In 1895, Wilhelm Roentgen started the use of attenuation-based x-ray projection (shadowgraph) imaging , which revolutionized medical diagnosis. This was followed in 1972 by the introduction of clinical computed tomography , which provided more accurate estimates of anatomic dimensions and three-dimensional relationships as well as increasing the ability to characterize different tissues by their x-ray attenuation coefficients (or “density,” expressed in Hounsfield units). The third major development of clinical relevance, which now appears to be in the making, is the use of x-ray–matter interactions other than attenuation to generate x-ray images. Early approaches to this methodology have been restricted to proof of principle, but it now seems that this approach is starting to be introduced into biomedical research applications. The article in this issue of Academic Radiology by Parham et al titled “Design and Implementation of a Compact Low-Dose Diffraction Enhanced Medical Imaging System” is an example of the recent increasing ability to use consequences of the differences in x-ray refraction by matter to image biologic tissues.
X-rays’ interaction with matter can be summarized by the relationship between the compound refractive index of matter ( n ) to its two components, β (the absorption index) and δ (the refractive index), such that n = 1 − δ − i × β, where i = √−1. The magnitude of both coefficients changes with x-ray photon energy, but the value of δ is at least two orders of magnitude greater than that of β at clinically relevant x-ray photon energies. Hence, the attraction of phase-based x-ray imaging is due to its potential for greatly enhanced contrast rendition . The magnitude of the refraction angle decreases with increased x-ray photon energy (ie, decreased wavelength), so there is a trade-off between the use of increased photon energy (to increase the fraction of x-rays that are transmitted through the specimen) and the decreasing magnitude of the refraction angle. It would appear from the study of Parham et al that 59-keV photons provide a reasonable trade-off between these opposing factors, and as indicated by Lewis , at this photon energy, the kinetic energy released in matter because of x-ray exposure is also at a minimum for a given number of x-ray photons exposing a fixed area.
Demonstration of phase-based x-ray imaging has been possible for more than two decades by the use of the intense monochromatic, quasi-coherent, and near-parallel x-ray beams generated by synchrotrons. Synchrotrons are particle (electron or positron) accelerators, occupying acres of ground, that generate intense x-rays by virtue of the acceleration experienced by the particles (moving at near the speed of light) when being forced around the bends of an elliptical circuit or by rapid changes in magnetic field (so-called wigglers). These systems are unsuited for widespread clinical application but have proved very useful for providing feasibility demonstrations of the physics principles involved in various x-ray imaging approaches. The prediction that tissues should have higher contrast differences than is possible using attenuation-based x-ray imaging at comparable x-ray exposures has been demonstrated. The demonstration that bench-top x-ray sources, which generate Bremsstrahlung radiation, can also be used for phase-based x-ray imaging makes widespread practical biomedical applications more likely .
A particular feature of the refraction of x-rays by matter is that small regions of rapid change in refractive index, such as occurs at the surface of collagen fiber bundles in the breast or at the synovial fluid surface of cartilage , can result in local focusing or defocusing, depending on the distance of the detector from a region of tissue, of the x-ray passing through that region. If the imaging plane is positioned at a suitable distance from this region, local brightening (or darkening) occurs, much like the bright lines generated on a swimming pool bottom by sunlight shining through the small waves on the water’s surface. This effect highlights the edges of the structure out of proportion to the differences in attenuation of the two tissues. This approach was well developed using synchrotron radiation , but Parham et al now clearly show that this can be done using a Bremsstrahlung x-ray source using clinically relevant x-ray photon energies. However, because this involves selecting a narrow bandwidth from the Bremsstrahlung using a diffraction crystal (which acts by redirecting the x-rays at an angle determined by the x-ray photon wavelength and the subangstrom distance between adjacent atoms in the crystal, which is the x-ray equivalent of an optical grating [with micrometer-width “scratches” on glass] making a rainbow from white light), the actual intensity of postdiffraction x-rays available for such imaging is quite limited. Hence, the clinically relevant parts of the body that can be imaged are the hand and a compressed breast. This is because the x-rays are attenuated by the tissue, which further reduces the x-ray flux to a level at which the quantum noise-to-signal levels are comparable .
The specific methodology demonstrated by Parham et al involves scanning a plane of x-rays through the region of the object imaged, as well as “rocking” the “analyzer” diffracting crystal, positioned between the specimen and the detector, which can accurately measure the minuscule angle of an x-ray after it was refracted by the tissue. With this bench-top system, this took hours and hence is suitable only for imaging isolated tissue specimens. However, in vivo scanning during this double-scanning process would suffer from motion blurring and/or distortion because of the focal plane shutter effect . The use of the synchrotron to provide scans of a postmortem finger and breast tissue still involved a scan lasting almost an hour, and this is likely to be acceptable only in a clinical research setting.
Another approach to phase-based imaging involves the use of Talbot gratings , which encode the exposing and/or transmitted x-rays. This approach is more accommodating of broad-bandwidth Bremsstrahlung radiation, but it involves precise alignment and motion control of these high-precision gratings, which are designed to alter the refraction and attenuation of the transmitted x-ray beam in a predictable manner. Any deviation from this predictable pattern of refraction and attenuation caused by the grid(s) can now be used to deduce the spatial distribution of the refraction caused by the object. An advantage of this approach is that an area can be imaged with one exposure, although that area must be imaged several times, with one of the gratings (ie, the analyzer gratings) displaced incrementally from exposure to exposure. Although this approach may well be the basis for more widespread clinical applications of phase-based x-ray imaging, the approach of Parham et al provides a start at demonstrating the potential clinical feasibility and utility of using the refraction of x-rays to highlight the outlines of microanatomic structures (within isolated tissue specimens) that have little difference in x-ray attenuation.
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