RU2184486C2 - Method and device for diagnosing oncological diseases - Google Patents

Abstract

FIELD: medicine; medical engineering. SUBSTANCE: method involves testing organs by applying various physical methods. Healthy tissues are investigated under irradiation with a monochromatic light beam to produce its fluorescence spectrum. Then, the tissue is excited with polychromatic light in wavelength range of 400-800 nm to built reflection spectrum. Suspected tissue of the same organ is investigated to produce reflection spectrum and fluorescence spectrum in the same way, compare the spectra between themselves, carry out computer processing of investigation results and calculated diagnostic parameter value from formula:

, where I_max is the spectral line maximum intensity in the 590-605 nm strip. I(578) is the spectral line maximum intensity at the point of 578 nm corresponding to blood absorption peak; I_max, I(578)n are related to healthy tissue, I_maxc and I(578)c are related to suspected tissue. q≈0, healthy tissue is diagnosed.

Description

 The invention relates to the field of spectrophotometric studies and can be used in the study, functional diagnosis of precancerous and cancerous conditions in oncology (in particular, for the study of dysplasia; glandular-solid and solid cancers; Skirr cancers; infiltrating cancers; fibroadenomas, etc.) and other branches of medicine, as well as in instrument making in the manufacture of medical equipment.

 Known methods and devices for detecting malignant and benign tumors in the human body, such as NMR diagnostics, X-ray computed tomography, thermography, ultrasound diagnostics, diagnostics using radioisotopes or with the introduction of photosensitizers.

[cm. e.g. N.I. Rozhnova. X-ray diagnosis of breast disease, 1993; B.Z. Shishkin. Radionuclides in the diagnosis and treatment of breast cancer, 1986; a. from. USSR 1320921, MKI A 61 B 6/00, declared 19.07.85, publ. 04/15/94. A method for diagnosing breast disease by thermography; RF patent 2013999, MKI A 61 B 6/00, pending. 01.16.91, publ. 06/15/94. A method for determining the functional state of the path of lymphogenous metastasis of gerota in breast cancer]
The results of determinations by known methods and devices are aggravated by significant errors due to, for example, inflammatory processes in tissues, artifacts, non-selective accumulation of diagnostic drugs, etc.

 Spectral luminescent methods and instruments for diagnosing blood and other biological tissues are also known, based on spectroscopy of intrinsic fluorescence of cell structures or the introduction of additional exogenous photosensitizers into an object.

[cm. for example, US patent 4,556,057, MKI A 61 B 6/08, NCI 128 / 303.1, claimed. 03/11/83, publ. 12/03/85. A device for diagnosing cancer using pulsed laser radiation; A.S. USSR 1681204, MKI G 01 N 33/52, decl. 05/10/89, publ. 09/30/91. A method for the study of histological preparations; a. from. USSR 1466704, MKI A 61 B 5/00, decl. 14.04.86, publ. 03/23/89. A method of intraoperative diagnosis of tissue viability, etc.]
However, the known methods and devices do not provide a stable registration of differences in the spectra of normal and cancerous tissues, do not allow to reduce the time of diagnosis of the disease, can cause the manifestation of adverse reactions from the human body.

 In addition, optical methods for diagnosing cancer are widely known, including measuring diffuse reflection and transmission coefficients of normal tissues and breast cancers.

[see, for example, A.N. Korolevich et al. Features of diffuse reflection and transmission spectra of normal and tumor tissues. Journal of Applied Spectroscopy, Volume 58, 5-6, May-June 1993, p. 555-559 etc.]
These methods, as a rule, are implemented on tissues obtained after surgery, the blood supply of which is impaired, and, therefore, the accuracy of the measurements is low. In addition, the determination time takes at least 2-3 hours.

 The closest in technical essence and the achieved result to the claimed invention is a method for the diagnosis of cancer (Method for determining cancerous tissue using visible natural luminescence), including testing the organ with known physical methods (palpation, mammography, etc.), the study of suspected tissue by exciting it with a bundle monochromatic light to obtain a fluorescence spectrum and comparing it with a similar spectrum of normal tissue (reference sample) followed by pyuternoy processing of the survey results.

