Echinococcosis is a chronic infectious disease with a high burden in China,1,2 which is mainly caused by Echinococcus tapeworm parasitic on the human body. The liver is the main target organ of the disease (>90%). In China, echinococcosis is mainly divided into 2 types: alveolar echinococcosis and cystic echinococcosis.3 The northwestern pastoralist region is one of the high incidence regions of the disease.4 Hepatic alveolar echinococcosis (HAE) infiltrates and grows outward in the form of exophytic spores, which easily invade blood vessels, bile ducts, and surrounding tissues and organs and even metastasize to various organs throughout the body through the portal venous system and lymphatic channels.5,6 HAE is uncommon, but its diffuse infiltration and tumor-like growth traits made the morbidity and fatality rate higher in late stage,7 which affects the patient's quality of life. Radical surgery is the method of choice for the disease.8
At present, the diagnosis of HAE is mainly based on epidemiological history, laboratory tests, clinical manifestations, and imaging findings. Because imaging is intuitive, accurate, and convenient, it is often used as the test of choice for HAE diagnosis. Ultrasound examination is convenient and rapid. It can be diagnosed immediately. It plays an important role in the early screening of clinical alveolar echinococcosis and the follow-up after treatment.9 Traditional computed tomography mainly displays the structural information of HAE. On energy spectrum computed tomography, the microvascular distribution of the lesion can be reflected according to the different iodine content. The iron overload of the lesion can also be analyzed by using a molten iron map. Magnetic resonance imaging (MRI) is widely used in the clinical study of HAE because of its high resolution of soft tissue and multidirectional and multiplane imaging. HAE seemed to be single or multiple hypointense shadows on T1WI and hyperintense on T2WI. Flake liquefaction necrosis area, punctate, and flake calcification can be seen in the lesion. On diffusion-weighted imaging (DWI), the edge of the lesion showed a banded high-signal area. Small vesicles can be seen around the lesion. No obvious enhancement was found in the lesions on an enhanced scan. The invasion of the bile ducts and vessels by HAE lesions mainly showed the thickening of the tube wall, narrowing of the pressure on the lumen, and partial truncation, which seemed to be indistinct from the lesion. It has been documented that when HAE invades the venous vessels, it is suggestive of predisposition to extrahepatic metastasis and a poor prognosis.10 Because the growth pattern of HAE is complex and easy to invade surrounding tissues, along with most patients with HAE being at an advanced stage, it brings great difficulties to the treatment. The study of the activity of HAE lesions has always been a hot and difficult point of clinical attention. It is reported in the literature that the marginal area of hepatic alveolar echinococcosis in the area with the most active growth and vigorous metabolism of alveolar echinococcosis.11 The marginal area comprised proliferative capillaries, acute and chronic inflammatory cell infiltration, and fibrosis.12,13 DWI sequences have advantages in evaluating the activity of HAE lesions and the visualization of small vesicles, which can be indirectly assessed by quantifying the magnitude of the apparent diffusion coefficient values, the activity of the lesion margin and the small vesicles, and the efficacy of medical therapy, thus providing imaging guidance for evaluation of the extent of resection in clinical practice. Because most patients are in the middle and late stages of treatment, it is difficult to realize the early research of HAE in the human body, so the research of HAE based on animal models becomes very important. Zeng14 found that the multivesicular-like structure was a characteristic alteration of HAE in mice through the investigation of animal models of vesicular spheroids at different stages, and the multivesicular-like structure was considered an early manifestation of HAE lesions. In addition, as the magnetic field strength continues to increase, the contrast-to-noise ratio and signal-to-noise ratio of the images continuously increase so do the spatial resolution and contrast of the magnetic resonance images, which can be used for high-resolution anatomic imaging. 7T small animal MRI has its own characteristic radiofrequency coil that reduces image signal-to-noise ratio loss, allowing the resolution of images to be significantly improved. The use of 7T small animal MRI has enabled intravital monitoring of HAE based on small animal models with an improved understanding of HAE. Because there are relatively few current reports on studying mouse HAE using 7TMRI, this study intends to analyze the MRI characteristics of HAE and understand the growth characteristics of HAE with the help of an animal model.
