Method and system for evaluating preeclampsia placenta through photoacoustic imaging and ultrasonic contrast

Abstract

The invention discloses a method and a system for evaluating preeclampsia placenta through photoacoustic imaging and ultrasonic contrast. The method comprises the following steps: S1, establishing a rat model for reducing uterus placenta perfusion; s2, monitoring the longitudinal change of the oxygenation degree of the pregnant mouse placenta by using a photoacoustic imaging method, and quantitatively evaluating the oxygenation state of the placenta through spectral analysis; s3, evaluating the perfusion condition of placenta microcirculation by using an ultrasound contrast method, and providing dynamic functional imaging by using ultrasound microbubbles as a tracer agent; and S4, evaluating the influence of drug therapy on the placenta function of the pregnant mouse by combining photoacoustic imaging and ultrasonic contrast methods, and monitoring and evaluating the changes of oxygenation, perfusion and angiogenesis of the placenta before and after the drug therapy. According to the invention, photoacoustic imaging and ultrasound contrast technologies are combined, and placenta oxygenation, perfusion and angiogenesis of the preeclampsia animal model are evaluated. The influence of drug therapy on the placenta function is monitored and evaluated, and a basis is provided for preeclampsia treatment.

Description

Technical Field

[0001] The present invention relates to the technical field of ultrasonic image recognition, and in particular, to a method and system for photoacoustic imaging and ultrasonic contrast agent to evaluate preeclamptic placenta. Background Art

[0002] Preeclampsia is a pregnancy-specific complication, accounting for approximately 3%-8% of pregnant women in China, while the incidence of severe preeclampsia is 0.3%-0.5%. The clinical features of this disease usually appear after 20 weeks of pregnancy, manifested as symptoms such as hypertension and proteinuria. It may also cause a series of serious maternal and fetal complications, including placental abruption, renal failure, disseminated intravascular coagulation, fetal growth restriction, and fetal distress, which is one of the main causes of maternal and perinatal mortality. According to data, the proportion of maternal deaths caused by preeclampsia in China accounts for up to 15% of the total deaths. In addition, women with a history of preeclampsia and their offspring have a significantly increased risk of long-term heart disease, hypertension, and cerebrovascular accidents, and the risk of cardiovascular-related death has increased by nearly 2 times. In recent years, the incidence of preeclampsia has shown an upward trend, which may be related to changes in multiple maternal factors, including advanced maternal age, obesity, multiple pregnancies caused by assisted reproductive technology, and lifestyle changes.

[0003] The placenta is a key organ for communication between the fetus and the mother, and its main functions include providing nutrition, gas exchange, discharging fetal metabolites, providing immune defense, and synthesizing and secreting hormones. Extensive research has shown that the disorder of uterine spiral artery remodeling leading to placental ischemia and hypoxia is an important link in the pathogenesis of preeclampsia. In patients with preeclampsia, the remodeling of the uterine spiral artery is incomplete, resulting in the failure of trophoblast cells to completely replace endothelial cells, which limits the dilation ability of the blood vessel ends, thus significantly reducing the placental blood perfusion volume. In addition, the accelerated blood flow velocity reduces the exchange efficiency of nutrients and oxygen between the mother and the fetus, which may trigger oxidative stress reactions in fetal cells. This placental dysfunction leads to the entry of placental-derived adverse factors into the maternal blood circulation, triggering a systemic inflammatory response and elevated blood pressure in the mother. At the same time, the function of vascular endothelial cells is damaged, triggering a series of pathological changes, including changes in osmotic fluid, coagulation cascade reaction, microthrombus formation, and reduction in blood volume, which may ultimately lead to the occurrence of preeclampsia.

[0004] It can be seen that although preeclampsia is clinically defined as newly occurring hypertension and proteinuria in the second and third trimesters of pregnancy, its root cause - the pathophysiological changes of the placenta - actually begin in the early stages of pregnancy. Currently, the most effective treatment for preeclampsia is delivery, but premature preterm birth increases the difficulty and cost of treatment and may also cause a variety of complications and sequelae. Therefore, monitoring placental function before the onset of clinical symptoms in pregnant women is crucial for identifying high-risk patients with preeclampsia.

