Lin Su, Guo-Qiang Wang, Li-Mei Zhang, Song-Hong Wu, Shu-Heng Li, Na Li, Yan Zhang, Jin-Peng Xu

1. Department of Cardiovascular Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China 2. Department of Nuclear Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China

3. Interventional Vascular Surgery, Affiliated Hospital of Hebei University, Baoding, Hebei 071000, China

4. Second Hospital of Baoding, Hebei Hepatobiliary Surgery, Baoding 071051, Hebei, China

Keywords:Positron emission computed tomography / computed tomography Calcification Infalmmation

ABSTRACT Objective: To explore the relationship between calcification of human vascular system and local inflammation using PET / CT. Methods: Patients who were treated with concurrent PET / CT in our hospital were collected continuously, and their arterial image data were analyzed in parallel with standardized uptake values. (SUV) and corresponding slice calcification score (CS) measurement. SUV values were collected and measured for slices with CS greater than 100. Patients were grouped according to CS, and the correlation analysis between SUV values and CS in each group was performed. Results: Overall CS and SUVmax (r = 0.62, P ＜0.05) and SUVmean (r = 0.59, P ＜0.05) were positively correlated, among which CS and SUV values were in the SUVmax (r = 0.72, P ＜0.05), SUVmean ( r = 0.59, P ＜0.05), SUVmax of CS 200-299 group (r = 0.71, P ＜0.05), SUVmean (r = 0.80, P ＜0.05), SUVmax of CS 300-399 group (r = 0.47, P ＜0.05 ), SUVmean (r = 0.53, P ＜0.05) were positively correlated, SUVmax (r = -0.17, P＞ 0.05), SUVmean (r = -0.07, P＞ 0.05) were negatively correlated in CS 400-499 group, CS There was no significant correlation between SUVmax (r = 0.22, P＞ 0.05) and SUVmean (r = 0.18, P＞ 0.05) in the ≥500 group. Conclusion: There is a certain correlation between the local vascular calcification area and the corresponding local inflammatory response in the calcification progress PET / CT has the potential to monitor early calcification.?Corresponding author: Xu Jinpeng.

1. Introduction

Cardiovascular disease is a common clinical disease, and calcification is a progressive disorder of calcium salt metabolism. Calcification can affect the coronary arteries, peripheral arteries and valves of the cardiovascular system. Previously, it was thought that calcification of the cardiovascular system is related to age and is a In recent years, evidence has shown that the underlying mechanism of cardiovascular system calcification is basically the same as embryonic bone cell formation, and it is likely to be an activated disease-regulating process [1]. Recent animal experiments have revealed the progress of calcification and inflammation. Correlation [2 3], suggesting that inflammation is related to the occurrence of early calcification, but human clinical observation results are still lacking. 18-fluorodeoxyglucose positron emission tomography / computed tomography (8 F-fluorodeoxyglucose positron emission tomography / computed tomography, 18 F-FDG PET / CT) is a molecular imaging technique that can be used to assess the level of inflammatory changes in the body [4 5]. This study uses PET / CT as an imaging tool to explore the human vascular system in vivo The relationship between calcification and local inflammation further validates the results of animal experiments and guides whether this method can be used clinically to monitor cardiovascular system calcification.

2. Materials and methods

2.1 Research object

Patients who were treated with pet / ct in the Affiliated Hospital of Hebei University from June 2017 to December 2018 were continuously collected, and their arterial imaging data were retrospectively analyzed. Patients were excluded according to the following criteria: age ＜40 years old; chronic inflammatory disease; ongoing Use anti-inflammatory drugs; patients with active malignancies or undergoing chemotherapy or radiotherapy. Collect images of all patients, and then analyze their pet and ct images, and further screen based on the results of image analysis.

