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FEATURE ARTICLE X-RAY OPTICS DEVELOPMENT FOR BIOMEDICAL IMAGING APPLICATIONS AT THE CANADIAN LIGHT SOURCE BY DEAN CHAPMAN, NAZANIN SAMADI, MERCEDES MARTINSON, BASSEY BASSEY, SHEILA BOIRE, GEORGE BELEV AND TOMASZ WYSOKINSKI he synchrotron provides an excellent source of x-rays for a number of research applications spanning a number of basic and applied science research areas. The Biomedical Imaging and Therapy beamlines [1,2] at the Canadian Light Source (CLS) with associated laboratories form a research facility that provides high intensity X-ray beams for both imaging and therapy applications of a wide range of biomedical systems from mice to humans to horses. A diagram of the facility at the CLS is shown in Fig. 1. Access to high intensity, tunable X-radiation allows a number of synchrotron specific imaging methods to be applied to a number of biomedical systems and problems. Examples are a number of phase related imaging methods such as analyzer based imaging or diffraction enhanced imaging, in-line phase contrast imaging, Talbot or grating interferometry based imaging, coded aperture imaging and Shack-Hartmann imaging. Absorption based imaging methods include K-edge subtraction imaging and conventional absorption based imaging. T The synchrotron’s unique broad band spectrum, intensity and small source size make it an ideal environment for testing new approaches to imaging and imaging optics. It has been likened to an “X-ray wind tunnel” for testing new ideas and to simulate possible clinical or laboratory applications of methods that are developed or advanced at the synchrotron. The X-Ray Imaging Group at the University of Saskatchewan and the Canadian Light Source are working on a number of imaging optics and systems in support of the biomedical imaging program at the biomedical beamlines. The purpose is to assist in solving unique imaging problems and to ensure that the SUMMARY X-ray optical research and development at the biomedical beamline at the Canadian Light Source is providing new and better systems for imaging of biological systems. facility remains a world leader in biomedical applications of synchrotron radiation research. In this paper, we will discuss some of the activities of this group and specifically some of our advances that will provide new tools for biomedical imaging research. K-EDGE SUBTRACTION ‘SPECTRALKES’ FROM KES TO K-Edge Subtraction (KES)1 at the synchrotron was originally developed for imaging of the human coronary anatomy at the Stanford Synchrotron Radiation Laboratory by Robert Hofstadter, Nobel laureate in physics 1961, and Edward Rubenstein, a cardiologist from the Stanford School of Medicine. This method utilizes two crossing line X-ray beams which were prepared to be just above and below the iodine K-edge at 33.17 keV [36]. After passing the subject located at the crossover, the two line beams were detected in a dual line X-ray detector. A simple algorithm allowed an image of the projected amount of iodine and water to be determined. The original application only required a resolution of a few hundred microns for successful human vasculature imaging; however, most applications require a resolution of a few microns to visualize smaller systems in greater detail. Our goal for small animal vasculature and a gene expression imaging program was to achieve a resolution in the range of 10’s of microns. For this to be achieved a small focus of the beam needed to be developed in order to sample an appropriately small region of the subject. Bent Laue (transmission X-ray case of diffraction) crystals had been used for some time to prepare the imaging beams needed for the simultaneous above and below K-edge beams needed for living (and thus moving) systems. The focus size of these systems was typically a few hundred microns and is set by an interesting interplay between a geometric focus caused by the overall bend of the crystal and a single ray or polychromatic focus that each ray experiences in traversing the thickness of the crystal. The single 1. Also known as Digital Subtraction Imaging, K-Edge Dichromography, Synchrotron Radiation Dichromographic Imaging for simplicity we refer to this method as K-Edge Subtraction Imaging. LA PHYSIQUE AU Dean Chapman, Bdean.chapman@ usask.ca, Anatomy & Cell Biology, Nazanin Samadi, Division of Biomedical Engineering, Mercedes Martinson, Bmercedes.m@ usask.ca, Bassey Bassey, Bbassey.bassey@ usask.ca, Physics and Engineering Physics, and Sheila Boire, Mechanical Engineering, University of Saskatchewan, Saskatoon, SK, S7N 5E5 George Belev, Bgeorge.belev@ lightsource.ca, and Tomasz Wysokinski, BTomasz. wysokinski@ lightsource.ca, Canadian Light Source, Inc., Saskatoon, SK S7N 2V3 CANADA / Vol. 70, No. 1 ( 2014 ) + 19 X-RAY OPTICS DEVELOPMENT Fig. 1 FOR BIOMEDICAL IMAGING . . . (CHAPMAN Layout of the Biomedical Imaging and Therapy beamlines facility at the Canadian Light Source which is comprised of two beamlines (a bend magnet beamline and a superconducting wiggler sourced beamline). The bend magnet is used in POE-2 and the wiggler beamline in POE-2 and SOE-1. ray focus typically occurs before the geometric focus and thus diverges. The crossing of these diverged beams at the geometric focus gives the beam size at focus. Bent Laue crystals have been successfully used to micro-focus X-ray beams [7,8] and we adopted this method for preparing a beam for a small animal imaging system (Fig. 2) [9]. We bent a silicon (5,1,1) wafer to an approximate 3 m radius and utilized the [3,1,1] reflection for our system. We measured the focal line size at approximately 88 microns which is appropriate for our application; this can be made smaller by preparing a specific crystal plate to be bent. One interesting aspect of achieving a small focus is that the angular energy dispersion of the crystal is very good. Typically in a bent Laue system used for human imaging the K-edge of iodine is blurred approximately by 1/3 of the