Application of < 18 > F-FDG PET quantification in simulation of weightlessness environment and preparation of curative effect monitoring product for treating weightlessness mice

Abstract

The invention discloses application of < 18 > F-FDG PET quantification in simulation of a weightlessness environment and preparation of a curative effect monitoring product for treating a weightlessness mouse. According to the invention, 18F-FDG PET imaging is used for evaluating the myocardial glucose metabolism function of a weightlessness body or simulating the weightlessness body and monitoring the curative effect of the Shenqi body resistance strengthening injection on improving myocardial glucose metabolism. The verification shows that the myocardial glucose uptake change prompted by 18F-FDG PET is prior to the myocardial structure and function change prompted by echocardiography. The 18F-FDG PET imaging provides irreplaceable glucose uptake information of an echocardiogram, and meanwhile, an objective quantitative evaluation method is provided for evaluating the curative effect of the Shenqi body resistance strengthening injection for improving myocardial glucose metabolism. The method is different from an existing myocardial structural image evaluation method.

Description

Technical Field

[0001] The present invention belongs to the technical field of PET imaging and specifically discloses 18 Application of F-FDG PET quantitative analysis in simulating weightlessness environment and preparing products for monitoring the therapeutic efficacy of weightlessness mice. Background Art

[0002] Humans have lived in the 1G gravity environment on Earth for a long time, and their physiological systems have adapted well to this environment. Compared with Earth, the sharp drop in gravity in space causes major adaptive changes in human physiology. All organ systems are affected to some extent, especially the cardiovascular system. Aerospace practices at home and abroad have shown that short-term and long-term manned space flights in a weightless environment have adverse effects on the cardiovascular system, which has become one of the most important factors restricting the development of manned space flight (Hughson, Helm and Durante. Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol, 2018, 15(3): 167-80.). Spaceflight eliminates the normal gravitational load on the cardiovascular system and induces cardiovascular deconditioning (Antonutto and di Prampero. Cardiovascular deconditioning in microgravity: some possible countermeasures. Eur J Appl Physiol, 2003, 90(3-4): 283-91; Hughson, Helm and Durante. Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol, 2018, 15(3): 167-80.). In addition, the altered cardiovascular function in space mainly causes physiological problems in the post-flight phase. Astronauts may experience dizziness, increased heart rate, arrhythmia, orthostatic intolerance, presyncope, and decreased exercise capacity (Antonutto and di Prampero. Cardiovascular deconditioning in microgravity: some possible countermeasures. Eur J Appl Physiol, 2003, 90(3-4): 283-91; Shen and Frishman. Effects of Spaceflight on Cardiovascular Physiology and Health. Cardiol Rev, 2019, 27(3): 122-26.).Therefore, it is of great significance to study the adverse effects of short-term and long-term weightlessness on the human cardiovascular system and explore the laws and mechanisms of adaptive changes of the cardiovascular system during weightlessness, which is crucial for finding preventive and protective measures against the adverse effects of weightlessness.

