In this study, multimodal transvaginal ultrasound combined with negative hysterography was used to detect tubal patency and uterine lesions, providing a simple, rapid, and accurate examination method for grassroots hospitals. Each mode of step-by-step CEUS attention is described as follows.
- 4D mode
The 4D mode can clearly display the three-dimensional images of the fallopian tube and uterine cavity , show the patency of each segment of the fallopian tube in real time, and directly display its shape, course, and contrast medium development to evaluate patency. It can also display the speed difference of bilateral fallopian tube development, show the diffusion of contrast medium around the ovary and the pelvis, and analyze a clear and intuitive image frame by frame.  The pictures are easily read by clinicians. Thus, unsurprisingly, in 4D mode we found that physicians in both high- and low seniority groups had the same diagnostic efficiency for tubal patency. However, if only 4D mode examination was used, the diagnostic success rate of the high- and low seniority groups was 86.7% (530pm 612). Notably, in 4D mode, attention should be paid to the injection dose of contrast medium suspension is also controlled at 5-10 mL. In some cases, the contrast medium cannot reach the umbrella end or be ejected, and most of the contrast medium diffuses too much into the pelvis affecting the follow-up modal examination. Approximately 13.3% (82-612) of the fallopian tubes in this group could not be diagnosed for the above reasons and can be combined with other modes to improve the diagnosis’ success rate.
- 3D mode
The 3D mode can directly display the shape and course of the fallopian tube through three-dimensional reconstruction, which aids diagnosis [4-8]. With skillful examination, 3D can completely capture the whole process of the contrast medium flowing in the fallopian tube to the umbrella end, and its three-dimensional imaging is clear and intuitive. In 3D mode, the physicians’ diagnostic efficiency for tubal patency in high- and low seniority groups is the same . Because length and course of the fallopian tube are different, the 3D mode scanning angle and phase can affect the fallopian tube display success rate, which requires higher examiner manipulation and proficiency. If the scanning time is too short, the contrast medium does not fill the fallopian tube, the image acquisition process is incomplete, and the whole picture of the fallopian tube cannot be displayed, which makes it difficult to analyze and results can be easily misjudged. However, it is difficult to determine whether there is contrast medium around the ovary. Moreover, when the intubation depth is too deep, the contrast medium flows along one side of the fallopian tube, affecting the development of the other side. Therefore, it is necessary to put the balloon back into the mini-channel and combine the other modes to verify the results. This study showed that 558 fallopian tubes could be successfully diagnosed in both the high- and low seniority groups in the 4D+3D group, and the diagnostic success rate was 91.2% (558x612), which was significantly higher than in the single 4D mode group (P<0.05). However, 54 fallopian tubes could not be displayed because of unfavorable scanning angle, intubation depth, previous contrast medium injection, and diffusion to the pelvis. Therefore, combining other modes to improve the diagnosis’ success rate is necessary.
- 2D mode
The modal operation method is flexible and can track the entire course of the fallopian tube dynamically, observe the ejection of the contrast medium at the umbrella end of the fallopian tube, and simultaneously observe the wrapping of the contrast medium around the ovary and the diffusion of the pelvic cavity. However, it requires higher manipulation and experience. Therefore, this study further enhances the 2D modal examination and verification (4D+3D+2D group) by combining 4D and 3D mode, which can improve the success rate of fallopian tube patency diagnosis. It can further verify the accuracy and credibility of the 4D and 3D mode diagnoses. This study showed that the success rate of tubal patency diagnosis in the 4D+3D+2D group was significantly higher than in the 4D+3D group in both the high- and low seniority groups (P<0.01). The diagnosis accuracy was further confirmed. However, because of the different fallopian tubes’ lengths and courses, it is difficult to display the entire fallopian tubes’ course on a single scan plane. Sixteen fallopian tubes in the high seniority group were not clear enough to make accurate diagnoses. In the low seniority group, 19 fallopian tubes could not be accurately diagnosed.