vertical size of the beam. Thus in these systems, fully 33% of the vertical beam size must be blocked to avoid edge crossing energies in the high and low energy beams. For the x-ray optic we have, the part of the beam that is involved in edge crossing is approximately 5% of the vertical beam size making blocking this part of a beam impractical. An advantage of using most of the beam is that the efficiency of the system is very high as most 20 + PHYSICS IN ET AL.) CANADA / VOL. 70, NO. 1 ( 2014 ) of the vertical profile of the beam is used and not blocked. This allows this optic to be very effectively used on a bend magnet beamline with good flux. A section of an image of the beam with an iodine filter is shown in Fig. 3. This is an image from the detector with an iodated filter placed in the beam for energy calibration purposes. The energy span of this image is approximately 500 eV which spatially corresponds to a vertical beam size of approximately 4 mm. Given the energy range covered and the spatially dispersed energies measured, a multiple energy algorithm [10] was implemented to extract composition information from the energies. This method fully accounts for the energy dependent shape of the absorption of materials. An example of the use of this system for imaging of iodated contrast material injected into the chest cavity of a mouse is shown in Fig. 4. Current research with this method is assessing methods of eliminating artifacts associated with the fact that the imaging beams are focused at the subject and that different energies take slighty different paths through the object. X-RAY OPTICS DEVELOPMENT Fig. 2 FOR BIOMEDICAL IMAGING . . . (CHAPMAN ET AL.) Schematic diagram of spectral-KES monochromator, object and detector. BENT LAUE BEAM EXPANDER One of the emerging areas of synchrotron biomedical research is full field dynamic imaging or movies that show how a system behaves physiologically. The biomedical beamline at the CLS could not be built with sufficient length to allow the beam size to expand beyond about 5 mm on the bend magnet beamline and 1cm on the insertion device beamline. We have begun a program to explore whether bent Laue optics could be used to vertically expand the imaging beam, effectively making the beamline appear to be at least 5 times longer. Bent Laue crystals behave somewhat like lenses, however, with the added complication of the need to satisfy the Bragg condition for the lattice planes used. A double crystal system was fabricated with two matched bent Laue crystals with appropriate bending radii and distances between them similar to the schematic shown in Fig. 5. As shown in the schematic, two bent Laue crystals are used to form the double crystal monochromator expander. The crystals are arranged such that the virtual focus of the first crystal becomes the source for the second crystal with an appropriate choice of bending radius. The virtual focus of the second crystal then becomes somewhat farther away depending on the radii and the crystal-crystal separation. Expansions beyond 5x have been achieved in preliminary experiments [11]. As an example, a portion of the beam from an expander system was used to acquire a computed tomography data set of a seed pod shown in Fig. 6. The imaging field was approximately 20 mm vertical 29 mm horizontal Fig. 3 Image of beam at detector with 30 mg/cm3 iodine solution. Image is a negative logarithm of a flat and dark field normalized image. Note the sharp transition in absorption at 33.17 keV corresponding to the K-edge of iodine. which corresponds to a beam whose vertical size is about 5 times larger than presently accessible using the BMIT bend magnet beamline. The imaging energy was 17.5 keV and (1,1,1) reflections were used for each crytal with a 19.5 degree asymmetry angle. The imaging flux (intensity per unit area) was approximately equivalent to that prepared by the double crystal monochromator utilizing Si (2,2,0) crystals at the same imaging energy. This level of flux is possible given greatly enhanced reflectivity width afforded by the bent crystal system. CONCLUSION A number of X-ray optical instrumentation programs are being pursued at the BMIT beamlines in support of the imaging LA PHYSIQUE AU CANADA / Vol. 70, No. 1 ( 2014 ) + 21 X-RAY OPTICS DEVELOPMENT Fig. 4 FOR BIOMEDICAL IMAGING . . . (CHAPMAN Example spectral-KES images of a mouse with iodated contrast material injected in the chest cavity. Figures a and c are water equivalent images with figures b and d iodine images. Figures c and d are projection images and figures a and b are computed tomography images. The computed tomography slices shown are taken near the location of the dashed line in the projection images. Fig. 6 Fig. 5 ET AL.) Double crystal bent Laue beam expander monochromator schematic. Two bent Laue crystals are used where the virtual focus of the first crystal becomes the effective source for the second larger bending radius crystal. The overall effect is to make the effective location of the second crystal’s virtual focus to be H/h times farther away than the real source. programs there. We have active projects in multiple energy imaging, variants of coded aperture imaging, Talbot interferometry imaging and a beam width doubling monochromator. Images of a seed pod. Figure a shows a projection image of the seed with a 20 29 mm field of view. Figure b shows the matching computed tomography sagittal section of the seed. All images were acquired at 17.5 keV. Normally such a large vertical acquisition would require 4 to 5 separate acquisition due to the limited vertical beam size (5 mm). These projects are directed to providing state of the art imaging systems and capabilities to the wide range of imaging programs. The two systems described here are in the process of being made more robust and implemented in the bend magent beamline. REFERENCES 1. T.W. Wysokinski, D. Chapman, G. Adams, M. Renier, P. Suortti and W. 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