[0003] Scientists have made a lot of efforts and practices in this regard. Some spaceflight data and ground simulation experiments have reported changes in cardiac structure and function during and after spaceflight, head-down bed rest, and hind limb unloading (or tail suspension) (Bungo, Goldwater, Popp, et al. Echocardiographic evaluation of space shuttle crew members. J Appl Physiol (1985), 1987, 62(1): 278-83; Dorfman, Rosen, Perhonen, et al. Diastolic suction is impaired by bed rest: MRI tagging studies of diastolic untwisting. J Appl Physiol (1985), 2008, 104(4): 1037-44; Goldstein, Edwards and Schroeter. Cardiac morphology after conditions of microgravity during COSMOS 2044. J Appl Physiol (1985), 1992, 73(2 Suppl):94s-100s; Perhonen, Franco, Lane, et al. Cardiac atrophy after bed rest and spaceflight. J Appl Physiol (1985), 2001, 91(2): 645-53; Sun, Ling, Zhao, et al. Panax quinquefolium saponin attenuates cardiac remodeling induced by simulated microgravity. Phytomedicine, 2019, 56: 83-93.). However, previous human and animal experiments mainly used echocardiography and magnetic resonance imaging to study the changes in cardiac structure and function in real or simulated weightlessness, or explored the changes in myocardial histology through in vitro animal experiments. So far, there has been no study that dynamically and non-invasively evaluates the changes in myocardial glucose uptake in real time at the molecular level in a weightless environment.Although free fatty acid β-oxidation is the main source of energy metabolism for normal cardiomyocytes under fasting conditions, the ability of cardiomyocytes to utilize glucose under stress conditions is crucial for maintaining myocardial physiological metabolic homeostasis and function (Wang, Xing, Zhang, et al. Time-restricted feeding alleviates cardiac dysfunction induced by simulatedmicrogravity via restoring cardiac FGF21 signaling. Faseb j, 2020, 34(11):15180-96.). 18 Fluoride-fluorodeoxyglucose positron emission tomography (F-FDG PET) 18 fluoro-fluorodeoxyglucosepositron emission tomography, 18 F-FDG PET is an important in vivo functional metabolic imaging method that can quantitatively evaluate local 18 F-FDG uptake is used to measure the utilization of exogenous glucose in the heart and evaluate myocardial glucose metabolism (van der Weerdt, Klein, Visser, et al. Use of arterialised venous instead of arterial blood for measurement of myocardial glucose metabolism during euglycaemic-hyperinsulinaemic clamping. Eur J Nucl Med Mol Imaging, 2002, 29(5): 663-9.). Myocardial glucose utilization has been reported to be regulated by myocardial energy status such as exercise, pressure overload and myocardial ischemia (Young, Russell, Yin, et al. Regulation of myocardial glucose uptake and transport during ischemia and energetic stress. Am J Cardiol, 1999, 83(12a): 25h-30h.). Considering the widely reported cardiac dysfunction in real and simulated microgravity, it is speculated that myocardial glucose uptake will change in weightlessness.

[0004] At the same time, some countermeasures, such as physical exercise, antioxidants and health supplements, have been proposed to protect the cardiovascular system from the adverse effects of microgravity (Antonutto and di Prampero. Cardiovascular deconditioning in microgravity: some possible countermeasures. Eur J Appl Physiol, 2003, 90(3-4): 283-91; Hughson, Helm and Durante. Heart in space: effect of the extraterrestrial environment on the cardiovascular system. Nat Rev Cardiol, 2018, 15(3): 167-80.). For example, Chinese herbal medicine has been shown to be a promising countermeasure against cardiovascular dysfunction (Sun, Ling, Zhao, et al. Panax quinquefoliumsaponin attenuates cardiac remodeling induced by simulated microgravity. Phytomedicine, 2019, 56: 83-93; Yuan, Alameddine, Coupé, et al. Effect of Chinese herbal medicine on vascular functions during 60-day head-down bedrest. Eur J Appl Physiol, 2015, 115(9): 1975-83.). ShenqiFuzheng injection (SFI) is a well-known traditional Chinese medicine, mainly composed of extracts of Codonopsis pilosula and Astragalus membranaceus (Liao, Hao, Huang, et al. Network pharmacology study reveals energymetabolism and apoptosis pathways-mediated cardioprotective effects of ShenqiFuzheng. J Ethnopharmacol, 2018, 227: 155-65.), and is a widely used adjuvant cancer treatment drug in clinical practice. Its efficacy has been confirmed in clinical trials, but its mechanism of action is still unclear.A large number of basic experiments and clinical practices have shown that SFI has a strong cardioprotective effect and has a therapeutic effect on cardiovascular diseases. Codonopsis extract has a cardiotonic effect, and Astragalus can regulate myocardial energy metabolism and inhibit cell apoptosis (Liao, Hao, Huang, et al. Networkpharmacology study reveals energy metabolism and apoptosis pathways-mediatedcardioprotective effects of Shenqi Fuzheng. J Ethnopharmacol, 2018, 227: 155-65.). It is still unclear whether SFI can improve myocardial glucose metabolism under microgravity conditions.

