A bibliometric analysis of contrast-enhanced ultrasound over the past twenty years

Introduction

Contrast-enhanced ultrasound (CEUS) is a pioneering diagnostic technique within the realm of ultrasound technology and one of the rapidly advancing technologies in today’s medical imaging domain. CEUS is divided into two main categories: one is intravenous injection, and the other is non intravenous injection. The ultrasound contrast enhancer injected through the intravenous route is mainly used for the diagnosis and efficacy evaluation of tumors in various organs and for the evaluation of microcirculation perfusion of tissues and organs. In addition to intravenous injection, contrast enhancers can also be injected into normal or pathologic lines in the body; for example, urine injection may show vesicoureteral reflux. Injection of contrast enhancers into various lumens can evaluate the patency of the lumen and determine the location and degree of lumen obstruction, such as cholangiography and salpingography. The contrast enhancer is dropped into the drainage tube to locate the position and patency of the drainage tube.

The technique of CEUS originated in the 1960s. Initially, Gramiak accidentally observed a phenomenon of “cloud-like” enhancement within the aorta on echocardiography. This occurred during the injection of oscillating normal saline via a left-sided heart catheter for X-ray aortography (1). From this juncture, researchers embarked on the exploration of CEUS techniques. Through numerous years of development, ultrasound contrast agents evolved across several generations of technological advancements. In 1994, the first ultrasound contrast agent approved by the Food and Drug Administration (FDA) in the United States for echocardiography was Albunex (Molecular Biosystems Inc., San Diego, CA, USA) (2), and the second-generation agent, Optison (GE HealthCare, Boston, BSN, USA) emerged in 1997 (3). Only at the start of this century did the third-generation contrast agent, SonoVue (Bracco, Milan, Italy) (4) arrive, initially in the European market and then China in 2004. This event signified the initiation of a new phase in CEUS research, facilitating its progressive integration into clinical practice.

The backscatter signal generated by microbubbles used in CEUS is the strongest and is capable of significantly improving the resolution, sensitivity, and specificity of ultrasound diagnostics. It effectively enhances the two-dimensional ultrasound images and Doppler blood flow signals of substantial organs such as the heart, liver, and kidneys. This enables the visualization and observation of blood perfusion in both normal and pathological tissues, facilitating the evaluation of the nature and severity of pathological changes. The advantage of CEUS technology lies in its ability to leverage the acoustic scattering properties of microbubbles, allowing for a clearer display of blood perfusion. This leads to distinctive imaging differences between pathological regions and normal tissues, thereby enhancing the diagnosis and differential diagnosis of certain diseases. Since the advent of CEUS technology, its applications have evolved from initially being used for the detection of heart-related conditions to now encompass the diagnosis and differential diagnosis of diseases involving various solid organs throughout the body. For instance, CEUS can be applied in cases of hepatic focal lesions, pancreatic focal lesions, renal focal lesions, blunt abdominal trauma, bladder ureteral reflux, and cerebral circulation and for assisting in percutaneous ablation procedures (5). With the growth in research in CEUS, there has been increased focus on its application in children. In 2016, the FDA approved the first ultrasound contrast agent for intravenous and bladder indications in children (6). Subsequently, the use of CEUS in pediatric cases has rapidly proliferated and is being applied in the diagnosis of abdominal organ focal diseases, such as liver and kidney conditions, and of abdominal trauma (7).

Today, research in this field has encompassed countless studies, both in China and internationally. The achievements in CEUS technology are widespread, with extensive investigations into various contrast agents and imaging techniques. There is an abundance of guidelines for contrast imaging tailored to different diseases, organs, and regions. However, there is a lack of comprehensive synthesis regarding the development trends, research priorities, and hotspots in CEUS technology. Bibliometric analysis allows for the quantitative assessment of scientific publications and identification of specific research trends, thus facilitating a better understanding of the current research progress and future directions in the field. Consequently, in order to more accurately characterize the research progress and developmental trends in CEUS technology, we analyzed the relevant literature published from 2002 to 2022. Through use of visualization tools including VOSviewer and CiteSpace, we developed visual representations of literature over the past two decades. Hotspots and methodologies in CEUS are summarized and discussed in the paper, with the aim of providing valuable insights for those who will be engaged in future CEUS research.

