One major goal of modern radiology is the improvement of image quality and subsequently the development of sophisticated radiographic methods which are capable of detecting low contrast and small size details in organic samples in particular in mammography where the requirements on contrast resolution and spatial resolution are extremely high. Significant improvements in image quality have been achieved by the SYRMEP (SYnchrotron Radiation for MEdical Physics) collaboration which has designed and built a beamline devoted to medical physics at the synchrotron radiation facility ELETTRA in Trieste (Italy). The detection system developed for digital mammography consists of a silicon pixel detector with a pixel size of 200 X 300 micrometers ² used in the `edge on' configuration in order to achieve a high conversion efficiency. The detector is equipped with a low noise VLSI amplifier chain; at present. Recently, a multilayer detector prototype has been implemented, consisting of a stack of three single silicon strip layers. This set-up provides a larger sensitive area and subsequently a reduction of the exposure time. Digital images of mammographic phantoms and of in vitro full breast tissue samples show a higher contrast resolution and lower absorbed dose when compared to conventional mammographic images. Besides, further promising studies have been initiated developing novel imaging methods based on the phase effects evidenced by the high degree of coherence of the SR source. At the SYRMEP beamline several experiments have been carried out in order to exploit the potentials of two different techniques, Phase Contrast and Diffraction Enhanced Imaging, respectively. Images showing better detail visibility and enhanced contrast were produced with dose lower or comparable to the conventional one.

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.

The most frequently occurring cancer in women is that of the breast where it accounts for almost 20% of all cancer deaths. The U.K. has the world's highest mortality rate from breast cancer with an increasing incidence of 25000 per annum. Characterizing the complex physiological and tissue changes that form the natural history of breast cancer is clearly important for understanding associated biological mechanisms and for diagnosis. We report the initial findings of a diffraction study of breast tissue collagen that we believe may be due to tumor genesis. Small angle, synchrotron X-ray scattering has enabled us to examine `core cut' biopsy specimens and characterize their collagen architecture. We present data that demonstrates possible structural differences between tumor and normal tissue. We discuss the implications of these findings in the context of using molecular structure characteristics as new and novel markers of disease progression.

Monochromatic x-ray CT has several advantages over conventional CT, which utilizes bremsstrahlung white x-rays from an x-ray tube. Although various types of monochromatic x-ray CT systems using synchrotron radiation have been developed using a parallel x-ray beam for imaging of small samples with a high spatial resolution, imaging of large objects such as the human body have not been developed yet. We have developed a fan-beam monochromatic x-ray CT using fluorescent x-rays generated by irradiating metal targets by synchrotron radiation. A CdTe linear array detector of 512 mm sensitive width was used in the photon counting mode. We made phantom experiments using fluorescent x-rays ranging from 32 to 75 keV. Monochromatic x-ray CT images of a cylindrical lucite phantom filled with several contrast media have been obtained. Measured CT numbers are compared with linear attenuation coefficients, and they showed a good linearity over a wide range of contrast media concentrations.

The existence of an optimal energy range for mammography has been demonstrated by several authors. Improvement in image contrast and reduction of patient dose can be achieved using narrow energy band X ray beams in the 16 - 24 keV range. Quasi-monochromatic X rays in the mammographic energy range have been produced via Bragg diffraction by making use of a conventional W-anode, Be-window X ray tube and a monochromator optical system based on a set of mosaic crystals. The mosaic crystals are high oriented pyrolytic graphite (002) which provide an interesting choice for monochromators because of their high integrated reflectivity compared to perfect crystals. The monochromator optical system consists of an array of ten crystals (2.8 X 6.0 cm² of size) which are assembled so as to produce in the image plane an irradiation field obtained with adjacent reflected beams. A scanning technique of the optical system has been applied in order to remove the spatial non- uniformities of the entire irradiation field. The source has been characterized in terms of beam size and monochromaticity, photon flux and exposure rate, field uniformity, capability in low contrast detection, dose reduction, and spatial resolution properties. The system provides a large field (10.5 X 12.0 cm²) of quasi- monochromatic X rays ((Delta) E/E equals 12%) at the energy of 18 keV. The spatial resolution capabilities of the sources are affected by the introduction of an active optical element such as a mosaic crystal monochromator. They may be optimized by choosing the proper irradiation geometry. The mean glandular dose delivered to the standard breast by the quasi-monochromatic source is about a half of those delivered by the conventional mammography units.

