CN102093668A - Preparation method of solid simulation body for optical breast imaging - Google Patents

Abstract

The invention belongs to the technical field of biomedical engineering and relates to a preparation method of a solid simulation body for optical breast imaging. The preparation method comprises the following steps: dissolving near infrared absorption dye in epoxy resin to prepare absorption mother solution; obtaining the spectral absorption curve of the mother solution, calculating the dosage of the absorption mother solution; calculating the dosage of titanium dioxide required by the simulation body according to the Mie scattering theory; weighting the absorption mother solution, weighting titanium dioxide according to the volume of the required titanium dioxide, mixing titanium dioxide, the absorption mother solution and epoxy resin to fully stir; placing the mixed solution in a vacuum pump, pumping out bubbles; preparing a mould according to the shape and volume of the required simulation body; adding the mixed solution and curing agent in the mould; stirring in a constant speed along one directly to mix evenly; and pumping out bubbles again; and performing low temperature solidification. By adopting the method of the invention, the solid simulation body for optical breast imaging which has stable physical properties and can be stored for long time, can be prepared.

Description

The optics breast imaging is made method with solid-state imitative system

Technical field

The invention belongs to the biomedical engineering technology field, relate to a kind of imitative system and make method.

Background technology

Over nearly more than 30 years, the sickness rate of mammary cancer occupies the first place of Urban Women tumor incidence always, and shows lasting high growth.Though the treatment technology of mammary cancer is improved, mortality ratio does not still have obvious decline, and its major cause mainly is that the middle and advanced stage case is more, and early discovery person is few.The world has 1,200,000 women to suffer from mammary cancer every year approximately at present, has 500,000 women to die from mammary cancer.Its Middle and North America, Northern Europe are the hotspots of mammary cancer, and its sickness rate is about the Asia, and is non-, and 4 times of Latin American have become the heavy burden of American-European countries.But the case fatality rate of U.S.'s mammary cancer is kept stable but, and this mainly is because of the extensive enforcement of mammary cancer early detection scheme in the U.S..Tradition thinks that China is that the low of mammary cancer sent out the area, but the sickness rate of mammary cancer rises year by year in recent years, and mortality ratio climbs up and up, and rate of growth is surprising.Current, the annual growth rate of China's breast cancer incidence reaches 3%-4%, is higher than the rate of growth in the whole world.

Most of both at home and abroad research thinks that most malignant breast tumors are inner and periphery can be visited and abundant blood flow information, and tumour is big more, and blood flow is abundant more; Organize classification high more, blood flow is abundant more.At this illness of mammary cancer, at present the most frequently used mammary gland early detection method and mammography and ultrasonograph technology are main, also have computerized tomography in addition, nmr imaging technique, the positron radioactivity tomography, heat picture inspection, diffuse optical tomography.

Respectively have superiority though above several method is used for breast cancer detection, shortcoming is separately also arranged.Make correct diagnosis in early days the treatment of mammary cancer is had decisive meaning, as clinical X-ray film making commonly used at present and ultrasonic all be the variation of surveying mammary cancer density, rather than molecular chemistry composition analysis, therefore these two kinds of technology all can't be distinguished canceration and innocent tumour reliably, can only can not be used as diagnosis as detecting suspected case.Have certain traumatic biological tissue cut sections for microscopic examination in order further to distinguish pernicious and innocent tumour, need to do usually, and section pathology shows that 70%-90% is benign.Fail to pinpoint a disease in diagnosis or mistaken diagnosis for fear of breast carcinoma of early stage takes place, often adopt several technology in conjunction with to the diagnosing of mammary cancer, this also is the key that improves early diagnosis.Obviously, for the malignant tumour of this high incidence of mammary cancer, studying does not a kind ofly have injury to human body, and cheap, susceptibility and specificity are up to standard, and the detection new technology of the breast carcinoma of early stage of being convenient to promote.In recent years, optical imaging method is owing to have undamaged characteristic and the great potential on the raising detection specificity, receive investigator's concern day by day, especially along with the development of near infrared light imaging technology, a kind of nearly external diffusion optical tomography technology (NIR-DOT) towards the mammary cancer early detection is obtaining broad research.

