A temperature field acquisition system and method based on nanoprobe photothermal sensitization

Abstract

The present invention discloses a temperature field acquisition system based on nanoprobe photothermal sensitization, which relates to the field of image processing technology, including: a CT imaging module irradiates a target tissue injected with nanoprobes by X-ray scanning infrared laser, and obtains real-time CT imaging; a CT value calculation module obtains the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image; a concentration estimation module obtains the real-time nanoprobe concentration at each coordinate according to the linear relationship between the CT value and the nanoprobe concentration; an internal heat estimation module obtains the real-time internal heat source intensity of the target tissue according to the real-time nanoprobe concentration; and a temperature field acquisition module estimates the current temperature field of the target tissue according to the real-time internal heat source intensity. The present invention, on the premise of obtaining the real-time temperature field, better controls the temperature field according to the actual degree of abnormal change of the abnormal tissue in subsequent processing, achieves a better treatment effect, and reduces damage to normal biological tissues.

Description

Technical Field

[0001] The present invention relates to the field of image processing technology, and in particular to a temperature field acquisition system and method based on nanoprobe photothermal sensitization. Background Art

[0002] With the gradual understanding of tumors, people have gradually realized the significant inhibitory effect of the tumor microenvironment on the therapeutic effect of tumors. The tumor microenvironment refers to the internal environment in which tumors are generated and grown. It is composed of malignant tumor cells, stromal cells, tumor-associated immune cells, extracellular matrix, incomplete blood vessels and lymphatic vessels, etc., and is involved in important biological processes such as tumor growth, invasion, metastasis, and immune escape. Compared with normal tissues, tumor tissues usually show abnormal blood vessels, weak acidity, hypoxia, high interstitial pressure, dense extracellular matrix, abnormal energy metabolism, etc. The complex tumor microenvironment has brought long-term challenges to the effective treatment of tumors. For example, the hypoxic microenvironment of tumors can inhibit the effects of chemotherapy drugs, radiotherapy, immunotherapy, photodynamic therapy, and sonodynamic therapy; dense extracellular matrix and high interstitial pressure make it difficult for therapeutic drugs to reach the inside of the tumor, resulting in the appearance of treatment blind spots.

[0003] As an alternative therapy for tumors, tumor hyperthermia has received more and more attention. Among them, photothermal therapy, which uses the photothermal effect to heat the tumor with a beam, has developed rapidly. This technology mainly uses specific targeted nanoparticles to gather in the tumor area, thereby converting light energy into heat energy more efficiently, increasing the temperature of the tumor area, killing cancer cells, and reducing damage to surrounding healthy tissues. However, experimental studies have found that although the introduction of nanoparticles has alleviated the damage of tumor photothermal therapy to surrounding healthy tissues, due to the high absorption characteristics of nanoparticles to light, the laser rapidly decays after reaching the interface between the tumor and normal tissue, causing the heat source to be concentrated in this area. Therefore, due to the effect of heat conduction, there is still the problem of overheating in the tumor area causing damage to normal tissues. In clinical treatment, the hyperthermia process is often manually controlled based on experience, and the accuracy of the operation is difficult to guarantee. Therefore, based on the current understanding of tumor occurrence and development, and in view of the complexity of the tumor microenvironment, how to reduce the scope of damage to normal biological tissues while ensuring the effectiveness of the hyperthermia process has become an urgent problem to be solved. Summary of the invention

[0004] In order to reduce the damage to normal biological tissues caused by uncontrollable temperature fields during the photothermal treatment of lesion tissues using nanoprobes, the present invention proposes a temperature field acquisition system based on nanoprobe photothermal sensitization, comprising:

[0005] A CT imaging module is used to obtain real-time CT imaging by scanning the target tissue with nanoprobes through infrared laser irradiation through X-rays;

[0006] A CT value calculation module is used to obtain the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image;

[0007] A concentration estimation module is used to obtain the real-time nanoprobe concentration step at each coordinate according to the linear relationship between the CT value and the nanoprobe concentration;

[0008] An internal heat estimation module is used to obtain the real-time internal heat source intensity of the target tissue in steps according to the real-time nanoprobe concentration;

[0009] The temperature field acquisition module is used to estimate the current temperature field of the target tissue according to the real-time internal heat source intensity. Further, in the CT imaging module, the acquisition of the CT value can be expressed as the following formula:

[0010] CTvalue(x,y,z,τ)=(1-g(x,y,z,τ))*|WW ul -WW ll |+WW ll

[0011] Where CTvalue(x,y,z,τ) is the real-time CT value at the three-dimensional coordinate (x,y,z) at temperature τ, g(x,y,z,τ) is the real-time grayscale density at the three-dimensional coordinate (x,y,z) of the CT image at temperature τ, and WW is ul WW is the upper limit of window width ll The lower limit of the window width.

