchrotron Light Laboratory in Trieste (Italy), an extensive research program in bio‐medical imaging has been developed since 1997. The core program carried out by the SYRMEP collaboration concerns the use of Synchrotron Radiation (SR) for clinical mammography with the aim of improving the diagnostic performance of the conventional technique. The first protocol with patients, started in 2006 has been completed at the end of 2009 and the data analysis is now in progress.
Regarding applications different from clinical imaging, synchrotron X‐ray computed microtomography (micro‐CT) is the most used technique, both in absorption and phase contrast. A new software tool, Pore3D, has been developed to perform a quantitative morphological analysis on the reconstructed slices and to access textural information of the sample under study.
1266(2010); http://dx.doi.org/10.1063/1.3478191View Description Hide Description
A clinical mammography program is in progress at the medical beamline SYRMEP of the Italian synchrotron radiation laboratory ELETTRA in Trieste. A conventional screen‐film system is utilized as detector for the examinations on patients. For the next experimental step a digital detector has been designed taking into account the essential requirements for mammography such as high spatial and contrast resolution, high efficiency for low dose examinations and high speed for short acquisition time. A double‐layer prototype has already been tested in the frame of the PICASSO project. In addition, an analyzer crystal set‐up for Diffraction Enhanced Imaging (DEI) has been available for many years at the SYRMEP beamline. Applying the DEI technique several successful experiments have been carried out in biomedical imaging and in particular in‐vitro breast imaging utilizing commercially available detectors. Recently a system upgrade yielded a double‐crystal analyzer set‐up with improved stability and higher angular resolution. In this study the PICASSO detector has been utilized in combination with the new analyzer set‐up for imaging in‐vitro breast tissue samples. In order to test the potential of the combined system planar and tomographic images have been acquired and the first results are here presented.
1266(2010); http://dx.doi.org/10.1063/1.3478192View Description Hide Description
Physiological studies in small animals can be complicated, but the complexity is increased dramatically when performing live‐animal synchrotron X‐ray imaging studies. Our group has extensive experience in high‐resolution live‐animal imaging at the Japanese SPring‐8 synchrotron, primarily examining airways in two‐dimensions. These experiments normally image an area of at a pixel resolution of 0.45 μm and are performed with live, intact, anaesthetized mice.
There are unique challenges in this experimental setting. Importantly, experiments must be performed in an isolated imaging hutch not specifically designed for small‐animal imaging. This requires equipment adapted to remotely monitor animals, maintain their anesthesia, and deliver test substances while collecting images. The horizontal synchrotron X‐ray beam has a fixed location and orientation that limits experimental flexibility. The extremely high resolution makes locating anatomical regions‐of‐interest slow and can result in a high radiation dose, and at this level of magnification small animal movements produce motion‐artifacts that can render acquired images unusable. Here we describe our experimental techniques and how we have overcome several challenges involved in performing live mouse synchrotron imaging.
Experiments have tested different mouse strains, with hairless strains minimizing overlying skin and hair artifacts. Different anesthetics have also be trialed due to the limited choices available at SPring‐8. Tracheal‐intubation methods have been refined and controlled‐ventilation is now possible using a specialized small‐animal ventilator. With appropriate animal restraint and respiratory‐gating, motion‐artifacts have been minimized. The animal orientation (supine vs. head‐high) also appears to affect animal physiology, and can alter image quality. Our techniques and image quality at SPring‐8 have dramatically improved and in the near future we plan to translate this experience to the Imaging and Medical Beamline at the Australian Synchrotron.
Overcoming these challenges has permitted increasingly sophisticated imaging of animals with synchrotron X‐rays, and we expect a bright future for these techniques.
1266(2010); http://dx.doi.org/10.1063/1.3478193View Description Hide Description
An X‐ray velocimetry technique is described which provides three components of velocity measurement in three‐dimensional space. Current X‐ray velocimetry techniques, which use particle images taken at a single projection angle, are limited to two components of velocity measurement, and are unable to measure in three dimensions without a priori knowledge of the flow field. The proposed method uses multiple projection angles to overcome these limitations. The technique uses a least‐squares iterative scheme to tomographically reconstruct the three‐dimensional velocity field directly from two‐dimensional image pair cross‐correlations, without the need to reconstruct three‐dimensional particle images. Synchrotron experiments demonstrate the effectiveness of the technique for blood flow measurement in opaque vessels, with applications for the diagnosis and treatment of cardiovascular disease.
