WO2021017418A1

WO2021017418A1 - Application of three-dimensional photoacoustic imaging in breast tumor scoring system and device

Info

Publication number: WO2021017418A1
Application number: PCT/CN2020/071292
Authority: WO
Inventors: 杨萌; 姜玉新; 王铭; 李建初; 齐振红; 苏娜; 赵辰阳; 唐天虹; 韦瑶; 桂阳; 张睿; 刘思锐
Original assignee: 中国医学科学院北京协和医院
Priority date: 2019-08-01
Filing date: 2020-01-10
Publication date: 2021-02-04
Also published as: LU102578B1; LU102578A1

Abstract

Provided are an application of three-dimensional photoacoustic imaging in a breast tumor scoring system and device; scoring comprises the following steps: (1) photoacoustic/ultrasound dual-modality imaging collection of image information of a breast tumor in vitro; (2) analyzing the collected image information and performing morphological and functional scoring, respectively; (3) combining the results of morphological and functional scoring to obtain a comprehensive score and determining whether the breast tumor has a malignant tendency result; if one or both of the morphological score and functional score is determined to be malignant, then considering the tumor to be malignant. A more stable quantitative result can be provided by means of three-dimensional tumor imaging. In comparison with performing breast three-dimensional photoacoustic imaging alone, the tumor area is depicted with the aid of ultrasound imaging, and it is possible to analyze the external and internal characteristics of the tumor separately, improving diagnostic sensitivity and specificity; a distinction is made between malignant and benign tumors on the basis of the threshold value of oxygen saturation (SO₂), and the invention has convenience, high repeatability, and more objective diagnosis.

Description

Application of three-dimensional photoacoustic imaging in breast tumor scoring system and equipment

Technical field

The invention relates to the technical field of medical diagnosis, in particular to the application of three-dimensional photoacoustic imaging in breast tumor scoring systems and equipment.

Background technique

Breast cancer is the most common malignant tumor in women. The global incidence of breast cancer is showing a high incidence in the 21st century, especially in my country, which ranks first among all tumors in women. Therefore, breast cancer has become a major public health problem threatening human health.

Currently, mammography and breast ultrasound (US) are the two most commonly used and most effective imaging methods in breast cancer screening. Mammography lacks the ability to provide morphology, and information about breast lesions is not applicable to dense glands, which hinders popularization. Ultrasonography is more sensitive in providing information about the shape and boundaries of breast lesions, regardless of the density of breast glands. In addition, color Doppler flow imaging (CDFI) and power Doppler imaging (PDI) can describe the detailed vascular characteristics of the lesion, which increases the diagnostic confidence for identifying breast cancer. However, although a lot of work has been done to realize the above-mentioned imaging modality quantitative analysis data algorithm, a reliable quantitative diagnosis method has not been developed, and the diagnosis still highly depends on the personal experience of the doctor. The accuracy of these conventional imaging modes for diagnosing early breast cancer, especially those breast cancers that do not have typical morphological features, is still limited. This drawback has caused many patients, especially some advanced breast patients, to undergo invasive examinations to obtain more diagnostic information and treatment information.

A new type of fusion imaging technology, photoacoustic ultrasound dual-mode imaging (PA/US) combines the high contrast of optical absorption and deep ultrasound detection. PA breaks through the deep barriers of high-resolution optical imaging in biological tissues, making it suitable for Breast imaging. With the rapid development of PA, there have been many clinical research reports of breast PA globally, but most of them are based on 2D PA/US imaging. The diagnosis of two-dimensional PA breast tumors mainly depends on the physician's subjective judgment on the image of the lesion, including:( 1) Select slices for image evaluation and analysis and (2) Image semi-quantitative scoring. The above processes all rely on physician experience and subjective judgment. Therefore, the positive image evaluation method with the ability of objective target quantitative analysis is of great value to improve the accuracy of diagnosis.

At present, there is no mature 3D equipment device used in the tumor scoring system of photoacoustic/ultrasound imaging technology.

Summary of the invention

The purpose of the present invention is to provide a three-dimensional photoacoustic imaging scoring system, equipment and application for breast tumors, which can use quantitative parameters to distinguish malignant and benign tumors. In addition, the present application uses three-dimensional imaging methods, which are more stable and objective than two-dimensional imaging. Quantify the results.

One aspect of the present invention provides the application of three-dimensional photoacoustic imaging in a breast tumor scoring system, including the following steps:

(1) Photoacoustic/ultrasound dual-modality imaging collects image information of breast tumors in vitro;

(2) Analyze the collected image information and perform morphological and functional scoring respectively;

(3) Combining the results of morphological score and functional score to obtain a comprehensive score and determine whether breast tumors have a malignant tendency; if one or all of the morphological score or functional score is judged to be malignant, the tumor is considered to be malignant.