[0012] Furthermore, in the concentration estimation module, the step-by-step acquisition of the nanoprobe concentration can be expressed as the following formula:

[0013]

[0014] Where, L c (x, y, z, τ) is the real-time nanoprobe concentration at the three-dimensional coordinate (x, y, z) at temperature τ, and A and B are constants.

[0015] Furthermore, in the internal heat estimation module, the acquisition of the internal heat source intensity can be expressed as the following formula:

[0016] Q r =f OTR (W L ,L C )

[0017] In the formula, Q r is the real-time internal heat source intensity, W L is the real-time infrared laser power density step, L C For real-time nanoprobe concentration stepping.

[0018] Furthermore, in the temperature field acquisition module, the acquisition of the temperature field can be expressed as the following formula:

[0019]

[0020] Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, ρ b is the density of arterial blood, c b is the specific heat of arterial blood, T b is the temperature of arterial blood, ω b is the blood perfusion rate.

[0021] The present invention also proposes a method for obtaining a temperature field based on nanoprobe photothermal sensitization, comprising the steps of:

[0022] S1: X-ray scanning infrared laser irradiates the target tissue injected with nanoprobes and obtains real-time CT imaging of the target tissue;

[0023] S2: acquiring the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image;

[0024] S3: obtaining the real-time nanoprobe concentration stepwise at each coordinate based on the linear relationship between the CT value and the nanoprobe concentration;

[0025] S4: Obtain the real-time internal heat source intensity of the target tissue step by step according to the real-time nanoprobe concentration;

[0026] S5: Estimate the current temperature field of the target tissue according to the real-time internal heat source intensity.

[0027] Furthermore, in the step S2, the acquisition of the CT value can be expressed as the following formula:

[0028] CTvalue(x,y,z,τ)=(1-g(x,y,z,τ))*|WW ul -WW ll |+WW ll

[0029] Where CTvalue(x,y,z,τ) is the real-time CT value at the three-dimensional coordinate (x,y,z) at temperature τ, g(x,y,z,τ) is the real-time grayscale density at the three-dimensional coordinate (x,y,z) of the CT image at temperature τ, and WW is ul WW is the upper limit of window width ll The lower limit of the window width.

[0030] Furthermore, in the step S3, the step-by-step acquisition of the nanoprobe concentration can be expressed as the following formula:

[0031]

[0032] Where, L c (x, y, z, τ) is the real-time nanoprobe concentration at the three-dimensional coordinate (x, y, z) at temperature τ, and A and B are constants.

[0033] Furthermore, in the step S4, the acquisition of the internal heat source intensity can be expressed as the following formula:

[0034] Q r =f OTR (W L ,L C )

[0035] In the formula, Q r is the real-time internal heat source intensity, W L is the real-time infrared laser power density step, L C For real-time nanoprobe concentration stepping.

[0036] Furthermore, in step S5, the acquisition of the temperature field can be expressed as the following formula:

[0037]

[0038] Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, ρ b is the density of arterial blood, c b is the specific heat of arterial blood, T b is the temperature of arterial blood, ω b is the blood perfusion rate.

[0039] Compared with the prior art, the present invention has at least the following beneficial effects:

[0040] (1) The temperature field acquisition system and method based on nanoprobe photothermal sensitization described in the present invention monitors the temperature field of abnormal tissue in the target tissue in real time based on the parameter information obtained by X-ray scanning. On the premise of obtaining the real-time temperature field, the temperature field can be better controlled according to the actual degree of abnormality of the abnormal tissue in subsequent treatment to achieve better treatment effect.

[0041] (2) Temperature field control under CT guidance can reduce damage to normal biological tissues and achieve higher accuracy. BRIEF DESCRIPTION OF THE DRAWINGS

[0042] Figure 1 This is a system structure diagram of a temperature field acquisition system based on nanoprobe photothermal sensitization;

[0043] Figure 2A method step diagram for obtaining a temperature field based on nanoprobe photothermal sensitization. DETAILED DESCRIPTION

[0044] The following are specific embodiments of the present invention and the accompanying drawings to further describe the technical solution of the present invention, but the present invention is not limited to these embodiments.

