by Vladimir BUSHUYEV, Dr. Sc. (Phys. & Math.), Physics Department, Lomonosov Moscow State University

In 1991 Russian scientists developed and patented a new method of producing X-ray images - roentgenograms - of weakly absorbing objects, including medico-biological ones. Since the discovery of X-rays by the German physicist, Prof. Wilhelm Roentgen, in 1895, they have found a whole range of applications in various fields of science and technology, including many uses in clinical practice. In this latter case we use the ability of X-ray to pass through materials and substances while being partially absorbed by them. As a result, doctors can, not only examine the inner organs of a patient, but take photographs of them.

ABSORPTION CONTRAST

X-rays, we know are hard electromagnetic radiation with a wavelength measuring about 1 A (10 ^-8 cm). Their most common source is the X-ray tube-a device consisting of an elongated glass vessel of 30-40 cm in length from which air is evacuated. At one end of this tube there is filament (cathode), and on the opposite end - a massive anode, made of some high- melting metal (copper, molybdenum, silver, tungsten). The voltage applied depends on the material and varies from 30 to 100,000 V and more. The electrons emitted by the cathode are accelerated by the strong magnetic field between the electrodes and bombard the anode at near-light velocity. The atoms of the latter are excitated, producing X-rays (consisting of what is known as bremsstrahlung with a broad spectrum and characteristic radiation - with a narrow one) which escapes from the tube through a special aperture, or window.

During radioscopy of an object under investigation the intensity of X-rays is decreased, being transformed into the inner energy of the irradiated material through the excitation and ionization of its atoms and molecules. The degree of damping of radiation depends on the absorption factor and thickness of

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Typical diagram of absorption roentgenoscopy:

1 - X-ray source; 2 - filter; 3 - beam of X-rays; 4 - investigated object; 5 - photo film.

the object through which the beam is passing. And the absorption factor is directly proportional to the density of the material and the wavelength of the X-rays cubed.

These characteristics are being used for studies of the inner structure of objects in different fields of science, such as materials studies, polymer physics, biophysics, biology and medicine. The traditional method of investigation of such materials, which are non-transparent in the visible band of the spectrum, is known as roentgenoscopy. It is based on an analysis of the spatial distribution of radiation intensity after its passage through some material and being weakened by absorption therein. Having said all that, let us now focus on the methods of investigation of the bodies of animals and humans.

A typical diagram of absorption roentgenoscopy (roentgenography, introscopy) can be described as follows: X-rays, passing through a special, selectively absorbing, filter (which cuts off the unnecessary longwave band of the spectrum), hit the object of investigation, pass through it in part, and end up on a photographic plate or film. The images thus obtained clearly show lighter spots, which correspond to denser bone structures, whose absorption factor for X-rays is high, and also dark, or dark-grey areas corresponding to the soft tissues. But these latter ones are not homogeneous in structure, containing, as they do, blood vessels, nerve fibers, lymph nodes, etc. And this is not to mention such vital organs as the heart, liver, lungs and so on, which all have inner structures of their own consisting of some fine (up to fractions of a millimeter), but vitally important "components".

And that means that the absorption techniques cannot be used for studies of organs with practically uniform density. This is connected with their only slightly different absorption factors and low contrast* in the images of smaller objects or sections thereof. In other words, a 99 percent darkening of the photo-film will reflect penetrating radiation with only one percent of it carrying useful information which, of course, is not enough for diagnosticians.

In fact, there are two ways of remedying the situation. The first involves increasing the length of exposure, which is absolutely unacceptable for living organisms because the absorbed dose of ionizing radiation will be substantially increased. In the second method X-ray contrast substances are administered into the patient's blood with salts of barium or ion-containing solutions. Due to large absorption coefficients of barium and iodine, the circulatory system is visible more clearly which makes it possible to detect blood vessel stenoses caused by the depositions of atherosclerotic patches on vessels' walls, or thrombosis. And even then the doses of X-rays have to be increased. What is more, the contrast substances are far from being harmless to man and can even be intolerable to some patients which is fraught with risks of lethalities.