Gaseous detectors are excellent candidates for x-ray imaging devices which are suitable in the energy range between 5 and 90 kV. Especially the extreme low inherent noise floor which in principle is limited by the read out electronics only in combination with the high flexibility in the choice of gases and the geometry result in high detective quantum efficiency values (DQE). A DQE close to one is valuable especially in medical imaging applications where in general the image quality is dose limited. Moreover, recent developments in gas amplification structures such as the Micro-CAT allow fast imaging with a single photon precision also for integrating devices resulting in high DQE values even for low photon flux applications.

A dedicated to nuclear cardiology mobile camera based on a detection matrix 15 X 15 cm of 2304 CdTe detector elements 2.83 X 2.83X 2 mm has been developed by an European Community support including Academic and Industrial Centers. The decision was taken to use CdTe since the maker (Eurorad-F) has a great experience in order to produce high grade, good homogeneity, stability and transport properties of hole twice greater than CdZnTe.

A medical imaging system providing both x-ray transmission and radionuclide measurements would allow correlation of structural and functional information. We therefore are evaluating a pixellated CdZnTe detector for combined x-ray CT and SPECT imaging with various readout electronics. Gamma-ray spectra of ⁵⁷Co measured using NIM electronics (2-microsecond(s) shaping time) and multichannel fast photon-counting electronics (50-ns shaping time) produced energy resolutions of 6.5 keV FWHM and 17 keV FWHM respectively at 122 keV. Fast photon-counting electronics achieved linear x-ray count-rate response up to 4 X 10⁵ cps. Dual-mode digital readout electronics are described, which promise to improve SPECT and x-ray CT performance in comparison to the fast-counting electronics. The leakage current and x-ray response with the dual-mode electronics are studied. The leakage current as small as tens of pA is measured, while detector current over 5 orders of magnitude is measured with linearity over 4 orders of magnitude. Results suggest that the CdZnTe detector is capable of performing both x-ray CT and SPECT with the fast photon-counting electronics, and the digital readout electronics can improve the x-ray CT performance.

A hand-size probe including 64 elementary 5 X 5 X 2 mm CdTe detectors has been optimized to detect the (gamma) tracer ⁹⁹Tc in the heart left ventricle. The system, has been developed, not for imaging, allowing acquisitions at 33 Hz to describe the labeled blood volume variations. The (gamma) -counts variations were found accurately proportional to the known volume variations of an artificial ventricle paced at variable rate and systolic volume. Softwares for on line data monitoring and for post-processing have been developed for beat to beat assessment of cardiac performance at rest and during physical exercise. The evaluation of this probe has been performed on 5 subjects in the Nucl Dep of Balatonfured Cardiology Hospital. It appears that the probe needs to be better shielded to work properly in the hot environment of the ventricle, but can provide reliable ventriculography, even under heavy exercise load, although the ventricle volume itself is unknown.

A probe system has been designed for the accurate location of areas of increased radionuclide uptake. Different type of applications are possible i.e. when precise position or even identification of the radionuclide is needed, like in wound investigation. In this paper, we restrict ourself to a system incorporating two probes, for the identification of `hot' lymph nodes, close to the surface of the body. Axillary lymph node involvement is a major prognostic indicator and treatment planning factor in both melanoma and breast cancer. However, sentinel node localization is relatively difficult often due to close proximity of the primary tumor. The developed instrument has a very sensitive detector, with good spatial resolution, able to discriminate between primary and scattered radiations.

In this paper, characterization of new, planar silicon avalanche photodiode arrays for high-resolution PET applications is discussed. High gain, monolithic 4 X 4 element APD arrays (2 mm pixels) have been fabricated using planar processes. These devices were characterized by measuring their gain (> 10³), quantum efficiency (60% at LSO emission) and noise (200 eV FWHM). Energy and timing resolution of these APDs were also measured by coupling them to LSO scintillators (2 X 2 X 10 mm) and were found to be 12% and 4 ns, respectively. An APD array was also coupled to a matching LSO array and successful experiments were conducted to identify the crystal which scintillated. Finally, initial experiments to measure depth of interaction have also been performed.

