We integrated fluorescent X-ray computed tomography (FXCT) and phase-contrast X-ray computed tomography (PCCT), and the feasibility of this fusion imaging was assessed for small animals. Brain tumor model of mouse and cardiomyopathic model of hamsters were examined. The brain and heart were extracted after intravenous injection of cerebral perfusion agent <sup>127</sup>I-IMP and myocardial fatty acid metabolic agent <sup>127</sup>I-BMIPP, respectively. Each target organ was fixed by formalin for FXCT and PCCT. Images were obtained three-dimensionally (3D), and the surface contour of brain and heart were determined from 3D-image after re-sampling for the description with the same spatial resolution. These images were fused interactively on displayed images by 3D image manipulation software. In FXCT, cerebral perfusion image with IMP and fatty acid metabolic image with BMIPP were clearly demonstrated at 0.5 mm and 0.2 mm spatial resolution, respectively. PCCT image with 0.03 mm spatial resolution depicted clearly the morphological structures of brain such as cerebral cortex, hippocampus, lateral ventricle and cerebellum, and for heart such as cardiac lumen, papillary muscle, left and right ventricle. On fusion image, localization and degree of abnormality of cerebral perfusion and myocardial fatty acid metabolism were easily recognized. Our results suggested that the integration of FXCT and PCCT is very useful to understand biological state corresponding to its anatomical localization even in small animal.
X-ray CT system with phase-contrast and fluorescent techniques are being developed for biomedical researches. We
have applied these techniques for in-vivo and ex-vivo imaging. The phase-contrast x-ray CT enables to reveal the
detailed morphological information of cancer lesion, and image quality of ex-vivo specimen was excellent comparing to
4.74T micro-MRI. Fluorescent x-ray CT could depict the functional information with high spatial resolution, and its
image quality was almost the same as autoradiogram. Improvement of imaging system with much high-speed data
acquisition will enable to use these techniques for new biomedical researches.
New synchrotron x-ray CT system with phase-contrast and fluorescent techniques are being developed for biomedical researches with the high-contrast and high-spatial resolution. We have applied these techniques for in-vivo and ex-vivo imaging. The phase-contrast x-ray CT (PCCT) was a highly sensitive imaging technique to depict the morphological information of the soft tissue in biological object, whereas fluorescent x-ray CT (FXCT) could depict the functional information concerning to specific heavy atomic number elements at very low content. Thus, the success of in-vivo imaging by PCCT and FXCT allows starting new approach to bio-imaging researches.
Micro-phase-contrast X-ray computed tomography with an X-ray interferometer (micro-phase-contrast CT) is in operation to obtain high spatial resolution images of less than 0.01 mm at the undulator beam-line 20XU of SPring-8, Japan, and we applied micro-phase-contrast CT to observe the organs of rats and hamsters. The excised kidney and spleen fixed by formalin were imaged. The fine inner-structures such as vessels, glomeruli of kidney and white and red pulps of spleen were visualized clearly about 0.01-mm spatial resolutions without using contrast agent or staining procedure. The results were very similar to those by optical microscopic images with 20-fold magnification. These results suggest that the micro-phase tomography might be a useful tool for various biomedical researches.
Fluorescent x-ray CT (FXCT) with synchrotron radiation (SR) is being developed to detect the very low concentration of specific elements. The endogenous iodine of the human thyroid and the non-radioactive iodine labeled BMIPP in myocardium were imaged by FXCT. FXCT system consists of a silicon (111) double crystal monochromator, an x-ray slit, a scanning table for object positioning, a fluorescent x-ray detector, and a transmission x-ray detector. Monochromatic x-ray with 37 keV energy was collimated into a pencil beam (from 1 mm to 0.025 mm). FXCT clearly imaged endogenous iodine of thyroid and iodine labeled BMIPP in myocardium, whereas transmission x-ray CT could not demonstrate iodine. The distribution of iodine was heterogeneous within thyroid cancer, and its concentration was lower than that of normal thyroid. Distribution of BMIPP in normal rat myocardium was almost homogeneous; however, reduced uptake was slightly shown in ischemic region. FXCT is a highly sensitive imaging modality to detect very low concentration of specific element and will be applied to reveal endogenous iodine distribution in thyroid and to use tracer study with various kinds of labeled material.
