Phantom and animal imaging studies using PLS ... - IEEE Xplore

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Hee-Joung Kim, Jin-O Hong, Kyu-Ho Lee, Hai-Jo Jung, Eun-Kyung Kim, Jung Ho Je, ... Wen-Li Tsai, Je-Kyung Seong, Seung-Won Lee, and Hyung Sik Yoo.
IEEE TRANSACTIONS ON NUCLEAR SCIENCE, VOL. 48, NO. 3, JUNE 2001

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Phantom and Animal Imaging Studies Using PLS Synchrotron X-Rays Hee-Joung Kim, Jin-O Hong, Kyu-Ho Lee, Hai-Jo Jung, Eun-Kyung Kim, Jung Ho Je, In Woo Kim, Yeukuang Hwu, Wen-Li Tsai, Je-Kyung Seong, Seung-Won Lee, and Hyung Sik Yoo

Abstract—Ultra-high resolution radiographs can be obtained using synchrotron X-rays. A collaboration team consisting of K-JIST, POSTECH, and YUMC has recently commissioned a new beamline (5C1) at Pohang Light Source (PLS) in Korea for medical applications using phase contrast radiology. Relatively simple image acquisition systems were set up on 5C1 beamline, and imaging studies were performed for resolution test patterns, mammographic phantom, and animals. Resolution test patterns and mammographic phantom images showed much better image resolution and quality with the 5C1 imaging system than the mammography system. Both fish and mouse images with 5C1 imaging system also showed much better image resolution with great details of organs and anatomy compared to those obtained with a conventional mammography system. A simple and inexpensive ultra-high resolution imaging system on 5C1 beamline was successfully implemented. We were able to acquire ultra-high resolution images for, resolution test patterns, mammographic phantom, fishes, and mice. The results showed that the 5C1 imaging system could be used for ultra-high resolution imaging studies in medical applications. Index Terms—Mammographic phantom, synchrotron X-rays, ultra-high resolution.

I. INTRODUCTION

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INCE Wilhelm Conrad Röntgen discovered X-rays on November 8, 1895 and its application for medical imaging, there have been great improvements in medical imaging physics and instrumentation. Magnetic resonance imaging Manuscript received October 25, 2000; revised April 23, 2001. This study was supported by the Brain Korea 4 project for Medical Science, Yonsei University. H.-J. Kim and J.-O. Hong are with the BK21 Project for Medical Sciences, Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Yonsei University, #134 Shinchon-Dong, Seodaemoon-Ku, Seoul, 120-751, Korea (e-mail: [email protected]; [email protected]). K.-H. Lee and J.-K. Seong are with the Medical Research Center, Research Institute of Radiological Science, Yonsei University College of Medicine, #134 Shinchon-Dong, Seodaemoon-Ku, Seoul, 120-751, Korea (e-mail: [email protected]; yslabanim @yumc.yonsei.ac.kr). H.-J. Jung is with the Research Institute of Radiological Science, Yonsei University College of Medicine, #134 Shinchon-Dong, Seodaemoon-Ku, Seoul, 120-751, Korea (e-mail: hjjung1 @yumc.yonsei.ac.kr). E.-K. Kim and H. S. Yoo are with the Department of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, #134 Shinchon-Dong, Seodaemoon-Ku, Seoul, 120-751, Korea (e-mail: [email protected]). J. H. Je and I. W. Kim are with Pohang University of Science and Technology, Pohang, 790-784, Korea (e-mail [email protected]). Y. Hwu and W.-L. Tsai are with the Institute of Physics, Academia Sinica, Taiwan. S.-W. Lee is with Yonsei University College of Dental School, #134 Shinchon-Dong, Seodaemoon-Ku, Seoul, 120-751, Korea (e-mail: ys1225@unitel. co.kr). Publisher Item Identifier S 0018-9499(01)05105-X.