The Scanning-Beam Digital X-ray (SBDX) system promises low- dose cardiac fluoroscopy and angiography with excellent image quality. The system demands a detector capable of high count rates and excellent detection efficiency. Cadmium zinc telluride (CdZnTe) is well suited to these requirements. The SBDX detector comprises sixteen 3-mm-thick, 13.5 mm X 13.5 mm tiles arranged in a 4 X 4 array. Each tile has 144 imaging elements. Thus, the entire detector measures 54.0 mm X 54.0 mm and includes 2,304 imaging elements on a 1.125 mm pitch. Because the SBDX system has a geometric magnification of 3.3, the imaging-element size is consistent with a system spatial-resolution of 2.2 lp/mm. The 3-mm thickness is chosen to guarantee a stopping efficiency of more than 90% at 120 kVp. Each detector tile is flip-chip mounted to a custom-designed integrated circuit using indium bump bonding techniques. Fabricated in a 1.2-micrometers CMOS process, the IC includes high-speed photon-counting circuitry that operates at rates up to 5 X 10⁶ counts/s(DOT)mm². The circuitry is designed both to maximize the achievable count-rate and to minimize false double counts due to charge sharing between elements. Testing confirms that the detector performs with minimum cross talk between elements at count rates in excess of 2 X 10⁶ counts/s(DOT)mm². Measurements of the detective quantum efficiency are presented. The relationship between material properties and detector performance is also discussed.

X-ray cameras in which a CCD is lens coupled to a large phosphor screen are known to suffer from a loss of x-ray signal due to poor light collection from conventional phosphors, making them unsuitable for most medical imaging applications. By replacing the standard phosphor with a solid-state image intensifier, it may be possible to improve the signal-to-noise ratio of the images produced with these cameras. The solid-state x-ray image intensifier is a multi- layer device in which a photoconductor layer controls the light output from an electroluminescent phosphor layer. While prototype devices have been used for direct viewing and video imaging, they are only now being evaluated in a digital imaging system. In the present work, the preparation and evaluation of intensifiers with a 65 mm square format are described. The intensifiers are prepared by screen- printing or doctor blading the following layers onto an ITO coated glass substrate: ZnS phosphor, opaque layer, CdS photoconductor, and carbon conductor. The total thickness of the layers is approximately 350 micrometers , 350 VAC at 400 Hz is applied to the device for operation. For a given x-ray dose, the intensifiers produce up to three times the intensity (after background subtracting) of Lanex Fast Front screens. X-ray images produced with the present intensifiers are somewhat noisy and their resolution is about half that of Lanex screens. Modifications are suggested which could improve the resolution and noise of the intensifiers.

Amorphous silicon (a-Si:H) matrix-addressed imager sensors are the leading new technology for digital medical x-ray imaging. Large-area systems are now commercially available with good resolution and large dynamic range. These systems image x-rays either by detecting light emission from a phosphor screen onto an a-Si:H photodiode, or by collecting ionization charge in a thick x-ray absorbing photoconductor with as selenium, and both approaches have been widely discussed in the literature. While these systems meet the performance needs for general radiographic imaging, further improvements in sensitivity, noise and resolution are needed to fully satisfy the requirements for fluoroscopy and mammography. The approach taken for this paper uses indirect detection, with a phosphor layer for x-ray conversion. The thin a-Si:H photodiode layer for detects the scintillation light. In contrast with the present generation of devices, which have a mesa-isolated sensor at each pixel, these imagers use a continuous sensor covering the entire front surface of the array. The p⁺ and i layers of a-Si:H are continuous, while the n⁺ contact has been patterned to isolate adjacent pixels. The continuous photodiode layer maximizes light absorption from the phosphor and provides high x-ray conversion efficiency.

The fabrication of polycrystalline HgI₂ thick film detectors using the hot wall physical vapor deposition, method is described. The X-ray response of these detectors to a radiological X-ray generator of 60 kVp has been studied using the current integration mode. The response expressed in (mu) A, the dark current expressed in pA/cm² and sensitivity expressed in (mu) C/R(DOT)cm² are given for these detectors for several thickness and grain sizes. The optimal sensitivity is compared with published data on the response to X-rays by polycrystalline PbI₂ and A-Se detectors.

The University of Connecticut Health Center and Xicon Technologies, LLC have been developing a high speed/high resolution x-ray detector called the XEBIT (X-ray sensitive Electron Beam Image Tube). The XEBIT is a direct conversion image detector that uses Thallium Bromide as the x-ray photoconductor. thallium bromide is a high Z material with a linear attenuation coefficient of 28.11 cm^-1 at 60 keV. This high stopping power results in a quantum efficiency in excess of 50% at 60 keV for 300 micron thick layers. The XEBIT has far superior contrast resolution with over 50 percent modulation at 5 line pairs per millimeter and does not suffer from veiling glare. This paper is a report on the works in progress of the XEBIT development, which s near clinical trials.

