Chinese Expert Consensus and Guidelines on Oral Contrast Gastric Ultrasonography for Scanning Technique and Imaging Acquisition

: Upper gastrointestinal (GI) abnormalities are one of the most common disease in clinical practice, and among them, gastric cancer is one of the most common causes of cancer-related death in China. However, conventional trans-abdominal ultrasound is difficult to evaluate GI diseases due to gas filled in the GI tract. With the development of oral contrast agents in China, ultrasonography with oral contrast agent has been used to visualize upper GI tract (i.e., stomach and duodenum) as well as its surrounding structures. The primary purposes of this consensus and guideline written by Chinese experts is to provide a coherent and clinical perspectives and practical protocol for using oral contrast in upper GI ultrasound, including four components: (1) indications and contraindications of gastric contrast ultrasound; (2) patients and instruments preparation; (3) scanning technique and imaging acquisition; (4) diagnosis of upper GI abnormalities.


Introduction
Gastric cancer is one of the most common causes of cancer-related death in China which ranks the second in morbidity and the third in mortality after lung cancer. The incidence of gastric cancer in China accounts for about 40% of the new cases worldwide every year [1]. Since conventional trans-abdominal ultrasound is difficult to evaluate GI diseases due to gas filled in the GI tract, oral contrast agent has great value of eliminating the air in gastric cavity and to help display the gastric wall layers and lesions [2]. Previous studies have demonstrated the value of gastric contrast ultrasound in gastric cancer as well as other gastric lesions. In 2018, Chinese guidelines for diagnosis and treatment of gastric cancer proposed the use of gastric contrast ultrasound examination as one of the conventional imaging modality for initial diagnosis of gastric cancer were published by National Health commission of China [3]. However, despite substantial advances and multiple studies that have been published in gastric contrast ultrasound [4]. Most of the information is fragmented and disorganized, and there is no clinical guidance about rational sequencing of the scan procedure and interpretation of the images. Thus, in order to standardize the clinical application of gastric contrast ultrasound, we gathered many experts from Gastro-intestinal ultrasound group of China Association of Medical Education and developed this guideline. We intend to provide assistance to practitioners performing a sonographic examination of the upper GI tract, and we believe following this guideline will maximize the detection of upper GI abnormalities.

Reference Sources
Publications about gastric ultrasound from January 1985 to 2020 were searched through PubMed and China National Knowledge Infrastructure (CNKI) database, and a combination of the following medical subject headings (MeSH) were used for the literature retrieval: (gastric or stomach) AND (distention or contrast-enhanced or oral contrast-enhanced). Combined with the clinical work experience of many domestic experts on gastric contrast ultrasound and the selected articles, we put forward the standard and consensus of gastric contrast ultrasound examination.

Preparation of the guideline
In May 2018, several GI ultrasound experts agreed to develop a consensus of gastric contrast ultrasound examination at the founding meeting of Gastroenterology Group of China Association of Medical Education. Subsequently, the consensus was gradually formed through the repeated discussions and revisions on several offline and online conferences. According to the evidence-based clinical imaging guidelines [5], the recommended strength of consensus is divided into level A (Highly recommended, the intervention or examination has sufficient evidence to support the expected effect), level B (Recommended, the intervention or examination has moderate-sufficient evidence to support the expected effect), level C (Against recommendation, the intervention or examination has enough evidence to support the unexpected effect) and level D (Without recommendation, the intervention or examination does not have enough evidence to support or reject the effectiveness). In the future, this consensus will continue to be improved based on the clinical utilization and feedbacks.
(4) Patients intolerable for gastroscopy. (5) Physical examination of healthy people and screening of high-risk population of gastric cancer.
(6) To examine and identify the compression and infiltration of gastric cavity caused by the lesions of adjacent organs (liver, biliary tract, pancreas, spleen, and kidney).