An image intensifier based computed tomography scanner and a tube source of x-rays are used to obtain the images of small objects, plastics, wood and soft materials in order to know the interior properties of the material. A new method is developed to estimate the degree of monochromacy, total solid angle, efficiency and geometrical effects of the measuring system and the way to produce monoenergetic radiation. The flux emitted by the x-ray tube is filtered using the appropriate filters at the chosen optimum energy and reasonable monochromacy is achieved and the images are acceptably distinct. Much attention has been focused on the imaging of small objects of weakly attenuating materials at optimum value. At optimum value it is possible to calculate the three-dimensional representation of inner and outer surfaces of the object. The image contrast between soft materials could be significantly enhanced by optimal selection of the energy of the x-rays by Monte Carlo methods. The imaging system is compact, reasonably economic, has a good contrast resolution, simple operation and routine availability and explores the use of optimizing tomography for various applications.
Compton scattering is a potential tool for the determination of bone mineral content or tissue density for dose planning purposes, and requires knowledge of the energy distribution of the X-rays through biological materials of medical interest in the X-ray and (gamma) -ray region. The energy distribution is utilized in a number of ways in diagnostic radiology, for example, in determining primary photon spectra, electron densities in separate volumes, and in tomography and imaging. The choice of the X-ray energy is more related to X-ray absorption, where as that of the scattering angle is more related to geometry. The evaluation of all the contributions are mandatory in Compton profile measurements and is important in X-ray imaging systems in order to achieve good results. In view of this, Compton profile cross-sections for few biological materials are estimated at nineteen K(alpha) X-ray energies and 60 keV (Am-241) photons. Energy broadening, geometrical broadening from 1 to 180 degree(s), FWHM of J(P<SUB>z</SUB>) and FWHM of Compton energy broadening has been evaluated at various incident photon energies. These values are estimated around the centroid of the Compton profile with an energy interval of 0.1 keV and 1.0 keV for 60 keV photons. The interaction cross sections for the above materials are estimated using fractions-by-weight of the constituent elements. Input data for these tables are purely theoretical.
Since synchrotron radiation (SR) has several excellent properties such as high brilliance, broad continuous energy spectrum and small divergence, we can obtain x-ray images with high contrast and high spatial resolution by using of SR. In 2D imaging using SR, air gap method is very effective to reduce the scatter contamination. However, to use air gap method, the geometrical effect of finite source size of SR must be considered because spatial resolution of image is degraded by air gap. For 2D x-ray imaging with SR, x-ray mammography was chosen to examine the effect of air gap method. We theoretically discussed the optimization of air gap distance suing effective scatter point source model proposed by Muntz, and executed experiment with a newly manufactured monochromator with asymmetrical reflection and an imaging plate.
Autoradiography is a useful imaging technique to understand biological functions using tracers including radio isotopes (RI's). However, it is not easy to describe the distribution of different kinds of tracers simultaneously by conventional autoradiography using X-ray film or Imaging plate. Each tracer describes each corresponding biological function. Therefore, if we can simultaneously estimate distribution of different kinds of tracer materials, the multispectral autoradiography must be a quite powerful tool to better understand physiological mechanisms of organs. So we are developing a system using a solid state detector (SSD) with high energy- resolution. Here, we introduce an imaging technique with a coded aperture to get spatial and spectral information more efficiently. In this paper, the imaging principle is described, and its validity and fundamental property are discussed by both simulation and phantom experiments with RI's such as <SUP>201</SUP>Tl, <SUP>99m</SUP>Tc, <SUP>67</SUP>Ga, and <SUP>123</SUP>I.
We are investigating possible medical applications of phase- contrast X-ray imaging using an X-ray interferometer. This paper introduces the strategy of the research project and the present status. The main subject is to broaden the observation area to enable in vivo observation. For this purpose, large X-ray interferometers were developed, and 2.5 cm X 1.5 cm interference patterns were generated using synchrotron X-rays. An improvement of the spatial resolution is also included in the project, and an X-ray interferometer designed for high-resolution phase-contrast X-ray imaging was fabricated and tested. In parallel with the instrumental developments, various soft tissues are observed by phase- contrast X-ray CT to find correspondence between the generated contrast and our histological knowledge. The observation done so far suggests that cancerous tissues are differentiated from normal tissues and that blood can produce phase contrast. Furthermore, this project includes exploring materials that modulate phase contrast for selective imaging.
