Contrast agents, also known as contrast media, are predominantly used in medical imaging examinations such as X-ray/CT enhancement, MRI enhancement, and interventional angiography (1–5). Their role is to optimize imaging visualization and create density or signal variations between normal tissue organs and pathological areas for precise diagnostic purposes. Common contrast agents include iodine-based agents, barium-based agents, and MRI contrast agents.

In medical imaging examinations, the use of contrast agents may lead to complications such as allergic reactions (6, 7), vasovagal responses (8), arrhythmias (9), and pulmonary edema (10). The most common complication is contrast agent extravasation (11–13), where the contrast agent (iodine or gadolinium) leaks from the vein into the surrounding soft tissues. Extravasation can result in pain, swelling, blistering, secondary wound infections, tissue adhesions, and even severe outcomes such as compartment syndrome and amputation. An analysis of U.S. data by Dykes et al. (14) showed that the average extravasation rate was 0.24%, and occurrence rates of mild, moderate, and severe injuries due to contrast agent extravasation were 94.6, 4.7, and 0.8%, respectively. These complications not only increase patient discomfort, extend hospital stays, and raise medical costs but also impact physicians’ ability to diagnose, treat, and rescue patients, ultimately affecting patients’ quality of life. To effectively prevent and reduce the occurrence of contrast agent extravasation, researchers need to delve into its mechanisms, influencing factors, and preventive measures. Factors affecting contrast agents include their characteristics (volume, concentration, viscosity, and temperature), injection instruments (various types of catheters), and injection techniques (patient injection sites, injection methods, and infusion rates). By studying the causes of extravasation, clinicians can mitigate adverse factors in clinical practice, improve contrast agents and their administration, and minimize extravasation, thereby reducing potential complications during imaging examinations. However, complete avoidance of contrast agent extravasation is challenging due to high-pressure injections, physical-chemical properties of contrast agent drugs, patient age, underlying diseases, and other factors (15). When extravasation cannot be avoided, targeted measures can be taken for high-risk individuals to reduce the harm caused by extravasation, such as selecting a high-pressure-tolerant central venous catheter for patients with malignant tumors.

The mechanisms of varying degrees of damage caused by contrast agent extravasation primarily include cellular toxicity (16), mechanical compression (17), and osmotic effects (18). In vitro studies have suggested that contrast agents can induce morphological changes and apoptosis in endothelial cells. The degree of mechanical compression correlates directly with the amount of extravasation. High-dose contrast agent extravasation can lead to severe rupture of external vein tissues, particularly with high-pressure injections or at hard-to-monitor injection sites. High-osmolarity contrast agents that leak into subcutaneous tissues increase local tissue osmotic pressure, leading to endothelial cell dehydration and local platelet aggregation, resulting in changes such as increased capillary permeability, leukocyte infiltration, and release of inflammatory chemoattractants such as prostaglandins E1 and E2, causing inflammation (19).

As medical imaging technology continues to advance, new types of contrast agents will emerge, necessitating continuous updating and enhancement of research on contrast agent extravasation. This study aimed to systematically review and analyze the research hotspots and development trends of contrast agent extravasation in medical imaging examinations through visual methods. We strived to provide valuable reference information for researchers and practitioners in related fields, offering safer and more effective technical support for clinical practice in medical imaging.

This study is the first to apply bibliometric methods, using visual analysis tools such as CiteSpace and VOSviewer, to comprehensively showcase the global dynamics of research on contrast agent extravasation in medical imaging. It vividly illustrates the trends, current status, research hotspots, and emerging frontiers over the past seven decades.

An analysis of the annual publication numbers revealed that the initial study reported in the WOS Core Collection database emerged in 1950 (20). However, since 1979, the number of publications has increased annually, which is closely associated with the rapid development and widespread adoption of medical imaging technologies such as ultrasound, CT, and MRI (31, 32). With the extensive use of advanced medical imaging technologies, the role of contrast agents in medical imaging examinations has become increasingly prominent, shedding light on the issue of extravasation of contrast agents. During this period, researchers not only continued to focus on contrast agent enhancement techniques but also delved deeper into exploring the mechanisms, prevention, and treatment methods of contrast agent extravasation, thereby propelling rapid progress in this research field (33).

In terms of the number of publications by country and co-occurrence analysis results, the United States leads significantly with 1,420 publications, representing one-third of the total global publication output, followed by Germany and China. In this research field, high intermediation centrality is primarily concentrated in European and American countries, indicating the substantial international influence of these nations. Among the 12,777 relevant research institutions worldwide, the University of California System (169 articles) and Harvard University (150 articles) stand out as the institutions with the highest publication volume, extensive collaborative networks, and significant impact. Analysis of author collaboration networks revealed the emergence of several large-scale networks of scholars driving advancements in the research field of extravasation of contrast agents in medical imaging.