Recommendations:
Oral contrast agent can eliminate the interference of gas in gastric cavity which allows ultrasound to display gastric wall, lesions, and the relationship with adjacent organs. It can be used as a supplementary method of gastroscopy based on its wide use in gastric diseases and clinical recognition. (Recommended level: A)

Contraindications of gastric contrast ultrasound were as follows:
(1) Patients with upper GI perforation, active massive hemorrhage of upper GI tract, upper GI obstruction, acute gastric distention, and other situations that need fasting.
(2) Patients with factors affecting ultrasound examination including fat hypertrophy and a large amount of gas in gastric cavity.

Recommendations:
The contraindications of gastric contrast ultrasound examination should be carefully evaluated based on the actual clinical situation. (Recommended level: C)

Recommendations for staff training
Radiologists who want to perform gastric contrast ultrasound need to pass the training to understand the anatomy of the stomach and its adjacent areas, to master the treatment of common gastric diseases, and to correctly use gastric ultrasound contrast agents to identify gastric wall structure and lesions. If the oral contrast agents are not available, water can be used to dilate the gastric cavity for the ultrasound examination. It should point out that the administration of water is only useful in the detection of larger gastric hyperechoic lesions, small or hypoechoic lesions are easily to be missed. For the examination of cardia and remnant stomach anastomotic stoma, ultrasonic examination should be carried out along with drinking oral contrast agent, the entire process during drinking and swallowing contrast agent should be observed dynamically using real time ultrasound imaging. During the examination, it is necessary to properly select the ultrasonic probe and communicate with the patients during the procedure. (Recommended level: A)

Ultrasound Equipment
Color Doppler ultrasound equipped with abdominal convex array probe (3.0~5.0MHz) and high-frequency linear array probe (5.0~12MHz) is recommended for routine use in adults and children.

Oral contrast agent
The commercially available oral contrast agent in China is dry powder product which is derived from rice and soya. It is reconstituted by adding 500 ml of boiling water into powder agent to form a palatable homogeneous suspension according to the instructions. The routine gastric contrast agent is recommended to be 500ml/ person for adult patients, and the amount should be adjusted based on the patient's own conditions (300-400ml for children and thin patients, and 800-1000ml for patients with larger gastric volume.

Intravenous contrast agent:
The ultrasound with combination of oral and intravenous contrast agent is called Double Contrast-enhanced Ultrasound (DCUS). It could display the gastric wall structures and the surrounding tissues, as well as the vascular perfusion of the lesions. DCUS has been used in differentiating the malignant lesion from benign lesion, staging and classification of gastric carcinoma. However, the accuracies of DCUS are currently varied and inconsistent, which needs to be tested by more relevant studies.

Patient position and ultrasound scanning sequence:
Supine and right lateral decubitus positions are most commonly used, followed by left side supine position and sitting position. The whole examination process should be finished in 15-20 minutes to avoid the evacuation of oral contrast agent. By using a continuous multidirectional (longitudinally and transversely) scanning method, the cardia, fundus, pylorus and duodenal bulb, ascending, and horizontal and descending part of duodena are examined dynamically and sequentially. For some patients with gastroptosis, standing or semi-sitting position can be adopted for examination.

Normal Gastric Wall on Contrast Ultrasound
The five layers' structure of normal gastric wall could be seen on high frequency ultrasonic image with oral contrast administration ( Fig. 1): (1) The 1 st hyperechoic layer is gastric mucous.

Recommendations:
The body position during examination should be chosen based on the habits of radiologists and the examination part, so that the oral contrast agent can fill the examination site satisfactorily to eliminate the interference of gas.

