CN1036118C - Tumor image diagnostic method and system - Google Patents

Abstract

The present invention relates to a tumor image diagnostic method and a system thereof in the field of medical diagnoses, which includes the steps, the basis and the method of tumor image diagnoses and a tumor image diagnostic system comprising the hardware and the special software of a computer image processing system. The present invention aims to early discover cancer pathological changes in the human body through the application of a cancer bioresearch result and the introduction of a computer image processing and analyzing system and discover and develop a tumor image diagnostic method and a tumor image diagnostic system with the advantages of high sensitivity, safety, convenience, no side effect on the human body and strong objectivity. The present invention can be applied to tumor early diagnoses in the clinics of all-level hospitals and health units, and is especially suitable for the large-scale tumor general surveys.

Description

Tumor image diagnostic method and system

The present invention relates to tumor image diagnostic method and system in a kind of area of medical diagnostics, be divided into step, foundation and the method for tumor image diagnosis and comprise Computerized image processing system hardware and the tumor image diagnostic system of Flame Image Process special-purpose software.

The method and system of existing inspection diagnosis cancerous protuberance have many types, as: the method for checking cancerous protuberance with the Chinese medicine meridian principle, but the angle of practical situation from the society, normally felt uncomfortable patient,, could find patient's cancerous protuberance by all kinds of laboratory examinations of hospital, since patient be in cancer in, late period, increased great difficulty for treatment and rehabilitation, the one-tenth current behind the corrective surgery is also shorter, and survival rate is lower.Yet the clear 62-30469 of disclosed Japan special permission communique JP discloses a kind of device of cell analysis, is used for the parameter of analyzing blood cell.Be that the blood sample that will gather directly spreads upon in the film-making without cultivating, observe, handle by image signal and judge that leukocytic classification and erythrocytic form seek information, use this device and analytical method and can not analyze tumor cell in microscopically.Therefore, up to the present, there still do not have a kind of reliable, simple and effective method or means can filter out cancerous protuberance patient's, particularly cancerous protuberance early diagnosis from the crowd to be more difficult.

The objective of the invention is to use the result of cancer biological study, introduce the Computer Image Processing analytical system, carninomatosis in the early discovery human body becomes, develop a kind of high sensitivity, safe, easy, to human body has no side effect, objectivity is strong tumor image diagnostic method and system.

The cancer biological study is the result show: cancerous cell takes place in human body, will cause the variation of multiple biochemical process in the body in the evolution, and these variations are even extremely small also can being embodied in blood system.Most cancerous cell all have the antigenicity different with normal cell, and this antigenicity can be by the immune system recognition of human body, and cause corresponding immunne response in the body.Be present in the immune just important component part of lymphocyte in the blood in a large number, their biological activity size can directly and reflect the progress degree of canceration in the body and the mutual relation of immune state delicately.Since the eighties, the silver dyeing nucleolus technology has been widely used in showing the size of activity of cell biology, confirmed already that the part that NOR can be dyed by silver in the cell can only be those biologically actives, and the nonhistones of regulating and controlling effect played in the rDNA zone that can carry out normal transcription on every side, therefore, entoblast can be shown the power of rDNA transcriptional activity in this cell by area, the size of integral optical density and the distribution of power energy spectrum thereof that silver dyes the zone, thereby reflects the height of this cell bio-activity comparatively exactly.

The present invention uses the tumor image diagnostic system, multiple canceration patient is dyed system's contrast test that intensity carries out with the silver of kernel in normal person and the inflammation patient peripheral blood lymphocyte to be found: significantly descend in the lymphocyte rDNA transcriptional activity canceration process in vivo that is reflected by nucleolar silver staining intensity, be starkly lower than normal person and non-tumor inflammation patient.This shows: the size of lymphocyte rDNA transcriptional activity can reflect the mutual relation of canceration progress degree and immunity of organism situation in the body delicately, thereby provide a kind of method completely newly, simple and feasible for the clinical diagnosis cancer.

The present invention relates to a kind of tumor image and detect diagnostic system, comprise organic section making equipment, the microscope of band camera interface, Computer Image Processing analytical system hardware, Computer Storage and printing peripheral hardware and special-purpose software are formed, wherein, Computer Image Processing analytical system hardware is by ccd video camera, the digital image acquisition disposable plates, video-frequency monitor, the computer of IBMPC compatibility and benchtop supply are formed, and Computer Storage and printing peripheral hardware and special-purpose software are supported the computer of IBMPC compatibility, and make system have the intelligent diagnostics self-learning function.