Similar to any imaging system development course, in optics breast imaging system triturating, before directly applying to the human body mammary tissue, to the main check that detects index and image reconstruction algorithm intrinsic performance such as its susceptibility spatial resolution and degree of quantization, all need design and make a kind of standard target body, be called the imitative body (Phantom) of optics, the optical parametric that should imitate body should have the optical parametric identical or approaching with mammary tissue, comprise uptake factor and scattering coefficient, can be used in the different optical imaging system measuring result being compared and studying.In addition, from use angle, require this imitative body have stable physical properties, can prolonged preservation and be easy to make.The China that is produced on of the imitative body of mammary tissue optics also belongs to blank, usually use based on the imitative system of the liquid state of Intralipid and make technology, on shape control, heteroplasmon embedding and reuse, has very big limitation, and in the world, its method of design has nothing in common with each other and manufacture craft is maintained secrecy though the solid-state imitative body of the independent development of each correlative study unit can be used, so the obtainable imageable target pattern of user is very limited.Because the research of mammary gland optical imaging method needs a large amount of different types of imitative bodies that use, so it is very necessary to efficient system and proof of algorithm that independent development and the solid-state imitative system of grasp are made technology, the present invention proposes the making method of the solid-state imitative body of a kind of optics breast imaging for this reason.

A large amount of tissue spectrum are learned and be studies show that near the 780nm wavelength, the optical parametric of normal galactophore tissue is: uptake factor: μ both at home and abroad _a≈ 0.005mm ^-1Reduced scattering coefficient: μ ' _s≈ 0.9mm ^-1(referring to: Durduran T, Choe R, CulverJ P, Zubkov L, Hoboke M J, Giammarco J, Chance B and Yodh A G, " Bulk optical properties of healthy female breast tissue, " Phys.Med.Biol.47,2847-2861,2002)

Summary of the invention

The objective of the invention is to propose a kind of solid-state imitative system of optics breast imaging that is applicable to and make method.Technical scheme of the present invention is as follows:

A kind of optics breast imaging is made method with solid-state imitative system, comprises the following steps:

(1) takes by weighing an amount of hear-infrared absorption dye and Resins, epoxy, and hear-infrared absorption dye is dissolved in the Resins, epoxy, make certain density absorption mother liquor;

(2) obtain the absorption spectrum curve of absorption mother liquor, and calculate the uptake factor of absorption mother liquor under λ=780nm;

(3) according to the linear relationship of uptake factor and dye strength, calculating uptake factor under wavelength X=780nm is μ _a=0.005mm ^-1The concentration of absorption mother liquor, in view of the above, calculate the multiple that the absorption mother liquor produced by step 1 should dilute;

(4) making reduced scattering coefficient according to the Mie scattering Theoretical Calculation is μ ' _s=0.9mm ^-1The volume content of the needed titanium dioxide of imitative body, the volume content here refers to that per unit volume contains the quality of titanium dioxide in the imitative body for preparing;

(5) multiple that should dilute according to absorption mother liquor takes by weighing absorption mother liquor, takes by weighing titanium dioxide according to the volume content of needed titanium dioxide, titanium dioxide, absorption mother liquor are mixed with Resins, epoxy and fully stirs;

(6) mixing solutions is put in the vacuum pump, is being lower than under 0.3～0.4 normal atmosphere, extract bubble wherein;

The shape of the imitative body of (7) doing as required and volume are prepared mould;

(8) under the lucifuge condition,, in mould, add mixing solutions and solidifying agent according to the suitable quality proportioning of Resins, epoxy and selected solidifying agent;

(9) add solidifying agent after, at the uniform velocity stir along same direction it mixed;

(10) mould is put in the vacuum pump once more, extracts the bubble in the mixing solutions that has added solidifying agent;

(11) mould is placed in 0～5 ℃ of thermostat container, treats its curing molding;

(12) solid with moulding takes out from mould, and it further is processed into solid-state imitative body, and the parameter of made solid-state imitative body is: wavelength X=780nm, uptake factor μ _a=0.005mm ^-1, reduced scattering coefficient μ ' _s=0.9mm ^-1

Optics breast imaging of the present invention is made method with solid-state imitative system, and in the 4th step, the volume content that adds titanium dioxide is 0.000704g/ml; The quality proportioning of Resins, epoxy and solidifying agent is 5: 2.