2.2 Pet-ct image acquisition and fdg uptake determination

RAY-SCAN 64 (Rui Kang, Beijing, China) PET-CT imaging device. Patients fasted for more than 6 hours before examination, when blood glucose concentration ＜150mg / dl, according to body weight, intravenous 18 F-FDG 5.55MBq / kg (0.15mCi / kg), instructing the patient to rest quietly, 50 minutes after injection, the patient was taken in a supine position and breathing quietly under PET-CT image acquisition. Scanning parameters: tube current 300mAs, peak voltage 120kV, layer thickness 2.0mm, The scanning speed is 0.5s, and the scanning time is automatically generated according to the selected range length, pitch and bed speed. The scanning range: from the pelvic floor to the skull base. After the CT scan is completed, a PET scan is performed to collect 6-8 beds, 2min / bed. Post-processing workstations were used for image reconstruction, and CT and PET fusions were performed.

At least 2 experienced physicians in imaging imaging performed vascular FDG uptake analysis and measurement of imaging data. When the opinions were not consistent, they were determined by the collective reading of the department. Evaluate vascular FDG uptake in the aorta, select the region of interest (ROI), and carefully adjust Size and position to include all tube walls and lumens, while excluding adjacent tissues, and measure the maximum standardized uptake value max (SUVmax) and average standardized uptake value mean (SUVmean) of each ROI. Calibration is required, and the FDG uptake of the inferior vena cava blood pool is selected to correct SUVmax and SUVmean to obtain the target blood ratio (TBRmax and TBRmeam, respectively).

2.3 Calcification integral measurement

The equipment's own image processing workstation was used to automatically perform the thoracic and abdominal aortic calcification score (CS) measurement, and the SUV value was collected and measured for the layer with CS greater than 100, and a total of 131 images of patients who met the conditional calcification score were collected.

2.4 Statistical analysis

SPSS 16 statistical software package (SPSS, Chicago, USA) was used for statistical analysis. Measurement data were expressed as mean ± standard deviation. Spearman correlation was used to analyze the correlation between SUV values and CS. Patients were grouped according to CS and divided into 100- 199,200-299,300-399,400-499, ≥500 groups, and the correlation analysis between SUV value and CS of each group.

3. Results

3.1 Pet / ct imaging

In most CT images, the obvious uptake of fdg can be seen in the same level (Figure 1); in the area without visual calcification, there is no obvious uptake of fdg (Figure 2); and in a few levels with very obvious calcification, also It can be seen that there is no significant uptake of fdg (Figure 3).

Figure 1: Obvious FDG uptake on CT image with obvious calcification (CS = 374.72; SUVmax = 1.07 SUVmean = 0.98).

Figure 2: No visual calcification area on CT image and no obvious FDG uptake.

Figure 3: FDG on CT image with obvious calcification No significant uptake (CS = 535.85; SUVmax = 0.57, SUVmean = 0.48).

3.2 Correlation analysis

3.2.1 Comparison of FDG

The distribution of 131 patients with calcified calcification scores greater than 100 in the aorta CT is shown in the following table (Table 1)

3.2.2 Correlation analysis

The calcification score was positively correlated with SUVmax (r = 0.62, P ＜0.05) and SUVmean (r = 0.59, P ＜0.05) (Figure 4) .Among them, the calcification score was in the 100-199 group, 200- The 299 group and the 300-399 group were positively correlated, and the 400-499 group was negatively correlated, and there was no significant correlation between the two groups ≥500. The correlation of each group is shown in the table below (Table 2).

Table 1 Comparison of FDG uptake by 5 arterial vessels (±s,n = 131)

Table 1 Comparison of FDG uptake by 5 arterial vessels (±s,n = 131)

CS Number of cases SUVmax SUVmean 100-199 21 0.52±0.08 0.41±0.11 200-299 12 0.69±0.16 0.58±0.16 300-399 19 0.88±0.09 0.75±0.10 400-499 12 1.17±0.12 1.05±0.11≥500 67 1.05±0.45 0.89±0.34 total 131 0.92±0.39 0.78±0.32