Methods

Data collection

Data collection serves as the foundation for literature analysis. Academic journals host articles that showcase the latest developments in scholarly research, underscoring the significance of and acquiring a substantial corpus of literature in necessary for conducting a comprehensive literature review. The Web of Science (WoS) database stands as a globally recognized, comprehensive repository of authoritative and influential journals.

For this study, we selected the WoS Core Collection (WoSCC) databases, specifically the Social Science Citation Index (SSCI) and the Science Citation Index Extended (SCIE), as the primary data sources. The search strategy to retrieve literature from the WoSCC database was as follows: TS = (“ultrasound contrast” or “contrast-enhanced ultrasonography” or “ultrasonic contrast” or “ultrasonics contrast-enhanced” or “contrast-enhanced sonographics” or “contrast-enhanced sonography” or “CEUS”); the time period was from January 1, 2002, to December 13, 2022, and the literature type was articles. Overall, we collected a total of 6,668 records. Within this dataset, we meticulously screened 25 abbreviations of CEUS, identifying those that were unrelated to the ultrasound contrast technique. Employing these specific keywords, we successfully excluded 64 unrelated articles, resulting in a final count of 6,604 articles for our analysis. Subsequently, we conducted an exhaustive review of the pertinent literature and discerned that certain non-English language articles were not germane to the scope of our study. As a result, we screened out 222 non-English language articles. Ultimately, we included 6,382 articles that were directly relevant to our research.

According to the above search query, we exported the complete records and references in TXT format. The exported document records included the title, authors, names of research institutions (research institutes, schools, hospitals), abstracts, journal names, publication dates, and other information. We then imported the data into VOSviewer software (Leiden University, Leiden, the Netherlands) and checked for duplicate data. The retrieved data were collected on March 1, 2023, to avoid potential biases caused by daily updates. In total, 6,382 records were retrieved, exported in the form of complete records and accompanying references, saved as a plain text file, and stored in the download_.txt format.

Data analysis

This study employed CiteSpace (version 6.1.R6), VOSviewer, and the “bibliometrix” package in RStudio (Posit, PBC, Boston, BSN, USA) for visual analysis of the selected literature. Table creation was carried out using Microsoft 365 on Windows (Microsoft Corp., Redmond, WA, USA), while Scimago Graphica was used to create national maps. Additionally, Microsoft PowerPoint was employed to design a flowchart illustrating the literature selection process. CiteSpace (Chaomei Chen, Philadelphia, PA, USA) is an efficient information visualization tool developed by Professor Chaomei Chen of Drexel University. It is a free Java application used for visualizing and analyzing trends and patterns in the scientific literature (8). VOSviewer, developed by Eck and Waltman is a visualization software known for its powerful features and user-friendly interface in co-occurrence and cocitation analysis (9). Metrics including the number of publications, average citations per publication, and h-index were obtained from WoS’s citation reports. The h-index was initially introduced as a measure of a researcher’s scientific output and is based on the count of publications that have been cited N times or more (N) (10). Nowadays, it is displayed in researchers’ profiles in citation databases such as Scopus, WoS, and Google Scholar.

Results

According to the retrieval process illustrated in Figure 1, we obtained a total of 6,668 records. Through citation analysis in WoS, these records received a total of 140,198 citations. After excluding self-citations, there were 100,177 external citations. These publications were sourced from 1,051 different journals and collectively cited 17,128 articles. The average citation frequency per article was 21.97, with an h-index of 127. This research involved 19,211 distinct authors.

Figure 1 The data collection and retrieval strategy. TS, topics; CEUS, contrast-enhanced ultrasound; DT, document type; N, number.

