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ZEMEDI-10433; No. of Pages 6 ARTICLE IN PRESS ORIGINALARBEIT Cadaveric and in vivo human joint imaging based on differential phase contrast by X-ray Talbot-Lau interferometry Junji Tanaka 1,∗ , Masabumi Nagashima 2 , Kazuhiro Kido 3 , Yoshihide Hoshino 3 , Junko Kiyohara 3 , Chiho Makifuchi 3 , Satoshi Nishino 3 , Sumiya Nagatsuka 3 , Atsushi Momose 4 1 Department of Radiology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan Department of Anatomy, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan 3 KonicaMinolta Medical and Graphic, Inc., 2970 Ishikawa-machi, Hachioji, Tokyo 192-8505, Japan 4 Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai, Miyagi 980-8577, Japan 2 Received 4 September 2012; accepted 9 November 2012 Abstract We developed an X-ray phase imaging system based on Talbot-Lau interferometry and studied its feasibility for clinical diagnoses of joint diseases. The system consists of three X-ray gratings, a conventional X-ray tube, an object holder, an X-ray image sensor, and a computer for image processing. The joints of human cadavers and healthy volunteers were imaged, and the results indicated sufficient sensitivity to cartilage, suggesting medical significance. Keywords: X-ray interferometry, a new imaging technology, in vivo imaging, cadavers and normal volunteers 1 Introduction The principle of medical X-ray imaging has not changed since the discovery of X-rays in 1895, in which image contrast depends on the attenuation of X-rays. Phase shifts also Darstellung von menschlichen Gelenken, in vivo und bei Verstorbenen, basierend auf Differential-Phasenkontrast durch Röntgen-Talbot-Lau-Interferometrie Zusammenfassung Wir entwickelten ein Röntgen-Phasen-Imaging-System, basierend auf Talbot-Lau-Interferometrie und bestehend aus drei Röntgengittern, einer konventionellen Röntgenröhre, einem Objekttisch, einem Röntgenbildsensor und einem Computer zur Bildverarbeitung. Anschließend untersuchten wir seine Nutzbarkeit für die Diagnostizierung von Gelenkerkrankungen, wobei die Gelenke von gesunden Probanden sowie von Verstorbenen dargestellt werden konnten. Die Ergebnisse zeigten eine ausreichende Sensitivität für Knorpel, was für die klinische Bedeutsamkeit unseres entwickelten Systems spricht. Schlüsselwörter: Röntgeninterferometrie, neue Röntgentechnik, Verstorbene und gesunde Probanden occur when X-rays pass through an object. If the phase shifts could be captured and imaged, an extremely high sensitivity would be attained because the interaction cross-section of the X-ray phase shift is about 1000 times larger than that of the attenuation, especially for light materials [1]. Thanks to the ∗ Corresponding author: Junji Tanaka, Department of Radiology, Saitama Medical University, 38 Morohongo, Moroyama, Iruma, Saitama 350-0495, Japan. E-mail: [email protected] (J. Tanaka). Z. Med. Phys. xxx (2012) xxx–xxx http://dx.doi.org/10.1016/j.zemedi.2012.11.004 http://journals.elsevier.de/zemedi ARTICLE IN PRESS 2 J. Tanaka et al. / Z. Med. Phys. xxx (2012) xxx–xxx development of X-ray digital imaging technology, novel X-ray imaging techniques were developed in the 1990s for visualizing low-contrast structures by quantitatively processing X-ray phase-contrast images. This is referred to as “X-ray phase imaging.” However, it is still not available for medical application because of the difficulty in its implementation in hospitals. X-ray Talbot interferometry based on the Talbot effect [2] is a relatively new differential phase-contrast technique, in which the refraction of X-rays is captured through interference and is visualized as distortion of the Moiré pattern [3,4]. It is characterized by the use of gratings and is also called “grating interferometry.” Since it can be used with broadband energy X-rays, its application in the medical setting has been expected. However, since the X-ray Talbot interferometer requires partial spatial coherence, the X-ray source available is limited