CN105169560A - Device and method used for controlling magnetic nano particle heating area - Google Patents

Abstract

The invention discloses a device for controlling the heating area of magnetic nanoparticles, which comprises at least one heating coil group, at least two heating area selection coils, and a driving circuit and a control circuit connected with the heating coil group and the heating area selection coil; the heating area The selection coils are associated with a set of heating coils, and the heating zone selection coils are distributed at least partially around the edge of the heating magnetic field generated by the heating coils. Calculate the corresponding DC selection magnetic field, AC heating magnetic field strength and frequency according to the different heating area positions required. Under the combined action of the DC selective magnetic field and the AC heating magnetic field, the diseased tissue in the selected specific area can be heated, while the normal tissue is protected from damage due to the regional selectivity. According to the selected heating area for heating diseased tissue, the present invention determines the selection magnetic field for selecting the heating area and the field strength and frequency of the heating magnetic field, so as to realize heating and killing of diseased tissue and protect normal tissue.

Description

A device and method for controlling the heating area of magnetic nanoparticles

technical field

The present invention relates to the technical field of magnetic nano-hyperthermia, to a structure for magnetic nano-particle heating, in particular to a magnetic nano-particle hyperthermia structure with selectable regions for hyperthermia heating, and more particularly to a control magnetic nano-particle hyperthermia structure. A device for heating a region of particles to realize targeted hyperthermia of magnetic nanoparticles and a realization method thereof. The targeted hyperthermia device is particularly suitable for hyperthermia targeting tumors and diseased tissues.

Background technique

Hyperthermia is a common form of physical therapy, which is mainly to heat the diseased body tissue in the living body so as to cause its death. In the process of hyperthermia, when the whole body of the organism or a certain local area is heated and its temperature rises, it will cause the blood vessels to dilate and increase the blood flow at the treatment site. While increasing the blood flow in the treatment area, hyperthermia can accelerate the body's metabolism, allowing nutrients to quickly reach the injured area and promote tissue healing. In addition, hyperthermia can also stimulate the immune system of the organism to eliminate viruses, bacteria and parasites. Tumor hyperthermia uses the physiological phenomenon that cancer cells are less resistant to heat than normal cells, and kills tumor cells after heating the tumor tissue. It is one of the hyperthermia methods called high-temperature hyperthermia. After the "green therapy". Tumor hyperthermia is generally divided into whole body hyperthermia and local hyperthermia. Local hyperthermia makes the local temperature of tumor tissue reach above 42.5°C, which can kill cancer cells in a relatively short period of time, while causing less damage to surrounding normal cells and tissues. At present, local hyperthermia can be divided into microwave radiation, radio frequency radiation, ultrasonic focusing, resistance heating, alternating magnetic field heating of magnetic particles and other methods according to the heating method. Due to various shortcomings, traditional hyperthermia methods such as microwave radiation, radio frequency radiation, ultrasonic focusing, and resistance heating are gradually being replaced by the method of heating magnetic particles with an alternating magnetic field.

The method of heating magnetic particles by an alternating magnetic field is a new hyperthermia method in recent years. Magnetic particle materials are injected or targeted into diseased tissues, and an alternating magnetic field is applied externally. Due to the existence of eddy current loss and hysteresis loss, the magnetic material generates heat, and the heat generation is related to the magnetic field strength, frequency, magnetic particle size, quantity and magnetic field direction. When the magnetic particles are nano-scale magnetic particle fluids, the heat is mainly generated by hysteresis loss under the excitation of the alternating magnetic field. In the process of hyperthermia, the heating area of the body is determined by the heating alternating magnetic field and the distribution of magnetic nanoparticles. However, due to the fluidity of magnetic particles, the fluid of magnetic nanoparticles will inevitably diffuse to normal tissues, causing normal tissues to can be heated or even damaged.

In the Chinese invention patent application number 201110144541.8, Southeast University proposed a magnetic nanoparticle magnetic induction thermal focusing system based on a composite magnetic field. Permanent magnets with the same polarity are arranged on both sides of the device that generates the alternating magnetic field. The distance between the centerlines of the variable magnetic field device is roughly equal, and the constant magnetic field generated by the permanent magnet is superimposed on the alternating magnetic field to realize the control of the thermal effect of the magnetic nanoparticles and the selective heating of the local position in the area where the magnetic nanoparticles are dispersed. However, the magnetic field produced by the permanent magnet is constant in this technical scheme. Once the permanent magnet is installed in place, only the thermal effect of the magnetic nanoparticles at the center of the pole of the relative permanent magnet can be controlled. At the center, it is impossible to flexibly adjust and select the heating area according to the position and shape of the tumor area, which is difficult to use in practice.

To sum up, the existing magnetic nano-hyperthermia structure heats the tissue where the magnetic nano-particle fluid is located, and the selection of the heating area is completely determined by the magnetic nano-particle fluid, or it can only heat a specific area. Therefore, on the one hand, the heating area is not completely controllable, and on the other hand, normal tissues are easily damaged.

Contents of the invention

In order to solve the technical problem that the heating area of the traditional hyperthermia structure is not completely controllable, the present invention proposes a device and method for controlling the heating area of magnetic nanoparticles, and realizes a controllable heating area and the characteristics of protecting normal tissues. Hyperthermia structure.

The object of the present invention is to provide a new magnetic nanoparticle hyperthermia structure with selectable heating regions, which controls the direct current (static) ) magnetic field strength, so as to realize the control of the position and size of the heating area, and finally achieve the purpose of selectively heating the diseased tissue. Magnetic nanoparticle heating is to use the alternating magnetic field applied to the heating coil to cause the magnetic nanoparticle fluid to generate hysteresis loss, thereby releasing heat to heat the body tissue in the area. Applying a static magnetic field in the direction of the body tissue can significantly reduce the Specific Absorption Rate (SpecificAbsorptionRate), through the setting of the static magnetic field of the heating area selection coil, the DC magnetic field in the area where the lesion tissue to be heated is zero (or lower than a certain threshold) , and the DC magnetic field of the surrounding normal tissue is relatively high, thus realizing the selective heating of the diseased tissue, although there may be magnetic nanoparticle fluid in the surrounding normal tissue, but due to the existence of a high DC magnetic field, it avoids heating of the normal tissue. tissue damage.