The applied method and system advantage of the present invention is:

Sampling simply, safely, have no side effect, easily be all those who are investigated acceptance

2. diagnostic message is to obtain in body inner blood medium-sized lymphocyte nuclear, and highly sensitive, information source is direct, has reduced the error diagnosis that error artificial and instrument is brought.

3. this method is a kind of non-epigamic routine examination method, and objectivity is strong, can reflect the information of canceration in the human body truly.

4. the Computer Image Processing equipment in the native system provides means and guarantee for accurately measuring, add up, calculating, make the conclusion that draws more accurate and perfect, avoid the interference of anthropic factor, greatly alleviated operator's working strength, improved the efficient of checking diagnosis.

Native system from the time-space domain, integral optical density, spectrum energy territory analyze the various information that obtained more all sidedly, got rid of the mistaken diagnosis that the specificity because of a certain index causes.

6. native system has learning functionality, and diagnostic criteria is all medical record data of storing according to system, is produced automatically by computer, belongs to a kind of intelligent diagnosis system, has improved the diagnosis accuracy and the technical merit of system.

7. native system relatively other diagnostic methods and system, cost is low, and the sensitivity height is simple to operate, easily promotes.

Introduce the operating procedure and the principle of tumor image diagnostic method of the present invention and system below:

1. blood specimen collection: everyone extracts 1～3 milliliter blood to the prescription on individual diagnosis patient, behind the adding anticoagulant, places test tube.

2. cell culture: blood sample is incubated in the RPMI-1640, places under 37 ℃ of constant temperatures, incubation time is 24～72 hours.

3. the preparation of print: the blood sample after will cultivating is isolated lymphocyte on centrifuge, is that print is made in the dyeing of 50% silver nitrate aqueous solution with concentration.

4. computer micro-image handle to detect: the print for preparing is placed the microscopically of band camera interface, the nuclear nucleolar silver staining intensity relative value of abundant on the print (10～15) is carried out the measurements and calculations of following index:

1. calculate the silver dyeing nucleolus integral area ratio:

S=silver dyeing nucleolus integral area/nucleus integral area $S=1/(m*n)*\underset{j=1}{\overset{m}{\mathrm{\Σ}}}\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\mathrm{Aij}/\mathrm{Bij}$ Wherein Aij is the integral area of silver dyeing nucleolus in each nucleus,

Bij is each nuclear integral area,

M is every group of film-making number,

N is observed cell number in every film-making.

2. calculate silver dyeing nucleolus integral optical density ratio:

I=silver dyeing nucleolus integral optical density (I.O.D.)/nucleus integral light

Density (I.O.D.) $I=1/(m*n)*\underset{j=1}{\mathrm{\Σ}}\underset{i=1}{\mathrm{\Σ}}\mathrm{Cij}/\mathrm{Dij}$ Wherein Cij is silver dyeing nucleolus and an integral optical density (I.O.D.) in each cell

Dij is each nuclear integral optical density (I.O.D.).

3. calculate the distribution ratio of silver dyeing nucleolus integrated power energy spectrum:

P=silver dyeing nucleolus power energy spectrum distribution integrated value/nucleus power

Energy spectrum distribution integrated value $P=1/(m*n)*\underset{j=1}{\overset{m}{\mathrm{\Σ}}}\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\mathrm{Eij}/\mathrm{Fij}$ Wherein Eij is that the power energy spectrum of silver dyeing nucleolus in each cell distributes long-pending

Score value,

Fij is each nuclear power energy spectrum distribution integrated value.

5. computerized diagnostic system compares S as a result, I, P value and the diagnostic criteria that calculates, and judges that this patient belongs to cancer patient, normal person or non-cancerous protuberance inflammation patient, printout case history diagnosis report.The standard of tumor image diagnostic system inspection diagnosis is: cancer patient's lymphocyte kernel silver dyes integral area ratio S and is lower than 7% normal person 7.5%～9.5%, and inflammation patient is greater than 9.5%; The nucleolar silver staining integral optical density is lower than 9% than I cancer patient, and normal people is 9.5%～11%, and inflammation patient is greater than 11%; Silver dyeing nucleolus power energy spectrum distribution integration is lower than 8% than P cancer patient, and normal people is 8.5%～11%, and inflammation patient is greater than 11%.