The present invention is according to the optical parametric of normal galactophore tissue, by Theoretical Calculation and experimental verification, determined to make the prescription of the imitative body of this kind tissue, and provided the concrete making method of imitative body, for the development and the experiment of optics breast imaging system provides basic substance.

Description of drawings

The absorption spectrum curve of the absorption mother liquor of the nir dye preparation that the embodiment of the invention of utilizing Fig. 1 adopts.

Embodiment

According to embodiment the present invention is elaborated below.

The material of the imitative body of the making that present embodiment is selected for use is made of base material, absorbing material and scatterer three parts.Wherein base material comprises Resins, epoxy, solidifying agent; Absorbing material is a hear-infrared absorption dye; Scatterer is titanium dioxide (TiO ₂) microparticle.Respectively material and making method that present embodiment adopted are done detailed description below.

The main raw that is adopted is as follows:

1) hear-infrared absorption dye

Model: cyanine dyes NIRD-09

Under the condition of lucifuge, the 1.5mg dyestuff is dissolved in the 100ml Resins, epoxy, and stirs with glass stick, be referred to as absorption mother liquor.The absorption spectrum curve (sample pool thickness is 10mm) that scans absorption mother liquor with spectrograph is (the scan light frequency band is 600～900nm, and the sampling interval is the quick single scanning of 1nm) as shown in Figure 1

2) Resins, epoxy (Epoxy Resin)

Model: Araldite GY257

Araldite GY 257 is a kind of low viscous modified bisphenol A epoxy resins, has favorable mechanical after the curing, is 500～650mpa.s 25 ℃ of following viscosity, and proportion is 1.15g/cm ³

3) solidifying agent (Hardener)

Model: Aradur 3233

Under 25 ℃, proportion is 1.0g/cm ³, the operating time is 30 minutes.The mass ratio of hardener dose and content of epoxy resin is 2: 5.

4) titanium dioxide (Ti02)

Model: Dupont Ti-Pure R-902+

Ti-Pure R-902+ is a kind of multi-usage rutile titanium dioxide pigment that adopts chloride process to produce, and titanium dioxide minimum weight per-cent is 93%; Proportion is 4.0g/cm ³Median particle size is 0.405 μ m; Under wavelength X=780nm, its specific refractory power is 2.6.

4. the calculating of correlative

(1) scattering coefficient method of calculation

Germany scientist Gustaf rice (Mie) has found that the scattering degree depends on the size of scattering particles and the ratio of incident wavelength is defined as dimensional parameters x to them

$x=\frac{\mathrm{\πD}}{\mathrm{\λ}}---\left(1\right)$

D is the diameter of scattering particles in the formula, and λ is a lambda1-wavelength.When 0.1＜x＜50, scattering is called as Mie scattering, is also referred to as the macrobead scattering.Select TiO for use ₂The about 405nm of particle diameter and the same order of magnitude of near-infrared band 650-900nm, be suitable for so Mie is theoretical.The calculating of Mie scattering, (referring to Wang Lihong V.and Wu Hsin-I, Biomedical Optics:Principle and Imaging, Chapter 2, John Wiley ﹠amp at first will to calculate the Mie coefficient; Sons, 2007).

$a_n=\frac{m^2{j}_n\left(\mathrm{mx}\right){\left[{\mathrm{xj}}_n\left(x\right)\right]}^{\′}-{\mathrm{\μ}}_1{j}_n\left(x\right){\left[{\mathrm{mxj}}_n\left(\mathrm{mx}\right)\right]}^{\′}}{m^2{j}_n\left(\mathrm{mx}\right){\left[{\mathrm{xh}}_n^{\left(1\right)}\left(x\right)\right]}^{\′}-{\mathrm{\μ}}_1{h}_n^{\left(1\right)}\left(x\right){\left[{\mathrm{mxj}}_n\left(\mathrm{mx}\right)\right]}^{\′}}$

(2)