A device for controlling the heating area of magnetic nanoparticles, comprising at least one heating coil group, at least two heating area selection coils, and a driving circuit and a control circuit connected to the heating coil group and the heating area selection coil;

The heating coil assembly generates an alternating heating magnetic field for generating heat from the magnetic nanoparticles;

The heating area selection coils generate a heating area selection static magnetic field, and the driving circuit adjusts the magnitude of the direct current input to each heating area selection coil to control the area and intensity of the heating area selection static magnetic field;

The heating area selection coil is associated with a heating coil group, the heating area selection coil is at least partially distributed around the edge of the heating magnetic field generated by the heating coil, and the direction of the static magnetic field generated by the heating area selection coil is perpendicular to the associated heating coil group The direction of the heating magnetic field, so that the heating magnetic field generated by the heating coil group is at least partially superimposed with the heating area selection static magnetic field perpendicular to the direction of the heating magnetic field, and the vertical direction superimposed on the area to be heated covered by the heating magnetic field The static magnetic field intensity is small for the heating area on the upper surface, and the heating area in the vertical direction superimposed on the area that does not need to be heated covered by the heating magnetic field has a large static magnetic field intensity.

The intensity of the static magnetic field selected for the heating area in the vertical direction superimposed on the area covered by the heating magnetic field that does not need to be heated is much greater than the intensity of the heating magnetic field, so that the magnetic nanoparticles in this area are almost inert under the action of the heating magnetic field. Generate heat or just generate less heat.

The heating coil group includes at least two heating coils, so that an alternating heating magnetic field with uniform intensity distribution is generated on the area to be heated; the edges of each group of heating coils are evenly arranged with multiple sets of heating areas associated with it Select the coil.

The device for controlling the heating area of magnetic nanoparticles includes a group of heating coils and eight heating area selection coils, the heating coil group includes two heating coils; the two heating coils are symmetrically arranged in two parallel planes in a coaxial manner The eight heating area selection coils are arranged between the two heating coils and distributed around the edges of the two heating coils, and each heating area selection coil is arranged on eight planes parallel to the axes of the two heating coils; Two of the eight heating zone selection coils are symmetrical about the axis of the heating coil.

The method for controlling the heating area of the magnetic nanoparticles comprises the following steps:

Step 1, determine the distribution radius of the heating area selection coil according to the heating object;

Step 2, according to the density of the heating area required by the heating object, determine the number of heating area selection coils;

Step 3, determining the radius of each heating area selection coil according to the distribution radius and quantity of the heating area selection coils;

Step 4, determine the number of turns of the heating zone selection coil according to the required static magnetic field strength;

Step 5, selecting the coil distribution radius according to the heating area to determine the radius of the heating coil;

In step 6, the number of turns of the heating coil is determined according to the particle size and characteristics of the magnetic nanoparticles.

The method for realizing the distribution radius of the heating region selection coil is: according to the cross-sectional area of the largest body to be heated by the hyperthermia structure, calculate the minimum coverage circle that can cover the cross section, and determine the minimum coverage circle Radius; then make the distribution radius of the heating area selection coils larger than the radius of the minimum coverage circle, and determine the distribution radius of the heating area selection coils.

The method for determining the quantity, radius and number of turns of the selected coils in the heating area is:

①i=1, j=1, initialize the number n of heating area selection coils, current I _i , number of turns N _i , heating coil radius r, and determine the distribution radius of heating area selection coils according to the cross section of the heating body;

② Divide the entire heating area selection coil distribution area into several diseased tissue areas, and number them as Ω _j , the maximum value of j is the number of diseased tissue areas, and discretize each segmented diseased tissue area Ω _j ;

③ For the jth lesion tissue area Ω _j , select the calculation model of coil area selection according to the heating area $\left\{\begin{array}{c}\underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\Σ}}}{h}_{\mathrm{piy}}=f(I_i,N_i)=0\\ \underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\Σ}}}{h}_{\mathrm{piz}}=g(I_i,N_i)=0\\ \underset{{\mathrm{\Ω}}_j}{\mathrm{\Σ}}\underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\Σ}}}{h}_p\≤\mathrm{\ζ},p\∈{\mathrm{\Ω}}_j\end{array}\right.$ Carry out calculation; Wherein, H _piy is the component on the y-axis of each heating area selection coil at point p, H _piz is the component of each heating area selection coil on the _z -axis at point p, f(I _i ) is corresponding to p The function of the magnetic field strength component on the y-axis direction at point place about the electric current in each heating region selection coil, g (I _i ) is the magnetic field strength component on the z axis corresponding to point p about the current function of each heating region selection coil function, ζ is any small value;

④ If the calculation model for the area selection of the above-mentioned heating area selection coil converges within the Ω _j -th area, then i=i+1, if all diseased tissue areas converge to the above-mentioned calculation model for the heating area selection coil area selection, then go to ⑤; otherwise j=j+1, go to ③ to calculate the next lesion tissue area; if the above-mentioned calculation model of heating area selection coil area selection does not converge in the lesion area Ω _j , then increase the turns of the heating area selection coil number N _i , if the number of turns N _i does not reach the upper limit of the maximum value of the heating magnetic field strength, go to ②, if the number of coil turns N _i of the heating area selection coil reaches the upper limit of the maximum value of the heating magnetic field strength, then increase the heating area Select the number n of coils, and change the radius r of the selected coils in the heating area, then go to ②;

⑤ Determine the number of coils n, the radius r and the number of turns N _i in the heating area, and the calculation process is completed.

The heating coil is a Helmholtz-like coil, the radius of the heating coil is greater than or equal to the distribution radius of the heating area selection coil, and the distance between the two heating coils is the diameter of the heating area selection coil.

Calculation model of the thermal power generated by the heating coil in the heating area of approximately zero DC magnetic field under the action of the heating area selection magnetic field

Among them, μ ₀ is the vacuum magnetic permeability, M _S is the saturation magnetization of magnetic nanoparticles, H _c is the coercive force of magnetic nanoparticles, ρ is the density of magnetic nanoparticles, f is the alternating current applied to the heating coil Magnetic field frequency, χ"(f) is the imaginary part of the complex magnetic susceptibility; x is the coordinate value of the magnetic field strength calculation point on the X axis, N _h is the number of turns of the heating coil, I is the current amplitude of the heating coil, r _h is the radius of the heating coil, z is the coordinate value of the Z axis, and θ is the calculation The angle between the point and the X-axis component.

The frequency f of the exciting magnetic field generated by the heating coil is in the range of 1 kHz-500 kHz, and the amplitude of the exciting magnetic field is in the range of 10A/m-100000A/m.

The beneficial effects of the present invention are reflected in:

(1) Regionally selective heating of body tissues is realized, that is, the range of the heating region is controlled by the magnetic nanoparticle fluid distribution and the region-selective DC magnetic field setting;

(2) Using n (n≥2) heating area selection coils, the number of heating area selection coils can be calculated and determined according to the required heating area space range and density, through the selection of the DC current input heating area selection coils To more accurately control the heating area, so that it matches the actual shape of the diseased tissue, and achieve better therapeutic effect;

(3) The present invention can realize that the DC magnetic field intensity of the lesion tissue area to be heated is zero or approximately zero after calculation by the designed algorithm, while the DC magnetic field intensity of the normal tissue is not zero, thereby realizing heating of the lesion tissue, and Normal tissue basically does not generate heat, even if the magnetic nanoparticle fluid that generates heat may diffuse to normal tissue, due to the existence of a DC magnetic field perpendicular to the heating magnetic field, it will not cause damage to normal tissue;

(4) Using the DC magnetic field perpendicular to the heating magnetic field, it can significantly reduce the specific absorption rate of body tissues, and protect the normal tissues around the diseased tissues more effectively.