[0005] Currently, the methods for evaluating placental function mainly include cordocentesis, magnetic resonance imaging (MRI), and ultrasound examination. Cordocentesis can directly detect indicators such as the oxygen saturation of fetal blood under ultrasound guidance, but this is an invasive examination with a risk of fetal loss, limiting its widespread promotion. Magnetic resonance imaging techniques, such as blood oxygenation level-dependent (BOLD) MRI and diffusion-weighted (DW) MRI, can provide functional imaging of the placenta, but these techniques are costly and sensitive to tissue movement, restricting their popularity in clinical applications.

[0006] Ultrasound examination is the main method for prenatal assessment of the placenta. By measuring two-dimensional biological indicators of the placenta and fetus, as well as Doppler spectra of the umbilical artery, uterine artery, etc., it indirectly reflects the function of the placenta. However, there are differences in the measurement techniques and parameter ranges used in different studies, and there is a lack of a unified diagnostic standard. This indicates that existing single imaging techniques cannot fully and accurately evaluate the function of the placenta. Therefore, there is an urgent need to develop multimodal imaging tools that can directly reflect key functional information such as oxygenation, perfusion, and angiogenesis of the placenta. Summary of the Invention

[0007] The purpose of the present invention is to provide a method and system for evaluating preeclamptic placenta by photoacoustic imaging and ultrasound contrast agent, which solves the technical problems that after long-term use, the upper mold base and the lower mold base will have slight misalignment, the positioning posts cannot be accurately inserted into the positioning slots during mold clamping, and the upper and lower mold bases cannot be closed, which cannot assist in positioning and hinders mold clamping, and the use is not reliable enough.

[0008] To achieve the above purpose, the present invention provides the following technical solutions:

[0009] On the one hand, the present invention provides a method for evaluating preeclamptic placenta by photoacoustic imaging and ultrasound contrast agent, including the following steps:

[0010] S1. Establish a rat model with reduced uteroplacental perfusion;

[0011] S2. Use photoacoustic imaging method to monitor the longitudinal changes of oxygenation in the placenta of pregnant rats, and quantitatively evaluate the oxygenation status of the placenta through spectral analysis;

[0012] S3. Apply ultrasound contrast agent method to evaluate the perfusion of placental microcirculation, use ultrasound microbubbles as tracers to provide dynamic functional imaging;

[0013] S4. Combine photoacoustic imaging and ultrasound contrast agent methods to evaluate the effect of drug treatment on the function of the placenta of pregnant rats, and monitor and evaluate the changes in oxygenation, perfusion, and angiogenesis of the placenta before and after drug treatment.

[0014] In some embodiments, S1 includes the following steps:

[0015] S11. During the estrus period of rats, female and male rats were caged together at a ratio of 1:1. Vaginal secretions of the rats were collected and smeared. The day when sperm were detected under an optical microscope was defined as day 0 of pregnancy in rats.

[0016] S12. A rat model with reduced uteroplacental perfusion was established.

[0017] S13. Thirty pregnant rats were randomly divided into 3 experimental groups, and RUPP surgery was performed on some of the experimental groups.

[0018] In some embodiments, S12 includes the following steps:

[0019] S121. The pregnant rats were anesthetized and fixed.

[0020] S122. The uterus of the pregnant rats was removed.

[0021] S123. The abdominal aorta above the bifurcation of the iliac vessels and below the renal artery was clamped with a vascular clamp.

[0022] S124. The uterus of the pregnant rats was repositioned and sutured.

[0023] In some embodiments, S2 includes the following steps:

[0024] S21. A small animal photoacoustic imaging system and a supporting bench-top laser were used to capture photoacoustic images of the placentas of pregnant rats.

[0025] S22. Vevo post-processing software was used to post-process the photoacoustic image data.