Figure 4 Correlation between calcification score and SUVmax and SUVmean

4. Discussion

Calcification is often present in cardiovascular disease. Pathological calcification associated with hypertension can be seen in atherosclerotic plaques. Calcification can reduce the compliance of arterial blood vessel walls. Microcalcification of plaque fiber caps can cause small plaques. Block rupture [6 7], which induces an acute cardiovascular event. Severe calcification of the heart valve will lead to stenosis or insufficiency of the valve, eventually leading to changes in heart structure and function [8-10]. Studies have found that heart valve calcification is similar to atherosclerosis There are changes in cellular inflammation and calcium salt deposition [11]. Animal experiments have found that in the initial stage of vascular calcification, endothelial cells are dysfunctional, which triggers a local inflammatory response, causing macrophage migration and T lymphocyte activation to release inflammatory factors. Activate VSMCs and valvular interstitial cells (VIC) to transform into osteoblast-like cells, and macrophage aggregation is associated with a series of elevated enzymatic levels, such as matrix metalloproteinases and cysteine protease (cathepsin S) (cathepsin K) [12] .The activation of related enzymes can regulate the cell proliferation process, while promoting osteogenic differentiation of VSMCs leading to calcification [13],Positive feedback between dysfunction and calcification drives the process of arterial calcification. Most viewpoints believe that the mechanism of valve calcification is roughly the same as that of vascular calcification [14]. Endothelial cells are activated, inflammatory cells are aggregated, and then inflammatory factors are released, eventually starting calcification. Pathological process.

Early atherosclerotic plaque calcification is called "spotty" calcification [15]. Calcification of late calcification is significant, but the inflammatory response is significantly reduced. Therefore, inflammation can be seen as the progression of calcification A proliferative process that results in the differentiation and activationof VSMC or VIC, and eventually forms calcium salt deposits in the arterial wall and heart valve. It is inferred from the above theory that since atherosclerosis and calcification have potentially the same inflammatory pathological mechanism, then the application for atherosclerosis Drugs with inhibitory effects on sclerosing inflammation should be able to combat possible calcification. Therefore, statin lipid-lowering drugs can be used as a possible treatment. Some retrospective studies have shown that the use of statins can combat aortic valve calcification Stenosis [16 17], but large-scale prospective randomized clinical trials do not support this view [18 19]. The conclusions of multiple studies suggest that we still lack a deeper understanding of the underlying mechanism of cardiovascular calcification, but inflammation may serve as One of the targets of diagnostic treatment.

Table 2 Correlation analysis

Currently, non-invasive examinations commonly used for calcification include ultrasound and CT, both of which are very sensitive to obvious tissue calcification, but their spatial resolution is relatively low, so cardiovascular calcification cannot be detected early and used to monitor the progress of calcification, and obvious calcification is often It has caused patients with clinical symptoms and limited treatment methods, so it is particularly important to monitor the progress of calcification with clinically available examination methods [20]. Positron emission tomography (PET) is a molecular imaging technique Local tracing calibration of inflammatory response [21]. 18 F-fluorodeoxyglucose (18 F-FDG) is taken up by cells through glucose transfer protein, thereby calibrating macrophages that are vigorously metabolized in the inflammatory response [22]. ) .Many recent animal experiments have confirmed the possibility of this technology for early diagnosis of calcification

[23]. This study attempts to explore the application of this imaging method to analyze the correlation between local inflammation and local calcification of blood vessels in the body, and to explore the application of this technique. The imaging method is used to detect early calcification in the body and monitor the possibility of calcification.

In this study, it can be found that for aortic levels with a calcification score less than 300, the suv value is positively correlated with the calcification score, and the correlation is better.In the related pet / ct image, we can also see that the calcification score has a higher level It can be seen that the radioactive uptake is more obvious (Figure 1) .For the aortic layer with a calcification score greater than 300, there is no obvious correlation between the two, and the radioactive uptake in the obvious calcification area is not high (Figure 3), and even negative correlation (calcification score). 400-499). The results verify that in the area of obvious calcification, the local inflammatory response will be reduced, suggesting that this detection method has the possibility of monitoring early calcification. The sample size in this study is relatively small, and the same sample lacks dynamic monitoring, further Enlarging the sample size and using this detection method to dynamically monitor the progress of calcification in the same sample should provide more evidence on the effectiveness of this method in monitoring calcification in vivo.