(MRI), computed tomography (CT), and positron emission tomography (PET) are examples of the advanced imaging modalities with spatial resolutions measured in millimeters. Most of the imaging modalities have been designed for better spatial resolution, three-dimensional (3-D) imaging capabilities, and functional imaging capabilities. Improvements in spatial resolution will play an important role in the detection of fine objects, such as microcalcifications with mammography system. Mammography systems provide the best resolution in conventional radiological imaging modalities in the clinical situation. However, accurate diagnosis in mammographic imaging requires resolutions of several tens of micrometers. The spatial resolution of the mammography system (GE Senographe DMR) was estimated as minimum 13 lp/mm by the visual evaluation of a radiologist in our institution, although the diagnosis of microcalcifications sometimes requires up to 20 lp/mm for improved differential diagnosis. Several groups have successfully improved image contrast and spatial resolution with monochromatic synchrotron radiation [1]–[4]. Fitzgerald [5] recently reviewed “phase-sensitive X-ray imaging” approaches that can detect X-ray phase shifts within soft tissues. A collaboration team consisting of the Kwangju Institute of Science and Technology (K-JIST), Pohang University of Science and Technology (POSTECH), and Yonsei University Medical Center (YUMC) has recently commissioned a new beamline (5C1) in Pohang Light Source (PLS) in Korea for medical applications using phase contrast radiology. Unlike the other monochromatic synchrotron X-rays used for mammographic applications, we used unmonochromatized synchrotron X-rays equipped with relatively simple and inexpensive imaging systems [6], [7]. They included silicon wafer attenuators, CdWO scintillators, a charge-coupled device (CCD) camera, and a digital video recorder for data acquisition. Synchrotron X-ray imaging may provide the quality of micrometer resolution images at the clinical stage. We report upon preliminary imaging studies of microresolution test patterns, mammographic phantom, and animals prior to applying these techniques to clinical situations.

II. METHODS A. Pohang Accelerator Laboratory (PAL) The Pohang light source (PLS) is a third-generation synchrotron radiation source consisting of a 2.0-GeV electron liner accelerator and an electron storage ring, which can boost electron energy to 2.5 GeV. The 150-m-long injector linac

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Fig. 1. Experimental setup on 5C1 beamline in the hutch.

injects 100-MeV electrons into the storage rings, which are further ramped to 2.0–2.5 GeV at a current of 250 mA. The 5C1 beamline was recently constructed for medical applications using unmonochromatized X-ray radiation in the energy range of 5–50 keV. The shape of the energy spectrum depends on the type and thickness of the attenuators used for the imaging studies. Synchrotron X-rays generated by a bending magnet ( 1 T) of the PLS storage ring are directly emitted into a hutch, containing the imaging systems under study. B. Imaging System on 5C1 Beamline The imaging system was set up within a hutch at the termination of the 5C1 beamline (Fig. 1). The imaging system used was relatively simple and inexpensive compared to other phase sensitive detecting systems [5]. The unmonochromatized synchrotron X-rays pass two sets of attenuators, which are composed of silicon wafers and optimize the X-ray energy spectrum (Fig. 2). One piece of silicon wafer was placed in the vacuum pipeline, and the other silicon wafers in the air within the hutch. The profile of the X-ray beam size was manually tailored by slits, to 12 6 mm to match the scintillator. The X-rays passing through the subject interact with the scintillator, which is a thin plate of CdWO (10 10 0.1 mm, Bicron Co., USA), and produce visible images. The visible image from the scintillator is enlarged by a magnification lens, and finally captured by the CCD camera (Fig. 2). Light photon images of the object are reflected through 90 by the gold-coated mirror placed just behind and at 45 to the scintillator, lens magnified, and finally reach the CCD camera (Fig. 2). Digital images are acquired using a CCD camera connected to either a computer or video recorder. A Sony™ DCR-TRV900 digital video recorder was used for real-time data acquisition. The distances between the objects and the scintillator were varied between 17 and 47 cm to optimize image quality.

