Keiji Umetani

Microangiographic assessment of collateral vessel formation following direct gene transfer of vascular endothelial growth factor in rats.

OBJECTIVE The development of collateral microvessels following therapeutic angiogenesis with vascular endothelial growth factor (VEGF) was investigated using a new system of microangiography that employs monochromatic synchrotron radiation (SR) and a high definition video system to visualize arteries with a spatial resolution of 30 microns. METHODS Ischemia was induced in the hindlimb of 20 rats by excision of the femoral artery, followed by transfection of the plasmid (400 micrograms) encoding VEGF or beta-galactosidase (control) into limb muscles. Microangiography was used to assess the development of collaterals in the ischemic limb four weeks after treatment. RESULTS Gene transfer of VEGF produced morphologically similar, but significantly more extensive, collateral networks at the microvascular level as compared with the naturally occurring collateral arteries in the control animals (angiographic score: 0.88 +/- 0.08 versus 0.54 +/- 0.05, p < 0.01). No adverse vascular effects such as hemangiomas and/or arteriovenous (AV) fistulae were observed following VEGF treatment. The vasodilator effect of papaverine was evident in relatively large vessels in both groups. At the microvascular level (diameter < 100 microns), however, papaverine induced significant vasodilation in the VEGF-treated animals, and almost no vasodilation in the controls. CONCLUSIONS SR microangiography allowed us to assess the development of small collateral arteries following VEGF-gene transfer. The information obtained may provide new insights regarding the collateral microcirculation and therapeutic angiogenesis.

High‐Spatial‐Resolution Medical‐Imaging System Using a HARPICON Camera Coupled with a Fluorescent Screen

A high-sensitivity HARPICON camera was developed for medical X-ray imaging using a fluorescent screen. It is an avalanche-multiplication-type image pick-up tube and is 32 times more sensitive than conventional tubes. The camera also has a wider dynamic range than conventional medical-imaging cameras because a maximum output signal current of 2.3 muA is obtained and, in high-illumination-intensity regions, photocurrent is not proportional to illumination intensity. The fluorescent screen is an intensifying screen of the type used for radiographic screen-film combinations in medical examination. An X-ray image on the screen is focused on the photoconductive layer of the pick-up tube using a coupling lens with f/0.65. Experiments were performed using monochromated X-rays at the Photon Factory. An image of a spatial resolution test chart was taken in a 525 scanning-line mode of the camera. The chart pattern of 5 line-pairs mm(-1 )(spatial resolution of 100 mum) was observed at an X-ray input field of 50 x 50 mm. Real-time digital images of the heart of a 12 kg dog were obtained at a frame rate of 60 images s(-1) after injection of a contrast medium into an artery. The images were stored in digital format at 512 x 480 pixels with 12 bits pixel(-1). High-spatial-resolution and high-contrast images of coronary arteries were obtained in aortography using X-rays with energy above that of the iodine K edge; the image quality was comparable with that of conventional selective coronary angiography.

Two-dimensional aortographic coronary arteriography with above-K-edge monochromatic synchrotron radiation

RATIONALE AND OBJECTIVES The diagnostic potential of two-dimensional aortographic coronary arteriography with synchrotron radiation was examined in dogs. METHODS The experiment was performed at a wiggler beam line by using a silicon monocrystal, fluorescent plate, and avalanche-type camera. The x-ray energy was adjusted to just above the iodine K-edge to obtain the highest contrast. Quantitative densitometry was used to compare intravenous coronary arteriography with aortographic coronary arteriography. RESULTS Aortographic coronary arteriography clearly depicted the branches of the coronary arteries such as the left anterior descending coronary artery, circumferential coronary artery, and right coronary artery to sizes of less than 0.2 mm without major overlap of coronary arteries. Intravenous coronary arteriography depicted only the branches of the left anterior descending coronary artery and right coronary artery with poor image quality. The ratio of contrast material dilution was about 2.4 to 3.4 in aortographic procedures, whereas in intravenous procedures it ranged widely from 7.7 to 15.6. CONCLUSION These preliminary investigations indicate that two-dimensional aortographic coronary arteriography with synchrotron radiation promises to be a minimally invasive and easily repeatable method of clearly imaging the coronary arteries.

Laser‐stimulable transparent CsI:Na film for a high quality x‐ray imaging sensor

Transparent films, which can be stimulated by laser beams after x‐ray irradiation, have been searched to improve the spatial resolution of digital x‐ray imaging sensors. As a result, evaporated CsI:Na films are found to be efficiently laser stimulable around 77 K. The modulation transfer function (MTF) of the film is evaluated using a scanning Ga1−xAlxAs semiconductor laser. The high MTF value (57% at 2 1p/mm), strong x‐ray absorption, and high stimulation efficiency of the film ensure a high quality sensor for digital radiography.