In a word, the present invention utilizes the influence of the DC magnetic field on the hysteresis loss and the magnetic relaxation loss heat production of the magnetic nanoparticles, calculates the relative position of the diseased tissue in the whole structure, and calculates the direct current (static temperature) of each coil of the heating selection coil group. ) magnetic field strength and direction, and at the same time calculate the corresponding magnetic field strength and frequency of the heating coil according to the specific heat absorption rate of the body tissue, and finally realize the hyperthermia effect of the optional heating area. The test results show that the structure of the invention can heat the diseased tissue more effectively and protect the surrounding normal tissue to the greatest extent.

Description of drawings

Fig. 1 is a flowchart of the present invention.

Fig. 2 is a schematic diagram of the structure of magnetic nanoparticle hyperthermia with optional heating regions proposed by the present invention (taking 8 heating region selection coils and 2 heating coils as an example).

Fig. 3 (a) is the three-dimensional view of the selected static field strength produced by the heating region selection coil in the heating region; (b) is the attached view of the selected static field strength generated by the heating region selection coil in the heating region; (c) is the heating region selection coil The front view of the selected static field strength generated by the area selection coil in the heating area; (d) the right view of the selected static field intensity generated by the heating area selection coil in the heating area.

Fig. 4 is the alternating magnetic field applied for heating in the present invention.

Fig. 5 is a schematic diagram showing the temperature variation of tumor and normal body tissue with time of applying an alternating magnetic field.

Detailed ways

In order to make the object, technical solution and advantages of the present invention clearer, and facilitate the understanding and implementation of the present invention by those of ordinary skill in the art, the present invention will be further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described here are only used to explain the present invention, not to limit the present invention. In addition, the technical features involved in the embodiments of the present invention described below may be combined with each other as long as they do not conflict with each other.

In order to better illustrate the present invention, the basic principles of magnetic nanothermotherapy are briefly introduced first. According to the existing literature, the magnetic nanoparticles used for hyperthermia are usually 5nm to 100nm, that is, from superparamagnetic nanoparticles to multi-magnetic domain magnetic nanoparticles. Magnetic nanoparticles generate heat due to hysteresis loss under the action of an external magnetic field. Under the action of an external alternating magnetic field, the thermal power P _C generated in each cycle is

P _C ＝μ ₀ f∮H _e dM(1)

Among them, μ ₀ is the vacuum magnetic permeability, f is the frequency of the alternating magnetic field applied to the heating coil, He is the intensity of the externally applied alternating magnetic field, and M is the _{magnetization} .

When the amplitude of the externally applied alternating magnetic field for heating is less than or equal to half of the anisotropic field, the hysteresis loss of the magnetic nanoparticles is zero; otherwise, when the externally applied alternating magnetic field is greater than the anisotropic field When the amplitude of the anisotropic field is half, the specific power dissipation SLP produced by the magnetic nanoparticles is

$\mathrm{<span\; class="notranslate">\; SLP</span>}<span\; class="notranslate">\; =</span>\frac{\mathrm{<span\; class="notranslate">\; 4</span>}{\mathrm{<span\; class="notranslate">\; \&mu;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}{\mathrm{<span\; class="notranslate">\; m</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}\mathrm{<span\; class="notranslate">\; f</span>}}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; -</span>{<span\; class="notranslate">\; (</span>\frac{{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}}{{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; e</span>}}}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 5</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 2</span>}<span\; class="notranslate">\; )</span>$

When the magnetic nanoparticles reach the saturation magnetization under the action of the external magnetic field, the maximum hysteresis loss can be obtained, thereby releasing the most energy, and the specific dissipation power SLP at this time is

$\mathrm{<span\; class="notranslate">\; SLP</span>}<span\; class="notranslate">\; =</span>\frac{\mathrm{<span\; class="notranslate">\; 4</span>}{\mathrm{<span\; class="notranslate">\; \&mu;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}{\mathrm{<span\; class="notranslate">\; m</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; c</span>}}\mathrm{<span\; class="notranslate">\; f</span>}}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 3</span>}<span\; class="notranslate">\; )</span>$

Among them, M _S is the saturation magnetization of magnetic nanoparticles, H _c is the coercive force of magnetic nanoparticles, and ρ is the density.

For a specific magnetic nanoparticle fluid, the heat generation is mainly related to the field strength and frequency of the applied magnetic field. At the same time, the generation of heat is also related to the average particle size, particle size distribution, material structure and magnetic properties, and even the surface coating material, the characteristics of the surrounding environment and the interaction between particles.

For magnetic single-domain particles with a particle size smaller than a certain value (typically 10nm), this nanoparticle exhibits superparamagnetic properties, and at the same time, due to the existence of anisotropy, it will produce Neel and Brown ) relaxation. Therefore, the power dissipation of nanoparticles is enhanced due to relaxation dissipation. Due to the existence of magnetic relaxation, the heat generation of such single magnetic domain nanoparticles is enhanced. The power dissipation generated by magnetic relaxation can be expressed as

$\mathrm{<span\; class="notranslate">\; SLP</span>}<span\; class="notranslate">\; =</span>\frac{{\mathrm{<span\; class="notranslate">\; \&mu;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}\mathrm{<span\; class="notranslate">\; \&pi;</span>}{\mathrm{<span\; class="notranslate">\; \&chi;</span>}}^{<span\; class="notranslate">\; \&prime;</span><span\; class="notranslate">\; \&prime;</span>}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; f</span>}<span\; class="notranslate">\; )</span>\mathrm{<span\; class="notranslate">\; f</span>}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; e</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}{\mathrm{<span\; class="notranslate">\; \&rho;</span>}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 4</span>}<span\; class="notranslate">\; )</span>$

where χ"(f) is the imaginary part of the complex magnetic susceptibility, and its value can be expressed as

${\mathrm{<span\; class="notranslate">\; \&chi;</span>}}^{<span\; class="notranslate">\; \&prime;</span><span\; class="notranslate">\; \&prime;</span>}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; f</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; =</span>\frac{{\mathrm{<span\; class="notranslate">\; \&chi;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}\mathrm{<span\; class="notranslate">\; f\&tau;</span>}}{\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; +</span>{<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; f\&tau;</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 5</span>}<span\; class="notranslate">\; )</span>$

τ is the relaxation time; χ ₀ is the initial magnetic susceptibility, which is equal to

${\mathrm{<span\; class="notranslate">\; \&chi;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}<span\; class="notranslate">\; =</span>{\mathrm{<span\; class="notranslate">\; \&mu;</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}{\mathrm{<span\; class="notranslate">\; m</span>}}_{\mathrm{<span\; class="notranslate">\; the\; s</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}\mathrm{<span\; class="notranslate">\; V</span>}<span\; class="notranslate">\; /</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; kT</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 6</span>}<span\; class="notranslate">\; )</span>$

V is the volume fraction of magnetic nanoparticles, k is the Boltzmann constant, T is the absolute temperature; a is a coefficient, and the value is from 1 to 3.

