Tomographic Imaging Using Monochromatic X-rays and Mosaic Crystals in the Geometry of Stationary Source, Object and Detector Frank Carroll, M.D. 1,3, Sarah Bixby, B.S. 2, George Thomas, B.S. 2, Robert Traeger, B.S. 1, James Waters, Ph.D. 3, Dale Evertson, Ph.D. 4, Marcus Mendenhall, Ph.D. 5, Cynthia B.Paschal, Ph.D.1,6, Caryl Brzymialkiewicz 6 And Gwen Banks 6. From the W. M. Keck Foundation Free Electron Laser Center At Vanderbilt University 1. - Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center 2. - School of Medicine, Vanderbilt University Medical Center 3. - Department of Physics and Astronomy, Vanderbilt University College of Arts and Sciences 4. - Department of Mechanical Engineering, Vanderbilt University School of Engineering 5. – W. M. Keck Foundation, Free Electron Laser Center at Vanderbilt University 6. - Department of Biomedical Engineering, Vanderbilt University School of Engineering Reprint requests: Frank Carroll, M.D., Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-2675. This research was funded by a Grant from The Office of Naval Research: ONR-N00014-94-1-1023 Abstract: Rationale and Objectives: -Tunable, pulsed, monochromatic X-rays are now available for use in imaging. In order to take advantage of the spectral, temporal and spatial uniqueness of these beams, development of useful X-ray optics and methods for data acquisition is required. Since differences in the linear attenuation of various tissues can be obscured using planar imaging, computed tomographic imaging is a natural extension of the first use of these X-rays. Our goal was to obtain tomographic information from a phantom, while keeping the X-ray source, the object to be imaged, and the detector all stationary. Materials and Methods: - Mosaic crystals mounted in a rotating frame were aligned with a monochromatized X-ray beam. The beam, object and detector remained stationary, while the crystals rotated. Perspective images were acquired using a fluorescent screen coupled to a CCD camera. The resultant images were used to compute the final tomographic “slices” of phantoms. Results: - Images reconstructed from the complete data set revealed three-dimensional information from the object. The X-ray beam acts as if it arises from a moving source, revolving in a coronal plane in front of the object. Conclusion: - Pyrolytic graphite mosaic crystals can be used to solve many of the problems created by a geometry in which movement of the X-ray source, the patient or the detector would be impossible or highly impractical. Tomographic images have been produced in this geometry, proving the potential for this new method of evaluating tissues, humans or materials. Keywords: Monochromatic X-rays, Mosaic crystals, Free-Electron Lasers, Computed Tomography, X-ray Optics, Mammography Introduction: Diagnostic imaging, such as that performed in humans for breast cancer screening or the characterization of palpable breast lumps, carries with it the burden of high radiation dose and a less than sterling record for sensitivity and specificity. Among the techniques under consideration to replace the current system is the utilization of pulsed, tunable, monochromatic X-ray beams, coupled to new detectors, and the collection of types of data heretofore unavailable (e.g.- Computed tomographic monochromatic images, time-of-flight images, and phase contrast images). As an extension of work by Johns and Yaffe (1), studies of linear attenuation characteristics were performed on normal and malignant breast tissues using monochromatic X-rays. These studies demonstrated that the malignant breast tissues absorb approximately 11% more monochromatic X-rays in the 14-18 keV range than do normal tissues (2). In other words, the cancers exhibit a higher effective atomic number than do the normal tissues. Since mammography, as now practiced, represents the three-dimensional breast as a twodimensional image on film, superimposing multiple structures upon one another, the effectively increased Z of the cancer would be superimposed on top of normal structures and the absorption differences would not be easily appreciated. Tomographic data would need to be collected to assist in unraveling these different tissues. However, the production of tunable, monochromatic X-rays by the Free Electron Laser (FEL) at Vanderbilt (3,4,5) now requires that the source of the X-rays remains stationary. Likewise, it is important that the patient remains still and the detector not move to obtain clearer images of small lesions. Taken all together, the stationary source, patient and detector are not conducive to the creation of tomographic images. Hard X-rays cannot be reflected by conventional optical surfaces such as mirrors, but they can be deflected through significant angles by Bragg diffraction off crystal planes. Monochromatic X-rays produced by the Vanderbilt FEL must be