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Perspective |
1 Department of Radiology and Radiological Sciences, Vanderbilt University
Medical Center, 1221 21st Ave. S., Nashville, TN 37232-2675.
2 Department of Physics and Astronomy, Vanderbilt University, Box 1807, Station
B, Nashville, TN 37235.
Received October 22, 2001;
accepted after revision March 4, 2002.
The Vanderbilt University project was supported by grants from the Office
of Naval Research (ONR-N00014-94-1-1023 and ONR grant #420-632-3913) and
Health Sciences Division, Eastman Kodak Corporation, Rochester, NY.
Monochromatic Versus Polychromatic X Rays
 Top Monochromatic Versus... Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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15
keV) are apt to be absorbed by the skin and subcutaneous tissues, yielding
little diagnostic information but contributing significantly to radiation
dose. X-ray photon energies above approximately 50 keV are less useful in
imaging and frequently undergo scattering in the imaged body part, reducing
signal-to-noise ratio, thus reducing the desirability of these energies as
well. An X-ray beam that is between 15 and 50 keV (not kVp), of narrow
bandwidth (a few kiloelectron volts), and tunable within that range to the
imaging task at hand would lend itself well to improvements in diagnostic
accuracy with reduced radiation dose to the patient.
Uses of Monochromatic X-Ray Beams in Medicine
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Current Practice in Mammography
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Monochromatic X Rays in Mammography
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Because the effective energy of current mammography units (Mo-Mo and Mo-Rh) is in the 16.8- to 19.7-keV range, additional work on breast specimens was performed at Brookhaven National Laboratories over the 14- to 18-keV range. This research confirmed that the apparent increase in linear attenuation continued through this lower energy range [2]. With cancerous lesions exhibiting, on average, a 10.9% increase in relative linear attenuation versus that of normal tissues, they should be easier to visualize using monochromatic beams in the range of 14-30 keV.
Unfortunately, long segments of normal tissues with low attenuation can become confused with short segments of high-attenuation tissue. This confusion illustrates the necessity of obtaining three-dimensional (3D) information from the breast in a reproducible way.
Breast Compression
The use of breast compression in mammography is understandable for reducing
radiation dose and spreading out architectural features relative to one
another; however, it is objectionable to most women, painful to many
[3], and lacks reproducibility
on a yearly basis [4]. If one
wishes to compile 3D information reproducibly in the breast by performing the
examination without compression, such a plan would increase the radiation dose
to the patient to unacceptable levels.
As a standard X-ray beam traverses a thick body part, the lower energy photons are basically filtered out of the beam in the first few centimeters of tissue. At each subsequent centimeter of tissue, the beam has essentially become "harder," and fewer photons remain in the beam to make their way to the detector. Because a monochromatic beam does not contain soft X rays, it does not undergo much hardening with the depth of tissue traversed. In this way, one does not need to start with a high flux to obtain the end result of more photons on the detector [5].
Computational techniques for the Monte Carlo assessment of glandular dose in mammography are available for both polychromatic spectra and monoenergetic beams. Monte Carlo techniques use specialized computer programs that track the absorption or scattering of millions of photons as they pass through computationally modeled matter. The course of the photon is randomly assigned, and the probability of its interacting at any given point or with any given element is determined by the flip of a coin. If heads, the type of interaction is calculated, the energy deposited noted, and the energy of the scattered photon determined. These calculations continue until the photon is extinguished or it exits from the organ. These calculations show that, in theory, monochromatic X-ray beams should increase contrast while they are, at the same time, allowing a decreased dose and examinations to be performed with less compression [6, 7].
Work also performed at Brookhaven has shown that in the range from 17-22 keV, radiation doses can be decreased even in large or uncompressed breasts, while the breasts maintain the same exposure to the detector. This decrease can be achieved with only minimal reduction in contrast [8].
In standard projection types of imaging performed using synchrotrons, the superiority of monochromatic mammography is becoming obvious [9, 10].
Obtaining 3D volumetric data from the breast without compression, resulting in the reproducibility of the visualized breast architecture year-to-year, would lend itself well to the use of computer-assisted diagnosis. Meaningful comparisons may be easier to make, particularly because of the ability of CT to eliminate overlapping structures, and small changes in the breast could be obvious because of the lack of any artificial distortion of the organ. This technique would need additional study to verify these suppositions. Even using polychromatic radiation, the potential for high signal-to-noise ratio images with low anatomic noise could be obtainable without compression at dose levels like those currently delivered by conventional mammography. Both in calculated and empiric observation experiments, attenuation differences between the various breast tissues, the contrast resolution obtainable, and the signal-to-noise ratios indicate that pursuit of 3D imaging of the breast should yield considerable success [11].