[0026] 5. A method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound according to claim 1, wherein S3 includes the following steps:

[0027] S31. A VEVO 3100 small animal photoacoustic imaging system and a transducer were used to capture ultrasound images of the placentas of pregnant rats.

[0028] S32. Vevo post-processing software was used to perform quantitative analysis of placental tissue perfusion on the collected raw ultrasound data.

[0029] In some embodiments, S4 includes the following steps:

[0030] S41. On the 14th and 18th days of pregnancy, proteinuria was measured and blood pressure of the pregnant rats was monitored by non-invasive tail artery pulse plethysmography.

[0031] S42. After imaging was completed on the 20th day of pregnancy in the pregnant rats, the fetuses and placentas were removed.

[0032] S43. Morphological observation of placental tissues to evaluate placental oxygenation, perfusion, and angiogenesis in the preeclampsia animal model.

[0033] On the other hand, the present invention provides a system for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound. Using the above method, it includes the following modules:

[0034] Rat model establishment module: used to establish a rat model with reduced uteroplacental perfusion;

[0035] Photoacoustic imaging analysis module: using photoacoustic imaging method to monitor the longitudinal changes of placental oxygenation in pregnant rats, and quantitatively evaluating the oxygenation status of the placenta through spectral analysis;

[0036] Contrast-enhanced ultrasound analysis module: applying contrast-enhanced ultrasound method to evaluate the perfusion of placental microcirculation, using ultrasound microbubbles as tracers to provide dynamic functional imaging;

[0037] Evaluation module: combining photoacoustic imaging and contrast-enhanced ultrasound analysis modules to evaluate the effect of drug treatment on the placental function of pregnant rats, monitoring and evaluating the changes in placental oxygenation, perfusion, and angiogenesis before and after drug treatment, and outputting the evaluation results.

[0038] Compared with the prior art, the present invention has the following beneficial effects:

[0039] The present invention longitudinally evaluates placental oxygenation, blood perfusion, and angiogenesis during the development of preeclampsia through a preeclampsia animal model, combined with various imaging and post-processing methods such as photoacoustic imaging and contrast-enhanced ultrasound. The aim is to deepen the understanding of the potential mechanisms of preeclampsia and develop a multimodal imaging system for evaluating placental microcirculation injury and prognosis in preeclampsia, so as to provide a scientific basis for the early prevention and treatment of preeclampsia. BRIEF DESCRIPTION OF THE DRAWINGS

[0040] Figure 1 It is a schematic diagram of the overall process of Embodiment 1 of the present invention. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0041] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all of the embodiments; based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0042] Embodiment 1:

[0043] Please refer to Figure 1 , a method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound, including the following steps:

[0044] S1. Establish a rat model with reduced uteroplacental perfusion, including the following steps:

[0045] 1. Experimental animals and preparations;

[0046] The rats selected for the experiment are all clean-grade SD female and male rats, purchased from Beijing Huafukang Biotechnology Co., Ltd. The body weight range of female SD rats is 200 - 250 g, and the age is between 90 - 120 days. The body weight range of male SD rats is 250 - 300 g, and the age is between 90 - 120 days. All the rats are raised in the Experimental Animal Center of the Basic Medical College of Sichuan University. Rat captive environment: room temperature 18 - 25 °C, indoor relative humidity 60% - 70%, without controlling drinking water and food. In addition, a 12-hour light is given every day to establish a day-night cycle.

[0047] During the estrus period of the rats, female and male rats are caged together at a ratio of 1:1. Every morning, observe the shedding of the vaginal plug of the female rats. Use a medical cotton swab to take the vaginal secretions of the rats and smear them. The day when sperm are detected under an optical microscope is defined as day 0 of rat pregnancy.