1266(2010); http://dx.doi.org/10.1063/1.3478194View Description Hide Description
Single‐shot in‐line phase‐contrast imaging with the Inverse Compton Scattering X‐ray source available at ATF (Accelerator Test Facility) at Brookhaven National Laboratory is experimentally demonstrated. Phase‐contrast images of polymer wires are obtained with a single X‐ray pulse whose time length is about 1 picosecond. The edge‐enhancement effect is clearly visible in the images and simulations show a quantitative agreement with experimental data. A phase‐retrieval step in the image processing leads to a accurate estimation of the projected thickness of our samples. Finally, a single‐shot image of a wasp is presented as an example of a biological sample.
1266(2010); http://dx.doi.org/10.1063/1.3478196View Description Hide Description
Differential phase‐contrast scanning x‐ray microscope/microtomography have been developed. A fast readout charge‐coupled device (CCD) camera coupled with a visible‐light conversion unit is used as a detector to record the transmitted intensity distribution of far‐field image for every pixel in a scan. Simultaneous absorption and phase‐contrast images are given from a single scan by image‐processing of the CCD frames. The system is constructed at BL20XU of SPring‐8, and its feasibility is demonstrated at the photon energy of 8 keV. A tantalum test chart is observed and its finest structure of 140 nm pitch pattern is clearly observed. Measured phase sensitivity is approximately λ/270. Some low‐Z element specimens are observed and obtained phase contrast image shows much higher sensitivity than that of absorption contrast.
1266(2010); http://dx.doi.org/10.1063/1.3478197View Description Hide Description
An x‐ray fast micro‐tomography system was developed at medical and imaging beamline BL20B2 in SPring‐8. We attempted a “continuous rotation method” whereby the sample keeps rotating in the beam during the measurement. The image acquisitions are synchronized with the trigger pulses branched from the stepper motor controller. An electron multiplier (EM)‐CCD camera (C9100‐02, 30 fps, 8 μm/pixel, Hamamatsu Photonics) and beam‐monitor AA40P (Hamamatsu Photonics) were used as an image detector. The effective pixel size of the detector was 4.9 μm/pixel and the spatial resolution was about 15 μm. The total measurement time for 900 projections has been reduced to 36 s. The reconstruction time was also reduced using GPGPU and SSD system. Using these techniques, preliminary experiment for 4‐D (time resolved 3‐D) micro‐imaging has also been performed.
1266(2010); http://dx.doi.org/10.1063/1.3478198View Description Hide Description
Recently there has been an increase in research activity into finding ways of marking cells in live animals for pre‐clinical trials. Development of certain drugs and other therapies crucially depend on tracking particular cells or cell types in living systems. Therefore cell marking techniques are required which will enable longitudinal studies, where individuals can be examined several times over the course of a therapy or study. The benefits of being able to study both disease and therapy progression in individuals, rather than cohorts are clear. The need for high contrast 3‐D imaging, without harming or altering the biological system requires a non‐invasive yet penetrating imaging technique. The technique will also have to provide an appropriate spatial and contrast resolution. X‐ray computed tomography offers rapid acquisition of 3‐D images and is set to become one of the principal imaging techniques in this area. Work by our group over the last few years has shown that marking cells with gold nano‐particles (GNP) is an effective means of visualising marked cells in‐vivo using x‐ray CT. Here we report the latest results from these studies. Synchrotron X‐ray CT images of brain lesions in rats taken using the SYRMEP facility at the Elettra synchrotron in 2009 have been compared with histological examination of the tissues. Some deductions are drawn about the visibility of the gold loaded cells in both light microscopy and x‐ray imaging.
1266(2010); http://dx.doi.org/10.1063/1.3478199View Description Hide Description
The structure of a whole eye of mouse was studied with an X‐ray Talbot grating interferometer. The distribution of crystallin concentration in the lens was quantitatively measured by X‐ray phase contrast tomography. A new technique to measure the crystallin concentration in the lens is proposed. By using the proposed method, the gradient of crystallin concentration in the lens was estimated. A ray‐trace of a mouse whole eye was performed with the refractive indices derived from the crystallin concentration.
1266(2010); http://dx.doi.org/10.1063/1.3478200View Description Hide Description
Angiogenesis is very important in tumor growth and metastasis. But in clinic, only vessels lager than 200 μm in diameter, can be observed using conventional medical imaging. Synchrotron radiation (SR) phase contrast imaging, whose spatial resolution can reach as high as 1 μm, has great advantages in imaging soft tissue structures, such as blood vessels and tumor tissues. In this paper, the morphology of newly formed micro‐vessels in the mouse 4T1 tumor samples was firstly studied with contrast agent. Then, the angiogenesis in nude mice tumor window model was observed without contrast agent using the SR phase contrast imaging at the beamline for X‐ray imaging and biomedical applications, Shanghai Synchrotron Radiation Facility (SSRF). The images of tumors showed dense, irregular and tortuous tumor micro‐vessels with the smallest size of 20–30 μm in diameter.