MATERIALS AND METHODS
Thirty specific pathogen-free (SPF) Balb/c mice (male, 18–20 g) were purchased from SPF Biotechnology Co, Ltd (Certificate No. 110324200103624731) and raised in the SPF animal room of our laboratory. The entry time was November 10, 2020, and the vaccination time was December 18, 2020. The protoscolex of Echinococcus multilocularis comes from the conservation of gerbils in our laboratory.
This protocol for animal experiments was reviewed by the laboratory animal ethics committee and conformed to the animal care, animal welfare, and ethical principles in accordance with relevant national regulations on laboratory animal welfare ethics.
Establishment of a Mouse Model of Alveolar Echinococcosis
The establishment of the mouse alveolar echinococcosis model was completed by the Department of Hepatobiliary Surgery of our hospital. Cytocapsular masses were collected under sterile conditions from the peritoneal cavity of gerbils infected with alveolar echinococcosis and sheared in normal saline (containing 0.8 × 103 U/mL penicillin and 1 mg/mL streptomycin), and the cells were treated with a 300-μm strainer to filter. The lower filtrate was then collected, the cells were treated with a 400-μm strainer to filter, and the alveolar echinococcosis on the filter mesh was collected and washed several times with normal saline (containing 0.8 × 103 U/mL penicillin and 1 mg/mL streptomycin). The survival rate of the alveolar echinococcosis reached more than 95% (microscopic observation).
At the 15th week of inoculation, the mouse HAE model was screened by small animal ultrasound and 30 normal surviving mice were screened by ultrasound. The abdomen was depilated and prepped, and the upper abdomen was fully exposed. Mice were positioned flat on the examination table in the supine position, and the probe surface smeared with the appropriate amount of coupling agent was placed directly on the abdominal wall. Multisection, full-range ultrasonography was performed, focused on examining the entire mouse liver to find abnormal intrahepatic echogenicity as a diagnostic criterion for successful vaccination. Twenty-six were successfully inoculated. Ten of them were selected for MR examination at 7.0T.
According to the morphology of the lesions, they were divided into multivesicular type group and cystic solid type group; whether the lesions invaded the portal vein was divided into portal vein invasion group and nonportal vein invasion group.
Inclusion and Exclusion Criteria
The inclusion criterion includes a mouse model of successful intrahepatic infection. The selected mouse model has complete MRI scanning sequences and has good image quality. The exclusion criterion includes HAE model in mice with other liver lesions.
Equipment and Parameters
The MR scanner, Bruker PharmaScan 7.0T/16-cm MR scanning system, was used for small animals (Bruker, Germany). The scanning coil is a mouse body coil.
The scanning parameters were as follows: T1WI: time of echo (TE): 2.9 ms, time of repetition (TR): 285.8 ms, flip angle: 90°, slice thickness: 1.0 mm, interslice distance: 1 mm, field of view (FOV): 35 mm × 30 mm, and number of excitations (NEX): 5.0; 24 frame images were acquired for each sequence. T2WI: TE: 25.0 ms, TR: 1991.99 ms, slice thickness: 1.0 mm, interlayer spacing: 1.0 mm, FOV: 35 mm × 30 mm, and NEX: 24; 24 frame images were acquired for each sequence. DWI: TE: 30.0 ms, TR: 1016.4 ms, b: 600 mm/s, slice thickness: 1.0 mm, interslice distance: 1.0 mm, FOV: 40 mm × 35 mm, and NEX: 40; 24 frames images were acquired for each sequence. Because the scanning time of conventional DWI sequence is relatively long and susceptible to interference from breathing, intestinal peristalsis, and heartbeat in mice, the widespread use of conventional DWI imaging is limited. In this study, DWI was performed using a single-shot spin-echo echo-planar imaging sequence, which is relatively fast and has little dependence on mouse respiration, bowel motility, and heartbeat, and a high signal-to-noise ratio.