Although movement toward monochromatic mammography will not occur overnight, the clinical trials to test its efficacy must be examined in the light of the economics of the quality of lives saved and the cost to the patient, insurers, and social programs. Monochromatic X-ray machines will be more costly than standard mammography but will certainly be designed and built in such a way that they will service many examination rooms simultaneously, thereby effecting cost efficiencies and making the scanners more attractive to imaging facilities [12].
Although full-field digital mammography has not yet been shown to improve diagnostic accuracy [13, 14], the coupling of monochromatic X rays with digital systems for image acquisition would seem appealing because of the low noise and improved sensitivity compared with most current film systems. Many factors favor such a digitized format.
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Because we currently use compounds containing metal atoms for their dense attenuation effects, we already have an arsenal of drugs that can be targeted by a monochromatic beam. Iodine, for example, will attenuate X rays much more effectively at 33.2 keV than at any other energy, because the binding energy of the k-shell electron is 33.2 keV. When hit by a photon at that energy, the k-shell electron is ejected from its orbit, extinguishing the incident photon. Because monochromatic beams of a narrow bandwidth can be tuned to that energy, they can be used to decrease the amount of contrast material needed for angiography or can be used to significantly reduce radiation dose to the patient.
At worst, angiographic procedures would experience a minimum of twofold improvement in the "figure of merit," which relates image quality to radiation integral dose to the patient. Even in the most difficult imaging geometries, monochromatic X-ray beams can deliver the same image quality at about half the radiation dose to the patient compared with that delivered by conventional tubes [15].
Iodine is not the only atom that is useful for such imaging tasks. Gadolinium, for example, has a k-shell binding energy of 50 keV. If used in place of iodine, gadolinium agents could further decrease the radiation dose to the patient. By tuning the energy of the monochromatic beam and increasing it from 33.2 to 50 keV, the beam becomes more penetrating, and the body becomes more transparent to the X rays, with a lower radiation dose. However, the gadolinium will then act more efficiently in stopping the beam wherever it is placed.
Drugs custom-made to contain atoms within the tunable range of the monochromatic machines can be used to tag tumors for both diagnosis and therapy. The patient would take this medication that, over time, circulates and accumulates in the target tissue. The machine can then be tuned to the appropriate energy of the k-edge of the atom used to visualize its location in neoplastic tissues. Such drugs using COX-2 agents are already under development [16].
In addition, absorption of an X-ray beam as it traverses a patient is essentially a reflection of the sum of absorptions by individual voxels. Each voxel contains different chemical elements, thereby extinguishing different energies in a polychromatic beam. An image obtained by a monochromatic beam at one energy will look different from an image obtained at another energy. By sampling the body or a body part with two or more monochromatic energies, one may interrogate the tissues as to their composition. Therapeutic uses of monochromatic X rays are possible because of the tunability of the beam to the k-edge of metals that can be designed into medications targeting tumors or vessels around tumors. Drugs tagged with metals have been given in small doses to allow slow accumulation in tumors. The monochromatic X-ray beam could be better directed to these tagged drugs if a portion of the drug were tagged with a metal having a magnetic moment that could be localized using MR imaging. When the drug is irradiated with the monochromatic beam, the k-shell electron of the metal tag will eject from its orbit creating a localized cascade of radiation that should add its tissue-damaging effects to those of the drug itself. This procedure can be particularly useful for infiltrating tumors that cannot be excised either because of their location or the inoperability of a patient [17].
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Mammographic imaging (whether using a standard X-ray tube or monochromatic X rays) still yields only absorption data. Density changes, either from differences in specific gravity of adjacent tissues or the interfaces of different tissue types in the breast, will produce inhomogeneities in the refractive index of breast tissues. Because organic matter is made up predominantly of light elements such as carbon, hydrogen, oxygen, and nitrogen, X-ray absorption coefficients for these elements in the body approach zero. However, even these light elements cause X-ray phase shifts that are large enough to be detected. In fact, the X-ray phase-shift cross-section for light elements is 100-1000 times larger than the corresponding X-ray absorption cross-section [18, 19].
This type of imaging requires new detectors and analyzers to cull this information from the transmitted beam. Among several methods currently being tested to fabricate an analyzer, one method uses a Laue crystal made of thin silicon-111 [20]. If used in conjunction with a monoenergetic X-ray beam, the crystal could test the usefulness of refraction and diffraction optics in producing images of inhomogeneity in the refractive index of various breast tissues.