 A device for implementing the known method consists of a light source (halogen lamp or argon laser), an optical communication unit, a radiation supply and collection system, a spectrum analyzer and a computer.

[cm. U.S. Patent No. 4,930,516, MKI A 61 B 5/00, NCI 128/665, claimed 04/25/88, publ. 06/05/90]
The described method and device for the diagnosis of cancer do not provide:
- accuracy of determination due to the use of averaged reference samples that do not take into account the individual characteristics of the organism, and the storage conditions exacerbate the determination errors;
- reliability as a result of the study of only the fluorescence of the suspected tissue;
- increased expressivity due to the need for long-term preparation of reference samples;
- the ability to determine oncological diseases of soft tissues due to in vivo analyzes using a probe (endoscope) from an optical fiber to examine the human hollow organs (stomach, lungs, urinary tract, intestinal tract, colon, throat, etc. )

 In addition, in the known method and device for the diagnosis of cancer there is no diagnostic parameter that allows you to classify the type of tumor.

 It should be noted that the known method, although characterized by expressivity, does not take into account the time of obtaining information about reference samples (preparation of normal tissues "in vitro", removal of their fluorescence spectra, formation of a data bank in a computer).

 It should also be noted that in the known invention, studies were performed on laboratory animals and the results were extrapolated to humans, which is not correct due to the mismatch of the fluorescence peaks of animal and human tissues.

 The objective of the present invention is to increase the diagnostic efficiency of the expressness of determination with the possibility of diagnosis in accordance with the morphological classification of tumors.

где Imax - интенсивность максимума линии спектра в области 590-605 нм;
I(578) - интенсивность минимума линии спектра в точке 578 нм, соответствующего пику поглощения крови;
Imaxn, I(578)n - для нормальной ткани;
Imaxc, I(578)с - для подозреваемой ткани,
причем при q≈0 - диагностируют нормальную ткань, а при 0<q<0 - наличие онкологического заболевания с конкретизацией вида опухоли по величине q.The problem is solved in that in a known method for the diagnosis of cancer, including testing an organ by known physical methods, examining a suspected tissue by exciting it with a beam of monochromatic light to obtain a fluorescence spectrum and comparing it with a similar spectrum of normal tissue, followed by computer processing of the research results, according to the invention Before examining suspected tissue, normal tissue of the same organ is examined by waking it up with a beam of monochromatic light to obtain a fluorescence spectrum and then exciting it with a beam of polychromatic light in the wavelength range of 400-800 nm to obtain a reflection spectrum, and when examining a suspected tissue before generating a fluorescence spectrum, excite it with a beam of polychromatic light to obtain a reflection spectrum that is compared with a similar spectrum of normal tissue; the condition of suspected tissue is judged by the ratio

where Imax is the intensity of the maximum of the spectrum line in the region of 590-605 nm;
I (578) is the intensity of the minimum of the spectrum line at 578 nm, corresponding to the peak of blood absorption;
Imaxn, I (578) n - for normal tissue;
Imaxc, I (578) s - for suspected tissue,
moreover, at q≈0, normal tissue is diagnosed, and at 0 <q <0, the presence of an oncological disease with a specification of the type of tumor in terms of q.

 The known device for the diagnosis of cancer, consisting of a light source, an optical communication unit, a radiation supply and collection system, a spectrum analyzer and a computer, according to the invention, contains an additional radiation source, and the radiation supply and collection system is mounted with a single medical needle having a monofilament inside hard fiber.

The implementation of the diagnosis of cancer in the claimed conditions using the proposed device increases:
- accuracy of determination by eliminating errors associated with the use of averaged reference samples, instead of which normal tissue of the same organ of a particular patient is used as the object of comparison;
- reliability due to the study of various characteristics (fluorescence and reflection) of the suspected tissue;
- expressity (not more than 10 s) due to the exclusion of the operations of preparation and study of reference samples.