[0005] Therefore, the present invention applies 18 F-FDG PET imaging is used to evaluate the myocardial glucose metabolism function of the body in weightlessness or simulated weightlessness and to monitor the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism. This is different from the existing myocardial structural imaging evaluation method. Summary of the invention

[0006] In view of the above, the present invention discloses 18 Application of F-FDG PET quantitative analysis in simulating weightlessness environment and preparing products for monitoring the therapeutic efficacy of weightlessness mice.

[0007] The above object of the present invention is achieved through the following technical solutions: The present invention first provides 18 Application of F-FDG PET quantitative analysis in simulating weightlessness environment and preparing products for monitoring the therapeutic efficacy of weightlessness mice.

[0008] Furthermore, the weightlessness environment includes a simulated weightlessness environment and a real weightlessness environment.

[0009] Furthermore, the weightless mice include simulated weightless mice and real weightless mice.

[0010] Furthermore, the quantification is Patlak quantification.

[0011] Furthermore, the efficacy monitoring product is Shenqi Fuzheng Injection.

[0012] Further, the following steps are included: (1) Using PET scanning to evaluate intravenous 18 Individual F-FDGs were dynamically scanned and reconstructed using the three-dimensional ordered subset expectation maximization algorithm; (2) Analyze the reconstructed PET images, delineate the regions of interest of the left ventricular myocardium and inferior vena cava (IVC) blood, and obtain the time activity curve (TAC) of the corresponding regions; (3) The TAC of the vena cava blood was used as the input function and the TAC of the left ventricular myocardium was used as the output function. The original TAC of the left ventricular myocardium was fitted using the Patlak model to obtain the myocardial 18 The F-FDG net uptake rate constant, Ki, is used to quantify myocardial glucose metabolism; (4) Compare the differences in left ventricular myocardial Ki before and after treatment in the same individual or between different treatments in different individuals to monitor the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism.

[0013] The present invention discloses 18 Application of F-FDG PET quantitative in simulating weightlessness environment and preparing therapeutic efficacy monitoring products for weightlessness mice. 18 F-FDG PET imaging is used to evaluate the myocardial glucose metabolism function of the body in weightlessness or simulated weightlessness and to monitor the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism. 18 F-FDG PET showed changes in myocardial glucose uptake before echocardiographic changes in myocardial structure and function. 18 F-FDG PET imaging provides information on glucose uptake that cannot be replaced by echocardiography, and also provides an objective quantitative evaluation method for evaluating the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism, which is different from the existing myocardial structural imaging evaluation method.

[0014] Description of the drawings.

[0015] Figure 1 Schematic diagram for constructing an animal model of hindlimb unloading to simulate weightlessness.

[0016] Figure 2 This is the extraction and optimization diagram of IVC IDIF of Patlak model.

[0017] in Figure 2 a is the time frame of dynamic PET image acquisition.

[0018] Figure 2 b is a schematic diagram of the Patlak model.

[0019] Figure 2 c: The LV VOI (dashed circle) was delineated in the early imaging period to extract TAC as LV IDIF, showing the flow direction after injection of radiotracer from the tail vein (right atrium → right ventricle → left atrium → left ventricle).

[0020] Figure 2d: The IVC VOI (dashed circle) is delineated in the early stage of imaging. TAC is extracted as the IVC IDIF. The IVC VOI is located above the kidney and below the myocardium.

[0021] Figure 2 e is an example of TAC for the left ventricular cavity (LV), inferior vena cava (IVC), global left ventricular myocardium (global), left anterior descending myocardium (LAD), left circumflex myocardium (LCX), and right coronary artery myocardium (RCA).

[0022] Figure 2 f: The corresponding Patlak diagram was obtained by fitting the Patlak model using the TAC obtained from LV as IDIF.