deflected though 40º to pass from the source in the high radiation vault to a shirtsleeves imaging laboratory on the second floor of the Keck FEL facility. Such a large deflection of X-rays below 21.2 keV can be achieved by first-order (002) diffraction off four graphite crystals or second-order (004) diffraction off two. However, perfect crystals have very small angular and energy acceptances. For example, using the data from Ref 7 we find that at 15 keV nearly perfect graphite has an angular acceptance (Darwin width) of 25”, or at a fixed angle, an energy acceptance of 4 eV. Pyrolytic graphite can be formed into mosaic crystals (6,7), also known as ideally imperfect crystals, which consist of many blocks randomly displaced. The displacements of the blocks are large compared to the X-ray wavelengths. The orientations of the blocks are described by the mosaic spread of the crystal, which is the full width at half maximum of the distribution of the normal to the planes in any block. In graphite the mosaic spread must be greater than 0.2º and is usually in the range 0.4º or 0.8º degrees. X-rays pass through the blocks until they find one oriented correctly for Bragg diffraction at their energy and incidence angle. The crystals selected for the FEL have mosaic spread of 0.4º, giving an energy acceptance at fixed angle of 840 eV at 15 keV. The first -order diffraction has 50 % reflection efficiency, while the second -order has 10 %. This material can also be bent, so that the curvature can be matched to the divergence of the beam, and hence the angular acceptance can be increased. Advanced Ceramics ®, Lakewood, OH, manufactured the crystals used in this work Our goal was to devise a method for the collection of tomographic information, keeping the monochromatic X-ray source, the imaged part, and the detector all stationary, by using mosaic crystals to effectively move the beam. Materials and Methods: A mammogram unit (Philips Diagnostat ®) Hamburg, Germany, and a continuous wave (cw) Mo X-ray tube (Kevex Inc., Scotts Valley, CA) were used as X-ray sources for this study. The mosaic crystals themselves monochromatized the X-rays from the standard sources. This approach was used to expedite the research, since these standard tubes produce a high enough photon flux for proof of principle, and can be used at any time, in contrast to one day a week use of the pulsed, tunable, monochromatic X-ray beams from the FEL, which is a multi-million dollar shared resource. The monochromatic beam from the FEL can be similarly aligned to the first crystal of the mosaic crystal rotator set. Analysis of the spatial distribution, frequency, and intensity of the X-rays delivered by the sources and as reflected from each of the crystals was performed first using a lithium drifted silicon detector cooled to liquid nitrogen temperatures. This was coupled to a Canberra ® 35 Plus Multichannel Analyzer (MCA), (Meridian, CT). However, a second detector, an AMPTEK XR-100CZT Bedford, MA, with a CdZnTe pickup that was thermoelectrically cooled and coupled to a Tracor Northern MCA, later replaced this detector. The output of the MCA in turn was connected to and displayed on a Macintosh PowerPC ® running Labview software (National Instruments, USA), from which the spectrum produced was displayed and stored as a file. The mosaic crystals used exhibit a mosaic spread of approximately 0.4 °, which is a reflection of the degree of randomization of the crystallites within the mosaic. These were manufactured by Advanced Ceramics , Lakewood, OH. This research was divided into four Stages: (I) - Obtaining images from an X-ray beam that had been reflected from multiple mosaic crystals simultaneously, (II) fabrication of a rotating device for the crystals and demonstrating the systems imaging capability, (III) replacement of film with a CCD camera for direct digital acquistion and the development of digital tomosynthesis using this unique beam geometry, and (IV) Improvement of X-ray photon flux by utilizing a bent mosaic crystal design. Stage I: The X-ray beam produced was separated into two equal beams by two mosaic crystals, with each portion of the split beam diverted by about 6 ° to either side of the path normally followed by these X-rays. (Figure 1) As the split, now monochromatized, beams reached a point 15 cm lateral to the centerline, they were then reflected back toward and beyond the original centerline at a 12 ° angle using a second set of mosaic crystals. The first "bounce" reduced the intensity of the desired X-rays at the usable frequency by 50%. The intensity of the X-rays reaching the second set of mosaics was reduced by 90% by that second "bounce", so that beyond the second crystal, at the desired frequency, only 5% of the intensity of the initial X-ray beam remained with which to image. A phantom was fabricated from radiolucent foam measuring 6 cm