Observation and analysis of microcirculation using high-spatial-resolution image detectors and synchrotron radiation

A microangiography system using monochromatized synchrotron radiation has been investigated as a diagnostic tool for circulatory disorders and early stage malignant tumors. The monochromatized X-rays with energies just above the contrast agent K-absorption edge energy can produce the highest contrast image of the contrast agent in small blood vessels. At SPring-8, digital microradiography with 6 - 24 micrometer pixel sizes has been carried out using two types of detectors designed for X-ray indirect and direct detection. The indirect-sensing detectors are fluorescent-screen optical-lens coupling systems using a high-sensitivity pickup-tube camera and a CCD camera. An X-ray image on the fluorescent screen is focused on the photoconductive layer of the pickup tube and the photosensitive area of the CCD by a small F number lens. The direct-sensing detector consists of an X-ray direct- sensing pickup tube with a beryllium faceplate for X-ray incidence to the photoconductive layer. Absorbed X-rays in the photoconductive layer are directly converted to photoelectrons and then signal charges are readout by electron beam scanning. The direct-sensing detector was expected to have higher spatial resolution in comparison with the indict-sensing detectors. Performance of the X-ray image detectors was examined at the bending magnet beamline BL20B2 using monochromatized X-ray at SPring-8. Image signals from the camera are converted into digital format by an analog-to- digital converter and stored in a frame memory with image format of 1024 X 1024 pixels. In preliminary experiments, tumor vessel specimens using barium contrast agent were prepared for taking static images. The growth pattern of tumor-induced vessels was clearly visualized. Heart muscle specimens were prepared for imaging of 3-dimensional microtomography using the fluorescent-screen CCD camera system. The complex structure of small blood vessels with diameters of 30 - 40 micrometer was visualized as a 3- dimensional CT image.

High-spatial-resolution and real-time medical imaging using a high-sensitivity HARPICON camera

A HARPICON(TM) camera has been applied to a digital angiography system with fluorescent-screen optical-lens coupling. It uses avalanche multiplication in the photoconductive layer for high-sensitivity imaging. The limiting spatial resolutions in the 1050 scanning-line mode of the camera are about 30 and 50 micro m at input field sizes of 20 x 20 and 50 x 50 mm on the screen, respectively. For high-speed imaging, the 525 scanning-line mode at a rate of 60 images s(-1) can be selected. High-quality images of coronary arteries in dogs were obtained by intra-aortic coronary angiography and superselective coronary angiography using a single-energy X-ray above the iodine K-edge energy.

Iodine K-edge dual-energy imaging for subtraction angiography using synchrotron radiation and a 2-dimensional detector

Abstract A 2-dimensional energy-subtraction imaging system using synchrotron radiation has been improved in a number of ways; especially the energy-switching mechanism in which a monochromator crystal is oscillated trapezoidally has been improved. These improvements have led to real-time imaging of the right coronary artery in a rabbit after an intravenous injection of a contrast agent. This artery has a diameter of about 0.5 mm. However, this system has limitations concerning the energy difference between two component exposures and the total time of acquiring two images. We have tested a new method. Since the crystal was too heavy to oscillate quickly, the next step was to make the energy switching faster than in the previous method by the use of lighter moving parts. An iodine filter is used in the new method. Filter-chopping of the X-ray beam switches the dual-energy imaging energies, because the iodine filter selectively absorbs high-energy X-rays rather than K-edge energy X-ray. Moreover, by the use of the iodine filter, the energy difference between two exposures can be decreased to less than half of that in the previous method. Preliminary studies on the new method were performed in rats.

Cis-Trans Photoisomerization of Perinaphthothioindigo for Use as a Photo-Imaging Sensor Using Fluorescence under He-Ne Laser Excitation

An imaging sensor based on the cis/trans isomerization of thioindigoid dyes is proposed. A photo-image (~500 nm) is stored as a density distribution of the trans-form in the cis-form material, and read out as fluorescence (~700 nm) from the trans-form by scanning with He-Ne laser (633 nm) excitation. As the fluorescence decay time of perinaphthothioindigo is 1.8 ns, the sensor permits rapid read-out. For light exposure L from 10-4 to 10-1 J/cm2 at 500 nm, the fluorescence intensity under laser excitation varies as L0.8.

X-ray refraction-contrast imaging using synchrotron radiation at SPring-8

An edge-enhanced imaging technique using the X-ray refraction effect for high contrast outline imaging have been investigated using a third generation of synchrotron radiation source. This technique can be applied to imaging of soft tissues that can not be imaged by conventional absorption- contrast imaging. We have attempted to apply this method to accurate diagnosis of the lung cancer with reduced absorbed dose. In preliminary experiments, we took images of a glass capillary tube and a nude mouse with a long object-to-detector distance using monochromatized X-ray and a high-spatial- resolution CCD-based image detector. Compared to conventional absorption-contrast images, the image contrast is enhanced at an interface between two materials by the X-ray refraction. In a chest image of the mouse, outline images of the alveoli, the bronchi and the trachea were visualized with higher contrast than that of the ribs. It may be effective for early detection of small lung cancer lesions.

First experiment by two-dimensional digital mammography with synchrotron radiation

Two-dimensional digital mammography with synchrotron radiation was developed to obtain high-contrast images. The system consisted of a single-crystal monochromator with an asymmetrically reflecting silicon 〈311〉 crystal, an avalanche multiplication-type pick-up tube camera with a fluorescent plate and lens-coupling system, and a workstation. The preliminary experiment was carried out with a synchrotron light source at the Photon Factory, KEK, in Tsukuba. Breast phantom and human breast specimen were imaged using 20 keV monochromatic synchrotron X-rays. These images were compared with images obtained by a conventional mammography system. The minimal detectable diameter of microcalcification on the breast phantom was 165 µm by the two-dimensional synchrotron radiation imaging system and 196 µm by the conventional mammography system. In the breast specimens, microcalcification and soft-tissue masses were clearly imaged and their contrasts improved by about 18% and 38%, respectively, in the two-dimensional synchrotron radiation system. The entrance surface dose of the two-dimensional synchrotron radiation system was about 400 mR, which was almost the same value as the 420 mR delivered by the conventional mammography system. Two-dimensional synchrotron radiation digital mammography is considered to be a powerful imaging modality for diagnosing breast tumors.