In the above-mentioned application, preferably, the function score uses the collected image information to quantitatively calculate the tumor oxygen saturation value as an evaluation criterion, and the oxygen saturation value includes the oxygen saturation value inside the tumor and the oxygen saturation value around the tumor , The oxygen saturation value inside the tumor and the oxygen saturation value around the tumor are both lower than 0.75-0.80 as the hypoxic tendency and malignancy as the evaluation standard.

The oxygen saturation value inside the tumor and the oxygen saturation value SO ₂ around the tumor are calculated by the following formula:

SO ₂ (r)=C _Hb (r)/(C _Hb (r)+C _deHb (r))=(PA(λ ₁ ,r)*ε _deHb (λ ₂ )-PA(λ ₂ ,r)* ε _deHb (λ ₁ ))/(PA(λ ₁ ,r)*(ε _deHb (λ ₂ )-ε _Hb (λ ₂ ))+PA(λ ₂ ,r)*(ε _Hb (λ ₁ )-ε _deHb (λ ₁ ))

Among them, Hb is endogenous oxygenated hemoglobin, deHb is deoxygenated hemoglobin,

PA(λ ₁ ,r)*=μ _a (λ ₁ ,r)=C _Hb (r)ε _Hb (λ ₁ )+C _deHb (r)ε _deHb (λ ₁ )

PA(λ ₂ ,r)*=μ _a (λ ₂ ,r)=C _Hb (r)ε _Hb (λ ₂ )+C _deHb (r)ε _deHb (λ ₂ )

λ ₁ =750 nm, λ ₂ =830 nm.

For the above-mentioned application, preferably, the evaluation criteria of the function score also include blood vessel density, that is, the blood vessel density of the tumor and the area around the tumor. The method is to divide the calculated number of pixels with SO ₂ >40% by the corresponding area The total number of pixels.

In the above-mentioned application, preferably, the tumor includes invasive breast carcinoma and intraductal tumor of the breast.

In the above-mentioned application, preferably, the breast tumor is T1 stage invasive breast cancer.

For the above-mentioned application, preferably, the morphological score is evaluated based on the following image information collected: the abundance of blood flow inside the tumor, the amount of blood flow around the tumor, the spatial progression of tumor blood vessels, and the penetration of the tumor into blood vessels.

For the above-mentioned application, preferably, the degree of blood flow within the tumor is 0-none, 1-less, and 2-rich as the score interval, and the number of blood flow around the tumor is 0-none, 1-less, 2-rich. As the scoring interval, tumor vascular space travel uses 0-rule and 1-irregular as the scoring interval, and tumor penetration into the blood vessel is 0-none, 1-present as the scoring interval. Specifically, the abundance of blood flow inside the tumor is less, that is, the ratio of the volume of the internal blood vessel to the volume of the nodule is less than 50%, and the blood flow richness of the tumor is rich, that is, the ratio of the volume of the internal blood vessel to the nodule volume is >50%; the amount of blood flow around the tumor Less means peripheral blood vessel distribution range <50% of nodule volume, abundant blood flow around tumor means peripheral blood vessel distribution range> nodule volume 50%; tumor vascular space runs regularly, that is, the blood vessels run smoothly, the diameter of the tube is evenly striped, and the branches gradually From thick to thin; the tumor vascular space runs irregularly, that is, the vascular runs are twisted, cystic expansion, and anastomotic branches are disordered. More specifically, if the blood flow inside the tumor is abundant, it is judged as a malignant tendency; if the blood flow around the tumor is abundant, it is judged as a malignant tendency; if the tumor vascular space runs irregularly, it is judged as a malignant tendency; the tumor penetrates the blood vessel to be judged as a malignant tendency.

For the above-mentioned application, preferably, the morphological score also includes the following collected image information: tumor vessel volume and tumor vessel spatial distribution, and the proportion of tumor vessel volume to nodule volume is 0-none, 1-less , 2-rich as a scoring interval, and the spatial distribution of tumor blood vessels is 0-uniform and 1-uneven as the scoring interval. Specifically, the tumor blood vessel volume accounts for a small proportion of the nodule volume, that is, the blood vessel volume accounts for less than 50% of the nodule volume, and the tumor blood vessel volume accounts for a rich proportion of the nodule volume, that is, the blood vessel volume accounts for more than 50% of the nodule volume; the tumor blood vessels are evenly distributed in space That is, the number and diameter of blood vessels in the symmetrical part of the nodule are uniform; the spatial distribution of tumor blood vessels is not uniform, that is, the number and diameter of blood vessels are unevenly distributed in the symmetrical part of the nodule.

In another aspect of the present invention, a breast tumor scoring system based on photoacoustic/ultrasound dual-modal imaging technology is provided, which includes an information acquisition module, an information analysis module, a calculation output module, and a judgment module. / Ultrasound imaging equipment is connected to obtain image information characteristic parameters of breast tumor tissue and its surrounding tissues; the information analysis module analyzes and gives morphological scores and functional scores according to the obtained image information characteristic parameters; the calculation output The module calculates the morphological score and the functional score respectively; the judging module determines the nature of the tumor based on the morphological score and the functional score.