[0023] Figure 2 g: The corresponding Patlak plot was obtained by fitting the Patlak model using the TAC obtained from IVC as IDIF.

[0024] Figure 3 Myocardial glucose uptake decreased rapidly after HU for 1 week, but left ventricular structure and function remained unchanged.

[0025] in Figure 3 a Comparison of Global_Ki of the whole left ventricular myocardium in different groups after HU for 1 week.

[0026] Figure 3 b is the Patlak diagram of the left ventricular myocardium in different groups after HU for 1 week.

[0027] Figure 3 c Polar coordinate bull's eye diagram of left ventricular myocardial Ki of representative individuals in different groups after HU for 1 week.

[0028] Figure 3 d is the left ventricular structure evaluated by echocardiography after HU for 1 week. The figure shows the left ventricular M-mode echocardiogram.

[0029] Figure 3 e Left ventricular function evaluated by echocardiography 1 week after HU.

[0030] Figure 3 a and Figure 3 e where n = 6, * P < 0.05, *** P < 0.001, ns = not significant, data are expressed as mean ± SEM.

[0031] Figure 4 shows that myocardial glucose uptake continued to adapt and left ventricular structure and function were impaired in the fourth week of HU.

[0032] in Figure 4 a Comparison of Global_Ki of the left ventricular myocardium in different groups after 4 weeks of HU.

[0033] Figure 4 b is the Patlak diagram of the left ventricular myocardium in different groups after 4 weeks of HU.

[0034] Figure 4 c Polar coordinate bull's eye diagram of left ventricular myocardial Ki of representative individuals in different groups after 4 weeks of HU.

[0035] Figure 4 d is the left ventricular structure evaluated by echocardiography after 4 weeks of HU. The figure shows the left ventricular M-mode echocardiogram.

[0036] Figure 4 e Left ventricular function evaluated by echocardiography 4 weeks after HU.

[0037] Figure 4 a and Figure 4 n = 6 in e, *P < 0.05, **P < 0.01, ***P < 0.001, ns = not significant, data are expressed as mean ± SEM.

[0038] Specific implementation method.

[0039] The present invention discloses 18 Application of F-FDG PET quantitative in simulating weightlessness environment and preparing therapeutic efficacy monitoring products for weightlessness mice. In order to describe the present invention in more detail, the technical scheme of the present invention is described in detail below in conjunction with the accompanying drawings and specific embodiments. Unless otherwise specified, the reagents, methods and equipment used in the present invention are commonly used reagents, methods and equipment in the art.

[0040] Example 1 Construction of simulated weightlessness animal model and grouping of animals.

[0041] 8-week-old adult male SPF normal Balb / c mice (n = 24) were randomly divided into 4 groups: (1) CTRNS: control + normal saline, (2) HUNS: hindlimb unloading + normal saline, (3) HUSFI: hindlimb unloading + Shenqi Fuzheng (HU + SFI), (4) CTRSFI: control + Shenqi Fuzheng (control + SFI). Normal saline or SFI were injected intraperitoneally (ip 20 mL / kg / day) for 28 consecutive days. The hindlimb unloading (HU) model is a well-known ground-based simulated weightlessness animal model established by the classic tail suspension method. The tail suspension cage used for modeling was purchased from Suzhou Suhang Technology Equipment Co., Ltd. The mouse to be suspended was gently grasped to minimize the stress of the mouse, and it was placed in a homemade mouse holder to limit its movement, with only the tail exposed, for the convenience of subsequent operations. Cut a medical cotton-based tape about twice the length of the pasting area (covering at least two-thirds of the tail length from the base of the tail) as the longitudinal traction tape, and place a plastic straw of the same width as the tape at the midpoint as the suspension point. Start pasting the traction tape along the base of the tail, cover the pasting area, bypass the plastic straw and paste it on the surface of the opposite tail, and press the tape to the tail. The width of the tape is selected according to the thickness of the base of the mouse tail (about 0.5 cm), ensuring that there is no overlap between the traction tapes on both sides of the mouse tail to prevent tail ischemia. Cut 3-4 short tapes and wrap them around the longitudinal traction tape in a C shape at even intervals to fix the longitudinal traction tape and prevent tail ischemia. Then wrap the traction tape and the mouse tail tightly with medical gauze to prevent the traction tape from falling off. The plastic straw passes through the S hook at the end of the stainless steel suspension chain of the suspension cage. The height of the suspension chain is adjusted so that the mouse's hind limbs are suspended in the air to remove the load, and the trunk is at an angle of about 30° to the bottom of the suspension cage, ensuring that the hind limbs cannot touch the bottom of the suspension cage when fully extended, and the mouse is always in a head-down position. The stainless steel suspension chain can rotate and slide 360° so that the mouse can move in an unrestricted direction using its forelimbs.