 In addition, the proposed method and device for the diagnosis of cancer expand the range of diagnosed tumors, providing the ability to analyze soft tissues, while containing a diagnostic parameter that allows you to classify the type of tumor.

 Analysis of the known technical solutions allows us to conclude that the claimed invention is not known from the level of the studied technology, which indicates its compliance with the criterion of "novelty."

 The essence of the claimed invention for a specialist does not follow explicitly from the prior art, which allows us to conclude that it meets the criterion of "inventive step".

 The ability to diagnose cancer in the conditions of the proposed method using the proposed device, made from commercially available items, indicates the compliance of the claimed invention with the criterion of "industrial applicability".

 The inventive "Method and device for the diagnosis of cancer" passed clinical trials in the clinical department of the regional oncology clinic in Novosibirsk.

 Figure 1 schematically shows the inventive device for the diagnosis of cancer.

Designations in figure 1:
Light sources:
1 - laser LTN-402,
2 - halogen lamp;
Optical communication unit:
3 - condenser
4 - rotary mirror
5 and 5 '- transmitting cable;
Radiation supply and collection system:
6 - translucent mirror
7 - lens (achromatic),
8 - universal connector standard SMA (input),
9 - universal connector standard SMA (output);
10 - spectrum analyzer (multichannel);
11 - computer;
12 is a one-time medical needle with an internal monofilament rigid optical fiber (not shown in FIG. 1).

In FIG. 2-5 are presented:
figure 2 - fluorescence spectrum of normal tissue;
figure 3 - reflection spectrum of normal tissue;
figure 4 - fluorescence spectrum of suspected tissue;
5 is a reflection spectrum of suspected tissue.

 The inventive device for the diagnosis of cancer works as follows.

 Light radiation from sources 1 or 2 through a condenser 3 is supplied through input fiber 5 via a fiber-optic cable 5 to input connector 8. Light radiation can be supplied either from laser 1 (for observing fluorescence) or from a halogen lamp 2 (for observation diffuse reflected radiation).

 Then the radiation is collected, focused by lenses 7 into a monofilament rigid optical fiber of a single-use medical needle 12 (the outer diameter of the needle is not more than 1 mm) and is fed directly to the area of the diagnosed tissue.

 Fluorescent or diffuse-reflected radiation is supplied through the same waveguide to a translucent mirror 6 and focused on the output connector 9, from which it is fed through a fiber-optic transmission cable 5 to a multi-channel spectrum analyzer 10. From the output of the spectrum analyzer 10, the signal is fed to the input of computer 11, the screen of which displays the fluorescence spectrum or diffuse reflection in graphical form.

 Example. Diagnosis of cancer.

 Patient Z., 49 years old, was admitted to the clinical department of the regional oncological clinic in Novosibirsk (medical history N 1416).

 After testing the mammary gland by known physical methods (palpation, mammography), the presence of a tumor process was previously established.

Then the patient was sent for spectrophotometric study, in which:
- before examining the suspected tissue, normal tissue of the same organ (mammary gland) was examined, for which a single medical needle (pos. 12, Fig. 1) was inserted to a depth of 5 mm, the laser was turned on (pos. 1, Fig. 1) and removed fluorescence spectrum of normal tissue after its excitation by a beam of monochromatic light with a wavelength of 532 nm, a power density of 2.1, a time of 5 s — see FIG. 2.

 After that, the laser was turned off, the halogen lamp was turned on (pos. 2, Fig. 1) and, without moving the needle, the reflection spectrum of normal tissue was taken after it was excited by a beam of polychromatic light in the wavelength range of 400-800 nm - see Fig. 3.