[0048] 2. Construct a preeclampsia model;

[0049] Adopt the method described by Granger JP et al. to establish a rat model with reduced uteroplacental perfusion (RUPP). The specific steps are as follows:

[0050] ① Anesthesia and fixation: Pregnant rats are operated under 2% isoflurane anesthesia and fixed in the supine position on the operating table. ② Preparation of the surgical area: Shave and disinfect the area from the last pair of nipples to the xiphoid process along the midline of the abdomen of the pregnant rats. ③ Surgical incision: Under sterile conditions, make an incision about 5 - 6 cm along the midline of the abdomen of the pregnant rats to expose the abdominal wall muscles. ④ Uterus extraction: Use a wet cotton swab to assist and gently extract the uterus, avoiding excessive pressure on the uterus. ⑤ Vascular clamping: Place a vascular clamp around the abdominal aorta above the bifurcation of the iliac vessels and below the renal artery, and then place a vascular clamp on each of the two uterine branches of the ovarian artery. ⑥ Uterus replacement and suture: After the operation, gently replace the uterus, rinse it with physiological saline, and then suture the abdominal wall and skin in sequence. ⑦ Postoperative treatment: Clean the blood and liquid around the incision with hydrogen peroxide to complete the operation. The criteria for successful construction of the preeclampsia model are: the blood pressure of pregnant rats increases by > 20 mmHg, and the 24-hour urinary protein increases significantly.

[0051] 3. Experimental grouping

[0052] Thirty pregnant rats were randomly divided into three groups: a simple pregnancy group (Control group, 10 rats), a RUPP surgery group (RUPP group, 10 rats), and a RUPP surgery plus pravastatin group (RUPP+PT group, 10 rats). RUPP surgery was performed on gestational day 13 in both the RUPP and RUPP+PT groups. The RUPP+PT group received a subcutaneous injection of 5 mg / kg / day starting on gestational day 14.

[0053] S2. Use photoacoustic imaging to monitor the longitudinal changes in placental oxygenation in pregnant mice, and quantitatively evaluate the oxygenation status of the placenta through spectral analysis.

[0054] Photoacoustic imaging was performed using a VEVO 3100 small animal photoacoustic imaging system and an Opotek Phocus HE desktop laser. An LZ-250 linear array probe (with 256 elements, 13-24 MHz broadband frequency, and a center frequency of 20 MHz) was used to capture ultrasound and photoacoustic images.

[0055] Pregnant mice were anesthetized with isoflurane and placed on a Vevo heated physiological imaging platform (maintained at 37°C). The mice were placed in a supine position with their limbs straight and secured. Abdominal hair was removed using depilatory cream to minimize interference during imaging. Throughout the imaging process, the animal's heart rate, respiratory rate, and body temperature were continuously monitored and maintained.

[0056] Photoacoustic imaging was performed on five placentas from each pregnant mouse on days 16, 18, and 20 of gestation. B-mode ultrasound was first used to locate the umbilical cord insertion point and determine the centerline of the placenta, thereby defining the imaging plane. Placentas with intact edges in the ultrasound image were selected for photoacoustic imaging. Photoacoustic images were acquired at wavelengths of 690 nm, 808 nm, and 950 nm, which correspond to the isoabsorption points of deoxyhemoglobin and the relative optical absorption peaks of oxyhemoglobin, respectively. For pregnant mice with no more than five surviving pups, all eligible placentas were included in the imaging. If there were more than five surviving pups, placentas distributed throughout the abdomen were selected for imaging to take into account regional differences in placental perfusion. After imaging was completed, the animals were allowed to recover from anesthesia for two days before the next imaging.

[0057] Photoacoustic data were post-processed using Vevo post-processing software. The software analyzed the photoacoustic signal intensity of the placenta at a wavelength of 808 nm, and the mean placental oxygen saturation was quantitatively analyzed from the linear raw data. Three regions of interest (the mesoplacental triangle, the basal region, and the labyrinthine region) were manually delineated, and the mean oxygen saturation in each region was calculated.

[0058] S3. Use ultrasound contrast imaging to evaluate the perfusion of the placental microcirculation and use ultrasound microbubbles as tracers to provide dynamic functional imaging.