We, a user group for medical applications of the SPring-8, have proposed the introduction of white X-rays from insertion devices to BMIC (BioMedical Imaging Center) for clinical uses so that enough photon fluxes to a subject is guaranteed. The photon flux, depending on various monochromatizing methods, was compared at the surface of the subject 200 m from a light source.
At aortic regurgitation state, 2D synchrotron radiation (SR) coronary arteriography (CAG) with aortographic contrast injection was examined theoretically and animal experiments were performed to confirm its diagnostic ability. This system consisted of a silicon monocrystal, fluorescent plate, avalanche-type pickup tube camera, and image acquisition system. The experiment was performed at synchrotron sources in the Photon Factory of Tsukuba. The x- ray energy was adjusted to just above the iodine K-edge. Theoretical calculation described that the coronary arteries overlapping on left ventricle could not be demonstrated well with a high signal-to-noise ratio by using the aortographic CAG with SR. The canine coronary arteries without overlap over the left ventricle were demonstrated clearly, however, the image quality appear to be reduced. The coronary artery overlapping over left ventricle could not be demonstrated well, however the transient reduction of left ventricular wall motion was revealed by transient stenotic procedure of left anterior descending coronary artery.
Fluorescent x-ray computed tomography (FXCT) is being developed to detect non-radioactive contrast materials in living specimens. The FXCT system consists of a silicon (111) channel cut monochromator, an x-ray slit and a collimator for fluorescent x ray detection, a scanning table for the target organ and an x-ray detector for fluorescent x-ray and transmission x-ray. To reduce Compton scattering overlapped on the fluorescent K(alpha) line, incident monochromatic x-ray was set at 37 keV. The FXCT clearly imaged a human thyroid gland and iodine content was estimated quantitatively. In a case of hyperthyroidism, the two-dimensional distribution of iodine content was not uniform, and thyroid cancer had a small amount of iodine. FXCT can be used to detect iodine within thyroid gland quantitatively and to delineate its distribution.
Recent development in phase-contrast X-ray computed tomography using an X-ray interferometer is reported. To observe larger samples than is possible with our previous X-ray interferometer, a large monolithic X-ray interferometer and a separated-type X-ray interferometer were studied. At the present time, 2.5 cm X 1.5 cm interference patterns have been generated with the X-ray interferometers using synchrotron X-rays. The large monolithic X-ray interferometer has produced interference fringes with 80% visibility, and has been used to measure various tissues. To produce images with higher spatial resolution, we fabricated another X-ray interferometer whose wafer was partially thinned by chemical etching. A preliminary test suggested that the spatial resolution has been improved.
Human tissues obtained from cancerous kidneys fixed in formalin were observed with phase-contrast X-ray computed tomography (CT) using 17.7-keV synchrotron X-rays. By measuring the distributions of the X-ray phase shift caused by samples using an X-ray interferometer, sectional images that map the distribution of the refractive index were reconstructed. Because of the high sensitivity of phase- contrast X-ray CT, a cancerous lesion was differentiated from normal tissue and a variety of other structures were revealed without the need for staining.
Fluorescent x-ray computed tomography (FXCT) is being developed to detect non-radioactive contrast materials in living specimens. The FXCT systems consists of a silicon channel cut monochromator, an x-ray slit and a collimator for detection, a scanning table for the target organ and an x-ray detector for fluorescent x-ray and transmission x-ray. To reduce Compton scattering overlapped on the K(alpha) line, incident monochromatic x-ray was set at 37 keV. At 37 keV Monte Carlo simulation showed almost complete separation between Compton scattering and the K(alpha) line. Actual experiments revealed small contamination of Compton scattering on the K(alpha) line. A clear FXCT image of a phantom was obtained. Using this system the minimal detectable dose of iodine was 30 ng in a volume of 1 mm<SUP>3</SUP>, and a linear relationship was demonstrated between photon counts of fluorescent x-rays and the concentration of iodine contrast material. The use of high incident x-ray energy allows an increase in the signal to noise ratio by reducing the Compton scattering on the K(alpha) line.