Publications

This study examined 6,382 relevant publications published in the WoSCC from 2002 to 2022. According to the citation report from WoS, as of March 1, 2023, these included publications received a total of 140,198 citations, averaging 21.97 citations per publication. The h-index for these publications was 127. When examining the temporal distribution of published papers over the 21-year period, there was a consistent upward trend, with annual citation counts steadily increasing. There were only two exceptions, in 2008 and 2014, where both the number of publications and citations underwent a slight decrease compared to the previous year. In all other years, there was a notable increase in both the number of publications and citations compared to the preceding year (Figure 2).

Figure 2 Citations and publications in the field of contrast-enhanced ultrasound from 2022. The bar and line combination chart represent the annual number of articles and citations on contrast-enhanced ultrasound.

Countries

A total of 39 countries contributed articles related to CEUS. Over the course of these 21 years, China emerged as the leading contributor, with 391 publications, followed by Japan (158 publications), Italy (147 publications), the United States (91 publications), Germany (85 publications), South Korea (46 publications), the United Kingdom (37 publications), France (31 publications), Romania (24 publications), and Canada (21 publications). In terms of citations, the top five countries were China (5,817 citations), Italy (5,627 citations), Germany (3,937 citations), Japan (3,184 citations), and the United States (3,105 citations). Among the top five countries in terms of publication and citation counts, only China is a developing country. Brazil, also a developing country, ranked 13th in terms of citation count (Table 1).

The top five countries with the highest average citation rates were Denmark (214.25 average citations), Australia (192 average citations), Norway (118.60 average citations), Brazil (104.70 average citations), and Spain (96.91 average citations). The country with the highest average number of publications per million people was Italy, followed by Denmark. Meanwhile, Denmark ranked highest in terms of average number of citations per million people, followed by Australia (Table 1). According to SCImago Graphica Beta 1. 0.26 analysis, China had the most collaborations with other countries, followed by Italy and Germany. China, Italy, and the United States had the most significant collaborations, with China and Italy having the highest level of cooperation (Figure 3).

Figure 3 The cooperative relationships between various countries. The size of the nodes represents the frequency of international cooperation, and the thickness of the line between nodes represents the tightness of the cooperation.

Institutions, journals, and authors

A total of 2,633 institutions published articles related to CEUS. The institution with the highest number of publications, indicating the highest productivity, was Sun Yat-sen University, followed by Shanghai Jiao Tong University and Fudan University. In the past 20 years, they published 35, 29, and 28 articles, respectively. The top five institutions in terms of citation count were the University of Verona (979 citations), Sun Yat-sen University (615 citations), the University of Trieste (550 citations), the University of Toronto (532 citations), and Fudan University (530 citations) (Table 2).

These 6,382 articles were published in 1,052 different journals. The journal with the highest impact, as indicated by the highest h-index, was the Journal of Ultrasound in Medicine, with an h-index of 26. This journal published 321 relevant articles over the past 21 years and was cited 2,156 times. The top five journals in terms of impact included the American Journal of Roentgenology, the European Journal of Radiology, Ultraschall in der Medizin, and the Journal of Clinical Ultrasound. Among the top 10 journals in terms of impact, Ultrasound in Medicine and Biology had the highest number of publications, with a total of 558 issues, while the Journal of Ultrasound in Medicine had the highest number of citations. Radiologia Medica had the highest impact factor, at 8.9 (Table 3).

In the 6,382 publications, a total of 24,183 authors were involved. In the analysis of author impact through biblioshiny (refer to Table 4), the author with the highest number of publications was Jung EM, who authored nearly 141 articles over the past 20 years. The most frequently cited author was Dietrich CF, with a total of 2,099 citations within the same 20-year period. He contributed to 91 relevant articles during this time. Notably, the author with the highest h-index was D’onofrio M, boasting an impressive h-index of 20.