in depth. On each 2-cm layer of foam, objects were embedded to offer some 3-dimensional perspective to the probing beams. (Figure 2 A, B and C) The phantom was held during imaging in a radiolucent holder which was positioned 30 cm farther along the optical bench than the second set of crystals. Ten cm beyond the phantom an X-ray cassette was placed as a detection device. Sterling/Dupont Microvision C X-ray film was used in the cassette, which contained Quanta Super Rapid screens. The films were developed in a tabletop processor using standard chemistries with 90 second processing. Initially images were made through a 360-degree arc at 45-degree increments rotating the phantom in the coronal plane, but keeping the beam, crystals and film in the same plane. Mosaic crystals possess a property known as parafocusing, in which the source is imaged with unit magnification in the bend plane. In the transverse plane, the beam is slightly defocused. In the X-ray transport system designed for the FEL, in which the beam is to be transported about 10 m, the aspect ratio of a circular beam is changed to about 5:7. In the imaging system described here, the final beam is rectangular, approximately 5 mm by 50 mm. To successfully image a large phantom with this beam, required incrementing the film cassette and phantom laterally in 5 mm steps. These images were converted on a flatbed scanner to digital images and were in turn cropped and registered using Adobe Photoshop 5.0. (San Jose, Ca.) The set of X-ray images can be viewed serially or as an animated movie loop of GIF formatted images. The GIF files were knitted into the movie loop using the GIF Construction Set from Alchemy Mindworks. (Beeton, Ontario) When seen as the animated movie, it appears as if the viewer is flying around in front of the phantom in the coronal plane. Additionally, stereo pairs were produced on each film as a result of this dual crystal geometry. Stage II: After the initial imaging success, a rotating frame was constructed for the mosaic crystals. (Figure 3) This set of studies was performed utilizing a second foam and balsa wood phantom containing K-edge materials (Rb, Sr, Y, Zr, Nb, Mo), a step wedge of breast equivalent material, an aluminum step wedge, silicone from a breast implant, wire letters and brass insignia. (Figure 4) The beam, phantom and film could now remain stationary, while the mosaic crystals were moved intermittently in a rotating arc. Each 45 degrees of rotation of this mosaic frame describes a location on a circle of reference, which is delineated by a full 360 degree sweep of the outer set of crystals in the coronal plane relative to the sample. Again, since the X-rays are monochromatized and angularly selected, the beam describes a narrow line of radiation necessitating a type of line scanning to cover the extent of the imaged object. Linear scanning to cover the breadth of the phantom was achieved by translation of the rotating crystal frame toward the stationary phantom and film. The imaging was performed using this intermittent translate/rotate mode of operation. Film images were again obtained and handled in the same fashion as during Stage I. Stage III: Film was then replaced by a charge-coupled device (CCD) camera housed in a light tight enclosure and focused on a fluorescent screen positioned in a window behind the phantom. The window was opaque to visible light. Under software control (PixelView,Version 3.10,© 1997-1999 PixelVision Inc. Beaverton, OR), the camera captured direct digital images of monochromatic x-ray attenuation by the phantom with a matrix of 525 x 550 to 1050 x 1100 pixels over a 131 x 138 mm field-of-view. The smaller matrix size was chosen for some experiments simply to reduce file sizes for easier management. The files were output in TIFF format but with 2 bytes/pixel. `Three types of images were collected for a complete experiment. First, a "dark current" image with no incident x-rays was collected to reveal the output of the CCD camera when there was no light present. (Figure 5A) Next, a series of "targetless" x-ray images, one at each of the eight angular positions of the crystal rotator, without the phantom in place was collected. These images contained information about beam non-uniformity necessary for flat-field correction. (Figure 5B) Finally, a series of eight images with the phantom ("target") in one place was collected. These images were corrected for dark current and flat-fielded using pixel-by-pixel computation of (target - dark) / (targetless - dark). In the background image areas outside the beam, where the value of the denominator of this equation was very small, an output pixel value of zero was recorded. The result is an image illustrating only the attenuation characteristics of the phantom. Next, the eight corrected images were combined using digital tomosynthesis to reconstruct tomographic images of planes at any arbitrary depth in the phantom.