6. storage of the case history of computer system and self study: whenever do a routine patient calculating, its result and case history are stored in the computer disk, whenever finish the patient of some, computer system is carried out statistical analysis to all medical record data automatically, determines new diagnostic criteria.Accompanying drawing 1 is the principle schematic of tumor image diagnostic system of the present invention; Accompanying drawing 2 is Digital Image Processing plate principle schematic of tumor image diagnostic system of the present invention.

Computer tumor image diagnostic system of the present invention comprises: a cover organic section making equipment [1], the optical microscope [2] of a band camera interface, a ccd video camera [6] and control power supply thereof, a Digital Image Processing plate [7], the personal computer of an IBMPC compatibility [8], a monitor [9] and a pin type output printer [4] and benchtop supply [10] etc.Whole system places on the workbench, print is placed on the optical microscope [2] of band camera interface, ccd video camera [6] microscopic cells is examined that image is taken in Digital Image Processing plate [7] and with pictorial display on monitor [9], computer [8] carries out image is analyzed special-purpose software, by the Digital Image Data of will gather in the Digital Image Processing plate [7], read in the computer [8] and carry out the silver dyeing nucleolus integral area ratio, the statistical computation of silver dyeing nucleolus integral optical density ratio and silver dyeing nucleolus power energy spectrum integration ratio, result of calculation is compared with diagnostic criteria, draw diagnosis, by impact printer [4] output diagnosis report, case history is stored in the disc storage of computer simultaneously.

Computer Image Processing analytical system hardware [3] is made up of computer [8], Computer Storage and printing peripheral hardware [4] and the benchtop supply [10] of ccd video camera [6], digital image acquisition disposable plates [7], video-frequency monitor [9], IBMPC compatibility; Ccd video camera [6] will be taken in the nuclei picture under the microscope [2] of camera interface, its picture signal is delivered in the digital image acquisition disposable plates [7], the computer of IBMPC compatibility [8] reads digitized view data in the digital image acquisition disposable plates [7] and carries out Treatment Analysis by the program of special-purpose software [5] defined, the pictorial display of acquisition process is on video-frequency monitor [9], the result of Treatment Analysis outputs to Computer Storage and prints peripheral hardware [4] and carry out data storage and printing, and benchtop supply [10] is given whole hardware system power supply.

Digital image acquisition disposable plates [7] is made up of preamplifier [11], sync separator [12], video a/d [13], video d/a [14], picture frame memorizer [15], address date commutation circuit [16], fast address generator [17], TV timing sequencer [18], control logic circuit [19], I/O decoder [20] and phase-locked loop circuit [21].The print for preparing is placed on the optical microscope [2] of band camera interface, make a video recording by ccd video camera [6], after the image analoging signal of output is amplified by preamplifier [11], being sent to video a/d [13] is digitized into and is Digital Image Data, picture frame memorizer [15] stores Digital Image Data, and video d/a [14] is reduced into image analoging signal with Digital Image Data and delivers on the video-frequency monitor [9] and demonstrate image.TV timing sequencer [18] produces TV time sequential pulse signal automatically, comprise line field synchronization pulse signal, row vertical blanking impulse signal, composite synchronizing pulse signal and composite blanking pulse signal, and these signals are sent to fast address generator [17] and video d/a [14], control the work schedule of fast address generator [17], go up and the compound television image analogue signal of helping of image analoging signal at video d/a [14] simultaneously.The fast address signal that fast address generator [17] produces is delivered on the address bus of picture frame memorizer [15] after being switched by address date commutation circuit [16] and computer [8] address signal.Be sent to control logic circuit [19] after the control command decoding of I/O decoder [20] with computer [8], after logical operations, control the work of each several part circuit by control logic circuit [19].Sync separator [12] is isolated synchronization pulse and is sent to phase-locked loop circuit [21] from the image analoging signal of input, carry out genlocing by phase-locked loop circuit [21].

