Real-time Thermographic Vein Visualization and Extravasation Monitoring During Radiopharmaceutical Injection for Bone Scintigraphy

Abstract

Background/Aim

Prevention of extravasation is important in nuclear medicine, given the growth of radioligand therapy and molecular-targeted radiopharmaceutical therapy. We used very-high-sensitivity infrared thermography to observe the puncture site in real time during radiopharmaceutical injection for bone scintigraphy and evaluated superficial vein visualization and the potential for extravasation monitoring.

Patients and Methods

A total of 23 patients undergoing bone scintigraphy (19 men, four women; mean age of 74.2±7.7 years) were studied. Using very-high-sensitivity infrared thermography (Optris PI 450; thermal resolution 0.04°C), skin-temperature changes around the puncture site were monitored continuously during a saline flush and radiopharmaceutical injection. The minimum skin temperature within 5 mm of the puncture site was compared before and during injection, and its relationship with body mass index and injection site was examined.

Results

No extravasation occurred, and bone scintigraphy was completed normally in all 23 patients. Superficial veins were clearly visualized in 19 out of 23 patients (83%): visualization succeeded in all forearm injections (4/4, 100%) but was poor in 4 out of 19 antecubital-fossa injections (21%). Among the 19 patients with venous visualization ≥5 mm, median minimum skin temperature within 5 mm of the puncture site decreased from 33.62°C before injection to 28.79°C during injection, with no temperature change suggestive of subcutaneous extravasation.

Conclusion

Real-time skin-temperature monitoring with very-high-sensitivity infrared thermography may aid superficial vein visualization and early detection of extravasation. Because visualization is affected by the site of injection, careful site selection and observation are warranted.

Introduction

Extravasation and infiltration – the inadvertent leakage of injected fluids into the surrounding perivascular tissue during administration of drugs, contrast media, and radiopharmaceuticals through intravenous catheters – have long been recognized as causes of serious clinical adverse events (1-4).

In nuclear medicine, the progress of precision oncology and the emergence of radioligand therapy and molecular-targeted radiopharmaceutical therapy have imposed a new level of rigor on the prevention of extravasation. Extravasation of a diagnostic radiopharmaceutical causes local retention, at the puncture site, of radioactivity that should otherwise distribute into the systemic circulation, resulting in suboptimal examinations; in positron-emission tomography, it can lead to underestimation of the standardized uptake value used to assess tumor activity, potentially causing misdiagnosis and additional radiation exposure from repeat examinations (1). A systematic review by van der Pol et al., which comprehensively collected and analyzed primary reports of such cases, highlighted that extravasation can deposit very high absorbed doses of therapeutic radiopharmaceuticals in the local soft tissue, potentially causing severe radiation necrosis (2).

Conventional monitoring for extravasation has relied on subjective methods, such as the patient’s report of pain and visual inspection or palpation by medical staff. These methods lack objectivity and reproducibility, and by the time signs become macroscopically apparent, it is often already too late (5). To address this problem, the clinical application of non-contact, non-invasive infrared thermography capturing skin-temperature changes in real time has been attempted.

In a prospective study of 257 patients receiving chemotherapy through a peripheral vein, Matsui et al. (5) observed the injection site every 15-30 min using thermography (detector resolution 160×120 pixels; thermal resolution 0.1°C), and identified extravasation in 26 patients, concluding that thermography is useful for predicting extravasation. However, few clinical reports have used a very-high-sensitivity infrared camera to observe changes in real time during injection, and as far as we are aware, no study has examined differences in visualization according to the injection site.

We previously reported a technique that uses the temperature gradient produced by injected materials to visualize superficial veins and extravasation with a very-high-sensitivity infrared thermographic camera (6). Building on that method, the present study used very-high-sensitivity thermography to observe, in real time, the temperature changes around the puncture site during actual radiopharmaceutical injection for bone scintigraphy and evaluated superficial vein visualization and the potential for extravasation monitoring.

Patients and Methods

Patients. We studied 23 patients (19 male, 4 female) who provided written informed consent to thermographic observation of the puncture site before and during injection of the radiopharmaceutical ^99mTc-methylene diphosphonate for bone scintigraphy (trial registration no. UMIN000035398). All patients scheduled to undergo bone scintigraphy at our Institution who provided written informed consent were enrolled; no other inclusion or exclusion criteria were applied. Age, height, body weight, and body mass index (BMI) were recorded for all patients. The study was approved by the Ethics Committee of Hamamatsu University School of Medicine (no. 18-219).