to either a microfocus X-ray tube or a synchrotron. Since the former cannot emit X-rays of sufficient flux and the latter is enormous, the clinical application of phase imaging has not been feasible. The use of an X-ray source of reasonable size and sufficient power is needed. F. Pfeiffer et al. solved this problem by X-ray TalbotLau interferometry [5], where a conventional X-ray tube is employed with a source grating in addition to the configuration of the Talbot interferometer. X-ray phase imaging can be performed with a reasonable exposure time, and we studied its feasibility for the diagnoses of joint diseases. We constructed an X-ray Talbot-Lau interferometer based on a design with a wave-optic simulation [6], and used it to capture images of joints of cadavers and healthy volunteers. We report here the first imaging results and discuss their clinical significance. 2 Material and methods 2.1 System configuration When a grating (hereafter, G1) is illuminated by X-rays of partial spatial coherence, self-images appear periodically downstream of G1 as a result of the Talbot effect. When the self-image is overlaid with another grating (G2) that has the same pitch as that of a self-image, a Moiré pattern appears. If an object is placed in front of G1, the wave-front of the X-rays is distorted and the Moiré pattern is also distorted. This is the Talbot interferometer. The phase information of the object can be extracted from the distorted Moiré patterns by the use of the fringe-scanning method [3]. In order to use an incoherent X-ray tube, a source grating (G0) is added near the tube, as shown in Fig. 1, to configure the Talbot-Lau interferometer [5] With Talbot-Lau interferometry, three different types of images can be simultaneously obtained by calculations: an attenuation image, a small-angle-scattering (dark-field) image [7], and a differential phase image. When X-rays pass an object, some X-rays are absorbed, and other X-rays are refracted by the object. The former effect results in an Figure 1. Schematic illustration of a Talbot interferometer modified with the Lau effect. Self-images 1, 2 and 3 are due to the X-ray beams B1, B2 and B3, respectively, from the slits of G0. The beams from G0 produce self-images constructively at the G2 plane, allowing the use of a conventional X-ray source. attenuation image, and the latter results in a differential phase image. When X-rays are refracted strongly, a corresponding contrast appears in the small-angle-scattering image [8]. For clinical diagnoses, the three images can be used complementarily. The basic design and specifications of our system were based on a simulation by W. Yashiro et al. [6]. An X-ray generator of a tungsten anode was operated with a tube voltage of 40 kVp, which was selected according to the simulation, and a tube current of 75 mA. The mean X-ray energy was 28 keV. The pitches of G0, G1 and G2 were 22.8 m, 4.3 m, and 5.3 m, respectively. The opening width of G0 was 7 m, and the duty cycle of G1 and G2 was 0.5. G1 and G2 were located 1.1 m and 1.36 m from G0, respectively. G1 was a /2 phase grating for 28 keV X-rays, and G2 was an amplitude grating, whose gold pattern height was 43 m. The object to be imaged was placed in front of G1. The area size of G1 and G2 was 60 mm x 60 mm, and the effective field of view was 49 mm x 49 mm taking account of the magnification of the image. All of the gratings were fabricated by X-ray lithography and gold electroplating [9]. A flat panel detector was located behind G2 and its pixel size was 85 m. A picture of the system is shown in Fig. 2(a). The FWHM values of the focal spot size of the X-ray tube and the LSF of the detector were 350 m and 90 m, respectively. The system spatial resolution was calculated to be 99 m from the FWHM values [6]. For the measurement of a differential phase image, a five-step fringe-scan was performed. ARTICLE IN PRESS J. Tanaka et al. / Z. Med. Phys. xxx (2012) xxx–xxx 3 Figure 2. Overviews of our Talbot-Lau interferometers: (a) A system for cadaveric specimens, where X-rays pass from the left to the right, through G0, the target object, G1, and G2 to the X-ray detector, and (b) A system for in vivo imaging, where X-rays pass from the upside to the downside. A system for in vivo imaging was next constructed with a vertical configuration, as shown in Fig. 2(b). The specifications of the system are the same as those of Fig. 2(a) except for the X-ray tube. The focal spot size of the X-ray tube was changed to 450 m (FWHM) to shorten the exposure time, and the system spatial resolution was 113 m. The X-ray tube was operated with a tube voltage of 40 kVp and a tube current of 100 mA. A three-step fringe-scan was performed with this system, and the total scan time for obtaining a differential phase image was 32 seconds including 19 seconds of X-ray exposure. 2.2 Human cadaveric specimens We first imaged small parts of a cadaver, such as a finger, with the approval of the ethics committee of Saitama Medical University, Japan. A cadaveric hand was procured from the anatomy laboratory of Saitama Medical University (it had been preserved in 70% ethanol for one year after immersion fixation with 10% formalin for two weeks after the death of the donor). Figure 3 shows the first images of a cadaveric thumb obtained by the system shown in Fig. 2(a). When these images were measured, the grating lines were oriented so that differential features were sensed in the horizontal direction. The fingers were oriented horizontally in Fig. 3(c). For each image-acquisition, the average radiation skin dose was 9 mGy, which was measured using an ionization-chamber dosimeter. The resultant images were evaluated and correlated with macroscopic anatomical structures by a radiologist (J.T.) and an anatomist (M.N.). 2.3 Tests on healthy volunteers With the approval of the ethics committee, in vivo imaging tests on 10 healthy volunteers followed the tests on the cadaveric specimens. The images were obtained with the system shown in Fig. 2(b). A volunteer sat by the machine and placed his/her hand on the imaging table, underneath which G1 was located. The hand was aligned and held in the field of view, which was indicated by a guide light. The direction of the fingers was perpendicular to the grating lines so that the structures in joints could be effectively visualized. Figure 4 shows one of the images of the metacarpophalangeal joint of the third finger. Other images were similar to Fig. 4. The average radiation skin dose was 5 mGy. 3 Results The differential phase images showed a somewhat relieflike appearance, in which compact bone surfaces and trabeculae of the cancellous part that run vertically are enhanced as shown in Fig. 3. When the finger was aligned upright, the attenuation image and the differential image shown in Fig. 3(a) and (b) were obtained, respectively, consistently with the macroanatomic structures shown in Fig. 3(c). The tendons such as the flexor pollicis longus, of the flexor pollicis brevis and of the extensor pollicis were depicted in the differential phase image, which was not shown in the attenuation image, as Stutman D et al. reported [10]. ARTICLE IN PRESS 4 J. Tanaka et al. / Z. Med. Phys. xxx (2012) xxx–xxx Figure 3. Images of human cadavers: (a) Attenuation image of a right thumb aligned in the upright position, and (b) corresponding differential phase image. The tendons, such as the tendon of the flexor pollicis longus muscle (black arrows) and the tendon of the extensor pollicis muscle (white arrows), are clearly depicted. (c) Anatomical confirmation of the right thumb. (d) Attenuation image of a metacarpophalangeal joints of the second and third fingers, and (e) corresponding differential phase image. The surface of the cartilage is depicted, as indicated by arrows. ARTICLE IN PRESS J. Tanaka et al. / Z. Med. Phys. xxx (2012) xxx–xxx 5 specimens and 10 healthy volunteers. This new imaging technology has potential for clinical application such as detecting lesions on