Keywords serve as concise summaries of the main themes and essential information in literature, enabling the exploration of research hotspots and directions in a specific field. Analysis of keyword co-occurrence in this field revealed that “magnetic resonance imaging,” “computed tomography,” “management,” “diagnosis,” and “contrast agent” are the top five keywords with the highest frequency of occurrence. Co-occurrence analysis and clustering uncovered the research hotspots and trends in the fields of medical imaging and drug delivery (34). The top three clusters, namely, “contrast media,” “fluorescein angiography,” and “focused ultrasound,” highlight the significance and activity of these technologies in medical diagnosis and treatment. Research findings indicated that there is an overlap between the clusters of “focused ultrasound” and “perfusion,” as well as between “rheumatoid arthritis” and “myelography.” This suggests a profound interdisciplinary integration that facilitates the generation of innovative outcomes. This high level of integration signifies that interdisciplinary research is propelling these fields toward more comprehensive and in-depth developments. Furthermore, the continuity over time of the clusters “contrast media,” “fluorescein angiography,” “focused ultrasound,” and “perfusion” indicates that these studies are not only current hotspots but are likely to maintain their research vitality and depth in the future, offering more innovative solutions and treatment strategies for clinical medicine.

Among the numerous keywords the term “gd dtpa” had the highest burst value of 20.51 indicating it is a highly representative research topic that has garnered widespread attention in imaging practices and become a focal point for researchers (35–37). The burst keywords in this field evolve continually. Before 2001 research primarily focused on the preliminary applications of contrast agents and their integration with imaging technologies. Keywords such as “contrast media,” “gadolinium dtpa,” and “computed tomography” indicate that researchers began to explore the application of contrast agents in imaging examinations such as CT to enhance image quality and diagnostic accuracy. Simultaneously the emergence of terms such as “capillary permeability” and “leakage space” signifies increasing attention to the phenomenon of contrast agent extravasation as researchers sought to understand the underlying mechanisms. From 2001 to 2014 the research focus shifted toward investigating the mechanisms of contrast agent extravasation and exploring its clinical significance. Keywords such as “endothelial growth factor,” “angiogenesis,” and “vascular permeability” illustrate researchers’ efforts to examine the mechanisms of extravasation at the cellular and molecular levels particularly regarding factors related to endothelial cells. In addition the emergence of terms such as “tumors” and “extravasation” indicates that the clinical relevance of contrast agent extravasation in diseases such as tumors gained attention with researchers attempting to evaluate disease progression and treatment efficacy through this phenomenon. From 2014 to the present research has concentrated on the application of multimodal imaging techniques and the comprehensive management of contrast agent extravasation. Keywords such as “optical coherence tomography,” “nanoparticles,” and “multimodal imaging” indicate that researchers started integrating various imaging technologies with emerging fields such as nanotechnology to more comprehensively assess contrast agent extravasation. Furthermore terms such as “prevalence,” “case report,” and “macular edema” reflect an increased emphasis on the prevalence of contrast agent extravasation clinical case analyses and potential complications indicating a growing focus on the clinical applications and risk assessments associated with the extravasation phenomena. It is important to note that the emerging significance of “multimodal imaging” is considerably high at this stage indicating that it may become a focal point of research in the near future (5, 38–40). The burst keyword analysis not only highlights the growth of interdisciplinary research but also indicates potential directions for future research investments and technological developments particularly in the advancement of biomedical imaging technologies.

This study conducts an in-depth analysis of the current status and trends regarding the extravasation of contrast agents in medical imaging examinations using bibliometric methods. Since its initial report in 1950, there has been a marked annual increase in related research literature, particularly after 1979. This trend is closely associated with the rapid advancement of medical imaging technologies. The focus of research is predominantly in the United States, with notable contributions from institutions such as the University of California System and Harvard University, showcasing their significant standing and influence in the international academic community. Through keyword co-occurrence and clustering analysis, the study identified “magnetic resonance imaging,” “computed tomography,” “management,” “diagnosis,” and “contrast agent” as the most frequently occurring keywords, revealing the current research hotspots and future directions. Particularly, the emergence of “gd dtpa” as a burst keyword underscores widespread attention to the safety and efficacy of contrast agents. In addition, the emerging keywords “case report,” “multimodal imaging,” and “leakage” indicate that research on contrast agent extravasation focuses on the analysis of rare cases, the application of multimodal imaging technologies, and an in-depth exploration of the mechanisms and preventive strategies. This reflects the latest developments in the field concerning clinical practice and technological innovation. Future efforts should emphasize precise prevention and management of contrast agent extravasation, optimize care strategies by incorporating individual patient differences, and explore the application of new technologies to reduce extravasation risk through enhanced international collaboration and technological exchange.