[0042] The mice in the control group (CTRNS and CTRSFI) were housed in the same tail suspension cages, but without tail suspension. The other conditions were the same as those in the HU group. Only one mouse was housed in each suspension cage for 4 weeks. The weight of the mice was measured once a day. The overall health of the mice was observed daily, whether the tail cuffs fell off, and whether the tails were ischemic and necrotic. All animals were housed in an environment of 22-24°C, with a 12 / 12 h light-dark cycle in the feeding room. The mice were fed normal feed and had free access to water. SFI was provided by Livzon Pharmaceutical Group Co., Ltd., and all SFI were from the same production batch. Figure 1 Schematic diagram for constructing an animal model of hindlimb unloading to simulate weightlessness.

[0043] Example 2 18 F-FDG PET quantitative monitoring of myocardial metabolism and the therapeutic effect of Shenqi Fuzheng Injection in simulated weightlessness mice.

[0044] The results were performed in the first and fourth weeks of modeling. 18 F-FDG PET imaging and echocardiography.

[0045] (1) microPET / CT imaging and image reconstruction: PET / CT images were acquired by a small animal microPET / CT imaging system (nanoScan PET / CT 82s). First, the pre-imaging mice were weighed and anesthetized with isoflurane (2% induction, 1% maintenance); a homemade indwelling needle was implanted in the tail vein, and the mice were placed in a prone position on the scanning bed. During the entire imaging process, the important physiological parameters of the animals were continuously monitored and recorded by a physiological monitoring system. The temperature of the scanning room was controlled at 22-24°C. After acquiring a CT positioning image to help plan the scanning area for PET / CT acquisition, the radioactive tracer was injected into the tail vein through the indwelling needle catheter. 18 F-FDG (10-15 μCi / g) was immediately used to acquire dynamic PET / CT images for 60 min. CT spiral scanning was then performed for image fusion and attenuation correction. Finally, 3D OSEM was used to reconstruct the acquired PET raw data into 25 frames (10 × 3 s; 3 × 10 s; 4 × 60 s; 6 × 150 s; 2 × 300 s, Figure 2 a). The main parameters are as follows: (1) CT locator scan parameters: tube voltage 35 kVp, tube current 980 uA, exposure time 170 ms; (2) CT spiral scan parameters: tube voltage 50 kVp, tube current 980 uA, exposure time 300 ms, pitch 1.0, projection number 20, Binning 1:4; (3) CT real-time reconstruction parameters: small voxel thin layer reconstruction, filter type butter worth, filter cutoff 100; (4) PET scan parameters: 1 FOV, field of view size 98.5 mm, consistent with mode 1-5; (5) PET reconstruction parameters: consistent with mode 1-5, voxel size 0.4, reconstruction method Tera-Tomo 3D (i.e. 3D OSEM), 4 iterations, 4 subsets, random, scatter and attenuation correction.

[0046] (2) PET image analysis: Dynamic raw data are analyzed using the software provided by the PET imaging system or recognized PET data analysis software in the field. Figure 2 c) and inferior vena cava ( Figure 2 d) Delineate the volume of interest (VOI) and obtain IDIF and myocardial 18 TAC of F-FDG dynamic uptake ( Figure 2 e).