In the coauthorship network (Figure 4), we identified approximately six distinct clusters representing different author groups. Within these six clusters, Ming-De Lu and Wen-Ping Wang were particularly active collaborators within their respective clusters. Among all the authors, Ming-De Lu stood out as the author with the highest number of collaborations with others.

Figure 4 The coauthorship network is depicted graphically. Each point represents an author, with larger points indicating a higher number of publications. Authors are grouped into clusters, denoted by different colors, and the links between them represent collaborations between authors.

Highly cited articles

The top 10 most cited articles are listed in Table 5. Among them, the two most cited articles are from Michel Claudon, titled “Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update 2012: A WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS and ICUS”. This article is a set of guidelines for CEUS in the liver and was jointly developed by the World Federation for Ultrasound in Medicine and Biology (WFUMB) and the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB). It was published in the official journals of both organizations, namely Ultrasound in Medicine and Biology for the WFUMB and Ultraschall in der Medizin (European Journal of Ultrasound) for the EFSUMB. Among the top 10 most cited articles, 4 are guidelines, and 7 articles focus on the diagnosis of liver-related diseases.

Keywords

We used VOSviewer to conduct a co-occurrence analysis of keywords to identify the distribution of research hotspots in CEUS studies. Within VOSviewer, a minimum word frequency threshold of 15 was established, and the top 100 most frequent keywords were selected to generate a label view of keyword co-occurrence. This approach allowed for the examination of research hotspots and core content within CEUS studies.

The most prominent keywords observed were “US”, “CEUS”, and “diagnosis”, indicating that the majority of research is centered around these three concepts. These keywords can be organized into eight distinct categories (Table 6, Figure 5): ultrasound in medicine, differentiation of benign and malignant lesions, liver cancer, vascular imaging, relevant guidelines for CEUS, breast scanning, kidney diseases, and abdominal surgery.

Figure 5 The co-occurrence of the top 100 most common keywords. The 100 keywords that occurred about 16 times were divided into eight clusters by different colors: cluster 1 = red, cluster 2 = green, cluster 3 = blue, cluster 4 = yellow, cluster 5 = purple, cluster 6 = light blue, cluster 7 = orange, and cluster 8 = brown. Each frame represents one keyword. The size of the nodes represents the frequency of occurrences, and the thickness of the line and distance between nodes represent the tightness of the relationship.

Additionally, by incorporating CiteSpace’s burst word analysis (Figure 6), we discerned that certain keywords including “children”, “safety”, “clinical practice”, “risk”, and “recommendation” emerged as notable keywords within the past five years. The analysis of burst words and keyword clustering served as a valuable tool for comprehending previous research trends and anticipating future research directions in the field of CEUS.

Figure 6 Top 25 keywords with the strongest citation bursts (sorted by the starting year of the burst).

Discussion

Bibliometrics and visualization analysis provide valuable tools for examining the past focus in a research field and anticipating future trends. In our study, we applied bibliometric methods to analyze the literature related to CEUS in the SSCI and SCIE databases. Our findings identified research hotspots, key directions, prolific authors, countries, and institutions in the field of CEUS over the past 21 years.

Through bibliometric analysis, we observed a consistent upward trend in the volume of publications during this 21-year period. The primary research focus of most author groups centered on the diagnosis and practical applications of CEUS in liver diseases. Notably, China emerged as the most productive country, with Sun Yat-sen University leading in terms of CEUS-related publications. The journal Ultrasound in Medicine and Biology ranked highest in the number of CEUS-related articles, while the most cited article was “Guidelines and good clinical practice recommendations for Contrast Enhanced Ultrasound (CEUS) in the liver - update 2012: A WFUMB-EFSUMB initiative in cooperation with representatives of AFSUMB, AIUM, ASUM, FLAUS, and ICUS”.

Furthermore, our visualization analysis revealed that the historical research hotspot primarily revolved around CEUS’s role in diagnosing liver diseases and evaluating the efficacy related therapies. Recent research trends have shifted toward the application of CEUS in pediatric diseases.