In this paper, we discuss recent progress that has been made in the development of high resolution X-ray imaging detectors using photoconducting films of lead iodide (PbI₂). PbI₂ is a wide bandgap semiconductor with high X- ray stopping efficiency. We have been investigating thick films of lead iodide which can be prepared in large areas in a cost effective manner. These films can be coupled to readout technologies such as amorphous silicon flat panel arrays and vidicon tubes to produce X-ray imaging detectors for applications such as mammography, fluoroscopy, X-ray diffraction and non-destructive evaluation. Recent results obtained when these PbI₂ films are coupled to 512 X 512 flat panel a-Si:H array are reported. This includes dark current, signal and resolution measurements. Properties of lead iodide films which are relevant to imager performance are also discussed.

We have developed a photon-counting 256ch CdTe line detector system for a monochromatic x-ray CT system using fluorescent x-rays generated by synchrotron radiation. The size of each detector element is 1.98 mm(w) X 1.98 mm(h) X 0.5 mm(t). Each element has two discriminators (an upper and a lower discriminator) and two 16-bit counters (an upper and a lower counter). Each discriminator rejects pulses having a pulse height lower than the chosen voltage limits. All pulses in between the upper and lower voltage limits were obtained by subtracting the upper counter value from the lower counter value. By changing the voltage limits, we can obtain an incident x-ray energy spectrum. Several energy spectra for the fluorescent x-ray and standard (gamma) -ray sources were measured by using this detector. The detector showed a sufficient energy resolution, and has been found to be suitable as a detector of monochromatic x-ray CT.

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.

Using parallel X-ray beam from undulator light source of the SPring-8, X-ray imaging based on refraction-enhanced contrast has been tested. Projection images were measured at X-ray energies of 8 keV and 28.8 keV with X-ray image detector that is placed at 5 - 6.5 m downstream from specimen. Transmission image of a test sample shows good agreement with ray-trace simulation. The intensity profile can be explained by refraction of X-rays. Deflection of transmitted beam is also measured by using fine X-ray beam collimated by a slit. The deflection angle of X-rays through the sample is around a few micro-radian. The result also well agrees with simple calculation based on geometrical optics. This technique is applied to observation of soft tissues of biological specimen. The result for lung image of nude mouse is presented, and difference between contact image (absorption-contrast) and refraction contrast image is discussed.

A synchrotron light source dedicated to medical applications is designed at NIRS. The synchrotron ring accelerates electrons up to 1.8 GeV and stores them with about 400 mA, and is equipped with two superconducting multipole wigglers to generate sufficient photon flux for medical diagnoses. One of the most interesting applications for us is monochromatic x-ray computed tomography (CT). It plays an important role in advancing heavy ion radiotherapy of cancers which is being performed at NIRS. The radiotherapy is carried out based on a treatment planning which is a protocol for irradiation of the heavy ion beam on a target to maximize dose distribution and a biological advantage. The treatment planning converts CT-number of tissues along paths of the heavy ion beam to electron densities in order to calculated end-of-range of the heavy ion beam. The conventional x-ray CT introduces uncertainty into the CT- numbers due to beam hardening effect. While the monochromatic x-ray makes the CT-scan free from the beam hardening effect. Furthermore, dual energy x-ray CT-scans give the electron density directly without conversion from the CT-number. We focus on the x-ray CT using two monochromatic x-rays, and outline its beamline and the compact ring.

The central nervous system of vertebrates, even when immature, displays extraordinary resistance to damage by microscopically narrow, multiple, parallel, planar beams of x rays. Imminently lethal gliosarcomas in the brains of mature rats can be inhibited and ablated by such microbeams with little or no harm to mature brain tissues and neurological function. Potentially palliative, conventional wide-beam radiotherapy of malignant brain tumors in human infants under three years of age is so fraught with the danger of disrupting the functional maturation of immature brain tissues around the targeted tumor that it is implemented infrequently. Other kinds of therapy for such tumors are often inadequate. We suggest that microbeam radiation therapy (MRT) might help to alleviate the situation. Wiggler-generated synchrotron x-rays were first used for experimental microplanar beam (microbeam) radiation therapy (MRT) at Brookhaven National Laboratory's National Synchrotron Light Source in the early 1990s. We now describe the progress achieved in MRT research to date using immature and adult rats irradiated at the European Synchrotron Radiation Facility in Grenoble, France, and investigated thereafter at the Institute of Pathology of the University of Bern.