1266(2010); http://dx.doi.org/10.1063/1.3478201View Description Hide Description
Traditionally, there are no methods available to detect the fine morphologic changes of cerebrovasculature in small living animals such as rats and mice. Newly developed synchrotron radiation microangiography can achieve a fine resolution of several micrometers and had provided us with a powerful tool to study the cerebral vasculature in small animals. The purpose of this study is to identify the morphology of cerebrovasculature especially the structure of Lenticulostriate arteries (LSAs) in living mice using the synchrotron radiation source at Shanghai Synchrotron Radiation Facility (SSRF) in Shanghai, China. Adult CD‐1 mice weighing 35–40 grams were anesthetized. Nonionic iodine (Omnipaque, 350 mg I /mL) was used as a contrast agent. The study was performed at the BL13W1 beam line at SSRF. The beam line was derived from a storage ring of electrons with an accelerated energy of 3.5 GeV and an average beam current of 200 mA. X‐ray energy of 33.3 keV was used to produce the highest contrast image. Images were acquired every 172 ms by a x‐ray camera (Photonic‐Science VHR 1.38) with a resolution of 13 μm/pixel. The optimal dose of contrast agent is 100 μl per injection and the injecting rate is 33 μl/sec. The best position for imaging is to have the mouse lay on its right or left side, with ventral side facing the X‐ray source. We observed the lenticulostriate artery for the first time in living mice. Our result show that there are 4 to 5 lenticulostriate branches originating from the root of middle cerebral artery in each hemisphere. LSAs have an average diameter of There were no differences between LSAs from the left and right hemisphere (p<0.05). These results suggest that synchrotron radiation may provide a unique tool for experimental stroke research.
Identification Of Molecular Structures Of Normal And Pathological Human Breast Tissue Using Synchrotron Radiation1266(2010); http://dx.doi.org/10.1063/1.3478202View Description Hide Description
Scattering profiles of human breast tissues were measured by x‐ray diffraction using a synchrotron radiation source in order to identify their structural features at molecular level Several parameters were extracted from these scattering profiles and statistically assessed using discriminant analysis. From this analysis, only the ratio between the peak intensities at and at as well as the FWHM were statistically significant and allowed distinguishing the human breast tissues with high accuracy, mainly for benign samples where it was found values of sensitivity and specificity of 100%.
1266(2010); http://dx.doi.org/10.1063/1.3478203View Description Hide Description
Aim: To visualize and validate iron deposition in two cases of multiple sclerosis using rapid scanning X‐Ray Fluorescence (RS‐XRF) and Susceptibility Weighted Imaging (SWI). Material and Methods: Two (2) coronal cadaver brain slices from patients clinically diagnosed with multiple sclerosis underwent magnetic resonance imaging (MRI), specifically SWI to image iron content. To confirm the presence of iron deposits and the absence of zinc‐rich myelin in lesions, iron and zinc were mapped using RS‐XRF. Results: MS lesions were visualized using FLAIR and correlated with the absence of zinc by XRF. XRF and SWI showed that in the first MS case, there were large iron deposits proximal to the draining vein of the caudate nucleus as well as iron deposits associated with blood vessels throughout the globus pallidus. Less iron was seen in association with lesions than in the basal ganglia. The presence of larger amounts of iron correlated reasonably well between RS‐XRF and SWI. In the second case, the basal ganglia appeared normal and acute perivascular iron deposition was absent. Conclusion: Perivascular iron deposition is seen in some but not all MS cases, giving credence to the use of SWI to assess iron involvement in MS pathology in vivo.
Benefits of Synchrotron Microangiography for Dynamic Studies of Smooth Muscle and Endothelial Roles in the Pathophysiology of Vascular Disease1266(2010); http://dx.doi.org/10.1063/1.3478204View Description Hide Description
Changes in endothelial and smooth muscle function compromise organ perfusion in the chronic disease states of diabetes, atherosclerosis and hypertension. Moreover, vascular dysfunction increases the likelihood of lethal acute events such as myocardial infarction and stroke, which are now leading causes of adult mortality. Many circulating and local tissue factors in these disease states contribute to impaired vasomotor regulation of the arterial vessels, leading to spasm, chronic constriction and eventually vessel remodelling. X‐ray contrast absorption imaging allows assessment of vessel lumen diameter and the factors contributing to steady‐state vessel calibre, however, conventional clinical devices (>200 μm resolution) are not adequate to detect microvessels or accurately assess function in real time. Using synchrotron imaging we are now able to detect small vessel calibres (∼30 μm) and quantify regional differences in calibre even under conditions of high heart rate (>500 bpm). Herein we describe recent experiments that were conducted at the Japanese Synchrotron, SPring‐8 using anaesthetised Sprague‐Dawley rats and C57Bl/6 mice and a synchrotron radiation contrast angiography (single narrow energy bandwidth) approach based on selective arterial injection of iodine contrast agents. Application of this approach to imaging of the heart and other vasculatures are described. Our studies show that within‐animal comparisons of 3–4 branching orders of arterial vessels are possible using small bolus contrast injections and appropriate contrast washout times (15–30 min) in many organ systems. Determination of relative calibre changes before and after any treatment allows us to evaluate the contributions of different endogenous factors and ligand‐receptor pathways in the maintenance of vasomotor tone. Finally, we will present our findings relating to novel therapies to prevent endothelial dysfunction in heart failure.