When the particle size is larger than 30nm, the coercive force _Hc and remanence will decrease with the increase of the particle size, resulting in a decrease in hysteresis loss power. The influence of the properties of the magnetic nanoparticle material on the heat generation performance will not be discussed here. In the present invention, the thermal power generated by the externally applied magnetic field strength and frequency on magnetic nanoparticles due to hysteresis dissipation and magnetic relaxation is mainly considered.

In simple terms, applying an alternating magnetic field to magnetic nanoparticles can transfer energy to magnetic nanoparticles through an alternating magnetic field and convert them into heat in various power dissipation modes (relaxation dissipation is much greater than hysteresis loss), thereby achieving Body tissue containing magnetic nanoparticles is heated. When a static magnetic field of a certain intensity is superimposed on a part of the area where the alternating magnetic field acts, and the direction of the superimposed static magnetic field is perpendicular to the direction of the alternating magnetic field, due to the existence of superparamagnetic properties and anisotropy, the superimposed static magnetic field can Change the relaxation characteristics of magnetic nanoparticles under the action of alternating magnetic field, especially in the region where the strength of the static magnetic field is much greater than that of the alternating magnetic field. The contribution of relaxation dissipation in the various power dissipations is drastically reduced. That is to say, the vertical static magnetic field superimposed on the alternating magnetic field makes the heat release method of magnetic nanoparticles change from relaxation dissipation to hysteresis loss, which greatly reduces the heat of magnetic nanoparticles within the range of strong static magnetic field. Conversion efficiency, thereby significantly reducing the heat released by magnetic nanoparticles to body tissues within the range of static magnetic field.

By controlling the size and direction of the DC current that generates the static magnetic field, the range and size of the static magnetic field can be controlled. By superimposing one or more vertical static magnetic fields with a specific range and strength on the alternating magnetic field area, the static magnetic field strength in a certain or certain areas can be made very small (such as the area where tumor tissue is located), and The static magnetic field strength in other areas is very high (such as the area where normal body tissue is located), so that the energy transmission of the alternating magnetic field to the magnetic nanoparticles is controlled within the designated area. When the designated area matches the target object that needs to be heated, that is The effect of "targeted hyperthermia" of magnetic nanoparticles can be realized.

In other words, by applying a static magnetic field in the vertical direction of the alternating magnetic field used to heat the magnetic nanoparticles, the heat production of the magnetic nanoparticles is reduced, so that the heat absorption rate of the corresponding body decreases slightly in the effect of the static magnetic field intensity at the tumor site, so It basically has no effect on the heat production and heat absorption rate of magnetic nanoparticles; and due to the large vertical static magnetic field on normal body tissues, the heat absorption rate is very low or even non-existent, thus achieving the purpose of protecting normal body tissues.

A device for controlling the heating area of magnetic nanoparticles, comprising at least one heating coil group and at least two heating area selection coils, the heating area selection coil and the heating coil are connected to a drive circuit and a control circuit that provide excitation current; the heating coil group is in An alternating heating magnetic field is generated in a specified direction; the heating coil group is associated with the heating area selection coils, the heating area selection coils are at least partially distributed around the edge of the heating magnetic field generated by the heating coils, and the heating area selection coils are generated in conjunction with the heating magnetic field The heating area selection static magnetic field with the direction perpendicular to each other; the action area of the heating area selection static magnetic field produced by each group of heating area selection coils is at least partially overlapped with the action area of the heating magnetic field to control the action area of the heating magnetic field so that the overlapping The heat release mode of the magnetic nanoparticles in the range is mainly changed from relaxation dissipation to hysteresis loss. Thus, when multiple heating area selection static magnetic fields generated by multiple heating area selection coils are superimposed on the heating magnetic field, the action area of the heating magnetic field is controlled to be consistent with the heating area of the target object, thereby achieving heating of the magnetic nanoparticles On-demand control of zones.

A method for controlling the heating area of magnetic nanoparticles mainly includes: determining the distribution radius of the heating area selection coils, determining the number of heating area selection coils, determining the radius and the number of turns of each heating area selection coil, and determining the heating coil radius, the number of turns number and alternating current. The process flow of the method for controlling the heating area of magnetic nanoparticles proposed by the present invention is shown in Figure 1, so that the structure of the magnetic nanoparticle heating coil and the heating area selection coil capable of determining the required heating area selection function is finally formed.

For the sake of simple description, a specific example of a device for controlling the heating area of magnetic nanoparticles is shown in Figure 2, which includes 2 heating coils, 8 heating area selection coils, and a driving circuit that provides excitation current for the heating area selection coil and the heating coil and control circuit (not shown in the figure). In actual implementation, the number n of heating area selection coils can be determined according to needs, n≥2. Two heating coils are located on a plane parallel to the YOZ plane in the three-dimensional Cartesian coordinate system, and the center of the circle is located on the X coordinate axis to form a heating coil group . The 8 heating area selection coils are evenly distributed in a circle around the X coordinate axis, and the centers of all heating area selection coils are evenly distributed on a circle on the YOZ plane, and the plane where each heating area selection coil is located is parallel to the X coordinate axis . The 2 heating coils and the 8 heating zone selection coils roughly form a cylindrical shape. On this roughly cylindrical device, two heating coils are coaxially arranged at intervals and located on the end face of the cylinder, and eight heating area selection coils are arranged between the two heating coils, each heating area selection coil is located The plane is parallel to the central axis of the heating coil and perpendicular to the plane where the heating coil is located.

In fact, according to the requirements of the target object to be heated, multiple heating coil groups can be used, and each heating coil group is correspondingly provided with one or more sets of heating area selection coils to form an optional heating area magnetic nanoparticle hyperthermia structure, when the target object to be heated has a special shape, such as a long tumor, this way of multiple heating coils is particularly advantageous. The drive circuit and the control circuit that respectively provide the excitation current for the above-mentioned heating coil group and the heating area selection coil can be designed using various known excitation drive solutions.

A method for controlling the heating area of magnetic nanoparticles, which can control the heating area of magnetic nanoparticles, specifically comprising:

Step 1: Determine the distribution radius of the heating area selection coils according to the heating object.