$b_n=\frac{{\mathrm{\μ}}_1{j}_n\left(\mathrm{mx}\right){\left[{\mathrm{xj}}_n\left(x\right)\right]}^{\′}-j_n\left(x\right){\left[{\mathrm{mxj}}_n\left(\mathrm{mx}\right)\right]}^{\′}}{{\mathrm{\μ}}_1{j}_n\left(\mathrm{mx}\right){\left[{\mathrm{xh}}_n^{\left(1\right)}\left(x\right)\right]}^{\′}-h_n^{\left(1\right)}\left(x\right){\left[{\mathrm{mxj}}_n\left(\mathrm{mx}\right)\right]}^{\′}}$

Wherein, m is the specific refractory power of the relative surrounding medium of particle, and m is an arithmetic number here, illustrates that particle is single scattering particles, does not absorb; μ ₁Be the magnetic field transmitance of particle, be generally 1 with respect to medium; j _n(z) and

Be the humorous Bei Saier function of n rank ball, z=x or z=mx.Wherein, the derivative function that Bessel's function is relevant is

[zj _n(z)]′＝zj _n-1(z)-nj _n(z)

(3)

${\left[{\mathrm{zh}}_n^{\left(1\right)}\left(z\right)\right]}^{\′}=z_{h-1}^{\left(1\right)}\left(z\right)-{\mathrm{nh}}_n^{\left(1\right)}\left(z\right)$

Here provide n=0, the humorous Bessel's function expression formula of 1 ball

j ₀(z)＝sin?z/z

j ₁(z)＝sin?z/z ²-cos?z/z

(4)

y ₀(z)＝-cos?z/z

y ₁(z)＝-cos?z/z ²-sin?z/z

Can obtain n=2 according to following recursion formula, 3,4, the Bessel's function value of L

$f_{n-1}\left(z\right)+f_{n+1}\left(z\right)=\frac{2n+1}{z}{f}_n\left(z\right)---\left(5\right)$

Can obtain Mie coefficient, scattering efficiency so according to above formula

$Q_{\mathrm{sca}}=\frac{2}{x^2}\underset{n=1}{\overset{\∞}{\mathrm{\Σ}}}(2n+1)({\left|a_n\right|}^2+{\left|b_n\right|}^2)---\left(6\right)$

Common n _Max=x+4x ^1/3+ 2.Can obtain the scattering cross-section of each particle thus

σ _sca＝Q _scaπa ² (7)

Correspondingly scattering coefficient is

μ _s＝ρσ _sca (8)

ρ is the number of unit volume scattering in particle, i.e. acceleration of concentration of scattering particle.

Average scattering cosine is

$g<\cos \mathrm{\&theta;}>=\frac{4}{Q_{\mathrm{sca}}{x}^2}\{\underset{n=1}{\overset{\&infin;}{\mathrm{\&Sigma;}}}\frac{n(n+2)}{n+1}\mathrm{Re}(a_n{a}_{n+1}^{*}+b_n{b}_{n+1}^{*})+\underset{n=1}{\overset{\&infin;}{\mathrm{\&Sigma;}}}\frac{n(n+2)}{n+1}\mathrm{Re}\left(a_n{b}_n^{*}\right)\}---\left(9\right)$

a ^*, b ^*Be respectively a, the conjugate complex number of b.

Therefore, reduced scattering coefficient is

μ′ _s＝(1-g)μ _s (10)

According to known μ ' _s, can be by the anti-acceleration of concentration of scattering particle ρ that releases of formula

$\mathrm{\&rho;}=\frac{{\mathrm{\&mu;}}_s^{\&prime;}}{(1-g){\mathrm{\&sigma;}}_{\mathrm{sca}}}---\left(11\right)$

Because with TiO ₂The approximate spheroid, TiO regarded as of microballoon ₂Median particle size be D=0.405 μ m, according to the sphere volume formula

${\mathrm{<figure-callout\; id="2"\; label="V\; TiO"\; filenames="HDA0000040289670000011.png"\; state="\{\{state\}\}">V</figure-callout>}}_{{\mathrm{TiO}}_{}}=\frac{4}{3}\mathrm{\&pi;}{\left(\frac{D}{2}\right)}^3---\left(12\right)$

Can obtain each TiO ₂The volume of ball, by

According to formula

$m=\mathrm{\&rho;}\&CenterDot;V_{{\mathrm{TiO}}_2}---\left(13\right)$

Can obtain each TiO ₂The quality m of ball ₀According to the number ρ that desires to join liquor capacity V and unit volume scattering in particle, can obtain the TiO of common needs ₂The number of ball is ρ V, by each TiO ₂The quality m of ball ₀, can obtain the common TiO of need ₂Quality be