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(Nuclear associates NY 07-510 and 07-501) and mammographic accreditation phantom model-156 (Gammex RMI) were imaged using the synchrotron X-ray imaging system and a conventional mammography system. For conventional mammography, the resolution test pattern (Nuclear associates NY 07-510) was imaged with the following acquisition parameters; 22 kVp, 20–25 mAs, and Mo/Mo bucky using magnification factors of 1.0 and 1.8. The higher magnification factor was chosen for direct comparison with the images obtained with the 5C1 synchrotron X-ray imaging system. The resolution test pattern (Nuclear associates NY 07-501) was imaged using both computed radiography (FCR, Fuji) and film at 22 kVp, 32 mAs, Mo/Mo bucky for CR and 23 kVp, 100 mAs, Mo/Mo bucky for film using a magnification factor of 1.0 and 1.8. Computed radiography (CR) was used to obtain digital data for direct comparison. CR data for the remainder of the studies were not acquired because of the inferior image quality compared to the film images. A mammographic accreditation phantom model-156 (Gammex RMI) was imaged at 28 kVp, 79-83 mAs, Mo/Mo bucky using a magnification factor of 1.0. A fish was imaged at 22 kVp, 20 mAs, and Mo/Mo bucky using magnification factors of 1.0 and 1.8. The mice were also imaged using acquisition parameters of 22 kVp, 10–20 mAs, and Mo/Mo bucky using magnification factors of 1.0 and 1.8. For the synchrotron X-ray studies, the imaging system was calibrated and the distances between the object and the scintillator, and between the scintillator and the CCD camera were optimized. A magnification factor of 10 was used for the majority of the studies to obtain ultra-high resolution images, and the imaging system was tested prior to experimentation. The zebra fish used in these experiments were provided by a local aquarium. The animals studied were male hairless mice (SKH-2, Charles River Co., USA, body weight: 20–25 g). The experimental mice were located in standing position by an animal holder in front of the scintillation detector. During the experimental procedures, animals were generally anesthetized and monitored in the usual manner. The Committee for the Care and Use of Laboratory Animals at YUMC reviewed all experimental procedures on the basis of Guide for Animal Experiments. High-resolution test patterns, mammographic accreditation phantom, fish, and mice were imaged using unmonochromatized synchrotron X-rays on 5C1 beamline at PLS. The image acquisition times ranged from 25 to 30 ms. The field of view of the CCD camera with a magnification factor of 10 was 4.5 mm 3 mm. This enabled final images to be completed by patching multiple small images using commercially available software installed on a personal computer. III. RESULT

C. Phantom and Animal Studies To compare the image quality and contrast of conventional mammography (GE Senographe DMR) and the PLS synchrotron X-ray system on the 5C1 beamline, high-resolution test patterns, mammographic phantoms, and animal studies were performed. Electron energy and average beam current of the 5C1 beamline at the time of experiments were 2.5 GeV and 100–150 mA, respectively. Both resolution test patterns

When the mammography system was used for imaging studies, the image resolution and contrast obtained with film appeared to be better than those obtained with the imaging plate (IP) using the CR system (Fig. 3). The film images were digitized for soft copy comparison. Because of the inferiority of CR image quality, film images were acquired for the remainder of the study. Synchrotron X-ray images had the highest resolution 5 lp/mm with the test pattern

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Fig. 2. Schematic diagram of radiation X-ray imaging system.

Fig. 3.

High-resolution test pattern images obtained with (a) film and (b) IP plate with FCR.