[0047] Patlak model fitting of PET data: Patlak model fitting was performed using IDIF as the input function and myocardial TAC as the output function (Patlak and Blasberg. Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab, 1985, 5(4): 584-90; Patlak, Blasberg and Fenstermacher. Graphical evaluation of blood-to-brain transfer constants from multiple-timeuptake data. J Cereb Blood Flow Metab, 1983, 3(1): 1-7.). Figure 2 b is a schematic diagram of the Patlak model, where C P (t) represents the plasma 18 The activity concentration of F-FDG, C i (t) represents the reversible tissue compartment 18 The activity concentration of F-FDG in a given ROI measured on a PET image, C ROI (t), can be expressed as: The activity concentration of a given ROI measured on the PET image, C ROI (t), can be expressed as: (1) Where V B represents the capillary volume fraction, and at the same time, the simplified model equation can be expressed as: (2) Integrate the above equation (2): (3) Combining equation (3) with equation (1), we can deduce: (4) Divide both sides of equation (4) by C P (t), we can get: (5) By definition (6) (7) Substituting into equation (5), the Patlak plot can be expressed by the straight line equation (8): (8) Given an input function C P (t) and the output function C ROI (t), the x and y values ​​at different time points can be calculated. Based on multiple paired x and y values, the slope K can be fitted by linear least squares method i , the intercept is V B Since the Patlak plot usually meets the linearity requirement after time t*, time points earlier than t* are usually omitted during fitting. The slope of the fitted line represents the FDG net influx (uptake) rate constant, K i In this embodiment, the data of the 21st to 31st frames (fitting time 15 to 60 minutes) are used for Patlak fitting analysis.

[0048] (3) Ultrasonic cardiogram (UCG): Echocardiograms were performed using the Vevo LAZR-X imaging system (Fujifilm VisualSonics, Canada) at the early (first week) and late (fourth week) stages of HU. (1) Animal preparation: Hair in the imaging area was removed in advance using a razor and depilatory cream. Mice were anesthetized with isoflurane (2% for induction and 1% for maintenance) and placed in a supine position on the imaging table. A small amount of ECG gel was applied to the copper sheet of the physiological information monitoring table and the mouse's limbs and feet were fixed on it to monitor the mouse's ECG and respiratory information. At the same time, in order to obtain the best imaging position, a medical gauze of appropriate thickness was placed under the animal's back and fixed with tape so that the heart was elevated in a superficial position. Select an MS400 probe and apply bubble-free coupling agent (obtained by centrifugation at 3000 rpm for 6 min) to the groove at the bottom of the probe, allowing it to overflow and ensuring that there were no bubbles. Apply enough ultrasound coupling agent to the area to be imaged. (2) Parasternal left ventricular long axis B ultrasound section: Place the probe vertically and contact the ultrasound coupling agent on the surface of the imaging area, with the notch facing the animal's head. Then rotate the probe counterclockwise about 45 degrees to obtain the parasternal long axis view, the left ventricular long axis section B ultrasound image, and continuously record the echocardiographic images of multiple cardiac cycles. (3) Parasternal left ventricular long axis M ultrasound section: Based on the parasternal left ventricular long axis B ultrasound section, the left ventricle is in a horizontal position, the M ultrasound measurement line is placed on the posterior edge of the papillary muscle, and the echocardiographic images of multiple cardiac cycles are continuously recorded. (4) Parasternal left ventricular short axis B ultrasound section: Based on the parasternal left ventricular long axis B ultrasound section, rotate the probe clockwise 90 degrees to obtain the parasternal short axis section, further adjust the y-axis displacement to obtain the correct section, and continuously record the echocardiographic images of multiple cardiac cycles. (5) Parasternal short-axis M-ultrasound image: Based on the parasternal left ventricular short-axis B-ultrasound section, the M-ultrasound measurement line was placed in the middle of the papillary muscle in the central area of ​​the left ventricle, and echocardiographic images of multiple cardiac cycles were continuously recorded. (6) Ultrasound image analysis: Vevo LAB software (Fujifilm VisualSonics, Canada) was used to analyze the imaging data and obtain quantitative parameters of LV structure and function. All quantitative parameters were obtained from the average measurement of at least 3 cardiac cycles.Measure systole LV anterior wall thickness (LVAWs) and diastole LV anterior wall thickness (LVAWd) during systole and diastole LV posterior wall thickness (LVPWs) and diastole LV posterior wall thickness (LVPWd) during systole and diastole LV internal diameter (LVIDs) and diastole LV internal diameter (LVIDd) during systole and diastole ventricular septal thickness (IVSs) and diastole interventricular septal thickness (IVSd) during systole and diastole using M-mode images. Using B-mode ultrasound or M-mode images, activate the LVtrace tool and use the measurement tool to trace along the ventricular endocardium during diastole to trace the endocardial region. Then repeat this step for systole. After all measurement steps are completed, the following calculated data can be obtained: diastolic and systolic area, diastolic and systolic volume, stroke volume, cardiac output (CO), ejection fraction (EF), left ventricular mass (LV mass), and fractional shortening (FS).

