SPring-8, the large synchrotron radiation facility

Imaging the interior of the human body

You may have seen images of the human brain or internal organs on the news or on health programs on TV, or, you may have actually seen images of your own internal organs during medical examination. Such images are obtained by diagnostic imaging, which is currently advancing at a rapid pace in the medical field. Diagnostic imaging is aimed at noninvasively detecting abnormalities, such as cancers, by visualizing the interior of the human body.

There are several methods of diagnostic imaging; for example, positron emission tomography (PET), which is used for cancer diagnosis, magnetic resonance imaging (MRI), which is used for visualizing hydrogen concentration in the body, and X-ray computed tomography (CT), which is being developed at SPring-8.

Computer processing of measured X-ray data

X-ray CT provides images of the interior of the body on the basis of the following principle. When X-rays are irradiated onto the body, some of them are absorbed by the body and the remaining X-rays penetrate through the body. The amount of penetrating X-rays is measured. This is the same principle underlying radiography. However, depth data are not included in the data thus obtained. By irradiating X-rays onto a rotating sample, necessary data are collected in all horizontal directions, thus reproducing cross-sectional images including the data in the depth direction by computer processing.

CT images are usually represented by shades of black and white. The sites with a high density such as bones are seen in white and those with a low density are seen in black. Furthermore, three-dimensional images can also be obtained by stacking cross-sectional images (Fig. 1). Although a huge amount of calculation is required to reproduce a three-dimensional image, current computers with improved performance enable the reproduction of three-dimensional images in a reasonable time. X-ray CT is used in various fields including material development as well as medicine because it enables internal observation without damaging samples.

Fig. 1 X-ray CT image of mouse chest.

The blue region represents the windpipe and the white regions represent bones.（Sera et al. 2004）

New-type CT measuring X-ray distortion

Measurement by X-ray CT and its technological development are carried out using three beamlines at SPring-8, BL20B2, BL20XU, and BL47XU. The main aims of this study are to improve the performance of X-ray CT and develop novel methods for obtaining high-quality images; thus, there is no need for large equipment used at medical sites. The X-ray CT system set at BL20B2 enables measurement of samples with a length of up to 20 mm with a resolution of about 10 μm (a micrometer is one-millionth of a meter). This resolution is 20- to 30-fold higher than that of the conventional CT system used in medicine, that is, about 200 - 300 μm per pixel.

Unfortunately, even the performance of X-ray CT is limited. For example, it is difficult to distinguish slight differences in the densities of tissues in a single organ, although large differences in the densities of bone and fat can be distinguished. To solve this problem, phase-difference X-ray CT, which is a new-type of X-ray CT based on a principle different from that of the conventional X-ray CT, is being developed at SPring-8.

In phase-difference X-ray CT, the distortion of a wavefront of X-rays passing through a sample is measured (Fig. 2). To measure the distortion of a wavefront, the wavefront of X-rays before passing through a sample should be free of distortion. Therefore, SPring-8 synchrotron radiation X-rays with a uniform wavefront are indispensable for phase-difference X-ray CT.

Fig. 2 Principle of phase-difference X-ray CT.

Synchrotron radiation X-rays are split into two: In route 1, X-rays penetrate a sample rotating in the horizontal direction and then enter a detector. In route 2, X-rays directly travel towards the detector (upper figure). When the X-rays hit a sample, the wavefront is distorted in accordance with the internal structure of the sample (lower figure). The distortion of the wavefront (phase difference) is measured by comparing the X-rays passing through routes 1 and 2. The degree of distortion is expressed by shading intensity in a CT image.

Control of nanometer scale

Dr. Naoto Yagi, the deputy director of the Research and Utilization Division at JASRI, and Dr. Kentaro Uesugi, a research scientist at the Division, are developing a phase-difference X-ray CT system. SPring-8 users require X-ray CT to have improved spatial resolution, concentration resolution, and time resolution, which are closely related to each other.