For the specific structural diagram in Figure 2, the planes where the coils for each heating area selection are located are parallel to the X axis, and the centers of all heating area selection coils are evenly distributed in a circle on the YOZ plane, and the radius of this circle is the distribution of the heating area selection coils radius. In the process of hyperthermia, the target heating object can be divided into one or more heating objects, each heating object is regarded as a unit to control the heating area, and the heating object needs to be placed in the above heating area selection coil and heating coil Therefore, the distribution radius of the heating area selection coil must be greater than the outline of the heating object, that is, the distribution radius of the heating area selection coil must be greater than the cross-section of the body to be heated, or the distribution radius of the heating area selection coil is determined by the largest cross-section of the body that can be heated. At the beginning of the design, first, according to the cross-sectional area of the largest body that needs to be heated for the hyperthermia structure, calculate the minimum coverage circle that can cover this cross-section, and determine the radius of the minimum coverage circle; then select the distribution of coils for the heating area The radius is larger than the radius of the minimum covering circle, so as to determine the distribution radius of the heating area selection coils. When the object to be heated is the human body, the distribution radius of the heating area selection coil can generally be determined to be 0.10m to 0.45m, and the size range of the distribution radius can meet the treatment needs of the limbs to internal organs of the human body.

Step 2: Determine the number of coils for heating area selection according to the density of the heating area required by the heating object.

The number of heating area selection coils can be selected according to the spatial range and density of the area to be heated, and its essence is to determine the number n of heating area selection coils. According to the effect of the static magnetic field perpendicular to the alternating magnetic field on the hysteresis loss and heat generation of magnetic nanoparticles, first determine the regional grid division within the distribution range of the heating area selection coil, and each regional grid is the maximum area range of hyperthermia. Then, by calculating the static magnetic field strength of each grid boundary, check whether the static magnetic field strength of each grid boundary meets the static magnetic field threshold, so as to determine whether the number of heating area selection coils meets the needs of heating area selection, if not Satisfied, then increase the heating area selection coil until the field strength of each boundary static magnetic field is satisfied.

Step 3: Determine the radius of each heating area selection coil according to the distribution radius and quantity of the heating area selection coils.

The radius of each heating area selection coil is calculated from the distribution radius and number of area selection coils determined in step 1 and step 2, so that each heating area selection coil covers the largest area space as possible. In the actual design process, the radius and number of heating zone selection coils may be adjusted due to subsequent calculations.

Step 4: Determine the number of turns of the heating region selection coil according to the required static magnetic field strength.

From the calculation formula of the magnetic field strength, it can be seen that within the spatial range of the required heating area, as shown in Figure 2, the magnetic field strength is generated by the heating area selection coil whose center of circle is distributed on the YOZ plane at any point in the included space range The vector sum of the DC magnetic field strength is determined. Then for any point p(x,y,z) within this range, the magnetic field intensity vector generated by the ith heating zone selection coil is

$\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; =</span>{<span\; class="notranslate">\; \&Integral;</span>}_{\mathrm{<span\; class="notranslate">\; L</span>}}{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}\mathrm{<span\; class="notranslate">\; d</span>}\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; l</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}}<span\; class="notranslate">\; \&times;</span>\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; /</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 4</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}{<span\; class="notranslate">\; |</span>\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; |</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 7</span>}<span\; class="notranslate">\; )</span>$

Among them, I _i is the length of the tiny element in the coil selected for the ith heating zone The current flowing in the conductor of , i≤4 ⁿ (n≥1); μ _pi is the radial unit vector of the selected coil from point p to the i-th heating area, is its radial distance; L is the integral path of the source current in the coil, and N _i is the number of turns of the i-th coil. In order to simplify the design and facilitate the calculation, the number of turns of each coil can be the same. Thus, it can be obtained that point p corresponds to the vector sum of the magnetic field intensity generated by each heating region selection coil on the YOZ plane as

$\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{{\mathrm{<span\; class="notranslate">\; 4</span>}}^{\mathrm{<span\; class="notranslate">\; no</span>}}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; =</span>\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{{\mathrm{<span\; class="notranslate">\; 4</span>}}^{\mathrm{<span\; class="notranslate">\; no</span>}}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{<span\; class="notranslate">\; \&Integral;</span>}_{\mathrm{<span\; class="notranslate">\; L</span>}}{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}\mathrm{<span\; class="notranslate">\; d</span>}\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; l</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}}<span\; class="notranslate">\; \&times;</span>\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; /</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 4</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}{<span\; class="notranslate">\; |</span>\stackrel{<span\; class="notranslate">\; \&Right\; Arrow;</span>}{{\mathrm{<span\; class="notranslate">\; u</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}}<span\; class="notranslate">\; |</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; no</span>}<span\; class="notranslate">\; \&Greater\; Equal;</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 8</span>}<span\; class="notranslate">\; )</span>$

Then the heating area selection coil selects the heating area, so it can be concluded that the calculation model of the area selection of the heating area selection coil is

$\left\{\begin{array}{c}\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{{\mathrm{<span\; class="notranslate">\; 4</span>}}^{\mathrm{<span\; class="notranslate">\; no</span>}}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; piy</span>}}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; f</span>}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; ,</span>{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 0</span>}\\ \underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{{\mathrm{<span\; class="notranslate">\; 4</span>}}^{\mathrm{<span\; class="notranslate">\; no</span>}}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; piz</span>}}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; g</span>}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; I</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; ,</span>{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; i</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 0</span>}\\ \underset{\mathrm{<span\; class="notranslate">\; \&Omega;</span>}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}\underset{\mathrm{<span\; class="notranslate">\; i</span>}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; 1</span>}}{\overset{{\mathrm{<span\; class="notranslate">\; 4</span>}}^{\mathrm{<span\; class="notranslate">\; no</span>}}}{\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}}}{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; p</span>}}<span\; class="notranslate">\; \&le;</span>\mathrm{<span\; class="notranslate">\; \&zeta;</span>}<span\; class="notranslate">\; ,</span>\mathrm{<span\; class="notranslate">\; p</span>}<span\; class="notranslate">\; \&Element;</span>\mathrm{<span\; class="notranslate">\; \&Omega;</span>}\end{array}\right.<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 9</span>}<span\; class="notranslate">\; )</span>$

Among them, H _piy is the component on the y-axis of each heating area selection coil at point p, H _piz is the component of each heating area selection coil on the _z -axis at point p, and f(I _i ) is corresponding to y at point p The magnetic field strength component on the axial direction is about the function of the electric current in each heating region selection coil, g (I _i ) is the function of the magnetic field strength component on the z axis corresponding to point p about the current function of each heating region selection coil, ζ is an arbitrarily small value, and Ω is the relative area range position of the diseased tissue relative to the thermal treatment structure. For the convenience of design, the number of turns of each heating zone selection coil can be set to be equal (of course, it can also be different, but the calculation process will be more complicated). If the above model cannot converge in the entire Ω range, increase the number of turns of the heating zone selection coil , if it reaches the upper limit of the number of turns of the heating area selection coil and still cannot converge, it means that the number of heating area selection coils set is too small, and the number of corresponding heating area selection coils needs to be increased. The calculation algorithm for this process is as follows:

①Initialize the number n of heating area selection coils, the current I _i , the number of turns N _i , the heating coil radius r (the initial value of i is 1), and determine the distribution radius of the heating area selection coils according to the cross-section of the heating body;

② Divide the entire heating area selection coil distribution area into several diseased tissue areas, and number them as Ω _j (the value of j depends on the fineness of the segmentation, the initial value is 1), and then discretize each segmented area ;

③ Calculate the jth lesion area Ω _j according to the above model formula (9);

4. If the above-mentioned model formula (9) converges in the Ω _j region, then i=i+1, if all regions converge to the above-mentioned model formula (9), then go to ⑤; otherwise j=j+1 goes to ③ Calculate the next lesion tissue area; if the above model formula (9) does not converge within Ω _j , then increase the number of turns N _i of the heating area selection coil, if the number of turns N _i does not reach the upper limit (what is the upper limit) turn to Go to ②, if the number of N _i coil turns reaches the upper limit, then increase the number n of the heating area selection coils, and change the radius r of the heating area selection coils, and then go to ②;

⑤ Determine the number of coils n, the radius r and the number of turns N _i in the heating area, and the calculation process is completed.

Through the above algorithm, the determination of the number, radius and number of turns of the heating area selection coil can be realized.

Step 5, select the coil distribution radius according to the heating area to determine the heating coil radius:

In order to obtain a relatively uniform heating magnetic field, the heating coil adopts the form of a Helmholtz (Helmholtz) coil, and the radius of the heating coil is greater than or equal to the distribution radius of the heating area selection coil, and the distance between the two heating coils is the heating area selection coil coil diameter and can be changed as required.

In step 6, the number of turns of the heating coil is determined according to the particle size and characteristics of the magnetic nanoparticles.

Studies have shown that in an alternating magnetic field, due to the existence of hysteresis loss and magnetic relaxation loss, magnetic nanoparticles will generate heat, which will heat the diseased tissue and induce apoptosis of the diseased tissue, thereby obtaining a better therapeutic effect. From the formulas (3) and (4), it can be known that the thermal power generated under the induction of the alternating magnetic field in the magnetic nanoparticle hyperthermia is proportional to the strength of the heating magnetic field and the frequency f of the alternating magnetic field. Therefore, theoretically, the greater the strength of the heating magnetic field and the higher the frequency, the higher the thermal power generated. However, since human tissues are composed of cells larger than microns, if the selected heating alternating magnetic field frequency f is too high, normal tissues will be heated due to the eddy current effect, thereby causing damage to normal tissues. The magnetic field generated by the heating coil is given below, assuming that the radius of the heating coil is r _h , the number of turns is N _h , and the current amplitude is I, one of the heating coils is located on the YOZ plane at x=0, and the other heating coil is located at x=0 r _h plane. Then the magnetic field at any point on the x-axis is

${\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; A</span>}}<span\; class="notranslate">\; =</span><span\; class="notranslate">\; (</span>\frac{{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}\mathrm{<span\; class="notranslate">\; I</span>}}{\mathrm{<span\; class="notranslate">\; 2</span>}{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; [</span>{<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; +</span>\frac{{\mathrm{<span\; class="notranslate">\; x</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}{{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; )</span>}^{<span\; class="notranslate">\; -</span>\frac{\mathrm{<span\; class="notranslate">\; 3</span>}}{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; +</span>{<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; +</span>\frac{{<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; x</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}{{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; )</span>}^{<span\; class="notranslate">\; -</span>\frac{\mathrm{<span\; class="notranslate">\; 3</span>}}{\mathrm{<span\; class="notranslate">\; 2</span>}}}<span\; class="notranslate">\; ]</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 10</span>}<span\; class="notranslate">\; )</span>$

And by symmetry we know that the radial component on the axis is zero. When H is expanded with x as a variable, the above formula becomes

${\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; A</span>}}<span\; class="notranslate">\; =</span>{\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; 0</span>}}<span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 1</span>}<span\; class="notranslate">\; +</span>\frac{\mathrm{<span\; class="notranslate">\; 15</span>}}{\mathrm{<span\; class="notranslate">\; 8</span>}{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}^{\mathrm{<span\; class="notranslate">\; 4</span>}}}{\mathrm{<span\; class="notranslate">\; x</span>}}^{\mathrm{<span\; class="notranslate">\; 4</span>}}<span\; class="notranslate">\; -</span>\frac{\mathrm{<span\; class="notranslate">\; 105</span>}}{\mathrm{<span\; class="notranslate">\; 48</span>}{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}^{\mathrm{<span\; class="notranslate">\; 6</span>}}}{\mathrm{<span\; class="notranslate">\; x</span>}}^{\mathrm{<span\; class="notranslate">\; 6</span>}}<span\; class="notranslate">\; +</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; \&Center\; Dot;</span><span\; class="notranslate">\; )</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 11</span>}<span\; class="notranslate">\; )</span>$

in, is the magnetic field strength at the center of the coil. From this we can see When the change is small, it becomes a uniform magnetic field in the X-axis direction. Outside the X-axis, according to Biot-Saval's law,

${\mathrm{<span\; class="notranslate">\; dH</span>}}_{\mathrm{<span\; class="notranslate">\; NA</span>}}<span\; class="notranslate">\; =</span>\frac{{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}\mathrm{<span\; class="notranslate">\; Idl</span>}\mathrm{<span\; class="notranslate">\; sin</span>}\mathrm{<span\; class="notranslate">\; \&theta;</span>}}{\mathrm{<span\; class="notranslate">\; 4</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; x</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; +</span>{<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; z</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; ,</span>}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 12</span>}<span\; class="notranslate">\; )</span>$

Then the corresponding magnetic field strength is

${\mathrm{<span\; class="notranslate">\; h</span>}}_{\mathrm{<span\; class="notranslate">\; NA</span>}}<span\; class="notranslate">\; =</span>\mathrm{<span\; class="notranslate">\; \&Sigma;</span>}\frac{{\mathrm{<span\; class="notranslate">\; N</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}\mathrm{<span\; class="notranslate">\; I</span>}\mathrm{<span\; class="notranslate">\; sin</span>}\mathrm{<span\; class="notranslate">\; \&theta;</span>}}{\mathrm{<span\; class="notranslate">\; 4</span>}\mathrm{<span\; class="notranslate">\; \&pi;</span>}<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; x</span>}}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; +</span>{<span\; class="notranslate">\; (</span>{\mathrm{<span\; class="notranslate">\; r</span>}}_{\mathrm{<span\; class="notranslate">\; h</span>}}<span\; class="notranslate">\; -</span>\mathrm{<span\; class="notranslate">\; z</span>}<span\; class="notranslate">\; )</span>}^{\mathrm{<span\; class="notranslate">\; 2</span>}}<span\; class="notranslate">\; )</span><span\; class="notranslate">\; ,</span>}<span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; -</span><span\; class="notranslate">\; (</span>\mathrm{<span\; class="notranslate">\; 13</span>}<span\; class="notranslate">\; )</span>$

Among them, x is the coordinate value of the magnetic field strength calculation point on the X-axis, z is the coordinate value of the Z-axis, and θ is the angle between the calculation point and the X-axis component.