[0049] In this embodiment, the results of Patlak model fitting using left ventricular cavity TAC and inferior vena cava TAC as input functions are compared. The activity of the left ventricular cavity does not converge to zero in the late imaging period, reflecting the overflow of myocardial tissue signals into the left ventricular blood pool ( Figure 2 e). However, accurate overflow correction is difficult to perform due to the limited blood volume of mice and the inability to repeatedly draw blood. In contrast, the overflow effect of the IVC is indeed less severe than that of the left ventricular (LV) cavity ( Figure 2 e). The data from frames 21 to 31 (fitting time 15 to 60 minutes) were used for Patlak fitting analysis. The results showed that the fitting results using IVC as the input function were generally better than those using LV as the input function (R 2 Larger) ( Figure 2fg). Therefore, even without partial volume correction, the inferior vena cava can still provide reliable and repeatable IDIF for Patlak fitting of mouse myocardial glucose uptake. Secondly, this example compares the changes in cardiac structure and function in simulated weightlessness mice. The experimental data show that the changes in myocardial metabolic function of weightless individuals precede the changes in myocardial structure. After 1 week of simulated weightlessness, the myocardial glucose uptake of mice decreases rapidly, but the left ventricular structure and function remain unchanged ( Figure 3 ); After 4 weeks of simulated weightlessness, myocardial glucose uptake was reduced in mice, and left ventricular structure and function were impaired ( Figure 4 ). In addition, this embodiment discusses 18 F-FDG PET imaging was used to monitor the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism. The results showed that in the early stage of HU, SFI significantly improved myocardial glucose uptake ( Figure 3 ), but in the late stage of HU, SFI had no significant effect on the recovery of myocardial glucose uptake, left ventricular structure and function ( Figure 4 ).

[0050] The above is specifically manifested in that after 1 week of HU, the overall left ventricular myocardial glucose uptake was the lowest in the HUNS group (Global_Ki comparison, CTRNS vs HUNS, 0.1250 ± 0.0243 vs 0.0710 ± 0.0054 min -1 , P < 0.05), while the other three groups had higher overall uptake (Fig. 3a, Table 1). More importantly, SFI significantly improved overall left ventricular myocardial glucose uptake ( Figure 3 aComparison with Table 1, Global_Ki, HUNS vs HUSFI, 0.0710 ± 0.0054 vs 0.1706 ± 0.0437 min -1 , P < 0.001). Figure 3b-c shows the fitted Patlak plots and the polar coordinate bull's eye plots of Ki of representative individuals. However, there were no significant differences in left ventricular structure (LVAWd, LVAWs, LVPWd, LVPWs, LV mass) and function (LV CO, LV FS, LV EF) among the four groups (Figure 3d-e). That is, in the first week of HU, dynamic 18 The changes in myocardial glucose uptake suggested by F-FDGPET precede the changes in cardiac structure and function observed by UCG.