1266(2010); http://dx.doi.org/10.1063/1.3478205View Description Hide Description
Microbeam Radiation Therapy (MRT) uses highly collimated, quasi‐parallel arrays of X‐ray microbeams of 50–600 keV, produced by 2nd and 3rd generation synchrotron sources, such as the National Synchrotron Light Source (NSLS) in the U.S., and the European Synchrotron Radiation Facility (ESRF) in France, respectively. High dose rates are necessary to deliver therapeutic doses in microscopic volumes, to avoid spreading of the microbeams by cardiosynchronous movement of the tissues. A small beam divergence and a filtered white beam spectrum in the energy range between 30 and 250 keV results in the advantage of steep dose gradients with a sharper penumbra than that produced in conventional radiotherapy. MRT research over the past 20 years has allowed a vast number of results from preclinical trials on different animal models, including mice, rats, piglets and rabbits. Microbeams in the range between 10 and 100 micron width show an unprecedented sparing of normal radiosensitive tissues as well as preferential damage to malignant tumor tissues. Typically, MRT uses arrays of narrow (∼25–100 micron‐wide) microplanar beams separated by wider (100–400 microns centre‐to‐centre, c‐t‐c) microplanar spaces. We note that thicker microbeams of 0.1–0.68 mm used by investigators at the NSLS are still called microbeams, although some invesigators in the community prefer to call them minibeams. This report, however, limits it discussion to 25–100 μm microbeams. Peak entrance doses of several hundreds of Gy are surprisingly well tolerated by normal tissues. High resolution dosimetry has been developed over the last two decades, but typical dose ranges are adapted to dose delivery in conventional Radiation Therapy (RT). Spatial resolution in the sub‐millimetric range has been achieved, which is currently required for quality assurance measurements in Gamma‐knife RT. Most typical commercially available detectors are not suitable for MRT applications at a dose rate of 16000 Gy/s, micron resolution and a dose range over several orders of magnitude. This paper will give an overview of all dosimeters tested in the past at the ESRF with their advantages and drawbacks. These detectors comprise: Ionization chambers, Alanine Dosimeters, MOSFET detectors, Gafchromic® films, Radiochromic polymers, TLDs, Polymer gels, Fluorescent Nuclear Track Detectors ( Mg single crystal detectors), OSL detectors and Floating Gate‐based dosimetry system. The aim of such a comparison shall help with a decision on which of these approaches is most suitable for high resolution dose measurements in MRT. The principle of these detectors will be presented including a comparison for some dosimeters exposed with the same irradiation geometry, namely a field size with microbeam exposures at the surface, 0.1 cm and 1 cm in depth of a PMMA phantom. For these test exposures, the most relevant irradiation parameters for future clinical trials have been chosen: 50 micron FWHM and 400 micron c‐t‐c distance. The experimental data are compared with Monte Carlo calculations.
1266(2010); http://dx.doi.org/10.1063/1.3478206View Description Hide Description
Monte Carlo based modelling of the dose distribution in the vicinity of concentrates of iodine (I) and gold (Au) binary radiotherapy agents has been performed for monochromatised synchrotron X‐rays. While the KERMA approximation, which ignores electron transport, is often acceptable for kilovoltage X‐ray dosimetry in X‐ray binary therapy, the range of photoelectrons and Auger electrons may be significant when compared to the microdostributed structure of the binary compound in which case corrections to the approximation may be necessary. Dose is calculated using EGSnrc for microdistributions associated with X‐ray radiation synovecotomy, where iodine is taken up in the synovial lining. Dose as a function of the volume of aggregation for an Au‐based contrast agent such as Au nanoparticles, ranging in diameter from 5 micron to 100 micron, were calculated using EGSnrc and Penelope, showing that the dose varies slowly for 90 keV X‐rays, where much of the dose delivered by short range photoelectrons while 80 keV X‐rays, just below the K‐edge of Au (80.729 keV) increases linearly with diameter. In general the dose varies slowly as a function of volume suggesting that only small corrections will be needed to account for effects due to the failure of electronic equilibrium.