Image processing and analyzing is that the computer [8] with digital image acquisition disposable plates [7] and IBMPC compatibility is that hardware foundation carries out.Computer [8] is reads image data from digital image acquisition disposable plates [7], after the image histogram density stratification, the tracking crisperding that has expansion or contraction algorithm by the density gradient threshold boundaries, thereby determine the silver dyeing nucleolus zone and the nuclear area of required processing, and the information in the determine zone done Integral Processing, calculate silver dyeing nucleolus integral area ratio and silver dyeing nucleolus integral optical density silver dyeing nucleolus power energy spectrum distribution when integration ratio in the localized area by computer [8] by described three formula

The intelligent diagnostics self-learning function is with the computer of IBMPC compatibility [8] and Computer Storage and to print peripheral hardware [4] be the hardware foundation realization.Computer disk memorizer [4] stores patient's case history result, and sets up patient's the database of case history.The boundary of the diagnostic criteria in the interior self study expert diagnosis of computer [8] algorithm is a computer [8] by inspected patient's medical history record, revises automatically and determines that along with the increase gradually of medical history record, the boundary of diagnostic criteria will be tending towards more accurate gradually.

The preparation method of the graphical analysis special-purpose software in the computer tumor image diagnostic system of the present invention is divided into: the nuclear Preprocessing Algorithm of print, silver dyeing nucleolus integral area ratio and silver dyeing nucleolus integral optical density be statistical computation algorithm, three major parts of case history storage self study expert diagnosis algorithm of silver dyeing nucleolus power energy spectrum integration ratio when.The nuclear Preprocessing Algorithm of print is at first the image that is absorbed to be carried out the rectangular histogram density stratification, has by the density gradient threshold boundaries and expands or the tracking crisperding of contraction algorithm, determines the silver dyeing nucleolus zone and the cell compartment of required processing.Described statistical computation algorithm is that pretreatment is determined that the information in the zone does the statistical computation of described three formula regulation respectively.Case history storage self study expert diagnosis algorithm be diagnostic result and the case history with each patient be stored in computer disk in, computer is by inspected patient's medical history record, automatically statistics is revised diagnostic criteria, thereby draws the diagnostic criteria more accurately based on more case histories.

Computer tumor image diagnostic system involved in the present invention, can be applied to hospitals at different levels and health unit and carry out the early diagnosis outpatient service of tumor, be more suitable in carrying out large-scale cancer screening, to filter out the high-risk group of tumor, and tracing observation, until making a definite diagnosis.Raising along with living standards of the people, very big variation has taken place in dietary structure, the prevalence of the prevalence of tumor, particularly malignant tumor is the trend of rising, and the enforcement of tumor image diagnostic method of the present invention and system will make a due contribution to the people's health.

Claims (7)

1. a tumor image detects diagnostic system, comprises organic section making equipment [1], the microscope [2] of band camera interface, and Computer Image Processing analytical system hardware [3], Computer Storage and printing peripheral hardware [4] and special-purpose software [5] are formed; Said Computer Image Processing analytical system hardware [3] comprises ccd video camera [6], digital image acquisition disposable plates [7], video-frequency monitor [9]; Computer of IBMPC compatibility [8] and benchtop supply [10]; Said Computer Storage and printing peripheral hardware [4] and special-purpose software [5] are supported the computer [8] of IBMPC compatibility; It is characterized in that said digital image acquisition disposable plates [7] is made up of preamplifier [11], sync separator [12], video a/d [13], video d/a [14], picture frame memorizer [15], address date commutation circuit [16], fast address generator [17], TV timing sequencer [18], control logic circuit [19], I/O decoder [20] and phase-locked loop circuit [21]; After amplifying by preamplifier [11] by the image analoging signal of ccd video camera [6] output, being sent to video a/d [13] is digitized into and is Digital Image Data, picture frame memorizer [15] stores Digital Image Data, and video d/a [14] is reduced into image analoging signal with Digital Image Data and delivers on the video-frequency monitor [9] and demonstrate image; TV timing sequencer [18] produces the TV time sequential pulse automatically, and being sent to fast address generator [17] and video d/a [14], the fast address signal that fast address generator [17] produces is delivered on the address bus of picture frame memorizer [15] after being switched by address date commutation circuit [16] and computer [8] address signal; Be sent to control logic circuit [19] after the control command decoding of I/O decoder [20] with computer [8], by the work of control logic circuit [19] control each several part circuit; Sync separator [12] is isolated synchronization pulse and is sent to phase-locked loop circuit [21] from image analoging signal, carry out genlocing by phase-locked loop circuit [21].