где Imax - интенсивность максимума линии спектра в области 590-605 нм;
I(578) - интенсивность минимума линии спектра в точке 578 нм, соответствующего пику поглощения крови;
Imaxn, I(578)n - для нормальной ткани;
Imaxc, 1(578)с - для подозреваемой ткани.Without removing the needle, they began to advance to the site of the tumor process, exciting the tissue with a beam of polychromatic light (from a halogen lamp) in the wavelength range of 400-800 nm with simultaneous removal of the reflection spectrum (see Fig. 5), comparing it with a similar spectrum of normal tissue (see figure 3), computer processing of the results of the study and the calculation of the value of the diagnostic parameter q according to the formula

where Imax is the intensity of the maximum of the spectrum line in the region of 590-605 nm;
I (578) is the intensity of the minimum of the spectrum line at 578 nm, corresponding to the peak of blood absorption;
Imaxn, I (578) n - for normal tissue;
Imaxc, 1 (578) s - for suspected tissue.

 The value of the diagnostic parameter q is fixed on the computer screen.

 Reflection spectra reflect the macroscopic structure of the tissue and are used to detect the location of the tumor.

 When the parameter q reached + 5% (in other cases, q = ± 5%), it was believed that the needle was in the tumor area.

 The halogen lamp was turned off, the laser was turned on, and the fluorescence spectrum of the suspected tissue was recorded (see Fig. 4) after its excitation by a beam of monochromatic light with a wavelength of 532 nm; power density 2.1; time 5 s.

 Fluorescence spectra reflect biochemical intracellular tissue processes.

 The obtained fluorescence spectrum of the suspected tissue (figure 4) was compared with the fluorescence spectrum of normal tissue (figure 2) with simultaneous computer processing of the results of the study and the calculation of the value of the diagnostic parameter q according to the formula above.

 The q value is fixed on the computer screen.

 Got q = 30%, which corresponds to the presence of cystic fibroadenomatosis (the diagnosis is confirmed by histology 9663-67).

 In conditions similar to the example, a study of 140 patients with both benign and malignant neoplasms in the body was conducted.

As a result of these studies, the following values of the diagnostic parameter q were established, which make it possible to classify the type of tumor:
-50 - -40% - dysplasia;
-40 - -20% - solid cancers;
-20 - -2% - Skirr cancers and any tumors with inclusion of Skirr cancer;
+2 - + 15% - infiltrating cancers;
+15 - + 25% - glandular solid cancers;
+25 - + 45% - fibroadenomas.

The use of the claimed "Method for the diagnosis of cancer and the device for its implementation" in comparison with the known method and device taken as a prototype [see US patent 4930516] provides the following technical and socially beneficial advantages:
- increase diagnostic efficiency and expressness of determination;
- the possibility of diagnosis in accordance with the morphological classification;
- reducing the invasiveness of the method;
- the possibility of using the proposed invention as a basis for the development of a new method of individualization of treatment of oncological diseases.

Claims (2)

1. A method for diagnosing cancer, including testing organs with physical methods, examining a suspected tissue by exciting it with a beam of monochromatic light to obtain a fluorescence spectrum and comparing it with a similar spectrum of normal tissue, followed by computer processing of the test results, characterized in that prior to the investigation of the suspected tissue, study of normal tissue of the same organ by excitation with a beam of monochromatic light and subsequent exciting it with a beam of polychromatic light in the wavelength range of 400-800 nm to obtain a reflection spectrum, and when examining a suspected tissue before obtaining a fluorescence spectrum, excite it with a beam of polychromatic light to obtain a reflection spectrum that is compared with a similar spectrum of normal tissue, while on the condition of the suspected tissues are judged by the ratio

where Imaxc, Imaxn are the intensities of the maximum of the spectrum line in the region of 590-605 nm for the suspected and normal tissues, respectively;
I (578) c, I (578) n is the intensity of the minimum of the spectrum line at 578 nm, corresponding to the peak of blood absorption, for suspected and normal tissues,
moreover, at q≈0 normal tissue is diagnosed, and at

- the presence of an oncological disease with specification of the type of tumor in magnitude q.  2. The device for the diagnosis of cancer, consisting of a source of monochromatic light radiation, an optical communication unit, a radiation supply and collection system, a spectrum analyzer and a computer, characterized in that it contains an additional polychromatic radiation source, and the radiation supply and collection system is mounted with a single a medical needle having a monofilament hard fiber inside.

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