In the above-mentioned scoring system, preferably, the morphological scoring is based on the following image information collected as evaluation criteria: the abundance of blood flow inside the tumor, the amount of blood flow around the tumor, the spatial progression of tumor blood vessels, the penetration of the tumor into the blood vessel, the tumor Internal oxygen saturation and oxygen saturation around the tumor; the function score quantitatively calculates the tumor oxygen saturation value based on the collected image information as an evaluation standard, and the oxygen saturation value includes the oxygen saturation inside the tumor and the oxygen saturation around the tumor The oxygen saturation value within the tumor and the oxygen saturation value around the tumor are all set to be less than 0.75-0.80 as hypoxic tendency and malignancy as the evaluation standard.

According to the above-mentioned scoring system, preferably, the degree of blood flow within the tumor is 0-none, 1-less, 2-rich as the scoring interval, and the amount of blood flow around the tumor is 0-none, 1-less, 2- Enrichment is used as the scoring interval, tumor vascular space travel is 0-rule, 1-irregular as the scoring interval, tumor penetration into the blood vessel is 0-none, 1-present as the scoring interval.

In the above-mentioned scoring system, preferably, the image information further includes tumor vessel volume and tumor vessel spatial distribution, and the ratio of tumor vessel volume to nodule volume is 0-none, 1-less, 2-rich as the scoring interval , The spatial distribution of the tumor blood vessels takes 0-uniform and 1-asymmetry as the scoring interval.

Another aspect of the present invention is to provide a two-dimensional and three-dimensional breast tumor scoring system and equipment based on photoacoustic/ultrasound imaging technology, which can distinguish malignant and benign tumors by using quantitative parameters.

One aspect of the present invention provides a breast tumor scoring system based on photoacoustic/ultrasound imaging technology. The system includes an information acquisition module, an information analysis module, and an output module.

The information acquisition module collects two-dimensional or three-dimensional image information through a photoacoustic/ultrasound imaging device to obtain image information characteristic parameters of breast tumor tissue and surrounding tissues;

The information analysis module classifies and calculates image information to obtain various characteristic parameters of the obtained image;

The output module combines the obtained characteristic parameters to make judgments.

Preferably, the information analysis module includes a function calculation module, and the function calculation module quantitatively calculates a characteristic parameter of the tumor oxygen saturation value based on the obtained image information for judgment.

Preferably, the oxygen saturation value includes the oxygen saturation value in the tumor and the oxygen saturation value around the tumor, and the oxygen saturation value in the tumor and the oxygen saturation value around the tumor are both less than 0.75-0.80, which means that hypoxia tends to be malignant. As an evaluation criterion.

Preferably, the information analysis module includes a morphology judgment module, the morphology judgment module is to determine the abundance of blood flow in the tumor, the amount of blood flow around the tumor, the space course of tumor blood vessels, and the penetration of the tumor in the obtained image information. Characteristic parameters such as blood vessel conditions are calculated or processed by software according to specific standards.

Preferably, the degree of blood flow within the tumor is 0-none, 1-less, and 2-rich as the scoring interval, and the amount of blood flow around the tumor is 0-none, 1-less, and 2-rich as the scoring interval. Spatial walking uses 0-rule and 1-irregular as the scoring interval, and tumor penetration into the blood vessel is 0-none, 1-with as the scoring interval.

Preferably, the morphological judgment module further includes the following collected image information: tumor vessel volume and tumor vessel spatial distribution, the proportion of the tumor vessel volume in the nodule volume is 0-none, 1-less, 2-rich as The scoring interval, the spatial distribution of the tumor blood vessels is 0-uniform and 1-asymmetry as the scoring interval.

Further, the present invention also provides a device including the above-mentioned scoring system, which includes an ultrasonic probe that collects sound and image information; the host is respectively connected to the light transmitting and light transmitting module and the ultrasonic phased array transmitting and receiving module through a two-core cable, It is used to drive the emission of laser and ultrasonic signals, and to receive photoacoustic signals and reflected ultrasonic signals for imaging; the processor converts specific parameters of the imaging signal into specific values; the output device outputs specific images and values.

Preferably, the ultrasonic probe includes a phased array probe, a convex array probe and a linear array probe.

Preferably, the processor is any commercially available charge-coupled device capable of converting photoacoustic images into digital signals.

Preferably, the output device is a printer.

The beneficial effects of the present invention are as follows:

Compared with the previous two-dimensional photoacoustic/ultrasound dual-mode imaging, the three-dimensional photoacoustic/ultrasound dual-mode imaging of the present invention has the advantage of being able to use quantitative parameters to distinguish malignant and benign tumors. The three-dimensional imaging also has more advantages than two-dimensional imaging. Robust quantitative results. As can be seen from Figure 7 the oxygen within the two regions of different malignancies Dimensional surface (Slice) saturation (SO ₂₎ varies greatly between slice values, select a single slice computed oxygen saturation (SO ₂₎ value representative to The oxygen saturation of the entire tumor is not accurate. Therefore, performing a three-dimensional tumor scan can provide more stable quantitative results. In addition, compared with pure breast three-dimensional photoacoustic imaging, the use of ultrasound imaging to describe the tumor area can analyze the external and internal features of the tumor separately, and improve the sensitivity and specificity of malignant tumor diagnosis. In addition, compared with the scoring system and equipment used in previous studies, the distinction between malignant and benign tumors based on the threshold of oxygen saturation (SO ₂ ) is more convenient, reproducible, and more objective in diagnosis.