(9,10) Each of the eight corrected images was shifted in two directions by a distance dependent upon the angle of the crystal rotator and the depth of the plane to be reconstructed and then summed with the other images, using Matlab software Version 5.2 (The MathWorks, Natick, MA) The resulting images show a single plane in focus with information from other planes out of focus. Some distortion in the images is engendered by the translation of the rotating frame, due to the magnification effect when the “line” source of the X-rays is moved closer to the object during imaging. Stage IV: To reduce imaging time and to improve the flux reaching the imaged part, a curved "bent" mosaic was designed to first capture more of the spherical wavefront of X-rays, focusing it to a small band on the second mosaic, (Figure 6 A, B) which in turn, is used to redirect the intensified beam onto the phantom. Results: X-rays from the mammography unit exhibit more bandwidth than those produced by the tunable, monochromatic beamline of the Free-electron laser. However, they suffice to prove the imaging principles, particularly in view of the fact that the crystals themselves serve to make the resultant beam near monochromatic. The spectrum from the X-ray tube, as determined by two detectors is shown in Figure 7A. The characteristics of the beam after the first crystal bounce are seen in Figure 7B and that after the second bounce in Fig 7C. The shape of the beam at the face of each crystal and at the image plane is shown next to the spectrum. The eight perspective images from various angles obtained in Stage I are shown in Figure 8. These images were obtained with the crystals stationary and the phantom rotating. They exhibit the perspective change, without backprojection algorithms applied. Figure 9 shows the eight raw data images obtained in Stage III with the CCD camera. These images were all made with the X-ray source, phantom and detector stationary. The crystals and their frame were the only portion of the imaging chain that rotated. The perspective changes are easily visible without reconstruction. Figure 10 represents one of the eight images from Stage III (see Figure 9) obtained from the CCD (a) before and (b) following dark current and flat-field correction. Figure 11 shows four representative computer reconstructed tomographic planes within the phantom, each approximately one cm deeper into the phantom than the image plane next to it. This reconstruction was the result of combining the eight corrected images from Stage III. Discussion: If we wish to take advantage of all of the temporal, spectral and spatial capabilities of tunable, monochromatic X-rays, we will need to develop unique X-ray optics. The development of mosaic crystal imaging devices, such as that described here, can be expanded for use even with standard X-ray tubes if they have adequate cooling built in. They can also be used at higher energies for just about any body part. Although the devices described here are directed toward lower energy X-rays (between 10 and 20 keV), mosaics, such as LiF and Be004, are currently available for use at higher energies. Graphite mosaics can be used up to 40 keV, but the scattering angles become shallower and larger optics are needed to perform efficient focusing. Use of a tomographic technique, such as that presented here, or with the use of back projection algorithms, we would also lessen the necessity for breast compression during imaging, since the superimposition of tissues is no longer problematic. When similar but more extensive arrangements of mosaics are coupled with more intense monochromatic X-ray sources, such as that currently under construction at the W. M. Keck Vanderbilt Free Electron Laser facility, full tomographic data sets could conceivably be obtained in a single 2 ps burst of monochromatic X-rays. References: 1. - Johns PC, Yaffe MJ. X-ray characterization of normal and neoplastic breast tissues. Phys Med Biol , 1987, 32:675-695. 2. - Carroll FE, Waters JW, Andrews WW, Price RR, Pickens DR, Willcott R, Tompkins P, Roos C, Page D, Reed G, Ueda A, Bain R, Wang P, Bassinger M. Attenuation of Monochromatic X-rays by Normal and Abnormal Breast Tissues. Invest Radiol , 1994, 29:266-272. 3. - US patent #4,598,415. Luccio AU, Brill BA. Method and apparatus for producing X-rays. Dated Jul 1, 1986. US Patent Office. 4. - Carroll FE, Waters JW, Price RR, Brau CA, Roos CF, Tolk NH, Pickens DR, Stephens WH. Nearmonochromatic X-ray Beams Produced by the Free Electron Laser and Compton Backscatter. Invest Radiol, 1990, 25:465-471. 5. – Carroll FE, Waters JW, Traeger RH, Mendenhall MH, Clark WW, Brau CA. Production of Tunable, Monochromatic X-rays by the Vanderbilt Free-Electron Laser. Proceedings SPIE Conference on FreeElectron Laser Challenges II, SPIE , 1999, vol. 3614, 139-146. 