[0051] After 4 weeks of HU, the overall left ventricular myocardial glucose uptake was significantly reduced in the HUNS group compared with the CTRNS group (Global_Ki comparison, CTRNS vs HUNS, 0.1408 ± 0.0436 vs 0.0739 ± 0.0348 min -1 , P <0.01). However, SFI did not improve global left ventricular myocardial glucose uptake ( Figure 4 aComparison with Table 1, Global_Ki, HUNS vs HUSFI, 0.0739 ± 0.0348 vs 0.1101 ± 0.0204 min -1 , P > 0.05). Figure 4b-c shows the fitted Patlak plots and representative Ki polar coordinate bull's eye plots. After 4 weeks of HU, the LV structure (LVAWd, LVAWs, LVPWd, LV mass) and function (LV CO, LV FS, LV EF) were impaired in the HUNS group compared with the CTRNS group ( Figure 4 de). Although SFI intervention can partially alleviate the structural and functional disorders of the heart, except for LVPWs, there was no significant statistical quantitative difference in left ventricular structure and function parameters between the HUNS group and the HUSFI group (Figure 4d-e). That is, after long-term HU, 18 The changes in myocardial glucose uptake suggested by F-FDG PET are complementary to the changes in cardiac structure and function observed by UCG. In the early stage of tail suspension, SFI is beneficial to improve myocardial glucose uptake, but in the late stage of tail suspension, SFI has no significant effect on myocardial glucose uptake, left ventricular structure and function.

[0052] Table 1 Global_K i Statistical description (mean ± SD, min -1 )

[0053] Based on the above, the use of 18 F-FDG PET imaging can evaluate changes in myocardial metabolic function at the molecular level in an early, dynamic, non-invasive and real-time manner, which provides an objective imaging quantitative method for in vivo evaluation of myocardial metabolic function in a weightless environment. 18 F-FDG PET showed changes in myocardial glucose uptake before echocardiographic changes in myocardial structure and function. 18F-FDG PET imaging provides information on glucose uptake that cannot be replaced by echocardiography, and also provides an objective quantitative evaluation method for evaluating the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism, which is different from the existing myocardial structural imaging evaluation method.

[0054] The above description of the embodiments is to facilitate the understanding and application of the present invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to the above embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made to the present invention by those skilled in the art based on the disclosure of the present invention should be within the scope of protection of the present invention.

Claims

1. 18 Application of F-FDG PET quantitative analysis in simulating weightlessness environment and preparing products for monitoring the therapeutic efficacy of weightlessness mice.

2. The use according to claim 1, characterized in that: The weightlessness environment includes simulated weightlessness environment and real weightlessness environment.

3. The use according to claim 1, characterized in that: The weightless mice include simulated weightless mice and real weightless mice.

4. The use according to claim 1, characterized in that: The quantification is the Patlak quantification.

5. The use according to claim 1, characterized in that: The efficacy monitoring product is Shenqi Fuzheng Injection.

6. The application according to claim 1, which mainly comprises the following steps: (1) Using PET scanning to evaluate intravenous 18 Individual F-FDGs were dynamically scanned and reconstructed using the three-dimensional ordered subset expectation maximization algorithm; (2) Analyze the reconstructed PET images, delineate the regions of interest of the left ventricular myocardium and inferior vena cava (IVC) blood, and obtain the time activity curve (TAC) of the corresponding regions; (3) With the TAC of vena cava blood as the input function and the TAC of left ventricular myocardium as the output function, the original TAC of left ventricular myocardium was fitted using the Patlak model to obtain the myocardial 18 The F-FDG net uptake rate constant, Ki, is used to quantify myocardial glucose metabolism; (4) Compare the differences in left ventricular myocardial Ki before and after treatment in the same individual or between different treatments in different individuals to monitor the efficacy of Shenqi Fuzheng Injection in improving myocardial glucose metabolism.

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