Now, a brief look at radiation doses received by patients which are determined by a ratio of the absorbed energy to the mass of the irradiated matter and can be assessed by their impact on a living organism. According to data of the RADON R&D Center, the natural radiation background is 7-14 mcR/h, that is 60-120 mR/year, while the annual permissible dose stands at 500 mR. Now, is this much or is this little? For the sake of comparison: during one radiophotography session a patient received 60 mR, and during roentgenoscopy-500 mR. The obvious conclusion is that you better visit the X-ray room not more than once a year.

PHASE CONTRAST

But harmful as this method of medical investigations can be, it seemed that there was no alternative to it. But is that really so? To answer

* Contrast - in this case, a ratio of the maximum difference of darkening of sections of the image of object under investigation to its mean level.- Auth.

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Introscopy diagram with the use of phase contrast: a - by Lauet, b - by Bragg. 1 - X-ray source; 2 - crystal monochromator; 3 - beam of parallel X-rays; 4 - object under study; 5 - crystal analyzer; 6 - T-beam; 7 - R-beam; 8 - photo film.

this question, let us examine some physical peculiarities of X-rays interaction with various objects.

We have already mentioned absorption. But there exists one more and very important property of X-rays which has been known for quite some time, but which found no practical applications: during passage from one medium into another their direction is deflected by a certain angle which depends on a number of factors. First of all, this is the index of refraction which depends on the properties of the media (material, density), then the incidence of the primary beam, position of the spot which it "targets" and the shape of the object under examination.

Missing among the aforesaid factors is one of the most important of them - the wavelength of the incident beam. For X-rays, as has been said already, this is very small which leads to angles of refraction on the level of units and fractions of an angular second. To make this more vivid, let us say that the latter is equal to the angle at which an observer sees the tip of a match located 400 m away. For a long time this phenomenon was dismissed as unpromising and being of no practical value for studies of the inner structure of objects, mainly because of the complexity of dealing with very small angles of refraction.

But back in 1991, practically at one and the same time and independently from each other, Russian physicists Victor Somenkov, Sana Shilstein and several others (Kurchatov Institute of Nuclear Physics, now "Kurchatovsky Institute" Federal Research Center) and Viktor Ingal and Yelena Belyaevskaya ("Burevestnik" R&D Center, St. Petersburg) developed and put into practice a new method of introscopy based on the effect of X-rays refraction. They proceeded from the fact that these rays are electromagnetic waves with wavelengths comparable with interplanar distances in crystals. Radiation reflection from atomic planes occurs in the same way as in optics, although in this case planes play the role of an array of identical "mirrors" parallel to one another and to the surface of the crystal. Waves reflected from them interfere between themselves and, as it turns out, these are angles of inci-

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dence, known as Bragg angles (named after the British physicist who discovered them in 1912) at which strong diffraction* reflection is observed. In simpler words, at a certain combination of the wavelength, crystal lattice pitch and Bragg angle one can register the reflected radiation on a film or plate.

And there is another scheme which was suggested in 1912 by the German physicist, later Honorary Foreign member of the USSR Academy of Sciences, Max Lauet, which also makes it possible to "capture" diffracted beams, and not only one, but two. The thing is that in this case the atomic "mirrors"- planes are located perpendicular to the crystal surface, and X-rays, passing through its border, are split into two beams-passing or transit (T-beam) and reflected (R-beam) which also lend themselves to registration.

But for the implementation of both these schemes it is necessary to have crystals of a highly perfect structure. Such do not exist in nature, but modern technologies make it possible to produce practically ideal monocrystals of silicon, germanium, gallium arsenide and several others. But how, using them, can one photograph the images of invisible parts of objects making use of the effect of refraction?

From an X-ray tube radiation passes through a device called crystal monochromator which singles out a narrow spectral (characteristic) beam and transforms it into an almost parallel one, then targeting it

* X-ray diffraction - their scattering by crystalline objects when diffracted beams are emitted in certain directions - the result of interference of secondary X-ray emission produced by the interaction of primary radiation with electron shells of atoms. - Ed.