Image Observation and Analysis
Double-blind reading of the imaging material was performed by 2 physicians who had been engaged in imaging diagnosis for more than 10 years; the results were recorded when the 2 physicians had the same opinion. If they have different opinions, an experienced chief doctor was chosen to read the film again and draw a conclusion. Reading record information included site, maximum mean diameter, morphology, borders, signal, invasion of the bile duct system, and its relationship with surrounding tissues.
Pathological Paraffin Section
At the end of the experiment, the experimental mice were killed and the tissues containing HAE vesicles were removed from the abdominal cavity. The pathological samples were left. After the specimens were fixed for 36 hours, the tissues were cut into 0.5 cm3 tissue blocks into an embedding cassette, dehydrated through different concentrations of ethanol solution, transparent through xylene solution, and then embedded in paraffin. The sections were cut consecutively by a paraffin microtome, and the thickness of each section was 3 µm.
Staining of Pathological Sections
Pathological paraffin sections were subjected to hematoxylin and eosin staining. Pathological paraffin sections were dewaxed and rehydrated with xylene solution, ethanol solution of different concentrations, and distilled water. The sections were then placed in hematoxylin solution for staining for 3 minutes, rinsed under tap water, differentiated in an ethanol solution, backed to blue under tap water, and restained with hematoxylin solution. Then, sections were placed in different concentrations of ethanol solution, xylene solution dehydration transparent, and neutral gum sealing.
Statistical analysis was performed using SPSS23.0 statistical software. All lesion diameters were recorded by means of metered data and expressed as (). The analysis of metered data between groups was performed using an independent samples t test, and P < 0.05 was considered statistically significant.
Distribution and Morphological Features of HAE Lesions in Mice
Of 30 mice HAE model, 26 showed abnormal lesions in the liver after ultrasound screening, of which 10 were randomly selected for 7TMRI examination. On the liver, a total of 63 lesions were identified in 10 mice, and the specific locations and morphological analyses are presented in Table 1.
TABLE 1 -
Site Ratio of Different Types of Hepatic Alveolar Echinococcosis Lesions in Mice (%)
|Left Lobe of Liver
||Right Lobe of Liver
||Hilar Part of Liver
||Left and Right Lobes
Analysis of Portal Vein Invasion by Intrahepatic HAE Lesions
Portal vein invasion showed that the wall of the portal vein and its branches were thickened. The lumen was narrowed, and the demarcation between the portal vein and the lesion was less clear for the vascular invasion. A total of 34 lesions invading the portal vein were obtained. The specific invasion is presented in Table 2. There were 18 (52.95%) multilocular cystic lesions and 16 (47.05%) cystic solid lesions that invaded the portal vein. The mean diameter of the lesions invading the portal vein was 7.87 ± 3.18 mm, and that of the lesions uninvading the portal vein was 5.46 ± 2.45 mm. The difference between portal vein invasion and lesion diameter was statistically significant at P < 0.05. The specific diameter sizes are presented in Table 3.
TABLE 2 -
Ratio (%) of Portal Vein Invasion at Different Sites of Hepatic Alveolar Echinococcosis Lesions in Mice
|Left Branch of Portal Vein
||Right Branch of Portal Vein
||Main Portal Vein
||Left Branch and Main Portal Vein
||Right Branch and Main Portal Vein
||Left Branch Right Branch and Main Portal Vein
|Left lobe of liver
|Right lobe of liver
|Hilar part of liver
|Left and right lobes
TABLE 3 -
Relationship Between Portal Vein Invasion and Mean Diameter of Lesions (
||Conditions of Portal Vein Invasion
||7.87 ± 3.18
||5.46 ± 2.45
Analysis of Maximum Diameter of Intrahepatic HAE Lesions
The average diameter of the lesions in the left lobe of the liver was greater than the hilar region and the right lobe of the liver among the 10 mice. The mean diameters of the cystic solid lesions in the left lobes of the liver, right lobes of the liver, and hilum of the liver were greater than those of the multilocular cystic lesions. There was no significant difference between the forms of the lesions (P > 0.05). The specific sizes are presented in Tables 4 and 5.