(Nuclear Associates NY 07-501) having a maximum capability of 5 lp/mm, showing much better image resolution and contrast than those obtained with the mammography system (Fig. 4). An ultra-high resolution (20 lp/mm) test pattern or the physical measurement method such as modulation transfer function (MTF) [11] may be needed to investigate further the resolution limitation using the synchrotron X-ray technique, and such an evaluation is underway with an ultra-high resolution test pattern having 8- m resolution capability (about 60 lp/mm). Another resolution test pattern (Nuclear associates NY 07-510) showed similar results, synchrotron radiation images showed much better spatial resolution and image contrast than those obtained with the mammography system (Fig. 5). Images obtained by the synchrotron X-ray method of the mammographic phantom model-156 were visually evaluated and compared with

those obtained using the conventional mammography system. Synchrotron X-ray images showed better spatial resolution and image contrast than the images obtained by conventional mammography (Fig. 6). Mammographic phantom data obtained with synchrotron X-ray could not be evaluated by scoring the images according to the American College of Radiology (ACR) criteria, since the size of imaging field by synchrotron X-ray was too small to image the full size of the mammographic phantom. Instead, we only compared a specific region obtained by synchrotron X-ray, and it showed much more detail of the simulated region within the mammographic phantom than that obtained by conventional mammography. Fish images obtained by synchrotron X-ray showed much better spatial resolution and better image contrast than those obtained by conventional mammography. The synchrotron X-ray image showed much more detail

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real time with synchrotron X-ray opens up possibilities not only for basic research but also for medical applications including angiogenesis, osteogenesis, and oncogenesis.

IV. DISCUSSION

Fig. 4. Resolution test pattern Model Nuclear Associates NY 07-501: (a) test pattern, (b) magnified test pattern, (c) test pattern image obtained using conventional mammography system, and (d) the test pattern image obtained with the synchrotron X-ray.

Fig. 5. Resolution test pattern Model Nuclear Associates NY 07-510: (a) test pattern, (b) magnified test pattern, (c) test pattern image obtained using the conventional mammography system, and (d) the test pattern image obtained with the synchrotron X-ray.

of bony structures and clear boundaries between bone and soft tissues (Fig. 7). We also performed preliminary studies on mice prior to any clinical trials, because we were interested to see whether the synchrotron X-ray can be used for acquiring ultra-high spatial resolution images in live animals in real time. The third generation of PLS synchrotron has a maximum energy of 2.5 GeV, with a peak X-ray radiation energy at 5C1 of 30 keV with our experimental setup. Synchrotron X-ray proved to have better spatial resolution and image contrast than the conventional mammography system. The synchrotron X-ray images showed great details of organs and mouse anatomy, probably to an extent not possible using other imaging modalities (Fig. 8). In vivo imaging capabilities in

Ionizing radiation has been widely used in medical applications for both diagnostic imaging and radiotherapy, since Wilhelm Conrad Röntgen discovered X-rays in 1895. Imaging technologies are continuously being changed from analog to digital, from single-slice to multislice, from planar to volume-based, from static to dynamic, and from low-resolution to high-resolution. Some of the advanced imaging modalities are CR, digital radiography (DR), functional MRI (fMRI), multislice CT, and digital subtraction angiography (DSA). Conventional X-ray imaging utilizes braking radiation and produces images with absorption characteristics. In contrast, synchrotron X-rays can produce images with main characteristics of phase contrast with beam collimation [8]–[10]. Although such applications are still in the research and development stages for clinical use, the high flux and brightness, tunable beams, time structure, and polarization of synchrotron radiation are proving to be an ideal X-ray source for many applications in medical science. In parallel to the activities in other SR facilities, such as ESRF, SPring-8, etc., we have successfully accomplished an in vivo animal imaging study at the micrometer resolution level. The synchrotron X-ray imaging techniques can provide high-quality radiographs with resolutions of a micrometer or submicrometer, which will enable the diagnosis of human bodies at the cellular level. Many important research programs have been undertaken, both in vitro and in vivo, especially overseas. In vitro applications include structural biology, X-ray microscopy, and radiation cell biology. In vivo applications include synchrotron angiography, bronchography, multiple energy computed tomography, microtomography, mammography, and radiation therapy. Although these programs are at their initial stages, the imaging methods required for ultra-high resolution involve phase effects, which are known as “phase contrast imaging” techniques. At this initial stage of program development, micro test patterns, mammographic phantoms, small fish, and mice, were well imaged using PLS synchrotron X-ray and the qualitative evaluation of the images obtained with SR X-ray system showed much better resolution and contrast than those obtained using a conventional mammography system. The fine internal and bony structures of fish were visualized with a resolution of only a few micrometers. Internal organs of mice were also visualized with a few micrometers resolution—in real time. These results indicate that the in vivo imaging capabilities in real time with the unmonochromatized synchrotron X-ray system at PLS open up possibilities not only for basic research but also for medical applications, including angiogenesis, osteogenesis, and oncogenesis. However, collaborative research studies between the various scientific medical groups are essential to make the synchrotron X-ray imaging technique applicable to the various clinical imaging requirements in humans.

