Physical methods in oncological diseases diagnostics
Synchrotron radiation application for oncological diseases risk forecasting
Tech Area / Field
- MED-DID/Diagnostics & Devices/Medicine
- ENV-EHS/Environmental Health and Safety/Environment
3 Approved without Funding
VNIIEF, Russia, N. Novgorod reg., Sarov
- Nizhny Novgorod State Medical Academy, Russia, N. Novgorod reg., N. Novgorod\nKurchatov Research Center, Russia, Moscow
- European Synchrotron Radiation Facility, France, Grenoble
Project summaryEarly diagnostics and opportune treatment are actual problems of the present-day medicine. One of the most important tasks within this field is the investigation of possibilities for oncological pathologies early diagnostics.
In the present-day oncology diagnostics of tumours consists of two stages: population mass examination in order to reveal tumours or their signs, and thorough examination of comparatively small groups selected during the screening in order to make the diagnosis more exact. The basic diagnostic test is the method of exfoliative cytology, when as objects under study the cells are used, which are somehow teared away into the environment from the tumour surface. The given examination enables not only tumour cells presence to be established, but some information of the neoplasm character – its tissue belonging and even histological structure – to be obtained. But perse punctures used to obtain matter for cytological examination present rather difficult and to some degree traumatizing operations, that is why puncturing could not be practiced as a mass method for early diagnostics.
Today to search for ways to improve nowaday methods of malignant growths early diagnostics the approaches are used that allow “tumour-body” system interaction to be taken into account. For this large effort is being applied to reveal growth markers. Wide spectrum of various growth markers necessitates that novel investigation methods be involved. Instrumental diagnostic techniques that make possible population screening examinations are of particular interest.
It is known that intracellular metabolism upset caused by diseases leads to changes in the bio-liquid chemical composition. Complicated dynamic processes that take place in the bio-liquids manifest themselves in morphological peculiarities of the structures developing during dehydration of the bio-liquid samples on solid substrates. At present original diagnostic methods built upon bio-liquid structural analysis are being developed and applied to clinical practice /1-3/. Bio-liquid solid phase structures are formed by molecules and mainly by microaggregates of organic and mineral substances dissolved in the bio-liquid. The structures specific peculiarities are defined by general physical-chemical properties of the bio-liquid, quantitative and qualitative composition of molecules of the given substances, their ability to establish intramolecular and intermolecular chemical bonds. As a result the bio-liquid structure carries integral information on the metabolism status of the organs washed by the bio-liquid and on the homeostasis of the body as a whole.
Biological liquid morphology is a new scientific line in the area of biology and medicine /4,5/. Bio-liquid structure formation at dehydration in an open volume on a solid substrate has clear regularities (phenomenon of dehydration self-organization). For example, when zone structures in a dried urine drop from patients suffering from proteinuria were being studied, there was revealed a phenomenon unknown before: ability of urine salts of patients with urolithiasis to crystallize in a protein medium (Shatokhina-Shabalin phenomenon) /6/. Basing on this phenomenon Litos test-system has been developed, which enables urolithiasis diagnosing at the preclinical stage. The Litos-sytem was patented and recommended to be applied to practice by the Ministry of Health of RF /7/. Today it is successfully used in Russian clinics.
Growth of malignant neoplasms is accompanied with specific micro- and macroelements metabolism upset at the level of the whole body, tissues, cells and at the subcell level as well /8/. The environment pollution with various toxicants, and heavy metals (HM) particularly, leads to the essential growth of probability of development of certain diseases, including malignant neoplasms /9-11/. Combination of morphological analysis with local element analysis for dehydrated bio-liquids of the body can serve as a new research instrument within the field of oncological diseases early diagnostics.
The present project goal is to develop a highly sensitive method for determining both vital and toxic chemical elements in the body biological liquid.
To detect heavy elements coming into the environment different up-to-date instrumental methods are used, among which nuclear methods hold an important position. Their distinctive features are high sensitivity, expressness, possibility of repeated analysis of one and the same assay, results independence of the aggregative state. Now at VNIIEF to study the assay element composition various techniques built upon nuclear reactions and roentgen fluorescent analysis (RFA) are employed. In particular, proton microprobe and a technique, in which total external reflection effect (TER) is used to improve spectra contrast /12-15/. These techniques having a detectability threshold of about 10–11 - 10–12 g (the relative one of about 10–6 - 10–8 g/g) are used in clinical diagnostics of some diseases, on these techniques ISTC projects #286 and #1229 are based.