${\mathrm{<figure-callout\; id="2"\; label="m\; TiO"\; filenames="HDA0000040289670000011.png"\; state="\{\{state\}\}">m</figure-callout>}}_{{\mathrm{TiO}}_{}}=\mathrm{\&rho;}\&CenterDot;V\&CenterDot;m_0---\left(14\right)$

(2) uptake factor method of calculation

For a layer material with uniform absorbing particle distribution, the radiating capacity that it absorbed or the percentage ratio of yield of radiation depend on the wavelength of absorbing material and incident radiation, and are directly proportional with the thickness of absorption layer.If absorbing material concentration is certain, then, can obtain seeing through the exponential relationship formula between yield of radiation and the absorber thickness to a succession of absorption thin layer summation or to determining the thickness integration.This relational expression is commonly referred to as Lambert's law.

If incide the initial radiation position I in the medium ₀,

$I=I_0{e}^{-{\mathrm{\&mu;}}_{a}l}$ A mistake! Do not find Reference source.

Or I=I ₀e ^-A, A=μ wherein _al

More than in two kinds of expression formulas, I ₀Be the input light intensity, I is the transmission light intensity that measures, and l is a medium thickness, and A=ln (I ₀/ I) be called as absorbancy.Therefore, obtain absorbancy by spectrograph, uptake factor is so

${\mathrm{\&mu;}}_a=\frac{A}{l}\ln 10$

(3) calculating of material requested consumption

Making volume is the imitative body of V, and wavelength X=780nm, uptake factor are μ _a=0.005mm ^-1, reduced scattering coefficient μ ' _s=0.9mm ^-1Proportion ρ according to Resins, epoxy ₁=115g/cm ³, the proportion ρ of solidifying agent ₂=1.0g/cm ³, required Resins, epoxy is 5: 2 with the ratio of the quality of solidifying agent, establishing the quality that needs Resins, epoxy is M ₁, the quality that needs solidifying agent is M ₂, the group that can establish an equation is as follows:

$\left\{\begin{array}{c}\frac{M_1}{{\mathrm{<figure-callout\; id="2"\; label="M"\; filenames="HDA0000040289670000011.png"\; state="\{\{state\}\}">M</figure-callout>}}_2}=\frac{5}{2}\\ \frac{M_1}{{\mathrm{\&rho;}}_1}+\frac{{\mathrm{<figure-callout\; id="2"\; label="M"\; filenames="HDA0000040289670000011.png"\; state="\{\{state\}\}">M</figure-callout>}}_2}{{\mathrm{\&rho;}}_2}=V\end{array}\right.---\left(15\right)$

Separate this system of equations and can obtain the quality of required Resins, epoxy and solidifying agent.

5, specifically make flow process

(1) the 1.5mg dyestuff is dissolved in the 100ml Resins, epoxy, and stirs, make solution with glass stick, here be referred to as absorption mother liquor, under λ=780nm, can get its absorbance A=0.644 by the mother liquor absorption spectrum curve, thus, the uptake factor of absorption mother liquor is:

(2) the imitative body of two 200mm * 120mm * 30mm volumes of making needs the mixing solutions of configuration Resins, epoxy and solidifying agent to be about V=1500ml.Can get the mass M of Resins, epoxy according to formula (15) ₁=1181g, the mass M of solidifying agent ₂=472g.

(3) according to Beer-Lambert law, the uptake factor and the concentration of dyestuff are linear, and calculating in view of the above and making uptake factor is μ _a=0.005mm ^-1Imitative body, the absorption mother liquor that needs is 50.6ml, i.e. M ₃=58.2g.

(4) calculate according to formula (1)～formula (11), make reduced scattering coefficient μ ' _s=0.9mm ^-1Imitative body, need titanium dioxide M ₄=1.056g.With 1.056g titanium dioxide, 58.2g is that the 50.6ml absorption mother liquor mixes with 1122.8g Resins, epoxy and abundant the stirring forms mixing solutions.

(5) owing in operating process, can make solution mix a certain amount of bubble, therefore mixing solutions is put in the vacuum pump, is being lower than under 0.3～0.4 normal atmosphere, bled 30 minutes, treat that the intravital bubble extraction of liquid can stop.