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at the object under investigation where it undergoes refraction. The values of refraction angles at different points depend on the inner structure of the object - the three-dimensional distribution of material within it. Then the rays fall upon the crystal analyzer and, being reflected from it (according to Bragg) or passing through, and splitting into T- and R-rays (according to Lauet diffraction pattern) are registered on film.

To get a better understanding of the process of image formation, let us consider three parallel beams. Let us say, one of them simply passing through an object, and the other two deflected at different angles depending on the density of the encountered material. And no matter how low this density can be-with the beam deflected only by tens and even hundredths of an angular second, everything will be recorded with practically 100 percent contrast, which means that any fine details of the inner structure of the object will be clearly visible on the film.

And the new method offers yet another and very important advantage. As has been said, the absorption factor of X-rays by a material, or substance, is proportional to the third power of the wavelength, while refraction angles only to its square. This makes it possible to reduce the doses of radiation absorbed by a patient by scores and even hundreds of times while having sharper contrast on the X-ray pictures and making them more "informative".

And it is easy to see that the new method of introscopy differs from the traditional one only by the addition of two crystals- monochromator, placed in front of the patient, and an analyzer located behind him. The only snag is that they have to be placed on special goniometric "props" which make it possible to turn the crystals at the required angles with high precision (such devices have long been used in X-ray diffractometry).

Now let us take a closer look at some of the results obtained in the very first experiments ofV. Ingal and Ye. Belyaevskaya. They began by taking X-ray pictures of a tank fish, which was 4 cm long, by the absorption method. And all they could see were its spine, ribs, fins and some details of the head with all the rest blurred on a dark-grey background. But pictures of the same fish made by the phase contrast method look quite different. One can clearly see details of the head, tongue, nose and mouth and also air bubbles. And one can also clearly see the spinal nerve column and its juncture with the brain and even a tiny worm which had been swallowed by the fish before the experiment.

The second example is even more convincing. On a traditional image of a white mouse one can see only the spine and the ribs, and even that not very clearly. On the phase-contrast pictures, taken in T- and R-beams, one can clearly see the arteries (thoracic and abdominal aortas, iliac-exterior), other and finer blood vessels and nerves and also lymphatic ducts, etc. with the latter ones being impossible to "picture" by no other known methods. The images thus obtained strike one with their clarity and sharp "relief. One gets an impression that what we are looking at is a section made with the scalpel.

Doctors are also pinning their hopes on roentgenoscopy for the early detection of malignant tumors. The conventional absorption method could not always cope with this task. And in 1997 the first results were obtained on the early detection of adenocarcinoma of the breast measuring 10х15 mm ² by the method of phase- contrast mammography. It turned out that the tumor image was of a similar quality as an optical one from a histological section of 3-5 mcm. The latter factor makes it possible to observe without a surgery the nature of morphological changes of the neoplasm and the propagation of metastases. On other such pictures it was possible to detect tumors of up to 1 mm in size and indurations with inclusion of calcium (microcalcinates) of up to 25 mcm.

To help one understand what introscopy is all about, I restricted myself to the "language" of geometrical optics, which is fair in dealing with objects with inner details of no less than 100 mcm. And in general one has to use a more precise concept-wave phase, which has established the term like "roentgen phase contrast". And with the advent of new intense sources of synchrotron X-rays it should be possible to obtain what we call phase-contrast images even without crystal analyzer which is very convenient in studies of objects of 1-100 mcm in size. This was put into practice for the first time in 1996 by Anatoly Snegiryov, Cand. Sc. (Phys. & Math.) and his colleagues (Institute of Problems of Technology of Microelectronics and Extrapure Materials, Chernogolovka) in obtaining X-ray holograms of fine organic fibers with the use of a high-coherence* beam from the ESRF synchrotron (Grenoble, France).

Until now we have been discussing applications of the X-ray phase contrast technique in biology and medicine. But it can also be used for studies of polymer and composite materials and products, and also in what we call phase-contrast defectoscopy, or flaw detection, to use a simpler term.

* Coherence-coordinated occurrence in time of several oscillatory or wave processes. - Ed.

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