[0059] Imaging was performed using a VEVO 3100 small animal photoacoustic imaging system and an LZ250 transducer (256 elements, 13 - 24 MHz broadband frequency, 20 MHz center frequency).

[0060] The pregnant mice were anesthetized with isoflurane and placed supine and fixed on the heated physiological imaging platform of Vevo. The abdominal hair was removed, and centrifuged ultrasonic coupling agent was applied to the lower abdomen.

[0061] First, B - mode ultrasound was used to locate the placenta. The placenta with clear edges and located at a lower position in the abdomen was selected for imaging to reduce the influence of respiratory movement. Color Doppler ultrasound was used to determine the mid - line of the placenta, marked by the placental cord insertion site. The ultrasound contrast agent used was SonoVue, a phospholipid microbubble encapsulating SF6 (manufactured by Bracco Switzerland). The powder was injected into 5 ml of physiological saline to form a microbubble suspension. It was injected via the tail vein (dose: 1.0 ml / kg), and then the catheter was flushed with 1 ml of physiological saline. During the injection process, nonlinear images were recorded using the CEUS mode, aiming to maximize the frame rate and minimize the width and depth of the imaging window. A 4 - minute CEUS video loop was continuously saved. From the 16th day of pregnancy, the above imaging steps were repeated every other day until the 20th day of pregnancy.

[0062] The Vevo post - processing software was used to perform quantitative analysis of placental tissue perfusion on the collected raw data. First, the image data was pre - processed to correct motion artifacts. Regions of interest (ROIs) were manually defined, including all regions of the placenta, and time - intensity curves (TICs) were fitted to obtain the following parameters: arrival time (AT), peak signal intensity (PI), time to peak intensity (PIT), and area under the curve (AUC).

[0063] S4. Combine photoacoustic imaging and contrast - enhanced ultrasound methods to evaluate the effects of drug treatment on the placental function of pregnant mice, and monitor and evaluate the changes in placental oxygenation, perfusion, and angiogenesis before and after drug treatment.

[0064] On the 14th and 18th days of pregnancy, blood pressure was monitored by non - invasive tail artery plethysmography. The experiment was carried out at a quiet room temperature of 25 - 26°C and in a warming cylinder at 37 - 39°C. After the rats were fixed, they were allowed to adapt to the environment for 5 - 10 minutes, and then their tails were fixed to the sensor for measurement. After the waveform was stable, at least 6 blood pressure measurements were continuously recorded, and the average of arterial pressure and venous pressure was calculated to determine the mean arterial pressure.

[0065] On the 14th and 18th days of pregnancy, pregnant rats were placed in standard metabolic cages to collect 24-hour urine. After the collection, the urine samples were centrifuged to remove the precipitate, and the supernatant was taken and stored at -40°C. Subsequently, the BCA method was used to determine the protein concentration in the urine: the supernatant was mixed with the BCA reagent, incubated at 37°C, and then the absorbance at a wavelength of 562 nm was measured by a photometer, and the protein concentration was calculated based on the standard curve to evaluate the level of proteinuria.

[0066] After imaging was completed on the 20th day of pregnancy in rats (GD20), the following steps were performed: ① Anesthesia was performed using a 3% sodium pentobarbital solution. ② The abdomen was opened and 5 ml of blood was collected. The sample was added to an anticoagulant tube containing 3.2% sodium citrate, and then centrifuged to separate the serum, which was stored at -80°C. ③ The abdominal aorta was clamped with a hemostatic forceps, and the fetus and placenta were removed by cesarean section, and the numbers were recorded. ④ The placenta, fetal membranes, and umbilical cord were removed, the umbilical cord was cut, and the fetus and placenta were blotted dry. ⑤ The weights of the fetus and placenta were measured, and 2 placenta samples were fixed in 4% paraformaldehyde and stored refrigerated for later use.