Description of the drawings

Figure 1 shows the definition of the tumor area and the area around the tumor in the embodiment of the present invention;

Figure 2 The average oxygen saturation of the benign group, malignant group and normal group in the tumor area and the area around the tumor;

Figure 3 By changing the SO ₂ threshold inside the tumor (Figure 3(a)) and the area around the tumor (Figure 3(b)), a receiver operating characteristic curve (ROC) drawn to distinguish malignant tumors from benign tumors;

Figure 4 depicts the PA/US fusion imaging results of malignant tumors (IBC) and benign tumors (fibroadenoma); more abundant, irregular, low SO ₂ blood vessels can be observed in the malignant tumor area and the surrounding area (Figure 4 (a)), which is different from benign tumors (Figure 4(b)) in vascular pattern;

Figure 5 Mammography and CD31 immunohistochemistry (IHC) blood vessel staining results; from the X-ray results Figure 5 (a) can be seen, because there is no obvious calcification and obvious boundaries, it is difficult to detect malignant tumors; According to the X-ray results of Figure 5(b), benign tumors cannot be identified as easily as ultrasound; from the results of IHC blood vessel staining, it can be seen that more CD31 blood vessel staining appeared in the malignant tumor area and the area around the tumor (Figure 5(c) )), which is different from benign tumors (Figure 5(d)), which is consistent with 2D PA/US imaging results;

Figure 6 shows the 3D blood vessel images of the same tumor shown in Figure 4 (a, b); abundant blood vessels can be seen in the area around the malignant tumor, while there are relatively few blood vessels in the area around the benign tumor; the tumor and the area around the tumor are shown Medium SO ₂ distribution (Figure 6(c, d)); Compared with benign tumors, significantly lower SO ₂ distribution can be seen in malignant tumors;

Figure 7 The average oxygen saturation (SO ₂ ) value of different two-dimensional sections in the malignant tumor area;

Fig. 8 is a structural block diagram of the breast tumor scoring system of the present invention;

Figure 9 is a structural diagram of the breast tumor scoring system of the present invention.

Detailed ways

The following examples are used to illustrate the present invention, but not to limit the scope of the present invention. Unless otherwise specified, the technical means used in the embodiments are conventional means well known to those skilled in the art. The present invention will be described in detail below with reference to the drawings and embodiments.

In this example, "3D" refers to three-dimensional, "PA" refers to photoacoustic, "US" refers to ultrasound, "IBC" refers to invasive breast cancer, "SO ₂ "refers to oxygen saturation, and "Hb" refers to oxygen Hemoglobin, "deHb" refers to deoxyhemoglobin, and "IHC" refers to immunohistochemistry.

PA/US dual-mode 3D imaging system

The dual-mode system in this study is based on a high-end clinical ultrasound machine (Resona 7, Mindray Bio-Medical Electronics Co., Ltd.), which can perform and collect data required for PA imaging. The delay and sum algorithm is used to reconstruct the PA imaging results online. The clinical linear probe (L9-3U, Mindray Bio-Medical Electronics Co., Ltd.) has 192 elements, the size of each element is 0.2 mm, and the center frequency is 5.8 MHz. The laser source is an OPO tunable laser (Spitlight 600-OPO, Innolas laser GmbH), which generates 700-850 nm laser pulses at 10 Hz. In our research, 750nm and 830nm are used for PA functional imaging. The time division multiplexing method is used to realize real-time imaging of PA/US with two wavelengths and SO ₂ mapping at a frame rate of 5 Hz. By scanning the probe on the breast skin surface, the system can perform local 3D bimodal functional imaging. During 3D image acquisition, the motor moves at a steady speed (1mm/s), and at the same time, a set of 2D US images and two-wavelength PA images are acquired at 0.2mm step intervals. The total scan length is 4cm and the total scan time is 200 seconds. . Download 3D imaging results for further data analysis.

In order to obtain 3D PA/US images, we imported the 2D SO ₂ map into Amira (version 6.0, Visage Imaging) and obtained the blood vessel map by extracting the surface of the SO ₂ map. Then the surface of the tumor area identified in B mode and the blood vessel map are imaged together with a certain degree of transparency.

patient

From November 2017 to January 2018, 46 consecutive patients with breast tumors smaller than 2 cm and receiving BIRADS scores of 3 to 5 were recruited from breast surgery clinics and inpatient departments. All patients were initially diagnosed with ultrasound, X-ray mammography, and/or MRI by an experienced imaging doctor. Three imaging physicians performed routine ultrasound examinations on all patients. These physicians have more than 10 years of diagnostic experience in ultrasound diagnosis of breast diseases. After the conventional ultrasound examination, 2D and 3D PA/US dual-modality imaging was performed. All patients underwent resection of the lesion and biopsy to obtain pathological results.

