by Alexander KARABUTOV, Dr. Sc. (Phys. & Math.), International Laser Center, M. V. Lomonosov Moscow State University
Over 400,000 people get afflicted with cancer in Russia every year. In many cases malignancy is diagnosed at advanced stages when costly combination treatment becomes necessary, often not effective. Unfortunately. The scope of the problem makes it imperative to search for reliable means of early diagnostics within everyone's reach.
Laser information technologies are one such breakthrough area.
Malignant neoplasms, if diagnosed at early stages (first or second, before secondary cancers), have good chances of cure and complete rehabilitation of patients. It all depends on early and urgent treatment. The same holds for mammary-gland tumors, and so there is good hope for such cases. The probability of mammary neoplasms increases with age, and that is why every woman over age 40 should undergo mammography (X-ray investigation, as a rule). This is common practice in the United States, for example. However, conventional techniques allow to identify tumors not smaller than 5 - 10 mm to a depth of 30 mm at best. Ultrasound diagnoses tumors as small as 5 - 6 mm to a depth of 25 - 30 mm. Unlike roentgenography, ultrasound is not accompanied by ionizing radiation harmful to sound tissues. But ultrasound is not used for mass medical examinations of the population. And what concerns nuclear magnetic resonance tomography (NMRT) now coming into use, it can give a three- dimensional image of a tumor lying no matter how deep. Unfortunately NMRT is both expensive and laborious, that is the diagnostics takes quite a bit of time.
But it is quite different with our method of laser optical-acoustic tomography (LOAT). It well supplements conventional techniques, and we are hoping it will be among state-of-the-art methods. LOAT produces optical images (in place of biopsy) of the investigated tissue. Such images are remarkable for high space and picture resolution showing a clear contrast between sound and neo-plastic tissues-in fact, dozens of times superior to that obtained by X-ray, ultrasonic or magnetic resonance tomography. Besides, LOAT radiation on several wavelengths makes it possible to spot heterogeneities and not only that: with the aid of this method we can collect quantitative information, for example, on the concentration of blood in the tissue and the degree of its oxygenation, i.e. oxygen saturation. Our method, unlike the conventional ones, enables the early detection and diagnostication of neoplasms (less than 3 mm in size) in depth (down to 70 mm). Besides, LOAT produces no ionizing radiation and works in real time; and many of the frames are updated thereby. In cost, LOAT can well compete with ultrasonic scanners, while it ensures a much higher image contrast, 20- to 50-fold as good.
Shorthand of mammary gland examination by LOAT.
The LOAT method was first conceptualized here in Russia. But it so happened that in 1983 it was patented in the United States and then received clearance for clinical uses (1997) in that country. As to the key technical ideas, some of them were realized in 1998 - 2001 when a group of Russian researchers (the author of the present article among them) was working in the University of Texas. The very first clinical tests in the hospital (Galveston, Texas), as twenty female patients were examined, showed the high efficiency of our method. For instance, doctors had trouble locating the tumor in one of the cases. Finally, using our tomograph, they could spot it on a silicone implant. Our apparatus performed fault-free in 19 other cases, too.
In 2002 the Russian Foundation of Basic Research and the Foundation Promoting the Development of Small Businesses in Science and Technology pooled efforts in financing the LOAT project. Clinical tests of the prototype are scheduled in the P.A. Herzen Oncological Institute of Moscow, in the Mammology Center of the Roentgenology Research Center and in the Medical Diagnostics Center of Moscow State University. Thereupon we aim to obtain permission from the Russian Federation's Health Ministry for clinical uses of our setup and for its production at Moscow's R&D enterprise ANTARES that has good experience in medical hardware manufacturing in cooperation with the Institute of Laser Information Technologies.
Now, about the specifics of the new method. We know that healthy and neoplastic tissues absorb light differently. The point is that malignant tissues have a higher concentration of blood within and thus the light absorption factor is higher respectively. Acted upon by laser pulse, malignant tissues are heated more. The different temperature distribution pattern is accompanied by pressure differentials that set the affected medium in motion. Off-loading (relief) is done by means of acoustic wave radiation. The faster the tissue is heated, the louder the sound (recall the bubbling and whistling kettle when boiling). The acoustic wave amplitude directly depends on the rate of temperature increase. Say, targeting a short laser pulse, we heat a body by 0.2°C, i.e. almost instantaneously. This excites an acoustic wave of 1 atm amplitude. In fact, optical-acoustic tomography makes use of much less intensive heating (a signal can be recognized at temperature down to 10 μK), quite sufficient for generating an acoustic wave of several Pa, i.e. 10-5 atm.
Since a tumor heats to higher temperature, the sound it gives off is two- threefold stronger than from the sound tissue. Data collecting and processing from dozens of points should be done within fractions of a second (in real time). To cope with this formidable job our laser center has designed and manufactured multielement focused piezoelectric antennae supplied with multichan-
An optical-acoustic image of a malignancy on a monitor screen.
nel charged preamplifiers and analog-to-digital converters, a world's unique technology. An acoustic signal is picked, numbered and fed to the screen of the central computer. The "snapshot" thus obtained is clearly distinct, its contrast range is so high that even a laboratory assistant can interpret it. Moreover, such kind of examination can be conducted in an automated mode.
We think this method may boost the diagnostics efficiency, for the image contrast of sound and cancerous tissues in LOAT is far superior to that achieved by other tomographies (by dozens of times, as we have said).
Furthermore, lightwaves are highly dispersive in biological tissues. We cannot take a clear picture of a tumor smaller than 5 mm seated as deep as 60 mm within the mammary gland since a beam of light penetrating to this depth is dispersed and, when bounced off, attenuates even more. Although Western scientists have suggested a number of optical methods of noninvasive biopsy, these are still at the clinical testing stage and do not show a sufficiently high resolution, be it 1 mm only, to a depth of more than 10 mm. But an acoustic signal, triggered with the absorption of a laser pulse, is not attenuated and not distorted. That is why tumor images thus obtained are quite clear. Well and good, but what about the nature of a neoplasm: malignant or benign? That is the problem! We can solve it by measuring the oxygenation level. The level is lower in the case of malignancy, and it is higher if the neoplasm is benign.
In technical terms, the diagnostic procedure is in two stages, though performed in split seconds. In the first stage, the tissue under study is irradiated by pulsed laser on alexandrite so as to determine blood concentration in tissues. Should some suspicious heterogeneity be detected (and this is the second stage!), a solid-state frequency- modulated laser is used so as to find out the level of oxygenation, and consequently, determine the nature of the neoplasm.
Our innovative diagnostic method allows to obtain two-dimensional tomograms in real time.
Mammography is not the only application domain of LOAT. As shown by experiments, this technique is effective in malignant melanoma diagnostics (this cancer is hard to diagnose by standard methods); it is likewise good for the mapping of blood vessels during complex surgeries, and for controlling the propagation of contrast agents in body organs, e.g., during photodynamic therapy.