[0067] The tissue samples were dehydrated with increasing concentrations of alcohol and xylene using a fully automatic dehydrator, then embedded in paraffin and sectioned. The sections were dewaxed, hydrated, and successively stained with hematoxylin, differentiated with hydrochloric acid alcohol, blued, and stained with eosin. Then, dehydration was performed with gradient alcohol, transparency was achieved with xylene, and finally sealed with neutral gum. The sealed sections were imaged using a Pannoramic 250 scanner, and the entire process followed the SOP to ensure standardization and reproducibility.

[0068] The tissue sections were first dewaxed to water treatment through a series of xylene and absolute ethanol. Subsequently, antigen retrieval was performed using a citrate buffer solution and heated using a microwave oven. Endogenous peroxidase was blocked with 3% hydrogen peroxide, and after washing with PBS, bovine serum was used for blocking. The primary antibody was incubated overnight in a wet box at 4°C, and the secondary antibody was incubated for 30 minutes at 37°C. After DAB color development, the nuclei were counterstained with hematoxylin, and finally dehydrated with gradient alcohol, made transparent with xylene, and sealed with neutral gum. The tissue was observed under low magnification using a microscopic imaging system, and 20X and 40X microscopic images were collected. The Halo data analysis system was used to calculate the positive area ratios of CD31, CD34, and HIF-1α.

[0069] Using an ELISA kit, the target antibody was immobilized on a 48-well microplate by the sandwich method to form a solid-phase carrier. The standard or sample was added to the microplate wells. After the target molecule was bound to the solid-phase antibody, a horseradish peroxidase-labeled secondary antibody was added. The unbound antibody was washed away, and TMB substrate was added for color development. TMB first turned blue and then yellow under the action of peroxidase. The content of the target molecule in the sample was proportional to the color intensity. The absorbance (OD value) was measured at a wavelength of 450 nm by an enzyme-linked immunosorbent assay analyzer to calculate the concentrations of PLGF and sVEGF.

[0070] Example 2

[0071] A system for photoacoustic imaging and contrast-enhanced ultrasound evaluation of preeclamptic placentas, using the above method, includes the following modules:

[0072] Rat model establishment module: Used to establish a rat model with reduced uteroplacental perfusion.

[0073] Photoacoustic imaging analysis module: Using photoacoustic imaging method to monitor the longitudinal changes of oxygenation in the placentas of pregnant rats, and quantitatively evaluating the oxygenation status of the placentas through spectral analysis.

[0074] Contrast-enhanced ultrasound analysis module: Applying contrast-enhanced ultrasound method to evaluate the perfusion of placental microcirculation, using ultrasound microbubbles as tracers to provide dynamic functional imaging.

[0075] Evaluation module: Combining the photoacoustic imaging and contrast-enhanced ultrasound analysis modules to evaluate the effects of drug treatment on the functions of the placentas of pregnant rats, monitoring and evaluating the changes in oxygenation, perfusion and angiogenesis of the placentas before and after drug treatment, and outputting evaluation results.

[0076] The system for photoacoustic imaging and contrast-enhanced ultrasound evaluation of preeclamptic placentas of the present invention can be installed in a computer device. The computer device includes a processor, a memory, and a computer program stored in the memory and executable on the processor, such as a program for photoacoustic imaging and contrast-enhanced ultrasound evaluation of preeclamptic placentas. Among them, the memory includes at least one type of readable storage medium, and the readable storage medium includes flash memory, mobile hard disk, multimedia card, card-type memory (such as: SD or DX memory, etc.), magnetic memory, magnetic disk, optical disc, etc. The processor is the control core of the electronic device, connecting various components of the entire computer device through various interfaces and lines, and by running or executing the programs or modules stored in the memory, and calling the data stored in the memory, to execute various functions of the computer device and process data.

[0077] The module of the present invention refers to a series of computer program segments that can be executed by the processor of a computer device and can complete fixed functions, and are stored in the memory of the computer device.