Among the 46 patients, two patients failed to image due to system failure; there were two other patients whose ultrasound showed that the distal end of breast lesions was more than 3.5 cm away from the skin layer. Due to the strong light attenuation in the tissue, the current system was beyond the effective range. Imaging depth. Of the remaining 42 patients, 18 patients had intraductal lesions or distant metastases, 16 had T1 invasive breast cancer (IBC) without distant metastases, and 8 had breast fibroids or breast disease. In this study, the imaging results of 16 patients with T1 stage IBC and 8 patients with benign lesions (6 breast fibroids and 2 breast diseases) were studied. Due to the different intrinsic pathogenesis of intraductal carcinoma in situ (DCIS) and invasive breast cancer, and the focus of this study is on early breast cancer detection, the present invention selected 16 T1 invasive breast cancers (IBC) without distant metastasis ), 8 cases of breast fibroma or breast disease were analyzed for later data.

Example 1 Construction of breast tumor scoring system

1. Data analysis and 3D image acquisition

In this application, the main two optical absorbers in breast tissue are endogenous oxyhemoglobin (Hb) and deoxyhemoglobin (deHb). Calculate the optical absorption coefficient of blood according to the following equation:

μ _a (λ,r)=C _Hb (r)ε _Hb (λ)+C _deHb (r)ε _deHb (λ) (1)

Among them, μ _a (λ,r) represents the optical absorption coefficient of blood, ε _Hb (λ) represents the molar extinction of endogenous oxygenated hemoglobin (Hb), and C _Hb (r) represents endogenous oxygenated hemoglobin (Hb) Ε _deHb (λ) represents the molar extinction of deoxyhemoglobin (deHb), and C _deHb (r) represents the concentration of deoxyhemoglobin (deHb).

The PA signal is proportional to the product of the light absorption coefficient μ _a (λ, r) and the luminous flux Φ (λ, r). The luminous flux depends on the wavelength (λ) and the spatial position (r). Since the absorption coefficient μ _a (λ) of background breast tissue at 750 nm and 830 nm is very close to the reduced scattering coefficient μs', in our study, the luminous flux is roughly the same after the laser irradiation power of each wavelength is normalized. Then, the SO ₂ at each pixel can be calculated with the following formula.

The above formula is obtained by the following method, the wavelengths used are λ ₁ =750nm, λ ₂ =830nm, and the luminous flux is

then

Considering the same laser energy,

versus

The difference is small and can be ignored, then (2) can be obtained through simultaneous equations (3) and (4).

Where PA(λ ₁ ,r)* is ignored

PA, PA(λ ₂ ,r)* is ignored

The PA, PA value can be directly collected by ultrasound probe. Any pixels with negative SO ₂ values were removed in the subsequent analysis.

For the 3D-PA/US quantitative calculation, the tumor boundary of each ultrasound section is first marked by an experienced doctor. Then, we calculated the minimum volume ellipse (LVE region) surrounding the 3D tumor region (Tumor region). By extending each of the three axis lengths of the LVE by 1.2 times, we obtain an extension ellipse region. We define the area inside the extended ellipse except the tumor area as the tumor surrounding region (Tumor surrounding region) as shown in Figure 1.

After marking the tumor and its surrounding tumor area, we calculated the average value of oxygen saturation inside the tumor and the average value of oxygen saturation around the tumor in the two areas. We set a threshold of 40% to reduce the influence of artifacts. Similarly, we also calculated the blood vessel density (vas den) of the tumor and the area around the tumor by dividing the calculated number of pixels with SO ₂ >40% by the total number of pixels in the corresponding area.

2. Statistical analysis

We use the non-parametric two-tailed Mann-Whitney U-test to calculate the statistical significance between the two groups. Bonferroni correction for multiple comparisons (number of trials: n=3), for the tumor area and the surrounding area, P value = 0.017, which is considered to be 95% statistically significant. The Hodges-Lehmann estimator was used to give the difference between the two groups and 95% statistical significance. Statistical analysis was performed using Matlab (Mathworks, Inc.).

3. Results

The results of 24 patients (16 T1 IBC and 8 benign lesions) were included in the statistical analysis. They were divided into three groups: benign group (fibroma or breast disease, n=8), malignant group (T1 stage IBC, n=16) and normal group (contralateral healthy breast, n=22). Of the 24 patients, 2 patients were excluded from the normal group due to the presence of lesions in the contralateral breast. The average SO ₂ values in the tumor and surrounding areas of the malignant group and the benign group are shown in Table 1 below:

Table 1

As shown in Figure 2(a), comparing the tumor area, the average SO _{2 of the} malignant group (Malignant) is 7.7% lower than that of the benign group (Benign) (95% confidence interval: 2.1%, 12.4%) (P=0.016), It is also 3.9% lower than the normal group (Normal) (95% confidence interval: 2.2%, 5.5% (P=0.010)). Compared with the area around the tumor (Figure 2(b)), the average SO _{2 of the} malignant group was 4.9% lower than that of the benign group (95% confidence interval: 1.6%, 8.4%) (P=0.009). The difference in the average SO ₂ between the benign group and the normal group was not significantly different at the 95% level.