2. a tumor image detects diagnostic method, comprise blood specimen collection, the preparation of cell culture and print, the print for preparing is placed carry out computer micro-image under the microscope [2] of band video camera [6] interface and handle and detect, it is to take in the nuclei picture for preparing print with microscope [2] that said micro-image is handled, it is characterized in that its picture signal is delivered in the digital image acquisition disposable plates [7], the computer of IBMPC compatibility [8] reads digitized view data in the digital image acquisition disposable plates [7] and carries out Treatment Analysis by the program of special-purpose software [5] defined, the pictorial display of acquisition process is on video-frequency monitor [9], the result of Treatment Analysis outputs to Computer Storage and prints peripheral hardware [4] and carry out data storage and printing, and benchtop supply [10] is given whole hardware system power supply.

3. detection diagnostic method according to claim 2 is characterized in that said blood specimen collection and cell culture are that everyone draws blood 1～3 milliliter, add anticoagulant after, be incubated in the RPMI-1640, place under 37 ℃ of the constant temperatures 24～72 hours.

4. detection diagnostic method according to claim 3, the preparation that it is characterized in that said print is to adopt silver to dye the method for film-making, it is with the blood sample after cultivating that silver dyes the film-making process, isolate lymphocyte, and then destroy its cell membrane and Cytoplasm, only keep nucleus, the silver nitrate aqueous solution of reuse 50% concentration is made print after the active ingredient in the kernel is dyeed.

5. detection diagnostic method according to claim 2, it is characterized in that said computer micro-image systems inspection diagnostic method, is that 10～15 the nucleolar silver staining intensity relative value of cell on the print is measured respectively by following three figure patterns that detect indexs:

1. silver dyeing nucleolus integral area ratio S

S=silver dyeing nucleolus integral area/nucleus integral area $S=1/(m*n)*\underset{j=1}{\overset{m}{\mathrm{\Σ}}}\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\mathrm{Aij}/\mathrm{Bij}$

2. the silver dyeing nucleolus integral optical density compares I

I=silver dyeing nucleolus integral optical density (IOD)/nucleus

Integral optical density (IOD) $I=1/(m*n)\underset{j=1}{\overset{m}{*\mathrm{\Σ}}}\underset{i=1}{\overset{n}{\mathrm{\ΣC}}}\mathrm{ij}/\mathrm{Dij}$

3. silver dyeing nucleolus power energy spectrum distribution integration compares P

P=silver dyeing nucleolus power energy spectrum distribution integrated value/nucleus merit

Rate energy spectrum distribution integrated value $P=1/(m*n)\underset{j=1}{\overset{m}{*\mathrm{\Σ}}}\underset{i=1}{\overset{n}{\mathrm{\Σ}}}\mathrm{Eij}/\mathrm{Fij}$

M is every group of film-making number,

N is observed cell number in every film-making,

Aij is the silver dyeing nucleolus gross area in each cell,

Bij is each nuclear area,

Cij is the integral optical density (I.O.D) of silver dyeing nucleolus in each cell,

Dij is each nuclear integral optical density (I.O.D.),

Eij is that the power energy spectrum distribution of silver dyeing nucleolus in each cell is long-pending

Score value,

Fij is each nuclear power energy spectrum distribution integrated value.

6. detection diagnostic method according to claim 3 is characterized in that described image processing and analyzing is that computer [8] with digital image acquisition disposable plates [7] and IBMPC compatibility is that hardware foundation carries out; Computer [8] is reads image data from digital image acquisition disposable plates [7], after the image histogram density stratification, the tracking crisperding that has expansion or contraction algorithm by the density gradient threshold boundaries, thereby determine the silver dyeing nucleolus zone and the nuclear area of required processing, and the information in the determine zone done Integral Processing, thereby calculate silver dyeing nucleolus integral area ratio and silver dyeing nucleolus integral optical density silver dyeing nucleolus power energy spectrum distribution when integration ratio by described three formula of claim 5.

7. tumor image according to claim 1 detects diagnostic system, it is characterized in that with the computer [8] and the Computer Storage of IBMPC compatibility and to print peripheral hardware [4] be hardware foundation realization intelligent diagnostics self-learning function; Computer disk memorizer [4] stores patient's case history, the boundary of the diagnostic criteria in the interior self study expert diagnosis of computer [8] algorithm is the medical history record of computer [8] by the inspected patient, automatically revise and determine, along with the increase gradually of medical history record, the boundary of diagnostic criteria will be tending towards more accurate gradually.

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