Spatial and concentration resolutions can be explained in terms of the resolution of images obtained and sample density. According to Dr. Yagi, time resolution is most important. Consider the measurement of human heartbeats. In a relaxed state, an adult heart beats about once per second; if one second is required to take one shot, images will become blurred because of the beating of the heart.

We can temporarily still the lungs by taking a deep breath and holding it while undergoing radiography, but we cannot stop heartbeats. According to Dr. Yagi, if the time required to take one shot is reduced, and measurements are repeated in accordance with the intervals of heartbeats, a clear image can be obtained. Thus, short-time shooting technology is necessary, and, owing to its development, we can currently obtain images at intervals of only 0.02 s.

The resolution has been improved to 200 nm (a nanometer is one-billionth of a meter) using a special technique. However, such a very close observation brings another problem. The components of the X-ray CT system contain metals, which expand by about 0.001% with a temperature increase of 1°C. If a 10-cm-long metal bar is used in the components, it will be elongated by 1 μm with a temperature increase of 1°C, making the high resolution of 200 nm (0.2 μm) meaningless.

Dr. Uesugi says, “We control the temperature of the X-ray CT system very carefully. Temperature controllers are not installed inside the experimental hutch because they are sensitive to changes in atmospheric temperature, so temperature is stabilized by air conditioners installed throughout the entire building.” Pointing at a transparent sheet (Fig. 3) covering the system, he says, “The greatest problem is wind. We found after repeated experiments that protection against wind is indispensable.” Because of the increased resolution, even a slight wind shakes a sample to a degree exceeding the pitch of a pixel (0.2 μm).

Fig. 3 Windbreak set to prevent sample from being shaken.

The control of wind and temperature is important to take advantage of the high resolution.

Use of X-ray CT in various fields

This article is mainly focused on the medical application of X-ray CT. However, according to Dr. Uesugi, phase-difference X-ray CT cannot immediately be applied to humans, as it is very difficult to take a photograph of a large sample with high resolution, and the cap of a PET bottle is the largest possible size that can be measured with the current technology. Moreover, the currently used medical X-ray CT system considerably meets existing demands in clinical practice, and there is no urgent need for phase-difference X-ray CT. In the field of materials, metals and semiconductors are satisfactorily measured by conventional X-ray CT. What, therefore, is the phase-difference X-ray CT used for? According to Dr. Yagi, it is effective for soft materials, such as biological samples and polymers, which slightly absorb X-rays, because it can be used to observe such materials at the molecular level, and therefore may be used to identify the causes of diseases and develop new drugs. They hope that this system will be used in various fields. The role of SPring-8 is to provide scientists in various fields the technologies to achieve their goals. The future application and potential of phase-difference X-ray CT developed by Dr. Yagi and Dr. Uesugi will depend on the SPring-8 users' valuable ideas and requirements.

Fig. 4 X-ray CT image of rat cerebrum

(provided by Dr. Hiroshi Onodera at Nishitaga National Hospital, JST-CREST).
A conventional X-ray CT image (left) shows only noise data, whereas a phase-difference X-ray CT image (right) shows clearly the brain structure.

Column: Various samples for analysis

Various samples to be measured are sent from SPring-8 users to the Biomedical Imaging Center, where the phase-difference X-ray CT system is installed. Among them, “raw” biological samples are stored in a refrigerator. When opening a foamed polystyrene box and removing its innumerable folds of wrapping, the interviewer found a biological sample soaked in solution. This may be shocking for people who are not familiar with biological samples, but such samples are precious and indispensable in medical research.

Dr. Uesugi, who has mainly studied earth science, had never seen such a biological sample, and also said, “At first, it was too shocking for me.” He is still not accustomed to biological samples; however, he is working on the development of the phase-difference X-ray CT system.

Dr. Yagi (right) and Dr. Uesugi (left) setting a sample onto the phase-difference X-ray CT system.

Interview and writing by Tomoaki Yoshito (Sci-Tech Communications Incorporated)

This article was written following an interview with Dr. Naoto Yagi, the deputy director of the Research and Utilization Division at JASRI, and Dr. Kentaro Uesugi, a scientist at the Division.