6. - Sparks CJ. Mosaic Crystals for Obtaining Larger Energy Bands and High Intensities from Synchrotron Radiation Sources. SSRL Report No. 78/04, May 1978. 7. - Ice GE, Sparks CJ. Mosaic Crystal X-ray Spectrometer to Resolve Inelastic Background from Anomalous Scattering Experiments. Nucl Instr and Methods in Physics Research , 1990, A291:110-116. 8. - Tompkins, PA. Application of Graphite Mosaic Monochromator Crystals for X-Ray Transport. Journal of X-Ray Science and Technology , 1994, 4: 301-311. 9. – Kruger RA, Sedaghati M, Roy DG, et al. Tomosynthesis Applied to Digital Subtraction Angiography. Radiology, 1984, 152:805-808. 10.- Maravilla KR, Murry Jr. RC, Horner S. Digital Tomosynthesis: Technique for Electronic Reconstructive Tomography. AJNR, 1983; 4: 883-888. Legend: Figure 1. - In Stage I of the study, a beam of X-rays from a mammogram tube, was split into two beams by two stationary mosaic crystals. Thus each half of the beam was reflected about 6 from the central axis of the system (an 11.9 bounce relative to the crystal face) onto two additional crystals which redirected them at 12 ° (23 relative) crossing the midline through the object and then onto the detector. In Stage II, the crystals were affixed to a rotating frame FR so that they could rotate 360 ° around a plane coronal to the object and film. The frame translates toward the object to allow for complete coverage of the specimen. Figure 2. -A. - First phantom developed to test the crystals, consisted of various metallic and non-metallic targets. The letters FEL were distributed three-dimensionally through the phantom, so that the name FEL would only appear as one word from a single perspective at 0 on the coronal circle followed by the rotating crystals in Stage II of the study. 2 B. - AP radiograph of the phantom. 2C. - Lateral radiograph of the phantom. Figure 3 – Mosaic crystal rotator. The crystals are attached to stages that in turn attach to the aluminum frame, which is the only portion of the device that rotates. The outer black shell is a temporary support device used while awaiting installation of cantilevered bearings for unobstructed rotation. Figure 4. – The phantom developed for Stage III contained letters similar to those in Phase I and II, however, MXI was attached to the face of the phantom as was the caduceus, while the letter L and the Vanderbilt shield were affixed to the rear of the phantom. The letters F, E, and L are at levels each approximately one cm. lower in the phantom. Figure 5. - Digital x-ray images obtained with crystal rotator and captured by CCD camera. (5A) Dark current image reveals camera output when no x-rays are used. (5B) Targetless image demonstrates effects of crystal on beam shape and uniformity in the absence of attenuating materials Figure 6. - A. - When an X-ray beam strikes a mosaic crystal, only those photons with the right energy will reflect at the desired angle. Additionally, only those photons at the right angle to the crystal will reflect at that same angle. Much of the beam is wasted because the spherical wavefront hits portions of the crystal at too steep or too shallow an angle for reflection. This leaves only a narrow, vertical beam of photons for imaging. 6B. - If one curves the mosaic to conform to the shape of the spherical wavefront, photons will reflect from more of the entire surface at the same energy if the angles 1,2 and 3 are equal. Figure 7. - Spectra from the MCA, are shown A. - before, B. - after one bounce, and C. - after two bounces off of the mosaic crystals. The shape of the X-ray beam is also shown with each spectrum. Since the mosaic spread of the crystals is large enough, it accepts photons from 17-19 keV, but eliminates the lower energy and higher energy photons. The monochromatic X-ray beam produced by the FEL gives a narrower bandwidth of radiation. Figure 8. - Plain film perspective shots from Stage I with angles marked. Figure 9. Raw data images from eight different angles and positions on the circle of rotation described by the mosaic crystal rotator, as captured by the CCD camera. (Stage III) Figure 10. – One of the eight images from Figure 9 corrected for dark current and beam inhomogeneities. . (A) Target image shows attenuation of x-rays by phantom with dark current and beam shape and uniformity effects evident. (B) Corrected image created by computing (target - dark) / (targetless - dark) on a pixel-bypixel basis with most background pixels set to zero. Figure 11. - Computed tomographic reconstructions of the phantom showing four different levels within the 3-dimensional phantom. Until the images were reconstructed the experimenters were unaware that the wire letter L had fallen off of the back of the phantom. Figure 1 . Figure 2. Figure 3 Figure 4 Figure 5 A Figure 6 A Figure 5 B Figure 6B Figure 7. Figure 8. Figure 9 A Figure 10 B Figure 11