TABLE 4 -
Mean Diameter of Different Parts of Hepatic Alveolar Echinococcosis Lesions in Mice (
|Left Lobe of Liver
||Right Lobe of Liver
||Hilar Part of Liver
||Left and Right Lobe of Liver
||8.15 ± 2.47
||5.74 ± 2.97
||6.21 ± 2.03
||5.67 ± 2.06
||4.30 ± 2.38
||4.37 ± 1.60
TABLE 5 -
Relationship Between Mean Diameter of HAE Lesions and Lesion Type in Mice at Different Location (
||Mean Diameter of HAE at Different Location (mm)
|Left Lobe of Liver
||Right Lobe of Liver
||Hilar Part of Liver
||Left and Right Lobe of Liver
|Cystic and solid lesion
||8.90 ± 3.36
||7.59 ± 3.10
||7.10 ± 1.14
|Multilocular cystic lesion
||7.43 ± 1.34
||5.18 ± 2.77
||5.87 ± 2.25
HAE indicates hepatic alveolar echinococcosis.
Analysis of Growth Properties of Intrahepatic HAE Lesions
The signal characteristics of HAE lesions in mice were hypointense, which varied in size, and the borders showed clear, multilocular cystic shape, with isointense septation visible in some of the larger lesions on T1WI (Fig. 1A, black arrow). The lesion showed multilocular cystic hyperintensity with no edema in the periphery on T2WI (Fig. 1B, black arrow). On DWI, the lesion showed multilocular cystic hypointensity (Fig. 1C, black arrow). The lesions are surrounded by high-signal shadows with different widths, and the high-signal shadows are semiannular and annular in irregular form. The components of some lesions have complex, small vesicular structures of varying sizes and solid components present simultaneously. Multiple small vesicles can be seen around the solid components, and the small vesicles are distributed in spots or clusters. The solid component seems to be isointense on T1WI (Fig. 1D, yellow arrow) and T2WI (Fig. 1E, yellow arrow) and hyperintense on DWI (Fig. 1F, yellow arrow).
Analysis of AE Lesions Within the Abdominal Cavity
The intraperitoneal lesions showed a diffuse distribution, lesions vary in size, and MRI signals were similar to those of liver lesions; they were mainly multilocular cystic. Intraperitoneal lesions increased faster than intrahepatic lesions in the same period, and the maximum diameter of lesions was larger (Fig. 2).
Hematoxylin and Eosin Stain Analysis
Inflammatory reaction zone and proliferative fibrous tissue comprised acute and chronic inflammatory cells such as neutrophils, lymphocytes, and plasma cells and can be seen in the junction area between the lesion and the normal liver tissue, with dilation and congestion of hepatic sinusoids. The liver tissue far away from the lesion has no pathological changes (Fig. 3).
Since the application of MRI to the clinic, MRI has been widely used in the study of HAE. Cao15 found that small vesicles were mainly located at the edge of the lesion, and the small vesicles were bioactive. It is inconsistent with the results that foci had multiple vesicle-like structural compositions and may be due to the relatively early stage in this study. Zhang16 found that magnetic resonance cholangiopancreatography was superior to other sequences in the evaluation of bile duct tree damage in patients with HAE. By examining the MRI of the early SD rats, Zeng 17found that the early rat HAE showed a single or multiple vesicular signal shadow. All 2 types of lesions were pathologically confirmed as the early stages of acercus growth. It is similar to the findings of this study. Zeng found that on DWI, the ring showed a slightly lower signal shadow around the lesion. It is inconsistent with the high-signal shadow with a visible band around the lesion found in this study.