[0078] Those skilled in the art will readily think of other embodiments of the present application after considering the specification and practicing the content disclosed herein. The present application is intended to cover any variations, uses, or adaptations of the present application, which follow the general principles of the present application and include the common general knowledge or conventional technical means in the technical field not disclosed in the present application.

Claims

1. A method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound, characterized in that, Including the following steps: S1. Establish a rat model with reduced uteroplacental perfusion; S2. Use photoacoustic imaging method to monitor the longitudinal changes of placental oxygenation in pregnant rats, and quantitatively evaluate the oxygenation status of the placenta through spectral analysis; S3. Apply contrast-enhanced ultrasound method to evaluate the perfusion of placental microcirculation, and use ultrasound microbubbles as tracers to provide dynamic functional imaging; S4. Combine photoacoustic imaging and contrast-enhanced ultrasound methods to evaluate the effect of drug treatment on the placental function of pregnant rats, and monitor and evaluate the changes in oxygenation, perfusion and angiogenesis of the placenta before and after drug treatment.

2. The method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound according to claim 1, wherein S1 includes the following steps: S11. During the estrus period of rats, female and male rats are caged together at a ratio of 1:

1. Take the vaginal secretions of rats and smear them. The day when sperm are detected under an optical microscope is defined as day 0 of pregnancy in rats; S12. Establish a rat model with reduced uteroplacental perfusion; S13. Randomly divide 30 pregnant rats into 3 experimental groups, and perform RUPP surgery on some experimental groups.

3. A method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound according to claim 2, characterized in that The said S12 includes the following steps: S121. Anesthetize and fix the pregnant rats; S122. Take out the uterus of the pregnant rats; S123. Clamp the abdominal aorta above the bifurcation of the iliac vessels and below the renal artery; S124. Replace and suture the uterus of the pregnant rats.

4. A method for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound according to claim 1, characterized in that, S2 includes the following steps: S21. Use a small animal photoacoustic imaging system and a supporting desktop laser to capture the photoacoustic images of the placenta of pregnant rats; S22. Use Vevo post-processing software to post-process the photoacoustic image data.

5. A method for evaluating preeclamptic placenta by photoacoustic imaging and ultrasound contrast enhancement according to claim 1, characterized in that, S3 includes the following steps: S31. Use a VEVO 3100 small animal photoacoustic imaging system and a transducer to capture the ultrasound images of the placenta of pregnant rats; S32. Use Vevo post-processing software to perform quantitative analysis of placental tissue perfusion on the collected raw ultrasound data.

6. A method for evaluating preeclamptic placenta by photoacoustic imaging and ultrasound contrast, according to claim 1, characterized in that S4 includes the following steps: S41. On the 14th and 18th days of pregnancy, measure proteinuria and monitor the blood pressure of pregnant rats by non-invasive tail artery pulse manometry; S42. After imaging is completed on the 20th day of pregnancy in pregnant rats, take out the fetus and placenta; S43. Observe the placental tissue morphology and evaluate the oxygenation, perfusion and angiogenesis of the placenta in the preeclampsia animal model.

7. A system for evaluating preeclamptic placenta by photoacoustic imaging and contrast-enhanced ultrasound, using the method according to any one of claims 1-6, characterized in that, Including the following modules: Rat model establishment module: used to establish a rat model with reduced uteroplacental perfusion; Photoacoustic imaging analysis module: use photoacoustic imaging method to monitor the longitudinal changes of placental oxygenation in pregnant rats, and quantitatively evaluate the oxygenation status of the placenta through spectral analysis; Contrast-enhanced ultrasound analysis module: apply contrast-enhanced ultrasound method to evaluate the perfusion of placental microcirculation, and use ultrasound microbubbles as tracers to provide dynamic functional imaging; Evaluation module: combine the photoacoustic imaging and contrast-enhanced ultrasound analysis modules to evaluate the effect of drug treatment on the placental function of pregnant rats, monitor and evaluate the changes in oxygenation, perfusion and angiogenesis of the placenta before and after drug treatment, and output the evaluation results.

Images