Optics using such a Laue analyzer produce simultaneous transmission and diffraction images of tissue samples. The investigation of synthesized images derived from optimum weightings of transmission and diffraction images should improve soft-tissue mass detectability.
Preliminary results using phantoms and excised tissues imaged with a Laue crystal analyzer and narrow slitlike beams of monoenergetic X rays appear in the literature [21, 22]. The data suggest the potential for increased sensitivity in the detection of soft-tissue masses. Experiments have already been performed using monoenergetic X-ray beam lines at synchrotrons. In these experiments, a Laue analyzer was placed behind the phantom or tissues at such a position relative to the X-ray detector that it yields simultaneously a transmitted X-ray beam and a refracted X-ray beam that do not overlap. Using an image storage plate as a detector and an 18-keV beam, researchers have coupled the phantom and image plate to a scanning stage and scanned them together through the exit X-ray beams from the Laue crystal. The images show excellent delineation of phase information.
Phase-contrast imaging with monochromatic X rays could also offer much quicker and more accurate assessment in patients with gunshot and combat wounds. Disruption of tissue planes, absence of flow in vessels, clothing and debris blown into the site of injury, and hematoma formation should all become more obvious without the use of contrast materials.
The images obtained via phase-contrast imaging are striking in their visual impact but leave one wondering how to interpret the data displayed. Much research will be required before the inevitable reeducation of radiologists who are daring enough to use this radically new technique.
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A single short high-intensity X-ray pulse (8 psec) and a rapidly gated (180 psec) multichannel plate-charge—coupled device combination must be used to temporally resolve the scattering events from the ballistic photons. Detectors for time-of-flight imaging are not yet available beyond the midteen kiloelectron volt range.
Small-Animal Imaging, Microscopy, and Metabolic Imaging
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Genetics researchers need imaging capabilities to study "knock-out" or "knock-in" mice. In these animals, a gene is removed or inserted, that is, knocked out or knocked in from the DNA sequence of a chromosome. To determine the anatomic consequences of such an alteration, imaging of the animal is undertaken. At the same time, other techniques are used to understand the metabolic and physiologic changes seen in the same animal. An attempt is then made to correlate the interrelationships between these structural and functional changes.
Using either direct or indirect methods, one can follow the development of angiogenesis around a tumor or the metabolism of a tissue by the accumulation or lack of various compounds. Work establishing the molar concentration needed for effective visualization remains a challenge.
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Production of Monochromatic X Rays
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Attempts at using custom-designed X-ray tubes made of various metals to emit individual characteristic X-ray frequencies are likewise not practical, and these tubes are not tunable across a broad energy range. Because most of the power delivered to these tubes is converted to heat, they are limited in the X-ray flux that they can produce. One new method for the practical production of pulsed tunable monochromatic X rays in a flux and geometry suitable for rapid human imaging, a laser synchrotron source, is described in the following paragraphs.
The phenomenon of inverse Compton scattering is one of the few physical processes that lends itself to production of such tunable monochromatic X-ray beams. This process consists of the counter propagation and headon collision of a tightly focused near-relativistic packet of electrons with an equally tightly focused intense pulse of photons. The photons scatter off the electrons at an interaction zone, and some of the energy of the electrons is imparted to the photons, effectively shortening their wavelengths. Hence an infrared photon goes into the process but is scattered back out as an X-ray photon (Fig. 1).
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Because Compton scattering requires sources of both high-energy electrons and intense infrared photons, the free-electron laser (a machine that uses such electrons to produce tunable infrared light) seemed a natural device to recombine both available beams to make monochromatic X rays [23].
In the summer of 1998, pulsed tunable monochromatic X rays were successfully produced by a beam line on the Vanderbilt University Free-Electron Laser (FEL), using the phenomenon of inverse Compton scattering [24,25,26,27]. Unfortunately, the process of using the FEL was somewhat cumbersome and inefficient. The radiation environment around an FEL was quite intense, necessitating redirection of the resultant X-ray beam out of a heavily shielded concrete vault, significantly reducing available flux for rapid human imaging [28]. Additionally, attempts to increase X-ray flux by more tightly focusing the electron beam in the interaction zone of the FEL led to poor performance by the entire machine and decreased the available infrared light.
By maintaining the desirable features of the FEL and disassociating X-ray generation from infrared light production, a group of scientists at the Vanderbilt FEL facility designed, built, and tested a superior, more compact high-brightness picosecond source. This new type of machine consists of a radiofrequency linear accelerator running in the single-pulse mode coupled to a tabletop terawatt laser. The device yields 1010 photons in each 8-psec pulse. The monochromatic X rays produced are tunable from 15 to 50 keV, in a bandwidth from 1.0% to 10.0%. The X rays radiate at a divergent half angle of about 10 milliradians from an apparent focal spot, which is the size of the focused e-beam and infrared beams at the interaction zone (20-50 µm) (Table 1). The geometry of the beam produced is therefore a conebeam covering a circular area. The machine is designed to service a multiroom facility (Figs. 2 and 3), runs in a "shirtsleeves" environment, is relatively compact, and emits so little background radiation that unbadged personnel can be in the same room with it while it runs.