Lesions Analysis (in the Liver)
A certain growth cycle is required for the formation of focal lesions in the liver after mice are injected intraperitoneally with a tissue suspension of vesicular Echinococcus.18 In this study, we found that most of the lesions were located in the right lobe of the liver. The reason behind this may be 2 aspects. On the one hand, it may be related to the way the mice were prepared for HAE. In this study, the mouse model of HAE was prepared by head control with right-sided intraperitoneal injection of vesicles. As the inoculation time increased, the lesion continually invaded surrounding tissues so that the range gradually increased. On the other hand, it may be caused by the direct invasion of the liver by some of the abdominal lesions. This is consistent with the findings of Yang Xiao Fei that the distribution of lesions was mainly in the right lobe of the liver,19 which was inconsistent with the findings of Yang19 who found that the volume of the right lobe of the liver was larger and the blood supply was rich.
The lesions were mostly multilocular cystic lesions. The distribution of multilocular cystic lesions was mainly in the right lobe of the liver, and the distribution of cystic solid lesions was mainly in the left lobe of the liver. The reasons are as follows: (1) The left lobe of the liver is close to the second hilum in anatomic position; the growth of the lesion is relatively fast, and its components are complex. This is consistent with the findings of the YANGXIAOFEI study.19 (2) The left lobe of the liver has a large volume and rich blood supply. (3) Intraperitoneal lesions directly invade the left lobe of the liver and growth in intrahepatic infiltrate.
Vascular Invasion Analysis
Li Hailong found that magnetic resonance arterial and magnetic resonance venous imaging had obvious advantages in showing the degree of vascular stenosis and the relationship with the lesion. The signs of portal vein invasion are as follows: (1) The venous vessels show a cutoff sign, (2) the lumen of venous vessels has an eccentric or irregular narrowing, and (3) intralesional veins have indistinct vascular margins.10 In this study, the lesions that invaded the portal vein were mainly distributed at the hepatic hilum. The reasons for portal vein invasion are as follows: (1) HAE cercariae through the peritoneal mesothelium reach the portal venous system and liver, invading the normal liver tissue, the venous system, and the bile duct system and (2) the liver has the characteristic of dual blood supply. This is consistent with the result that Xiaofei Yang et al19 found that HAE has the characteristics of “venophilic vessels.” The portal vein is mainly invaded by the lesions in the left lobe of the liver, which was inconsistent with the findings of Yang Xiaofei et al19 that the lesions in the right lobe of the liver are prone to invade the portal vein. We also found that the left branch of the portal vein was mainly invaded. The average diameter of lesions with portal vein invaded was greater than the noninvaded lesions. The reasons are as follows: (1) The diameter of the lesion gradually increased, and the components of the lesion tended to be mixed, with increased invasiveness and more compression of the portal vein. (2) Portal vein has a thin wall and small luminal pressure, and the lesion is easily invaded.19
Diameter Size Analysis
We found that the mean diameter of the lesions in the left lobe of the liver is greater than that in the hilum and right lobe of the liver. The reasons are as follows: (1) It may be that the left lobe has a large volume, rich blood supply, and relatively rapid progression of the lesion. (2) It may be related to the mode of intraperitoneal injection, the location, and the direct infiltration of the lesions into the liver in the abdominal cavity. The mean diameter of lesions with a predominantly cystic solid component was greater than that of lesions with a predominantly multilocular cystic component. The reasons are as follows: As the disease progresses, the diameter of lesions continues to increase, the degree of fibrosis worsens, and the composition within the lesion also tends to be complex and variable.
MRI Signal Feature Analysis
The marginal band of HAE lesions has been a hot spot and difficult point, and the marginal band shows a high signal on DWI; the reason is that the site is rich in proteins, inflammatory cells, and metabolites, which have restricted diffusion and therefore seem hyperintense on DWI. It is consistent with the results of the circular hyperintense shadow that can be seen at the periphery of HAE reported in some literature.20–22 In the future, we will use 7T small animal MRI to dynamically observe the hepatic alveolar echinococcosis lesions in mice and analyze the dynamic evolution process of the marginal zone of the lesions.