The shape of the imitative body of (6) doing as required and volume are prepared suitable mould, calculate needed above-mentioned mixing solutions.

(7) under the lucifuge condition, in mould, add the mixing solutions quality that calculates respectively, according to the ratio (5: 2) of mixing solutions in the Theoretical Calculation and solidifying agent, in each mould, add quantitative solidifying agent more respectively.

(8) after adding solidifying agent, at the uniform velocity stir, prevent to mix too much bubble to same direction.Because the operating time of the solidifying agent that uses has only 30 minutes, so churning time was controlled within 10 minutes.

Every part of mixing solutions that adds solidifying agent that (9) will prepare is put in the vacuum pump once more, and the bubble that mixes in the draw out operation process was controlled at 0.3～0.4 normal atmosphere lower pumping 20 minutes.

(10) end of waiting to bleed, the model that fills the mixing solutions that adds solidifying agent is placed in 5 ℃ of thermostat containers (owing to can produce a large amount of heat in the solidified process, dyestuff is heated the change of character can take place, the uptake factor of the imitative body of final influence), treat its curing molding.

(11) solid of moulding takes out from mould, according to different needs, can carry out retrofit to its shape again according to concrete needs, finally becomes the solid-state imitative body with required optical parametric and geometrical shape.

The optical parametric of imitative body is finally determined (referring to peak, He Huiyuan, horse by " Curve Matching " of reflection/transmission measuring light flow and photon diffusion model by time resolved spectrum measuring technology (TRS), " based on the optical parameters of turbid media method of calculation of temporal resolution reflection measurement ", University Of Tianjin's journal, Vol.41:757-761,2008).

Claims (3)

1. an optics breast imaging is made method with solid-state imitative system, comprises the following steps:

(1) takes by weighing an amount of hear-infrared absorption dye and Resins, epoxy, and hear-infrared absorption dye is dissolved in the Resins, epoxy, make certain density absorption mother liquor;

(2) obtain the absorption spectrum curve of absorption mother liquor, and calculate the uptake factor of absorption mother liquor under λ=780nm;

(3) according to the linear relationship of uptake factor and dye strength, calculating uptake factor under wavelength X=780nm is μ _a=0.005mm ^-1The concentration of absorption mother liquor, in view of the above, calculate the multiple that the absorption mother liquor produced by step 1 should dilute;

(4) making reduced scattering coefficient according to the Mie scattering Theoretical Calculation is μ ' _s=0.9mm ^-1The volume content of the needed titanium dioxide of imitative body, the volume content here refers to that per unit volume contains the quality of titanium dioxide in the imitative body for preparing;

(5) multiple that should dilute according to absorption mother liquor takes by weighing absorption mother liquor, takes by weighing titanium dioxide according to the volume content of needed titanium dioxide, titanium dioxide, absorption mother liquor are mixed with Resins, epoxy and fully stirs;

(6) mixing solutions is put in the vacuum pump, is being lower than under 0.3～0.4 normal atmosphere, extract bubble wherein;

The shape of the imitative body of (7) doing as required and volume are prepared mould;

(8) under the lucifuge condition,, in mould, add mixing solutions and solidifying agent according to the suitable quality proportioning of Resins, epoxy and selected solidifying agent;

(9) add solidifying agent after, at the uniform velocity stir along same direction it mixed;

(10) mould is put in the vacuum pump once more, extracts the bubble in the mixing solutions that has added solidifying agent;

(11) mould is placed in 0～5 ℃ of thermostat container, treats its curing molding;

(12) solid with moulding takes out from mould, and it further is processed into solid-state imitative body, and the parameter of made solid-state imitative body is: wavelength X=780nm, uptake factor μ _a=0.005mm ^-1, reduced scattering coefficient μ ' _s=0.9mm ^-1

2. optics breast imaging according to claim 1 is made method with solid-state imitative system, it is characterized in that, in the 4th step, the volume content that adds titanium dioxide is 0.000704g/ml.

3. optics breast imaging according to claim 1 is made method with solid-state imitative system, it is characterized in that, the quality proportioning of Resins, epoxy and solidifying agent is 5: 2.

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