Publications

The purpose of this study was to identify the research trends and hotspots in CEUS from 2002 to 2022. The overall trend in the number of publications from 2002 to 2022 shows an upward trajectory. However, there were instances in 2003, 2008, and 2014 when the number of publications was lower than that of the previous year. During our research, we incidentally analyzed the publication volume of three-dimensional ultrasound technology between 2002 and 2022. We found that although the publication volume of literature related to this technology exhibited an overall increasing trend, the rate of increase was not as rapid as that for CEUS publications. This indicates that CEUS is indeed a promising new technology with development prospects and has received significant attention in recent years.

Starting from 2014, there has been a steady and consistent increase in the annual publication count, with the most significant growth observed from 2018 to 2021. This suggests a stable upward trend in research related to CEUS. The increase in publications after 2008 may be attributed to the publication of the second edition of the CEUS guidelines in that year, which updated the guidelines for the application of CEUS in liver diseases and introduced some non-liver applications. Additionally, it may be due to increased research into new technologies, such as contrast harmonic technology, which was first used in endoscopic ultrasound (EUS) in 2008 (11).

The decrease in the number of publications in 2022 compared to that in 2021 may be attributed to the fact that the WoS database had not yet fully updated the articles related to CEUS in 2022 at the time of the analysis.

Countries

These publications not only exhibited dynamic temporal trends over the years but also showcased the diversity among different countries. China, Japan, and Italy occupied the top three positions, accounting for approximately 11% of the total publications. Collaboration between countries in the research of CEUS has become a global challenge, with an increased focus on advancing this technology. Although China and Brazil had the highest number of publications and citations, when normalized by population size, other countries surpassed China in terms of both publications and citations per million people. European countries such as Italy and Germany, as well as Asian countries such as Japan and South Korea, exceeded China in both the total number of papers and citations per million people. The reason why Italy ranked second in citation count is largely because the widely used contrast agent SonoVue originates from Italy. China, being the country with the most international collaborations, collaborated with the United States, Italy, and Germany, among others. The primary contrast agents, SonoVue and Levovist, are from Italy and Germany, respectively, which may explain the higher level of international collaboration with these countries. China demonstrated close collaborative relationships with neighboring countries, such as Japan and South Korea, as well as with countries in Europe and the Americas. This indicates that geographical distance is not a limiting factor in international cooperation in academic research.

Affiliations

Of the top 10 most prolific academic institutions, 7 were located in China, indicating a high level of productivity in this field among Chinese academic institutions. The remaining 3 universities in the top 10 were from Italy, the United States, and Japan. The institution with the highest publication output was Sun Yat-sen University, which focused predominantly on the application of CEUS in liver diseases (12-14). Furthermore, this institution made significant contributions to the integration of CEUS with radiomics, extending its research beyond conventional approaches (15-18). As the second most productive institution, Shanghai Jiao Tong University made substantial contributions to the application of CEUS in diseases of the superficial organs, such as breast cancer (19,20). They also contributed to distinguishing between benign and malignant thyroid tumors and the detection of lymph node metastasis, among other areas (21,22).

Authors

Wen-Ping Wang, Yi Dong, and Feng Mao formed an author team within a research cluster due to their close collaboration. Their team primarily has focused on the application of ultrasound intervention techniques in abdominal diseases and have made significant contributions to the diagnosis of liver diseases via CEUS. The article titled “Imaging features of fibrolamellar hepatocellular carcinoma (HCC) with contrast-enhanced ultrasound” (23) published in Ultraschall in der Medizin in 2021 was cited 16 times, highlighting the journal’s substantial influence over the past two decades, with an h-index of 17. Another highly collaborative research group consisted of Ming-De Lu, Xiao-Yan Xie, and Wei Wang. Similar to the team of Wen-Ping Wang, this group has made significant contributions to the use of CEUS in liver diseases. However, their recent research has diverged toward integrating ultrasound imaging with radiomics in the context of liver diseases. Notably, in 2019, this team published an article titled “Ultrasound-based radiomics score: a potential biomarker for the prediction of microvascular invasion in hepatocellular carcinoma” (15), which was featured in European Radiology. The main collaborative focus of teams led by Christoph D, Paul SS, and Fabio P is the development of guidelines for CEUS. These guidelines, referenced in several publications (24-26), have predominantly been published in Ultraschall in der Medizin and Ultrasound in Medicine and Biology. These two journals have been recognized as popular platforms for CEUS research over the past two decades. Most of their articles have been published in the Journal of Ultrasound in Medicine, Ultrasound in Medicine and Biology, and Clinical Hemorheology and Microcirculation.