Equipment. A very-high-sensitivity infrared thermographic camera (Optris PI 450; Optris, Berlin, Germany) was used (Figure 1). The detector has a resolution of 382×288 pixels and a detection range of −20°C to 100°C, with a thermal resolution of 0.04°C, allowing the detection of very small temperature differences.

Figure 1.

Observation of the puncture site during radiopharmaceutical injection for bone scintigraphy using a very-high-sensitivity infrared thermographic camera (Optris PI 450; Optris, Berlin, Germany).

Observation and analysis. Before injection of the radiopharmaceutical, an intravenous line was secured, and room-temperature normal saline was injected while the temperature change around the puncture site was monitored by thermography; the temperature change was then monitored continuously during injection of the radiopharmaceutical. Venous visualization on the thermographic images was assessed visually and classified as: clear visualization extending ≥5 mm from the puncture site; faint visualization limited to within 5 mm of the puncture site; or no visualization. The minimum skin temperature within 5 mm of the puncture site was measured before and during injection, and its relationship with BMI and injection site was examined. The room temperature at the time of observation was recorded. Data are presented as the mean ± standard deviation or the median (range).

Results

Patient characteristics. Patient characteristics are shown in Table I. The mean age was 74.2±7.7 years, height 163.2±6.4 cm, body weight 65.2±11.4 kg, and BMI 24.4±3.4 kg/m². The median room temperature at the time of injection was 21.4°C (range=19.8-23.2°C). The injection site was the antecubital fossa in 19 patients and the forearm in 4. Bone scintigraphy was completed normally in all patients, and no extravasation was observed during injection.

Table I. Characteristics of the 23 patients included in the study.

BMI: Body mass index; TVV: thermographic venous visualization. +: Clear venous visualization ≥5 mm from the puncture site accompanying the skin-temperature change produced by the injected fluid; Faint (≤5 mm): visualization limited to within 5 mm of the puncture site; None: no visualization.

Thermographic vein visualization. Thermographic imaging based on skin-temperature change demonstrated both a temperature change produced by the injected fluid and clear venous visualization in 19 patients (Figure 2). In two patients (cases 10 and 12) the vein was not visualized, and in two others (cases 8 and 20) visualization was limited to within 5 mm of the puncture site. One of the two patients without visualization had a relatively high BMI (25.3 kg/m² in case 10) and were both women. All four patients with no or limited visualization had received an antecubital-fossa injection.

Figure 2.

Thermographic images acquired during radiopharmaceutical injection, illustrating the three categories of venous visualization: (A) clear (≥5 mm), (B) faint (≤5 mm), (C) none.

No extravasation occurred in any of the 23 patients, and bone scintigraphy was obtained normally. Notably, in case 17, no blood backflow was obtained at cannulation but the vein was visualized on thermography, allowing the radiopharmaceutical to be injected safely.

Skin-temperature change before and during injection. For the 19 patients in whom the vein was visualized ≥5 mm from the puncture site, the minimum skin temperature within 5 mm of the puncture site before and during injection is shown in Figure 3. The mean and median minimum skin temperatures were both 33.6°C (range=31.3-36.1°C) before injection, whereas they were 29.4°C and 28.8°C (range=26.3-33.3°C), respectively, during injection. The minimum skin temperature decreased during injection in all 19 patients.

Figure 3.

Box-and-whisker plots showing the minimum skin temperature within approximately 5 mm of the puncture site before and during radiopharmaceutical injection (n=19). The horizontal line within each box represents the median, the box represents the interquartile range, and the whiskers indicate the range of non-outlier values. Open circles represent outliers.

Discussion

In this study, we used very-high-sensitivity infrared thermography to observe the puncture site in real time during radiopharmaceutical injection for bone scintigraphy, and obtained three main findings: (i) superficial veins were clearly visualized in 19 out of 23 patients (83%); (ii) veins were visualized in all forearm injections (4/4, 100%) but poorly visualized in 4 out of 19 antecubital-fossa injections (21%); and (iii) even when venous visualization was poor, no temperature change suggestive of subcutaneous extravasation was observed.

The principle of this method is to use the temperature gradient between the room-temperature saline or radiopharmaceutical and the body surface as, in effect, a contrast agent, thereby visualizing the (low-temperature) injected fluid flowing within the vein as a change in skin temperature. This represents a real-time clinical application, in the setting of radiopharmaceutical injection, of the technique we previously demonstrated in phantoms and volunteers in which the temperature gradient produced by injected materials is used to visualize veins and extravasation (6).