By changing the SO ₂ threshold of the tumor area (Figure 3(a)) and the area around the tumor (Figure 3(b)), draw a receiver operating characteristic curve (ROC) for distinguishing malignant tumors from benign tumors curve. In this example, the SO ₂ threshold in the tumor area is set to 0.769 to 0.794, the sensitivity for diagnosing malignant tumors is 100%, the specificity is 62.5%, and the area under the ROC curve is 0.81. In this embodiment, the SO ₂ threshold in the area around the tumor is set to 0.776 to 0.781, the sensitivity for diagnosing malignant tumors is 100%, the specificity is 75%, and the area under the ROC curve (AUC) is 0.84. Based on experience, the inventors set the internal oxygen saturation (SO ₂ ) value of the tumor and the surrounding oxygen saturation (SO ₂ ) value of less than 0.75-0.80 as the evaluation standard for hypoxic tendency and malignancy, which is a comprehensive benign and malignant tumor The ROC curve is drawn to ensure the best sensitivity and specificity. In order to better judge benign and malignant tumors, we also adjust the ROC curve threshold range according to actual needs, such as increasing the SO ₂ range to improve the specificity of malignant tumor diagnosis, and reducing the SO ₂ range to Improve the sensitivity of malignant tumor diagnosis.

Figure 4(a) depicts the PA/US fusion imaging results of malignant tumors (IBC), and Figure 4(b) depicts the PA/US fusion imaging results of benign tumors (fibroadenoma). Abundant, irregularly shaped blood vessels with lower SO ₂ can be observed inside and around the malignant tumor (corresponding to Table 1 malignant sample 11, the SO ₂ inside the tumor is 0.72, and the surrounding SO ₂ is 0.75, which is lower than the set threshold) (Figure 4(a)), which is different from the blood vessel pattern of benign lesions (Figure 4(b)) (corresponding to Table 1 benign sample 6 tumor internal SO ₂ is 0.84, peripheral SO ₂ is 0.79, higher than the set threshold). As shown in Figure 4(a), there are multiple blood vessels (>3, or interwoven into a network) inside the tumor, and the blood flow abundance score is 2-rich; multiple blood vessels appear in multiple areas around the tumor, and the blood flow number is scored 2-rich The score of tumor vascular space running is 1-irregular; the score of tumor penetration into blood vessel is 1-yes.

For malignant cases, it is difficult to accurately grade malignant tumors based on the results of conventional ultrasound, because malignant tumors may have a similar regular shape to benign tumors. In addition, the results of X-ray mammography and CD31 immunochemical (IHC) blood vessel staining are shown in Figure 5. Figure 5(a) of the X-ray photography results shows that because the tumor has no obvious calcification and clear boundaries, it is difficult to detect malignant tumors on X-ray photography. The X-ray results in Figure 5(b) show that benign tumors cannot be identified as easily as conventional ultrasound. The results of IHC blood vessel staining showed that more CD31-stained blood vessels appeared in and around malignant tumors (Figure 5(c)), but there was no such situation in and around benign tumors (Figure 5(d)), which is similar to 2D PA /US imaging results are consistent.

Example 2. Scoring application examples

In May 2018, one patient with a breast tumor smaller than 2 cm and a BIRADS score of 4 was recruited from the breast surgery clinic. The blood vessel images of the patient are shown in Figure 6(a,b).

Figure 6(a) The proportion of the volume of blood vessels in the tumor in the volume of the nodule>50%, the blood flow is rich, score 2 points; the distribution range of the peripheral blood vessels of the tumor>the volume of the nodule is 50%, the blood flow quantity is rich, the score is 2 points; the tumor vascular space Distorted walking, cystic expansion, disordered and irregular anastomotic branches, score 1 point; tumor penetrates blood vessel, yes, score 1 point; Figure 6 (a) total score 6 points. According to the morphological score, it was judged as malignant tendency. Figure 6(a) The SO ₂ inside the tumor is 0.72, and the surrounding SO ₂ is 0.75, which is lower than the set threshold, and it is judged as malignant tendency according to the functional score. In summary, Figure 6(a) is judged to be malignant.