Articles

The most frequently cited article was a collaborative effort involving experts from prominent ultrasound associations worldwide, including the Asian Federation of Societies for Ultrasound in Medicine and Biology (AFSUMB), the American Institute of Ultrasound in Medicine (AIUM), the Australasian Society for Ultrasound In Medicine (ASUM), Federación Latinoamericana de Sociedades de Ultrasonido (FLAUS), and the International Contrast Ultrasound Society (ICUS). It presents the third set of recommendations for the use of contrast agents in CEUS and provides specific guidelines for this imaging technique. The second most cited article was another set of guidelines. The analysis of the top 10 most cited articles over the past two decades revealed that a predominant research focus has been liver-related diseases. This underscores the importance of liver diseases in the field of CEUS research.

Keywords

Keywords play a pivotal role in aiding researchers in ascertaining the trends in a given field and guiding their research focus. According to keywords, it is evident that the primary emphasis of CEUS technology has been disease diagnosis. The keywords could be organized into eight distinct categories: (I) ultrasound in medicine, (II) differentiation of lesion malignancy, (III) liver cancer, (IV) vascular imaging, (V) guidelines of CEUS in children, (VI) breast scanning, (VII) kidney diseases, and (VIII) abdominal trauma.

Cluster analysis of keywords, specifically cluster 1, cluster 2, cluster 3, cluster 5, cluster 6, and cluster 7, highlights the exceptional ability of CEUS technology in distinguishing between benign and malignant focal lesions in solid organs. CEUS achieves this by employing the real-time contrast imaging, which, under low mechanical index conditions, minimizes microbubble destruction, significantly prolongs the duration of contrast enhancement, and enables continuous enhancement of solid organs. This, in turn, increases the contrast between lesions and normal tissues/organs, ultimately resulting in effective enhanced imaging (27).

Through different lesion-enhancement patterns, CEUS greatly augments ultrasound’s ability to detect and accurately diagnose focal liver lesions. For instance, liver hemangiomas exhibit peripheral nodular enhancement in the arterial phase, which is followed by gradual centripetal filling during the portal venous phase, with continued enhancement into the delayed phase. In the case of focal nodular hyperplasia (FNH), the arterial phase shows rapid and intense enhancement, often in the form of centrifugal or radiating patterns, with well-defined, overall high enhancement at peak intensity. This enhancement remains consistent in the portal venous and delayed phases. Conversely, malignant HCC exhibits high enhancement during the arterial phase, followed by rapid washout in the delayed phase. Liver metastases often present as ring-like enhancement during the arterial phase, with some hypervascular tumors exhibiting overall enhancement, followed by a decline during the portal venous phase. Several articles (14,28) indicated that the Liver Imaging Reporting and Data System (LI-RADS) scoring system combined with CEUS has excellent performance in the diagnosis of HCC. The modified CEUS LI-RADS LR-5 categorization demonstrates a reasonable level of sensitivity (0.77) in diagnosing HCC (28). CEUS demonstrates high diagnostic sensitivity, with an overall sensitivity of 81% for FNH, 86% for diagnosing hemangiomas, and a sensitivity of 80–90% in the detection of liver metastases, making it comparable to contrast-enhanced computed tomography (CECT) (25).