[0045] Embodiment 1

[0046] The construction of tumor nanomedicines and the combination of multimodal tumor treatments such as photothermal, photodynamic, and radiotherapy have improved the therapeutic effect of tumors to a certain extent. For example, nanocarriers with photothermal properties can not only effectively kill tumor cells by local light heating, but also improve hypoxia, inhibit DNA repair inhibition, and inhibit tumor vascular endothelial growth factor through thermal sensitization effects to enhance the effect of radiotherapy. However, due to the complex microenvironment of the tumor area and the individual differences of tumor patients, the temperature control of the tumor area is often unstable, which in turn affects the overall therapeutic effect of tumor cell killing based on temperature regulation, and even causes damage to normal biological tissues. Based on the above problems, such as Figure 1 As shown, the present invention proposes a temperature field acquisition system based on nanoprobe photothermal sensitization, comprising:

[0047] A CT imaging module is used to obtain real-time CT imaging by scanning the target tissue with nanoprobes through infrared laser irradiation through X-rays;

[0048] A CT value calculation module is used to obtain the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image;

[0049] A concentration estimation module is used to obtain the real-time nanoprobe concentration step at each coordinate according to the linear relationship between the CT value and the nanoprobe concentration;

[0050] An internal heat estimation module is used to obtain the real-time internal heat source intensity of the target tissue in steps according to the real-time nanoprobe concentration;

[0051] The temperature field acquisition module is used to estimate the current temperature field of the target tissue based on the real-time internal heat source intensity.

[0052] In order to obtain relevant parameter information of the tumor area in the target tissue, the present invention emits X-rays through a CT imaging module (that is, an X-ray imaging device such as a CT imager) to scan the target tissue injected with nanoprobes under infrared laser irradiation to obtain real-time CT imaging with grayscale density information. Since abnormal tissue areas such as tumor areas have obvious differences in parameter information such as tissue density and tissue perfusion compared to normal tissues, the specific manifestation on the CT image is that the grayscale density information is large. At the same time, due to the irradiation of the infrared laser, the nanoprobes gathered in the tumor tissue area produce photothermal sensitization, and under thermal ablation, the tissue state of the abnormal tissue will also change, so the CT value at the abnormal tissue changes in real time. Based on this feature, we can accurately identify the abnormal tissue area according to the grayscale density information, and obtain relevant parameter information based on the change of CT value. Among them, in the CT value calculation module, the acquisition of real-time CT value can be specifically expressed as the following formula:

[0053] CTvalue(x,y,z,τ)=(1-g(x,y,z,τ))*|WW ul -WW ll |+WW ll

[0054] Where CTvalue(x,y,z,τ) is the CT value at the three-dimensional coordinate (x,y,z) at temperature τ, g(x,y,z,τ) is the real-time grayscale density of the CT image at the three-dimensional coordinate (x,y,z) at temperature τ, and WW is ul WW is the upper limit of window width ll The lower limit of the window width.

[0055] At the same time, there is a linear relationship between the concentration of the nanoprobe and the CT value:

[0056] CTvalue(x,y,z,τ)=A·L c (x,y,z,τ)+B

[0057] Therefore, the step-by-step acquisition of the nanoprobe concentration in the concentration estimation module can be expressed as follows:

[0058]

[0059] Where, L c (x, y, z, τ) is the real-time nanoprobe concentration at the three-dimensional coordinate (x, y, z) at temperature τ, and A and B are constants.

[0060] After obtaining the real-time nanoprobe concentration, due to the specific absorption of infrared laser by the aggregated nanoprobe material, light energy is converted into heat energy, and its intensity can be determined by the nanoprobe concentration and infrared laser power density. Therefore, we can obtain the current internal heat source intensity of the target tissue through the internal heat estimation module based on the real-time nanoprobe concentration and the known real-time infrared laser power density step by step. Specifically, it can be expressed as the following formula:

[0061] Q r =f OTR (W L ,L C )

[0062] In the formula, Q r is the real-time internal heat source intensity, W L is the real-time infrared laser power density step, L C For real-time nanoprobe concentration stepping.

[0063] According to the real-time internal heat source intensity and based on the Arrhenius bioheat transfer equation, the temperature field acquisition module acquires the temperature field according to the relevant parameters in the target tissue, which can be specifically expressed as the following formula:

[0064]

[0065] Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, ρ b is the density of arterial blood, c b is the specific heat of arterial blood, T n is the temperature of arterial blood, ω b is the blood perfusion rate.