Matsui et al. (5) used thermography with a detector resolution of 160×120 pixels and a thermal resolution of 0.1°C, observing the injection site at 15- to 30-min intervals, and demonstrated its usefulness for predicting extravasation. In contrast, we performed continuous real-time observation using a very-high-sensitivity camera with 382×288-pixel resolution and 0.04°C thermal resolution. This higher sensitivity enabled the minuscule temperature gradient accompanying the injection to be captured over time and made it possible to visualize the intravenous course of the injected fluid itself. Although no extravasation occurred among the 23 patients presented, we previously reported that with very-high-sensitivity thermography, it was possible to detect subcutaneous extravasation as early as 5 s after its onset (6); the use of very-high-sensitivity thermography may therefore allow the early detection of subcutaneous leakage.

Regarding differences in visualization according to injection site, it was not possible to clearly determine a relationship with BMI or sex in this study. However, when the puncture is made in the antecubital fossa and the arm is thick with subcutaneous fat such that the vein runs deeply beneath the skin, the temperature gradient to the skin surface may be attenuated, resulting in poor visualization. Indeed, all four poorly visualized cases involved antecubital-fossa injection, whereas all forearm injections were well visualized. The forearm, where superficial veins run relatively shallowly, may be a site well suited to this method.

Gillespie et al. (7) used a smartphone-mounted thermographic camera to observe skin-temperature changes during a saline flush before therapeutic injection in five patients undergoing radiopharmaceutical therapy and concluded that thermography is a potentially low-cost, non-invasive, and accessible tool for visualizing fluid-flow dynamics and assessing extravasation or venous patency before and during radiopharmaceutical therapy delivery. Our results support this potential in the clinical injection setting while also showing that visualization can be affected by the site of injection, meaning that caution is required in its application. Furthermore, unless a very-high-sensitivity thermographic camera is used, the detection of subcutaneous extravasation may be delayed.

Gebruers et al. (8) reported a systematic review of the consequences and management of extravasation of therapeutic radiopharmaceuticals. Although extravasation of diagnostic radiopharmaceuticals (e.g., those used for positron-emission tomography) is generally regarded as harmless, therapeutic agents are administered at much higher radioactivity levels, and leakage into tissue carries a risk of severe radiation-induced skin and soft-tissue injury such as necrosis; their review proposed a standardized management procedure for clinicians to follow when extravasation occurs or is suspected. It is therefore clear that it is important to detect extravasation early and to minimize the volume of fluid that leaks into the tissue. The real-time skin-temperature monitoring demonstrated here may be useful for such early detection (2, 9). In addition, as in case 17, when blood backflow was not obtained at cannulation, confirmation of venous visualization by thermography can provide supplementary information for safer injection.

This study has several limitations. Firstly, the sample size was small (23 patients) and the study was at a single center. Secondly, because no actual extravasation occurred, we were not able to directly evaluate the sensitivity of thermography for detecting extravasation itself. Thirdly, because the method depends on the temperature gradient between the (room-temperature) fluid injected and the body surface, visualization may be reduced under conditions in which this temperature difference is small. Future multicenter, large-scale prospective studies that include extravasation cases are needed to clarify detection sensitivity and specificity, and the optimal observation conditions.

Conclusion

Real-time skin-temperature monitoring with very-high-sensitivity infrared thermography during radiopharmaceutical injection for bone scintigraphy clearly visualized superficial veins in 19 out of 23 patients (83%) and may be useful for the early detection of extravasation. Because visualization is affected by the site of injection, such as the antecubital fossa, careful site selection and observation are warranted.

Conflicts of Interest

The Authors declare that they have no conflicts of interest in relation to this study.

Authors’ Contributions

Conceptualization, M.K., S.G. and K.N.; Investigation and data curation, M.K., K.K., T.I., K.W., R.Y. and K.N.; Writing - original draft preparation, M.K. and K.N.; Writing - review and editing, Y.T., K.O. and S.G. All Authors have read and agreed to the published version of the manuscript.

Artificial Intelligence (AI) Disclosure

During the preparation of this manuscript, a large language model (Claude Sonnet 5, Anthropic) was used solely for language editing and stylistic improvements in select paragraphs. No sections involving the generation, analysis, or interpretation of research data were produced by generative AI. All scientific content was created and verified by the authors. Furthermore, no figures or visual data were generated or modified using generative AI or machine learning–based image enhancement tools.