In the diagnosis of breast cancer, there are distinct early- and late-stage contrast-enhancement patterns in benign and malignant breast lesions. Malignant tissues exhibit unique features, including early rapid enhancement, centripetal filling, claw-shaped enhancement, higher maximum intensity, and continued contrast agent accumulation in the late phase. In contrast, benign tissues are characterized by delayed enhancement, centrifugal filling, uniform enhancement, and minimal contrast agent retention within the lesion during the late phase (19). CEUS demonstrates high sensitivity and specificity in distinguishing malignant from benign breast lesions, with values of 100% and 87.5%, respectively (29). In addition to diagnosing the breast cancer lesion itself, ultrasound contrast agent can be used for sentinel lymph node CEUS (SLN-CEUS). Compared to B-mode US, SLN-CEUS has proven to be a superior diagnostic technique for SLN in patients with early breast cancer, demonstrating advantages across multiple diagnostic parameters. SLN-CEUS has a negative predictive value of 90.2% and an accuracy of 80.7% (30).

In addition to its role in diagnosing certain solid organ lesions, as evident from cluster 8, CEUS has also been applied in the diagnosis of blunt abdominal trauma, particularly affecting solid organs such as the spleen, liver, pancreas, and kidneys. Compared to the established gold standard of computed tomography (CT) scans for blunt abdominal trauma diagnosis, CEUS offers several advantages. It is free of ionizing radiation, enabling rapid bedside examinations without the need for patient transportation, reduces patient exposure to ionizing radiation, and features few contraindications or rare allergic reactions (31). Solid organ injuries typically present as nonenhancing defects with well-defined borders, especially during the venous phase. Hematomas may appear as ill-defined edematous areas with hypoechoic images and reduced perfusion. Lacerations can be identified as linear or branched hypoechoic bands perpendicular to the organ capsule, potentially associated with capsule discontinuity. In the case of active bleeding, it may initially manifest as microbubble extravasation in the peritoneal or retroperitoneal space. The absence of organ perfusion may indicate complete detachment of the vascular pedicle (32).

Our analysis of the frontiers and hotspots in CEUS revealed a significant shift in focus over the past five years. The newly emerged keywords indicate a growing interest in the safety of CEUS technology and its application in pediatric cases. Research by Aikaterini N and colleagues highlights that CEUS is the most frequently employed modality in pediatric abdominal cases for diagnosing and distinguishing focal liver lesions, monitoring and evaluating the efficacy of treatments for solid abdominal tumors, and assessing intra-abdominal parenchymal injuries in specific cases of blunt abdominal trauma (33). Furthermore, specific air-containing contrast agents are primarily used for applications such as transcranial Doppler therapy for brain arteriovenous malformations, Legg-Calvé-Perthes disease, and splenic injuries.

Our study suggests that the new research trend in CEUS may involve its application in pediatric-related diseases. Our findings may highlight new research directions for investigators, thereby promoting the implementation of CEUS in pediatric diseases. The use of CEUS could potentially help address some challenging-to-diagnose and challenging-to-treat pediatric conditions.

Limitations

Several limitations to this study should be mentioned. First, the publications analyzed were sourced exclusively from the WoSCC database’s SCI-E and SSCI, which might result in a relatively limited pool for retrieval, although it is important to note that the WoSCC database rigorously evaluates literature and is commonly used for bibliometric analysis (34). Second, the articles included in the analysis were limited to those in English, but the search was supplemented by references cited in the publications. Third, while the initial retrieval and screening of literature was conducted with care, it is impossible to entirely eliminate selection bias. We established a strict set of screening criteria, which led to the exclusion of many noncompliant documents. Finally, this study employed bibliometric methods to macroscopically analyze the influence of countries, institutions, journals, authors, and keywords on prescription supplements, revealing to some extent, the future research trends and hotspots in this field. Nevertheless, the impact of related policies, healthcare systems, and government agencies on the systematic development of CEUS warrants further investigation.

Acknowledgments

Funding: None.

Footnote

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-24-480/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions relating to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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