[0066] Then, after obtaining the real-time temperature T at the three-dimensional coordinate (x, y, z) under the target tissue temperature τ, the current temperature field of the target tissue can be obtained. From the real-time temperature field, the equivalent radiotherapy dose coefficient ξ(x, y, z, t) and the real-time infrared laser power density in thermal sensitization adaptive radiotherapy can be obtained through the power control module in the subsequent data process.

[0067] W L =ξ(x,y,z,τ)·D(x,y,z)

[0068] Where D(x,y,z) is the three-dimensional prescription dose set by the physician / physicist based on the experience of radiotherapy alone. Before the onset of thermal sensitization (before infrared laser irradiation), ξ=1, W L=D(x,y,z); As the thermal sensitization effect takes effect, the equivalent radiotherapy dose coefficient of the local tissue gradually decreases. In thermal sensitization radiotherapy, a smaller radiotherapy dose than that required for radiotherapy alone can achieve an equivalent therapeutic effect.

[0069] Embodiment 2

[0070] In order to better understand the technical points of the present invention, this embodiment describes the present invention in the form of method steps. Figure 2 As shown, a method for obtaining a temperature field based on nanoprobe photothermal sensitization includes the following steps:

[0071] S1: X-ray scanning infrared laser irradiates the target tissue injected with nanoprobes and obtains real-time CT imaging of the target tissue;

[0072] S2: acquiring the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image;

[0073] S3: obtaining the real-time nanoprobe concentration stepwise at each coordinate based on the linear relationship between the CT value and the nanoprobe concentration;

[0074] S4: Obtain the real-time internal heat source intensity of the target tissue step by step according to the real-time nanoprobe concentration;

[0075] S5: Estimate the current temperature field of the target tissue according to the real-time internal heat source intensity.

[0076] Furthermore, in step S2, the acquisition of the CT value can be expressed as the following formula:

[0077] CTvalue(x,y,z,τ)=(1-g(x,y,z,τ))*|WW ul -WW ll |+WW ll

[0078] Where CTvalue(x,y,z,τ) is the real-time CT value at the three-dimensional coordinate (x,y,z) at temperature τ, g(x,y,z,τ) is the real-time grayscale density at the three-dimensional coordinate (x,y,z) of the CT image at temperature τ, and WW is ul WW is the upper limit of window width ll The lower limit of the window width.

[0079] Furthermore, in step S3, the step-by-step acquisition of the nanoprobe concentration can be expressed as the following formula:

[0080]

[0081] Where, L c(x, y, z, τ) is the real-time nanoprobe concentration at the three-dimensional coordinate (x, y, z) at temperature τ, and A and B are constants.

[0082] Furthermore, in step S4, the acquisition of the internal heat source intensity can be expressed as the following formula:

[0083] Q r =f OTR (W L ,L C )

[0084] In the formula, Q r is the internal heat source intensity, W L is the real-time infrared laser power density step, L C For real-time nanoprobe concentration stepping.

[0085] Furthermore, in step S5, the acquisition of the temperature field can be expressed as the following formula:

[0086]

[0087] Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, ρ b is the density of arterial blood, c b is the specific heat of arterial blood, T b is the temperature of arterial blood, ω b is the blood perfusion rate.

[0088] In summary, the temperature field acquisition system and method based on nanoprobe photothermal sensitization described in the present invention monitors the temperature field of abnormal tissue in the target tissue in real time based on the parameter information obtained by X-ray scanning. On the premise of obtaining the real-time temperature field, the temperature field is better controlled according to the actual degree of abnormality of the abnormal tissue in subsequent treatment to achieve better treatment effects. Temperature field control under CT guidance can reduce damage to normal biological tissues with higher accuracy.

[0089] It should be noted that all directional indications in the embodiments of the present invention (such as up, down, left, right, front, back, etc.) are only used to explain the relative position relationship, movement status, etc. between the components under a certain specific posture (as shown in the accompanying drawings). If the specific posture changes, the directional indication will also change accordingly.

[0090] In addition, in the present invention, descriptions such as "first", "second", "one", etc. are only used for descriptive purposes and cannot be understood as indicating or implying their relative importance or implicitly indicating the number of the indicated technical features. Therefore, the features defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the present invention, the meaning of "plurality" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined.

[0091] In the present invention, unless otherwise clearly specified and limited, the terms "connection", "fixation", etc. should be understood in a broad sense. For example, "fixation" can be a fixed connection, a detachable connection, or an integral connection; it can be a mechanical connection or an electrical connection; it can be a direct connection or an indirect connection through an intermediate medium, it can be the internal connection of two elements or the interaction relationship between two elements, unless otherwise clearly defined. For ordinary technicians in this field, the specific meanings of the above terms in the present invention can be understood according to specific circumstances.