- HI mode
The flow of the contrast medium in the fallopian tube can be observed clearly and dynamically in this mode, and the entire process of the fallopian tube can be displayed through flexible manipulation. Even if a part of the fallopian tube is intermittently displayed because of the surrounding intestinal gas, the judgment of its patency is not affected. Indeed, this study showed that the success rate of fallopian tube patency in the high- and low seniority groups was significantly higher than in the 4D+3D+2D+HI group (P<0.01). All 612 fallopian tubes in the high seniority group and 610 fallopian tubes in the low seniority group were diagnosed successfully. The diagnosis was less affected by the shortcomings of single-modal examination, which improved accuracy and reliability.
- Negative hysterography
Negative hysterography directly showed uterine malformations, and the sensitivity and specificity for the diagnosis of uterine malformations in this study were 100%. and three-dimensional reconstruction showed a semi-circular irregular localized eminence. In this study, a case of scar diverticulum after cesarean section was missed because the diverticulum was small and fissure-shaped, water sac occlusion affected the imaging, and the case was complicated by large intimal polyps, who only focused on intimal polyps and ignored small diverticula during examination, resulting in missed diagnosis.
When the uterine cavity was filled with negative contrast media, the contrast between the endometrium and the lesions was enhanced, and endometrial polyps and submucosal myomas were clearly displayed. This showed irregular, round, or nodular localized protuberances or depressions of the uterine cavity . In this study, two cases of endometrial polyps were missed because the polyps were small and located in the lower segment of the uterus, and water sac occlusion affected the imaging. Two cases were misdiagnosed, one as submucosal myoma because of a large polyp and the other as uterine adhesion. Two cases of submucosal leiomyomas were misdiagnosed. All missed cases were endometrial polyps with submucosal myoma, but only endometrial polyps were misdiagnosed as submucosal myomas. In negative hysterography, because the sonogram of endometrial polyps is similar to that of submucosal myoma, they are easily misdiagnosed, especially when the two lesions coexist. To improve the display rate of endometrial polyps, the examination should occur 3-5 days after menstruation. The endometrium in the early stages of hyperplasia is hypoechoic and thin, therefore, polyps can be easily detected. The endometrium’s echo in the secretory phase is slightly enhanced and thicker, thus easily confused with intimal hyperplasia. Notably, when a submucosal myoma undergoes ischemic degeneration, the local echo can be highly echoic and easily confused with intimal polyps, resulting in misdiagnosis [11-12]. Through a comparative examination of hysteroscopy, it was found that the lesions missed by negative hysterography were often small, with uneven thickness of the intima, and occlusion of the water sac in the uterine cavity. Therefore, to avoid missing small lesions, at the end of the examination, while removing the tube and simultaneously injecting normal saline, we should focus on observing the middle and lower segments of the uterus (the position occupied by the balloon). In this study, three cases of uterine adhesion were missed, 2 cases were misdiagnosed because the endometrium was too thin, “with only a slight adhesion, the adhesion band was fine and filamentous, 3D-TVS coronal image adhesion was not obvious and missed diagnosis. One case was adhesion with multiple endometrial polyps. Only endometrial polyps were diagnosed without uterine adhesion.
Negative hysterography can not only improve uterine lesions detection rate but also re-evaluate tubal patency through fluid flow in the uterine cavity and the fallopian tube [13-14]. The continuous flow of fluid in the fallopian tube is strong evidence of patency, and the patency of the fallopian tube can be reflected by observing the flow of fluid in the uterine cavity from the corners of the uterus on both sides of the fallopian tube. If the injection speed is the same and the fallopian tube wall is smooth, the lumen thickness is uniform and the direction of the fallopian tube is smooth, the liquid passes smoothly and flows quickly through the cavity. If the fallopian tube wall is not smooth (e.g., due to inflammation) and is slender or unevenly thick, stiff, or twisted, the liquid’s flow slows down. If the fallopian tube’s proximal end is blocked, and the fluid accumulates at the corresponding corners of the uterus without flowing into the fallopian tube, eddy currents may occur.
Limitations of this study
This study’s sample size was small, and a certain bias error was introduced. Because of radiation exposure risks, only a few patients underwent X-ray Lipiodol radiography, and few patients underwent tubal patency. Therefore, comparative studies on other tubal patency examination methods. Contrast-enhanced ultrasound operations are only performed by senior doctors, thus high- vs low seniority diagnosis comparisons are impossible.