Therefore, the calculation model of the thermal power generated by the heating coil in the heating area of approximately zero DC magnetic field under the action of the heating area selection magnetic field can be established

The H _NA in the above formula is calculated by formula (13), and the solution range is determined by Ω given in formula (9).

Through the above calculation model, the range and strength of the static magnetic field required to be generated by the heating area selection coil can be designed from the shape of the target object to be heated, and then the static magnetic field current intensity of each heating area selection coil can be calculated, so as to realize the magnetic nanometer Accurate control of the particle heating zone.

Verification example:

In order to verify the effectiveness of hyperthermia in the above-mentioned controlled magnetic nanoparticle heating area, experiments can be designed to verify the designed device. According to the basic principle of heating area control given above, the key to heating area selection is to calculate the DC (static) magnetic field intensity generated by each coil according to the number, distribution and number of turns of the heating area selection coil, and then make the corresponding heating area The DC (static) magnetic field strength in the heating zone is zero or lower than the corresponding threshold, while the DC (static) magnetic field strength outside the heating range is higher. When the heating coil is applying an alternating magnetic field, due to the existence of magnetic nanoparticles in the lesion tissue area, and the strength of the direct current (static) magnetic field perpendicular to the heating alternating magnetic field is zero or very small, the heating effect is not affected; For the surrounding normal tissue, even if there are magnetic nanoparticles diffused into this area, due to the existence of a DC (static) magnetic field perpendicular to the heating alternating magnetic field, the normal tissue will not be heated basically, thus realizing the protection of the normal tissue .

In the exemplary design example, according to the thermal treatment object, the heating area is firstly determined to select a coil distribution radius of 0.40m, which can meet the needs of the general heated object. According to the distribution radius of the heating area selection coils and formula (9) and the corresponding algorithm, the number of heating area selection coils is calculated to be 8, the radius of each heating area selection coil is 0.13m and the number of turns is 500 respectively. In order to ensure the uniformity of heating, the radius of the heating coil should be greater than or equal to the distribution radius of the heating area selection coil, which is 0.42m in this example, and the number of turns of the heating coil is 200. In the test, the liver is used as the heating object, and the center coordinates of the tumor are assumed to be located in a sphere with a radius of 0.05m at the relative coordinates of the hyperthermia structure (0,-0.115,-0.059), and the same center coordinates are covered outside the tumor , a normal liver tissue sphere with a radius of 0.1 m. The magnetic nanoparticles with particle size distribution of 14±5nm are injected into the corresponding tumor area, and the distribution concentration in the tumor area is 30g/m ³ .

Figures 3(a)-3(d) respectively show the three-dimensional view, top view, front view and right view of the static magnetic field strength distribution of the heating region selection coil. The current applied by each coil is calculated according to the algorithm corresponding to the steps in the embodiment, the difference is that only one or several Ω _j areas need to be calculated here. In this example, the corresponding DC current is calculated from 19.8A to 60.1A. Figure 3(a) is a three-dimensional cross-sectional view of the static magnetic field generated by the selective coil in the heating area. For the convenience of illustration, the intersection point of the three-dimensional cross-section is placed at the coordinates of the center of gravity of the tumor (0, -0.115, -0.059). Therefore, it can be seen from the section diagram that the magnetic field strength within the 0.05cm area centered at the coordinates (0,-0.115,-0.059) is much smaller than that of the surrounding area, that is to say, the alternating heating magnetic field within the central area The heat generated is far more than that of the surrounding area, and the range of the heating area acted by the heating magnetic field matches the shape of the tumor, thereby achieving targeted hyperthermia for the tumor target. Figure 3(b) is a front view showing only the YOZ plane, from which the distribution and relative position of the magnetic field intensity of the tumor region on the YOZ plane can be clearly seen. Figure 3(c) and Figure 3(d) are the corresponding top view and right view. It can also be seen that the static magnetic field strength is the smallest at the center of the tumor, and the magnetic field strength within 0.05m is much smaller than that in the surrounding normal tissue magnetic field strength.

Fig. 4 shows the alternating magnetic field for heating applied to the tumor and normal body tissue regions. The frequency and field strength are also calculated by solving the calculation model formula (14), which are 100kHz and 5A respectively. It can be seen from FIG. 4 that the intensity of the alternating magnetic field in the tumor area is uniformly distributed, so that uniform heating of the tumor tissue can be achieved.

Fig. 5 is a schematic diagram showing the temperature variation of tumor and normal body tissue with time of applying an alternating magnetic field. As the heating time changes, it can be seen from Figure 5 that the temperature at the core of the tumor tissue gradually rises from 37°C to above 44°C, while the edge of the normal tissue and the tumor remains at 40°C, while the normal tissue is only 37°C. The purpose of heating tumors while protecting normal tissues. Experiments have proved that the structure provided by the present invention, which can selectively control the magnetic nanometer heating area, is of great significance to the research of thermotherapy devices.

Although the above examples are specifically described for specific area heating of tumor sites, those skilled in the art can understand that the technical solution proposed by the present invention is also applicable to any other application scenarios that need to control the heating area of magnetic nanoparticles.

It is easy for those skilled in the art to understand that the above descriptions are only preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention, All should be included within the protection scope of the present invention.