Some of the lesions are complex and have solid components. The real component showed a high signal on DWI. The reason may be that as the course of the disease progressed, the lesion became more fibrotic and the diffusion restriction of water molecules aggravates, thus manifesting as hyperintense areas on DWI. It is reported that the main manifestation of early lesions is multivesicular structures in the interior and that multivesicular structures are considered to be the main pathological manifestations of early HAE.23,24 Zeng et al25 through their study of 157 rat models of early HAE found that lesions seemed to be single or multiple cystic structures. In this study, the lesions were mainly multilocular saccular with irregular solid components seen in some lesions; the reason may be that relative to the early lesions, the disease progressed with longer inoculation time, the intralesional fibrous tissue component increased, and the lesions consisted of multilocular saccular without solid components gradually converging toward complex and small vesicles of varying size with solid component structure. In this study, there are no obvious calcification and large liquefaction necrosis around and inside, which is different from the manifestations of human HAE lesions, which may be that human HAE lesions are mostly in the middle and late stages.
Analysis of Abdominal Cavity Lesions
The intraperitoneal lesions showed a diffuse distribution, with more lesions than intrahepatic. Because we chose the methrepare animal model of secondary mouse hepatic alveolar echinococcosis, which is easy to operate on and has a high survival rate, it is however poorly targeted and has a low rate of liver infection.26 In the abdominal cavity, MRI findings were similar to those of liver lesions. This study found that the growth rate of intraperitoneal lesions was faster than that of intrahepatic lesions. On the one hand, the reason may be that the mesenteric veins in the abdominal cavity are widely distributed. On the other hand, owing to the large space in the abdominal cavity, it is conducive to the growth of lesions.
In summary, we achieved noninvasive MRI monitoring of mouse HAE, as well as analysis of its growth properties, which confirmed the multivesicular structures as characteristic manifestations of mouse HAE and provided meaningful value for the study of the growth activity of HAE. This is an early presentation of the HAE. The recognition of early lesions can help us to develop treatment early. Because of the insufficient detection and understanding of early HAE lesions in humans, the best treatment is often lost in the clinic. MRI studies of HAE in small animals can provide new ideas for the clinical treatment of early lesions. Later, we analyzed the dynamic evolution of HAE lesions by studying different HAE lesions in mice to provide guidance for the choice of clinical treatment and surgical methods.
However, there are certain weaknesses. In this study, the sample size is small, the mouse model of HAE was prepared by intraperitoneal injection of tissue suspension of alveolar Echinococcus, the lesions in the abdominal cavity were diffusely distributed, and the number of lesions in the liver was relatively small, which may cause some deviation to the experimental results. It is expected that the dynamic observation of the mouse model of HAE by using 7T small animal MRI in the later stage, the dynamic evolution of mouse HAE under different periods will be clarified, which will provide meaningful value and new ideas for clinical research on the growth characteristics of hepatic alveolar echinococcosis.
1. Cadavid Restrepo AM, Yang YR, Mc Manus DP, et al. The land-scape epidemiology of echinococcoses. Infect Dis Poverty. 2016;5:13.
2. Torgerson PR, Keller K, Magnotta M, et al. The global burden of al-veolar echinococcosis. PLoS Negl Trop Dis. 2010;4:e722.
3. Wen H, Vuitton L, Tuxun T, et al. Echinococcosis: advances in the 21st century. Clin Microbiol Rev. 2019;32:e00075-18.
4. Ping L, Jinshan C, Jinhua L, et al. National Hydatid prevention and Control Technology Symposium. China Anim Health. 2017;19:66–68.
5. Yin G, Bao H. Evaluation value of diffusion-weighted magnetic resonance in hepatic alveolar echinococcosis. Chin J Bases Clin Gen Surg. 2016;5:530–534.
6. Abdu I. Clinical and experimental study of multi-technique MRI to evaluate the imaging characteristics and evolution of hepatic alveolar echinococcus disease. Xinjiang Medical University, 2018:34–50.