[0092] In addition, the technical solutions between the various embodiments of the present invention can be combined with each other, but it must be based on the fact that ordinary technicians in the field can implement it. When the combination of technical solutions is contradictory or cannot be implemented, it should be deemed that such combination of technical solutions does not exist and is not within the scope of protection required by the present invention.

Claims

1. A temperature field acquisition system based on nanoprobe photothermal sensitization, characterized in that: include: A CT imaging module is used to obtain real-time CT imaging by scanning the target tissue with nanoprobes through infrared laser irradiation through X-rays; A CT value calculation module is used to obtain the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image; A concentration estimation module is used to obtain the real-time nanoprobe concentration distribution at each coordinate according to the linear relationship between the CT value and the nanoprobe concentration; An internal heat estimation module is used to obtain the real-time internal heat source intensity of the target tissue according to the real-time nanoprobe concentration distribution; A temperature field acquisition module is used to estimate the current temperature field of the target tissue according to the real-time internal heat source intensity; In the CT imaging module, the acquisition of CT value can be expressed as the following formula: In the formula, For temperature Next 3D coordinates The real-time CT value at For CT images at temperature Next 3D coordinates Real-time grayscale density at is the upper limit of the window width, The lower limit of the window width.

2. A temperature field acquisition system based on nanoprobe photothermal sensitization as claimed in claim 1, characterized in that: In the concentration estimation module, the acquisition of the nanoprobe concentration distribution can be expressed as the following formula: In the formula, For temperature Next 3D coordinates The real-time nanoprobe concentration at , A and B are constants.

3. A temperature field acquisition system based on nanoprobe photothermal sensitization as claimed in claim 2, characterized in that: In the internal heat estimation module, the acquisition of the internal heat source intensity can be expressed as the following formula: In the formula, Q r is the real-time internal heat source intensity, W L is the real-time infrared laser power density distribution, L C For real-time nanoprobe concentration distribution, is the photothermal effect function.

4. A temperature field acquisition system based on nanoprobe photothermal sensitization as claimed in claim 3, characterized in that: In the temperature field acquisition module, the acquisition of the temperature field can be expressed as the following formula: Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, is the density of arterial blood, is the specific heat of arterial blood, is the temperature of arterial blood, is the blood perfusion rate, is the Laplace operator.

5. A method for acquiring temperature field based on nanoprobe photothermal sensitization, characterized in that: Includes steps: S1: X-ray scanning infrared laser irradiates the target tissue injected with nanoprobes and obtains real-time CT imaging of the target tissue; S2: acquiring the real-time CT value at each coordinate in the three-dimensional space of the target tissue according to the real-time CT image; S3: Obtain the real-time nanoprobe concentration distribution at each coordinate based on the linear relationship between the CT value and the nanoprobe concentration; S4: Obtain the real-time internal heat source intensity of the target tissue based on the real-time nanoprobe concentration distribution; S5: estimating the current temperature field of the target tissue according to the real-time internal heat source intensity; In the step S2, the acquisition of the CT value can be expressed as the following formula: In the formula, For temperature Next 3D coordinates The real-time CT value at For CT images at temperature Next 3D coordinates Real-time grayscale density at is the upper limit of the window width, The lower limit of the window width.

6. A method for acquiring temperature field based on nanoprobe photothermal sensitization as claimed in claim 5, characterized in that: In the step S3, the acquisition of the nanoprobe concentration distribution can be expressed as the following formula: In the formula, For temperature Next 3D coordinates The real-time nanoprobe concentration at , A and B are constants.

7. A method for acquiring temperature field based on nanoprobe photothermal sensitization according to claim 6, characterized in that: In the step S4, the acquisition of the internal heat source intensity can be expressed as the following formula: In the formula, Q r is the internal heat source intensity, W L is the real-time infrared laser power density distribution, L C For real-time nanoprobe concentration distribution, is the photothermal effect function.

8. A method for acquiring temperature field based on nanoprobe photothermal sensitization as claimed in claim 7, characterized in that: In step S5, the acquisition of the temperature field can be expressed as the following formula: Where ρ is the density of the target tissue, c is the specific heat of the target tissue, λ is the thermal conductivity of the target tissue, T is the real-time temperature of the target tissue, is the density of arterial blood, is the specific heat of arterial blood, is the temperature of arterial blood, is the blood perfusion rate, is the Laplace operator.

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