Their goal consists in development and creation of a highly sensitive RFA technique on the base of TXRF effect and VNIIEF-developed selective thin-film sorbents. A possibility is not excluded for these sorbents to be used for metal traces detecting in bio-liquids. Microbeams of monochromatic synchrotron radiation (SI) being applied to the RFA task of HM detecting in the bio-liquids will allow the utmost capabilities of RFA technique within the given task to be achieved. As SR presents by itself electromagnetic radiation of high brightness, it will contribute both to measurement time decrease and the method sensitivity improvement (through a possibility of energy choice) as well. The beam dimensions can vary within a wide range from hundreds to units of micrometers. And in contrast to proton excitation, the element analysis can be carried out throughout the whole thickness of a bio-sample and requirements to electroconductivity and heat resistance can be excluded. By now there has been gleaned a considerable experience of SR employment in applied tasks, including those relevant to bio-medical studies.
The topics discussed in the project are the points of collaboration with the scientific collective of ESRF synchrotron (France) end Photon Factory, IMSS (Institute of Material Structure Science, Japan).
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3. E.G. Rapis, G. Yn. Gasanova. Auto wave process in the dynamics of phase transition in protein film // Sov. Phys. Tech. Phys. – 1991 - 36(4) - P. 406-412.
4. V.N.Shabalin, S.N.Shatokhina Principles of bio-liquids autowave self-organization // Bulletin of RAMS. - 2000, № 3, pp. 45-49.
5. V.N.Shabalin, S.N.Shatokhina Structural form of information in biological liquids // Col. «Actual problems of gerontology » - М., 1999. - pp. 139-143.
6. V.N.Shabalin, S.N.Shatokhina About the phenomenon of lithogenic salts pathological crystallization at urolithiasis // Collection of proceedings of scientific-practical conference “Crystallographic investigation methods in medicine”, Moscow - 1997. - pp. 25-29.
7. Europatent ЕР # 0 504 409 Method of diagnosing complicated urolithiasis and prognosticating urolithiasis / В1. V.N.Shabalin, S.N.Shatokhina. – registration date 1996.
8. G.A.Babenko Malignant growth, metals and chelating agents. Biological role of microelements. - М.: Science, 1983.
9. E.E.Tecutskaya, L.I.Sof’ina et al. Methods and practice of control of heavy metals content in bio-media. // Gigiena i sanitariya– 1999 - № 4 – pp. 72-74.
10. S.P.Smotrova, S.M.Chesnokova et al. Selenium deficit under conditions of environment pollution // Materials of III international scientific-practical conference “Physics and radio-electronics in medicine and bio-technology” – Vladimir, 1998. – pp. 304-305.
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12. V.T.Punin, S.N.Abramovich, M.E.Buzoverya, V.V.Chulkov et al. Bio-liquid element analysis with proton microprobe technique // Materials of 2-nd International conference. Almaaty: INP SNC RK - 1999. - v.1 – pp. 226-235.
13. V.T.Punin, S.N.Abramovich, M.E.Buzoverya, V.V.Chulkov, A.P.Morovov et al. RFA technique capabilities for some eye pathologies diagnosing // Materials of 2-nd International conference. Almaaty: INP SNC RK - 1999. - v.1 – pp. 278-281.
14. A.P.Morovov, Yu.V. Ignatiev, A.E.Lakhtikov, V.V.Chulkov et al. Wideband monochromators in roentgen fluorescent analysis with total external reflection // VAN&T, ser.: Reactor physics, special issue (Materials of Х1 International seminar on precise measurements in nuclear spectrometry) – 1997. – pp. 236-241.
15. S.N.Abramovich, A.P.Morovov, V.V.Nazarov, V.V.Chulkov Methods of middle and heavy elements detecting in ecological monitoring task // Materials of Х1 International seminar on precise measurements in nuclear spectrometry) – 1997. – pp. 234-235.
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