Figure 6(b) The proportion of the volume of blood vessels inside the tumor to the volume of the nodule is less than 50%, and the blood flow is less, and the score is 1 point; the distribution range of the peripheral blood vessels of the tumor is less than 50% of the nodule volume, and the number of blood flow is less, and the score is 1 point; the tumor vascular space There is no distortion, cystic expansion, and anastomotic branch disorder. The score is ruled and the score is 0; the tumor does not penetrate the blood vessel, the score is 0; Figure 6(b) The total score is 2 points. According to the morphological score, it was judged as a benign tendency. Figure 6(b) The SO ₂ inside the tumor is 0.84, and the surrounding SO ₂ is 0.79, which is higher than the set threshold, and it is judged as benign tendency according to the functional score. In summary, the tumor is judged to be benign in Figure 6(b).

After pathological diagnosis and clinical diagnosis, the patient was indeed a benign tumor.

Embodiment 3. Tumor scoring system and equipment based on photoacoustic/ultrasound imaging technology

As shown in Figure 8,

A tumor scoring system based on photoacoustic/ultrasound imaging technology. The system includes an information acquisition module, an information analysis module, and an output module,

The information acquisition module collects two-dimensional or three-dimensional image information through a photoacoustic/ultrasound imaging device to obtain image information characteristic parameters of tumor tissue and surrounding tissues;

Wherein, the information analysis module includes a function calculation module and a morphology judgment module. The function calculation module quantitatively calculates the characteristic parameters of the tumor oxygen saturation value based on the obtained image information for judgment, wherein the oxygen saturation value includes the tumor The internal oxygen saturation value and the surrounding oxygen saturation value of the tumor, the internal oxygen saturation value of the tumor and the surrounding oxygen saturation value of the tumor are all taken less than 0.75-0.80 as the hypoxic tendency and malignancy as the evaluation standard.

The morphological judgment module is to calculate or process the characteristic parameters of the acquired image information such as the richness of blood flow inside the tumor, the amount of blood flow around the tumor, the space of the tumor blood vessel, the situation of the tumor penetrating into the blood vessel, etc. according to specific standards. .

Preferably, the degree of blood flow within the tumor is 0-none, 1-less, and 2-rich as the scoring interval, and the amount of blood flow around the tumor is 0-none, 1-less, and 2-rich as the scoring interval. Spatial walking uses 0-rule and 1-irregular as the scoring interval, and tumor penetration into the blood vessel is 0-none, 1-with as the scoring interval. The morphological judgment module also includes the following collected image information: tumor vessel volume and tumor vessel spatial distribution, the proportion of the tumor vessel volume in the nodule volume is 0-none, 1-less, and 2-rich as the scoring interval, The spatial distribution of the tumor blood vessels is 0-uniform and 1-asymmetry as the scoring interval.

As shown in FIG. 9, the present invention also provides a device including the above-mentioned scoring system, which includes an ultrasonic probe 1 for collecting sound and image information; a host computer 2, which is connected to the light emitting and light transmitting module and the ultrasonic phased array transmission through a two-core cable. It is connected with the receiving module to drive the emission of laser and ultrasonic signals, and to receive the photoacoustic signal and the reflected ultrasonic signal imaging; the processor 3 converts the specific parameters of the imaging signal into specific values; the output device 4 outputs specific images and values .

Preferably, the ultrasonic probe 1 includes a phased array probe, a convex array probe and a linear array probe.

Preferably, the processor 3 is any commercially available charge-coupled device capable of converting photoacoustic images into digital signals.

Preferably, the output device 4 is a printer.

Although the general description and specific embodiments have been used to describe the present invention in detail above, some modifications or improvements can be made on the basis of the present invention, which is obvious to those skilled in the art. Therefore, these modifications or improvements made without departing from the spirit of the present invention belong to the scope of the present invention.

Industrial applicability

The three-dimensional photoacoustic imaging of the present invention can be used industrially in a breast tumor scoring system and equipment, and has industrial applicability.

Claims

The application of three-dimensional photoacoustic imaging in breast tumor scoring system is characterized in that it includes the following steps:

(1) Photoacoustic/ultrasound dual-modality imaging collects image information of breast tumors in vitro;

(2) Analyze the collected image information and perform morphological and functional scoring respectively;

(3) Combining the results of morphological score and functional score to obtain a comprehensive score and determine whether breast tumors have a malignant tendency; if one or all of the morphological score or functional score is judged to be malignant, the tumor is considered to be malignant.
The application according to claim 1, wherein the function score quantitatively calculates the tumor oxygen saturation value based on the collected image information as an evaluation criterion, and the oxygen saturation value includes the oxygen saturation value inside the tumor and the surrounding tumor The oxygen saturation value, the oxygen saturation value inside the tumor and the oxygen saturation value around the tumor are all less than 0.75-0.80 as hypoxic tendency and malignancy as the evaluation standard.
The application of claim 2, wherein the oxygen saturation value inside the tumor and the oxygen saturation value SO 2 around the tumor are calculated by the following formula:

SO 2 (r)=C Hb (r)/(C Hb (r)+C deHb (r))=(PA(λ 1 ,r)*ε deHb (λ 2 )-PA(λ 2 ,r)* ε deHb (λ 1 ))/(PA(λ 1 ,r)*(ε deHb (λ 2 )-ε Hb (λ 2 ))+PA(λ 2 ,r)*(ε Hb (λ 1 )-ε deHb (λ 1 ))