Claims (10)

1. A device for controlling the heating area of magnetic nanoparticles, characterized in that: comprising at least one heating coil group, at least two heating area selection coils and a drive circuit and a control circuit connected with the heating coil group and the heating area selection coil; The heating coil assembly generates an alternating heating magnetic field for generating heat from the magnetic nanoparticles; The heating area selection coils generate a heating area selection static magnetic field, and the driving circuit adjusts the magnitude of the direct current input to each heating area selection coil to control the area and intensity of the heating area selection static magnetic field; The heating area selection coil is associated with a heating coil group, the heating area selection coil is at least partially distributed around the edge of the heating magnetic field generated by the heating coil, and the direction of the static magnetic field generated by the heating area selection coil is perpendicular to the associated heating coil group The direction of the heating magnetic field, so that the heating magnetic field generated by the heating coil group is at least partially superimposed with the heating area selection static magnetic field perpendicular to the direction of the heating magnetic field, and the vertical direction superimposed on the area to be heated covered by the heating magnetic field The static magnetic field intensity is small for the heating area on the upper surface, and the heating area in the vertical direction superimposed on the area that does not need to be heated covered by the heating magnetic field has a large static magnetic field intensity. 2. The device for controlling the heating area of magnetic nanoparticles according to claim 1, characterized in that: the heating area in the vertical direction superimposed on the area that does not need to be heated covered by the heating magnetic field selects the intensity of the static magnetic field Far greater than the intensity of the heating magnetic field, the magnetic nanoparticles in this region hardly generate heat or only generate less heat under the action of the heating magnetic field. 3. The device for controlling the heating area of magnetic nanoparticles according to claim 1 or 2, characterized in that: the heating coil group comprises at least two heating coils, so that a uniform distribution of intensity is generated on the area to be heated. Alternating heating magnetic field; the edge of each group of heating coils is uniformly arranged with multiple groups of heating area selection coils associated therewith. 4. according to the device of the control magnetic nanoparticle heating zone described in claim 3, it is characterized in that: the device of described control magnetic nanoparticle heating zone comprises a group of heating coils and eight heating zone selection coils, and the heating coil group comprises Two heating coils; the two heating coils are symmetrically arranged in two parallel planes in a coaxial manner; the eight heating area selection coils are arranged between the two heating coils and distributed around the edges of the two heating coils, And each heating area selection coil is arranged on eight planes parallel to the axes of the two heating coils; two of the eight heating area selection coils are symmetrical with respect to the axes of the heating coils. 5. according to the device of the control magnetic nanoparticle heating zone described in claim 1, it is characterized in that, the method for its control magnetic nanoparticle heating zone, the steps are as follows: Step 1, determine the distribution radius of the heating area selection coil according to the heating object; Step 2, according to the density of the heating area required by the heating object, determine the number of heating area selection coils; Step 3, determining the radius of each heating area selection coil according to the distribution radius and quantity of the heating area selection coils; Step 4, determine the number of turns of the heating zone selection coil according to the required static magnetic field strength; Step 5, selecting the coil distribution radius according to the heating area to determine the radius of the heating coil; In step 6, the number of turns of the heating coil is determined according to the particle size and characteristics of the magnetic nanoparticles. 6. The device for controlling the heating area of magnetic nanoparticles according to claim 5, characterized in that: the realization method of the distribution radius of the heating area selection coil is: according to the transverse direction of the largest body that needs to be heated according to the hyperthermia structure Cross-sectional area, calculate the minimum coverage circle that can cover this cross section, and determine the radius of the minimum coverage circle; then make the distribution radius of the heating area selection coil larger than the radius of the minimum coverage circle, and determine the distribution radius of the heating area selection coil . 7. The device for controlling the heating zone of magnetic nanoparticles according to claim 5, characterized in that: the determination method of the quantity, radius and the number of turns of the heating zone selection coil is: ①i=1, j=1, initialize the number n of heating area selection coils, current I _i , number of turns N _i , heating coil radius r, and determine the distribution radius of heating area selection coils according to the cross section of the heating body; ② Divide the entire heating area selection coil distribution area into several diseased tissue areas, and number them as Ω _j , the maximum value of j is the number of diseased tissue areas, and discretize each segmented diseased tissue area Ω _j ; ③ For the jth lesion tissue area Ω _j , select the calculation model of coil area selection according to the heating area $\left\{\begin{array}{c}\underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\&Sigma;}}}{h}_{\mathrm{piy}}=f(I_i,N_i)=0\\ \underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\&Sigma;}}}{h}_{\mathrm{piz}}=g(I_i,N_i)=0\\ \underset{{\mathrm{\&Omega;}}_j}{\mathrm{\&Sigma;}}\underset{i=1}{\overset{4^{\mathrm{no}}}{\mathrm{\&Sigma;}}}{h}_p\&le;\mathrm{\&zeta;},p\&Element;{\mathrm{\&Omega;}}_j\end{array}\right.$ Carry out calculation; Wherein, H _piy is the component on the y-axis of each heating area selection coil at point p, H _piz is the component of each heating area selection coil on the _z -axis at point p, f(I _i ) is corresponding to p The function of the magnetic field strength component on the y-axis direction at point place about the electric current in each heating region selection coil, g (I _i ) is the magnetic field strength component on the z axis corresponding to point p about the current function of each heating region selection coil function, ζ is any small value; ④ If the calculation model for the area selection of the above-mentioned heating area selection coil converges within the Ω _j -th area, then i=i+1, if all diseased tissue areas converge to the above-mentioned calculation model for the heating area selection coil area selection, then go to ⑤; otherwise j=j+1, go to ③ to calculate the next lesion tissue area; if the above-mentioned calculation model of heating area selection coil area selection does not converge in the lesion area Ω _j , then increase the turns of the heating area selection coil number N _i , if the number of turns N _i does not reach the upper limit of the maximum value of the heating magnetic field strength, go to ②, if the number of coil turns N _i of the heating area selection coil reaches the upper limit of the maximum value of the heating magnetic field strength, then increase the heating area Select the number n of coils, and change the radius r of the selected coils in the heating area, then go to ②; ⑤ Determine the number of coils n, the radius r and the number of turns N _i in the heating area, and the calculation process is completed. 8. The device for controlling the heating region of magnetic nanoparticles according to claim 5, characterized in that: the heating coil is a Helmholtz coil, and the radius of the heating coil is greater than or equal to the distribution radius of the heating region selection coil. The distance between the heating coils selects the diameter of the coils for the heating area. 9. The device for controlling the heating region of magnetic nanoparticles according to any one of claims 5 to 8, characterized in that: the heating coil, under the action of the selective magnetic field in the heating region, is in the heating region of approximately zero DC magnetic field Calculation model of thermal power generated within Among them, μ ₀ is the vacuum magnetic permeability, M _S is the saturation magnetization of magnetic nanoparticles, H _c is the coercive force of magnetic nanoparticles, ρ is the density of magnetic nanoparticles, f is the alternating current applied to the heating coil Magnetic field frequency, χ"(f) is the imaginary part of the complex magnetic susceptibility; x is the coordinate value of the magnetic field strength calculation point on the X axis, N _h is the number of turns of the heating coil, I is the current amplitude of the heating coil, r _h is the radius of the heating coil, z is the coordinate value of the Z axis, and θ is the calculation The angle between the point and the X-axis component. 10. The device for controlling the heating area of magnetic nanoparticles according to any one of claims 1, 2, 4, 5, and 8, wherein the frequency f range of the excitation magnetic field that the heating coil needs to generate is 1kHz- 500kHz, the amplitude range of the excitation magnetic field is 10A/m-100000A/m.