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Devices such as this open the way for practical imaging of humans using monochromatic or near-monochromatic beams. The machine described previously was completed in the late spring of 2001 and has recently achieved stable imaging fluxes with each "shot." Among the first images obtained with this new device are those of phantoms in which each image was obtained with a single 8-psec shot (Fig. 4A,4B). Not all detector systems or film and screen combinations will work with such fast beams; hence the speckles in the images represent noise in the detector itself. Because the new machine is now on line, we can explore applications such as those described in my article and elsewhere. This opportunity opens an exciting new chapter in imaging technologies.
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On a different scale, Pellegrini [29] is extending the capabilities of the FEL itself into the self-amplified spontaneous emission mode for the production of tunable coherent high-peak—power soft X rays that will have a wave-length range of 2-4 nm, corresponding to the water window most suitable for imaging biologic samples.
Additionally, a bright, coherent hard X-ray source has been proposed for construction in Germany [30]. This source, almost 19 km long, would enable X-ray holographic imaging and other probe experiments not now possible even with the brightest synchrotrons.
Rapidity of Imaging and Dose Rate
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Because X rays are penetrating by nature, standard optics are of little use in attempting to bend or deflect a monochromatic beam to reach a laboratory or to take advantage of different projections in diagnostic imaging. However, X-ray wavelengths are of the same order of magnitude as the spacing between the planes of atoms in crystals (d-spacing). Because X rays go through a plane in a crystal, each atom scatters some of the X rays. Constructive interference will occur if the atoms and planes are at the proper angle to the beam, and it will appear that the X rays have been reflected. Using pure crystals is difficult, and the radiation tends to reflect in bands that are not useful for imaging. However, randomly oriented planes in mosaic crystals can correct this deficiency.
Mosaic crystals are manufactured of graphite that has been folded and compressed repeatedly under great temperature and pressure or vapor deposited in sufficient thickness onto a rigid substrate. This process creates a mosaic of crystal planes oriented in different directions. Because the crystal is made of carbon (a low Z material), the X-ray beam can penetrate the surface of the crystal without significant absorption until it finds the proper d-spacing needed for reflection at the Bragg angle. Graphite has one of the highest reflection efficiencies of 30-50% at 10-12°. It can, therefore, be used to deflect the monochromatic beams for various types of imaging requiring modification of the angle of incidence.
Multilayer X-ray mirrors are also available for lower X-ray energies. They are capable of reflections of X rays up to about 20 keV with good efficiency but at low angles, typically 1-10° [32]. Multicapillary glass optics are also capable of concentrating, focusing, or collimating X rays at angles and efficiencies similar to those of the multilayer mirrors. [33, 34].
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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Military and Industrial Applications
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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However, the pulsed nature of beams that can be produced by new devices opens the window to fast imaging of fast processes. Because picosecond pulses can be produced, the monochromatic beam could be used to study the internal workings of turbines that are operating at full speed, full load, and highest operating temperature. To these pulsed beams, the turbine would appear to be standing still. Deformation of internal components such as turbine blades or bearings would be obvious. Explosive processes such as failure modes of tank armor with kinetic weapons would also be amenable to scrutiny.
In conclusion, tunable monochromatic X rays can broaden our capabilities in rapid human imaging. They can help deliver information heretofore unavailable in a practical setting while simultaneously reducing the radiation dose to patients. Now that these monochromatic X-ray beams are available in a practical format and intensity, many more applications for them will arise over the next decade.
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TopMonochromatic Versus...Uses of Monochromatic X-Ray...Current Practice in MammographyMonochromatic X Rays in...K-Edge ImagingPhase-Contrast ImagingTime-of-Flight ImagingSmall-Animal Imaging,...Protein CrystallographyProduction of Monochromatic X...Rapidity of Imaging and...X-Ray OpticsInstantaneous CTMilitary and Industrial...References |
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  F. E. Carroll, M. H. Mendenhall, R. H. Traeger, C. Brau, and J. W. Waters Pulsed Tunable Monochromatic X-Ray Beams from a Compact Source: New Opportunities Am. J. Roentgenol., November 1, 2003; 181(5): 1197 - 1202. [Full Text] [PDF]
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