7. Liu R, He J, Wang H, et al. Contrast study of hepatic alveolar echinococcus lesions measured by contrast-enhanced ultrasound and contrast-enhanced CT. Clin J Med Off. 2019;47:750–751.
8. Salm LA, Lachenmayer A, Perrodin SF, et al. Surgical treatment strategies for hepatic alveolar echinococcosis. Food Waterborne Parasitol. 2019;15:e00050.
9. Tappe D, Frosch M, Sako Y, et al. Close relationship between clinical regression and specific serology in the follow-up of patients with alveolar echinococcosis in different clinical stages. Am J Trop Med Hyg. 2009;80:792–797.
10. Li H, Bao H, Fan H, et al. CT features of hepatic alveolar echinococcosis invading venous vessels. Chin J Plateau Med Biol. 201;42:269–272.
11. Le Moigne F, Durieux M, Bancel B, et al. Impact of diffusion-weighted MR imaging on the characterization of small hepatocellular carcinoma in the cirrhotic liver. Magn Reson Imaging. 2012;30:656–665.
12. Ren B, Wang J, Liu W, et al. Image characteristics and tissue of hepatic alveolar echinococcosis margin zone on MR diffusion weighted imaging comparison analysis of pathological changes. Chin J Radiol. 2012;46:57–60.
13. Toshiya K. Recent advances in surgical strategies for alveolar echinococcosis of the liver. Surg Today. 2019;50:1–8.
14. Zeng HC. Dynamic observation and analysis of hepatic alveolar echinococcosis in rats with multi-imaging. Xinjiang Medical University. 2013:62–71.
15. Cao JY. MRI multimodal imaging study on the activity of hepatic alveolar echinococcosis. Qinghai University, 2018:12–14.
16. Zhang H, Bao H, Li W. Multi-modal magnetic resonance imaging of liver vesicular package preoperative evaluation of parasitosis. Chin J Plateau Med. 2020;30:10–15.
17. Zeng H, Guo L, Hu X. Application value of MRI-DWI in early stage of hepatic echinococcosis in rats. J Xinjiang Med Univ. 2015;38:1203–1206, 1212.
18. Kern P. Clinical features and treatment of alveolar echinococcosis. Curr Opin Infect Dis. 2010;23:505–512.
19. Yang X, Kang Y, Qiao Y, et al. Magnetic resonance imaging evaluation of characteristics of vascular invasion in intermediate and advanced hepatic alveolar echinococcosis. Exp Ther Med. 2019;17:4197–4204.
20. Zhang H, Bao H, Li W, et al. Preoperative evaluation of hepatic alveolar echinococcosis by magnetic resonance multimodal imaging. J Alt Med. 2020;30:10–15.
21. Zheng J, Jing W, Zhao J, et al. Diffusion-weighted MRI for the initial viability evaluation of parasites in hepatic alveolar echinococcosis: comparison with positron emission tomography. Korean J Radiol. 2018;19:40–46.
22. Cao J, Bao H, Yang X, et al. Evaluation of the activity of microcysts in hepatic alveolar echinococcosis by magnetic resonance diffusion weighted imaging. J Clin Radiol. 2018;37:428–431.
23. Becce F, Pomoni A, Uldry E, et al. Alveolar echinococcosis of the liver: diffusion-weighted MRI findings and potential role in lesion characterization. Eur J Radiol. 2014;83:625–631.
24. Rubini-Campagna A, Kermarrec E, Laurent V, et al. Hepatic and extrahepatic alveolar echinococcosis: CT and MR imaging features. J de Radiologie. 2008;89:765–774.
25. Zeng H, Wang J, Liu W, et al. Evaluation of experimentally induced early hepatic alveolar echinococcosis in rats with ultrasonography. Radiol Infect Dis. 2016;3:114–119.
26. Zhou Q, Ren L, Zhang L, et al. Research progress in animal models of hepatic alveolar hydatidosis. J Clin hepatobiliary Dis. 2017:2247–2250.