the surface of cartilage with a resolution of around 100 m. We have already proceeded to the next step with patients. These phase images shown here are totally distinct from absorption radiography, therefore we need to establish protocols for diagnoses. Then, detailed analysis of the imaging quality from a clinical point of view should be performed extensively. Although we consider that the current field of view is acceptable for the first clinical use of this imaging system, we are also enlarging the field of view to depict various other parts of the human body. 5 Conclusion We conducted a preclinical study of X-ray phase imaging based on X-ray Talbot-Lau interferometry. We constructed a system with an X-ray Talbot-Lau interferometer using a conventional X-ray tube and installed it in a hospital. The surface of the cartilage in finger joints was clearly depicted with both cadavers and 10 healthy volunteers. The potential of the system for the diagnoses of joint diseases has been demonstrated. Acknowledgement Figure 4. Images of a healthy volunteer: (a) Attenuation image of a metacarpophalangeal joint, and (b) corresponding differential phase image. The surface of the cartilage is depicted, as indicated by arrows. When metacarpophalangeal joints of fingers were placed in the field of view, the attenuation image and the differential image were obtained, as shown in Fig. 3(d) and (e) respectively. The surface of the cartilage is clearly depicted in Fig. 3(e). The metacarpophalangeal joint of the third finger of a healthy volunteer is shown in Fig. 4(a) and (b), where cartilage is as clearly depicted as in Fig. 3(e). This result shows that the fixation in formalin played no role in the cartilage contrast and sufficient sensitivity to cartilage can be expected in in vivo imaging. 4 Discussion In this trial, the technique of differential phase imaging was preliminarily tested to evaluate its potential for the diagnoses of joint diseases. The results show superior characteristics in the images of joint cartilages both of cadaveric We express deep gratitude to the radiologic technologists: Mr. Yukihito Wada, Mr. Hiroaki Kawasaki, Mr. Masaya Hirano, Mr. Masato Endo, Department of Radiology in Saitama Medical University, and Mr. Felix Thiele, medical student from the Charité Universitätsmedizin Berlin, for their advice and contributions to this study. This study was supported by the SENTAN project of Japan Science and Technology Agency. References [1] Momose A. Recent Advances in X-ray Phase Imaging. Jpn J Appl Phys 2005;44:6355–67. [2] Talbot HF. Facts Relating to Optical Science. Philos Mag 1836;9:401–7. [3] Momose A, Kawamoto S, Koyama I, Hamaishi Y, Takai K, Suzuki Y. Demonstration of X-ray Talbot Interferometry. Jpn J Appl Phys 2003;42:L866–8. [4] Weitkamp T, Diaz A, David C, Pfeiffer F, Stampanoni M, Cloetens P, et al. X-ray Phase Imaging with a Grating Interferometer. Opt Express 2005;13:6296–304. [5] Pfeiffer F, Weitkamp T, Bunk O, David C. Phase Retrieval and Differential Phase-Contrast Imaging with Low-Brilliance X-ray Sources. Nat Phys 2006;2:258–61. [6] Yashiro W, Takeda Y, Momose A. Efficiency of Capturing a Phase Image Using Cone-Beam X-ray Talbot Interferometry. J Opt Soc Am A 2008;25:2025–39. [7] Pfeiffer F, Bech M, Bunk O, Kraft P, Eikenberry EF, Brönnimann CH, et al. Hard X-ray Dark-Field Imaging Using a Grating Interferometer. Nat Mat 2008;7:134–7. ARTICLE IN PRESS 6 J. Tanaka et al. / Z. Med. Phys. xxx (2012) xxx–xxx [8] Yashiro W, Terui Y, Kawabata K, Momose A. On the Origin of Visibility Contrast in X-ray Talbot Interferometry. Opt Express 2010;18:16890–901. [9] Noda D, Tanaka M, Shimada K, Hattori T. Fabrication of Diffracting Grating with Height Aspect Ratio Using X-ray Lithography Technique for X-ray Phase Imaging. Jpn J Appl Phys 2007;46: 849–51. [10] Stutman D, Beck TJ, Carrino JA, Bingham CO. Talbot phase-contrast X-ray imaging for the small joints of the hand. Phys Med Biol 2011;56:5697–720. Available online at www.sciencedirect.com