We have shown so far that 3D structures in biological sot tissues such as cancer can be revealed by phase-contrast x- ray computed tomography using an x-ray interferometer. As a next step, we aim at applications of this technique to in vivo observation, including radiographic applications. For this purpose, the size of view field is desired to be more than a few centimeters. Therefore, a larger x-ray interferometer should be used with x-rays of higher energy. We have evaluated the optimal x-ray energy from an aspect of does as a function of sample size. Moreover, desired spatial resolution to an image sensor is discussed as functions of x-ray energy and sample size, basing on a requirement in the analysis of interference fringes.
We describe a new system of fluorescent x-ray computed tomography applied to image nonradioactive contrast materials in vivo. The system operates on the basis of computed tomography (CT) of the first generation. The experiment was also simulated using the Monte Carlo method. The research was carried out at the BLNE-5A bending-magnet beam line of the Tristan Accumulation Ring in Kek, Japan. An acrylic cylindrical phantom containing five paraxial channels of 5 and 4 mm diameters was imaged. The channels were filled with a diluted iodine-based contrast material, with iodine concentrations of 2 mg/ml and 500 (mu) g/ml. Spectra obtained with the system's high purity germanium (HPGe) detector separated clearly the K<SUB>(alpha</SUB> ) and K<SUB>(beta</SUB> 1) x-ray fluorescent lines, and the Compton scattering. CT images were reconstructed from projections generated by integrating the counts in these spectral lines. The method had adequate sensitivity and detection power, as shown by the experiment and predicted by the simulations, to show the iodine content of the phantom channels, which corresponded to 1 and 4 (mu) g iodine content per pixel in the reconstructed images.
We have been developing phase-contrast x-ray computed tomography (CT) to make possible the observation of biological soft tissues without contrast enhancement. Phase-contrast x-ray CT requires for its input data the x-ray phase-shift distributions or phase-mapping images caused by an object. These were measured with newly developed fringe-scanning x-ray interferometry. Phase-mapping images at different projection directions were obtained by rotating the object in an x-ray interferometer, and were processed with a standard CT algorithm. A phase-contrast x-ray CT image of a nonstained cancerous tissue was obtained using 17.7 keV synchrotron x rays with 12 micrometer voxel size, although the size of the observation area was at most 5 mm. The cancerous lesions were readily distinguishable from normal tissues. Moreover, fine structures corresponding to cancerous degeneration and fibrous tissues were clearly depicted. It is estimated that the present system is sensitive down to a density deviation of 4 mg/cm<SUP>3</SUP>.
In this paper, we describe a 3D computed tomography (3D CT) using monochromatic x-rays generated by synchrotron radiation, which performs a direct reconstruction of 3D volume image of an object from its cone-beam projections. For the develpment of 3D CT, scanning orbit of x-ray source to obtain complete 3D information about an object and corresponding 3D image reconstruction algorithm are considered. Computer simulation studies demonstrate the validities of proposed scanning method and reconstruction algorithm. A prototype experimental system of 3D CT was constructed. Basic phantom examinations and specific material CT image by energy subtraction obtained in this experimental system are shown.
For the evaluation of cardiac morphology and cardiac dynamics from a time series of angiograms, reliable and precise extraction of coronary arteries in each image is the key technology. An algorithm to detect vessel contour with high reliability is developed using the characteristics of coronary artery motion. The movement of coronary arteries is relatively larger than that of background tissues, so we can get high contrast vessel contour by substraction between two time different spatially differentiated images. This spatiotemporal operation gives us better coronary artery detection in the presence of noise than other spatial operations by using accumulation of spatiotemporal subtraction images for the interval where the background movement is negligible. Detected coronary artery branches are described with blood vessel segment sequence for the right and left angiogram. These two vessel structures are compared and the correspondences found. Thus 3D coronary artery structure is determined and displayed on the CRT. The effectiveness is discussed on actual dynamical coronary angiogram compared with spatial operation on the time frozen single image. Our algorithm works satisfactorily in this example.