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Fig. 6. Mammographic accreditation Phantom Model-156. (a) Phantom approximately equivalent to a 4.2-cm–thick compressed breast consisting of 50% glandular and 50% adipose tissue. (b) Schematic view of detail contains fibers of diameter 1.56, 1.12, 0.89, 0.75, 0.54, and 0.40 mm; specks with diameters of 0.54, 0.40, 0.32, 0.24, and 0.16 mm; and masses with decreasing diameter and thickness of 2.00, 1.00, 0.75, 0.50, and 0.25 mm. (c) Phantom image obtained with the mammography system. (d) A magnified image of (c) for comparison of the mammography system and synchrotron X-ray. (e) Image obtained with the synchrotron X-ray imaging system.

Fig. 7. Zebra fish images. (a) Fish (b) Fish image obtained with the mammography system. (c) Magnified fish image of (b) for comparison purposes. (d) Fish image obtained with the synchrotron X-ray imaging system.

V. CONCLUSION A beamline 5C1 was recently constructed at the PLS synchrotron radiation facilities in Korea. A simple and inexpensive imaging system was set up and tested on test patterns, phantom, fish, and mice. The images obtained with unmonochromatized synchrotron X-rays were compared to those obtained with a conventional mammography system. Images obtained with synchrotron X-rays showed much better spatial resolution and contrast, and the detailed structure of internal organs and their anatomy. The results indicate that simple and inexpensive unmonochromatized synchrotron X-ray imaging can be applied

Fig. 8. Experimental setup for mouse imaging using 5C1 beamline. (a) Mouse setup. (b) Mouse image obtained with conventional mammography system. (c) Magnified mouse image of (b) for comparison . (d) Mouse image obtained with the synchrotron X-ray imaging system.

for many scientific applications in the medical field, although further research studies are required to develop these techniques in clinical applications. ACKNOWLEDGMENT The authors wish to acknowledge Prof. O.-S. Chae for image acquisition and processing, Y.-C. Kim, S.-S. Yoon, I.-W. Kim, H.-S. Kang for technical assistance, H.-K. Kim, S.-W. Kang for image processing, and Y.-K. Kim, D.-W. Chang for their help in the preparation of the experimental setups and animal studies.

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[7] Y. Hwu and H. Hsieh et al., “Coherence-enhanced synchrotron radiology: Refraction versus diffraction mechanisms,” J. Appl. Phys., vol. 85, pp. 3406–3408, Oct. 1999. [8] T. J. Davis, D. Gao, and T. E. Gureyev et al., “Phase-contrast imaging of weakly absorbing materials using hard X-rays,” Nature, vol. 373, pp. 595–598, Feb. 16, 1995. [9] S. W. Wilkins and T. E. Gureyev et al., “Phase-contrast imaging using polychromatic hard X-rays,” Nature, vol. 384, pp. 335–338, Nov. 28, 1996. [10] D. Chapman, W. Thomlinson, and R. E. Johnston et al., “Diffraction enhanced X-ray imaging,” Phys. Med. Biol., vol. 42, pp. 2015–2025, 1997. [11] E. Samei, M. Flynn, and D. Reimann, “A method for measuring the presampled MTF of digital radiographic systems using an edge test device,” Med. Phys., vol. 25, pp. 102–113, Jan. 1998.