Among them, Hb is endogenous oxygenated hemoglobin, deHb is deoxygenated hemoglobin,

PA(λ 1 ,r)*=μ a (λ 1 ,r)=C Hb (r)ε Hb (λ 1 )+C deHb (r)ε deHb (λ 1 )

PA(λ 2 ,r)*=μ a (λ 2 ,r)=C Hb (r)ε Hb (λ 2 )+C deHb (r)ε deHb (λ 2 )

λ 1 =750 nm, λ 2 =830 nm.
The application according to claim 1, wherein the evaluation criterion of the function score further includes blood vessel density.
The application according to claim 4, wherein the blood vessel density method is to divide the calculated number of pixels with SO 2 >40% by the total number of pixels in the corresponding area.
The application according to claim 1, wherein the breast tumors include breast invasive carcinoma and breast ductal tumors.
The application according to claim 6, wherein the breast tumor is T1 invasive breast cancer.
The application according to claim 1, wherein the morphological score is based on the following image information collected as evaluation criteria: the abundance of blood flow inside the tumor, the amount of blood flow around the tumor, the spatial progression of tumor blood vessels, and tumor penetration Vascular condition.
The application according to claim 8, characterized in that the degree of blood flow within the tumor is 0-none, 1-less, and 2-rich as the score interval, and the amount of blood flow around the tumor is 0-none, 1-less. , 2-rich as the scoring interval, tumor vascular space progression is 0-rule, 1-irregular as the scoring interval, tumor penetration into the blood vessel is 0-none, 1-present as the scoring interval.
The application according to claim 9, wherein the morphological score further includes the following collected image information: tumor vessel volume and tumor vessel spatial distribution, and the proportion of tumor vessel volume to nodule volume is 0-none. , 1-less and 2-rich are used as scoring intervals, and the spatial distribution of the tumor blood vessels is 0-uniform and 1-asymmetry as the scoring intervals.
A breast tumor scoring system based on photoacoustic/ultrasound imaging technology is characterized in that the system includes an information acquisition module, an information analysis module, and an output module,

The information acquisition module collects two-dimensional or three-dimensional image information through a photoacoustic/ultrasound imaging device to obtain image information characteristic parameters of breast tumor tissue and surrounding tissues;

The information analysis module classifies and calculates image information to obtain various characteristic parameters of the obtained image;

The output module makes a judgment in combination with the obtained characteristic parameters.
The scoring system according to claim 11, wherein the information analysis module comprises a function calculation module, and the function calculation module quantitatively calculates the characteristic parameter of the breast tumor oxygen saturation value based on the obtained image information to make a judgment.
The scoring system according to claim 12, wherein the oxygen saturation value includes the oxygen saturation value in the tumor and the oxygen saturation value around the tumor, and the oxygen saturation value in the tumor and the oxygen saturation value around the tumor The evaluation criteria were all lower than 0.75-0.80 as hypoxic tendency and malignant.
The scoring system according to claim 11, wherein the information analysis module further comprises a morphological judgment module, and the morphological judgment module evaluates the abundance of blood flow in the tumor and the periphery of the tumor in the obtained image information. The characteristic parameters such as the amount of blood flow, the space travel of the tumor blood vessel, and the penetration of the tumor into the blood vessel are calculated or processed by software according to specific standards.
The scoring system of claim 14, wherein the blood flow within the tumor is 0-none, 1-less, and 2-rich as the scoring interval, and the amount of blood flow around the tumor is 0-none, 1- Less and 2-rich are used as the scoring interval, tumor vascular space progression is 0-rule, 1-irregular as the scoring interval, and tumor penetration into the blood vessel is 0-none, 1-present as the scoring interval.
The scoring system according to claim 14 or 15, wherein the morphological judgment module further comprises the following collected image information: tumor blood vessel volume and tumor blood vessel spatial distribution, and the proportion of the tumor blood vessel volume to the nodule volume 0-none, 1-less, and 2-rich are used as scoring intervals, and the spatial distribution of the tumor blood vessels is 0-uniform and 1-asymmetric as the scoring intervals.
The equipment comprising the scoring system according to any one of claims 11-16, characterized in that it comprises an ultrasonic probe for collecting sound and image information; the host is connected to the light emission and light transmission module and the ultrasonic phased array transmission and The receiving module is connected to drive the emission of laser and ultrasound signals, and to receive photoacoustic signals and reflected ultrasound signals for imaging; a processor to convert specific parameters of the imaging signal into specific values; an output device to output specific images and values.
The device of claim 17, wherein the ultrasonic probe includes a phased array probe, a convex array probe, and a linear array probe.
17. The device of claim 17, wherein the processor is any commercially available charge-coupled device capable of converting photoacoustic images into digital signals.
The apparatus according to claim 17, wherein the output device is a printer.