Recommendations:
Standard measurement methods are as follows: In patients with tumors, the length, width, and thickness of gastric solid mass should be measured on the largest section of the tumor. It should be noted that in order to avoid the error of linear measurement, the larger lesions should be measured at multiple points along the gastric wall; For patients with ulcer, the diameter and depth of ulcer should be measured. (Recommended level: A)

Diagnosis of Upper GI Abnormalities
(1) Gastroesophageal reflux [6][7][8][9] (Fig. 7): Recommendations: The probe should be placed under the xiphoid during the gastric filling process, the opening of the sphincter at the lower esophagus should be dynamically observed on the long axis section. The manifestation of gastroesophageal reflux can be seen as intermittent reflux along the gastric -cardia -esophageal pathway to the lower esophagus. (Recommended level: A) (2) Esophageal hiatus hernia [10][11][12][13] (Fig. 8): Recommendations: The probe should be placed under the xiphoid. The long axis section of the cardia should show that the gap of esophageal hiatusis enlarged (larger than 2cm), and some gastric echoes are detected above the diaphragm (Recommended level: A) (3) Gastritis [14][15][16][17] (Fig. 9):

Recommendations:
Gastric ulcer is characterized by pitting in mucosa with a regular and symmetrical shape on both sides. The continuity of mucosal is interrupted, but the gastric wall layers at the bottom of the shallow ulcer are clear. However, in some cases, the submucosal at the bottom of the deep ulcer can be interrupted, which should be carefully distinguished from ulcerative gastric cancer. (Recommended level: A) (5) Gastric polyps [15,[21][22][23][24][25] (Fig. 11):

Recommendations:
Based on the clinical stage, gastric cancer can be roughly divided into early and advanced gastric cancer. Early gastric cancer mostly shows slight thickening (≤5mm) and hypoechoic changes of the gastric wall with interrupted mucosal or submucosa layer. Gastric contrast ultrasonography, however, is not sensitive enough to differentiate early gastric cancer from gastric ulcer or gastritis. Advanced gastric cancer is characterized by obvious local or diffuse thickening (>5mm) and hypoechoic changes of the gastric wall with abnormal structures. According to the invasion depth of gastric wall, T staging can be evaluated by gastric contrast ultrasound, and the use of DCUS might improve the diagnostic performance of T staging of gastric cancer.

Recommendations:
In addition to gastric stromal tumors, gastric contrast ultrasound was shown to have high sensitivity but low specificity to gastric lymphoma, neuroendocrine tumor, heterotopic pancreas, and lipoma etc. Therefore, its value of evaluating gastric protuberant lesions needs to be further

Recommendations:
Gastric stromal tumor originates from the muscularis propria of the gastric wall can be shown in gastric contrast ultrasound. The tumor presents with a round or lobulated lesion with a clear boundary and smooth surface. Small tumors are isoechoic, while some larger ones are hetero-echoic due to the necrosis in the tumor. DCUS might help to diagnose of gastric stromal tumor and locate the liquefaction necrosis. (Recommended level: A) (8) Other gastric protuberant lesions [22,[24][25]39,41,[45][46] (Fig. 15):

Recommendations:
Gastric varices is characterized by dilation and tortuosity of the gastric wall veins in the gastric fundus and cardia in gastric contrast ultrasound. The veins display as tubular reticular or honeycomb like anechoic dark area with abundant blood flow signals. Lowspeed venous spectrum could be detected by Doppler technique. (Recommended level: A)

Examination Report
A formal gastric contrast ultrasound examination report should include: the description about the condition of the cardia and pylorus (opening, closing, and reflux), gastric wall(smoothness, thickness, continuity, and activity),and masses(location, shape, size, boundary, the relationship with the hierarchical structure of gastric wall, blood flow, the relationship with surrounding organs whether there are enlarged lymph nodes around the stomach).

Recommendations:
The above items list the contents should be included in the final report of a gastric contrast ultrasound examination. (Recommended level: A)

Summary
Gastric contrast ultrasound has been more widely used than ever, the clinical value of this technology in some gastric diseases needs to be further evaluated by more high quality studies. Therefore, this consensus mainly focused on the indications and contraindications of gastric contrast ultrasound, patients and instruments preparation, scanning technique and imaging acquisitions, as well as diagnosis of upper GI abnormalities hoping to help standardize the applications of GI contrast ultrasound, and maximize the detection of upper GI abnormalities.