Advances in the application of auxiliary imaging techniques in parathyroid diseases

Abstract

Hypoparathyroidism is one of the main complications after total thyroidectomy, severely affecting patients’ quality of life. How to effectively protect parathyroid function after surgery and reduce the incidence of hypoparathyroidism has always been a key research area in thyroid surgery. Therefore, precise localization of parathyroid glands during surgery, effective imaging, and accurate surgical resection have become hot topics of concern for thyroid surgeons. In response to this clinical phenomenon, this study compared several different imaging methods for parathyroid surgery, including nanocarbon, indocyanine green, near-infrared imaging techniques, and technetium-99m methoxyisobutylisonitrile combined with gamma probe imaging technology. The advantages and disadvantages of each method were analyzed, providing scientific recommendations for future parathyroid imaging. In recent years, some related basic and clinical research has also been conducted in thyroid surgery. This article reviewed relevant literature and provided an overview of the practical application progress of various imaging techniques in parathyroid surgery.

Key Words: Imaging technique, Parathyroid gland, Thyroid surgery, Hypoparathyroidism, Complication

Core Tip: Hypoparathyroidism is one of the main complications after radical thyroidectomy, which seriously affects the quality of life. How to effectively protect parathyroidism and reduce the incidence of hypoparathyroidism has been a key research field in thyroid surgery. In view of this clinical phenomenon, this study introduced different methods of parathyroid imaging during surgery, analyzed their advantages and disadvantages, and provided scientific suggestions for subsequent parathyroid imaging.

INTRODUCTION

Hypoparathyroidism is one of the main complications after radical thyroidectomy, which seriously affects the quality of life. How to effectively protect parathyroidism and reduce the incidence of hypoparathyroidism has been a key research field in thyroid surgery. Hypoparathyroidism can be divided into temporary hypoparathyroidism and permanent hypoparathyroidism, with the incidence of 10%-60% and 1%-4%, respectively[1]. Therefore, the accurate localization of parathyroid glands, effective imaging, and precise surgical resection have become hot topics of concern for thyroid surgeons. In recent years, there have been some related basic and clinical research in thyroid surgery.

Thyroid surgery mainly focuses on the removal of the thyroid gland and parathyroid glands, as well as lymph node dissection. The extent of resection and lymph node dissection directly affects the incidence of postoperative recurrence and complications. The incidence of hypocalcemia after surgery can reach 15%-30%, if the parathyroid glands are damaged[2]. With the increasing maturity of auxiliary imaging techniques, various imaging techniques such as carbon nanoparticles, and indocyanine green (ICG) have been applied in thyroid surgery.

Preoperative ultrasound images were used to examine the parathyroid localization technique

Ultrasound is often used for the diagnosis and preoperative localization of parathyroid diseases. At present, it has been reported that the sensitivity of preoperative ultrasonography in the diagnosis of parathyroid glands ranges from 70% to 90% and the accuracy ranges from 74% to 94%[2]. The ultrasonic detection rate was about 75.74%, and it was shown that the size of the detected parathyroid gland was positively correlated with the level of serum parathyroid hormone[3]. The advantages of ultrasound in the diagnosis and preoperative localization of parathyroid diseases are simple, economical application, no radiation damage, and repeated examination. However, ultrasound also has many drawbacks. For parathyroid adenomas less than 10 mm in diameter, ultrasound can be difficult to distinguish between diseased parathyroid glands and thyroid nodules, especially convex nodules at the edge of the thyroid, and nodules located on the dorsal side of the thyroid. It is also not easy to distinguish the adjacent relationship between the diseased parathyroid gland and the surrounding tissue, and depends to some extent on the diagnostic experience and instrumentation of the ultrasound examiner[4].

Preoperative four-dimensional computed tomography imaging technique for detecting parathyroid location

Four-dimensional computed tomography (4D-CT) is an emerging parathyroid imaging method that has been increasingly used to locate parathyroid adenomas since it was first reported in 2006. In the study of Kelly et al[5], in the scanning process of parathyroid adenoma localization using 4D-CT, there were statistically significant differences in some parameters among parathyroid adenoma, thyroid gland and lymph nodes at 25 s and 55 s respectively, and the difference between parathyroid adenoma and lymph node was the greatest at 25 s. The difference between parathyroid adenoma and thyroid was the greatest at 55 s. The main advantages of 4D-CT are that it can well distinguish the parathyroid gland from the surrounding thyroid nodule and lymph node, etc, providing doctors with accurate anatomical information and improving the accuracy of intraoperative positioning. Moreover, 4D-CT has broken through the disadvantage that ultrasonography is difficult to diagnose multiple adenomas[5], and has a good sensitivity to the diagnosis of multiple adenomas.

INTRAOPERATIVE PARATHYROID IMAGING AND LOCALIZATION TECHNIQUE

Image of parathyroid gland in the application of nano-carbon staining

With the development of nanotechnology, nanomaterials have been widely used in the medical field. Nano carbon are nano-scale colloidal particles with a diameter of approximately 150 nm. They exhibit a high lymphotropic property. The intercellular space of human capillary lymphatic endothelial cells is approximately 120 nm-500 nm. Due to the small intercellular space of the human capillary endothelial cells, when nano carbon are injected into the thyroid tissue, they do not enter the blood vessels but quickly enter the lymphatic system. They aggregate and accumulate in the lymphocyte area, causing the lymph nodes within the thyroid and drainage area to turn black. At the same time, the parathyroid glands do not become stained black. This allows surgeons to clearly differentiate between the parathyroid glands and lymph nodes, making the surgical procedure safer and more efficient.

According to relevant literature, the incidence of transient parathyroid gland dysfunction after thyroid surgery can be as high as 60%. However, intraoperative use of nano carbon for localization can reduce the probability of postoperative parathyroid gland dysfunction to approximately 7%, demonstrating the advantages of this approach. In recent years, domestic and foreign scholars have also explored the application of nano-carbon in secondary surgery, and adopted the method of nano-carbon injection guided by ultrasound before surgery to avoid the problems of imprecision and insufficient diffusion of nano-carbon injection due to scar and adhesion in the operative area. Zhang et al[6] found that among thyroid cancer patients undergoing secondary surgery, 75% of patients in the nano-carbon group identified more than 3 parathyroids during surgery, which was significantly higher than 36.5% in the blank control group (P < 0.05). Meanwhile, the nano-carbon group had more lymph node sweeps and a lower incidence of postoperative complications of temporary hypoparathyroidism. However, although nano carbon are safe, non-toxic, and provide good staining effects as lymphatic tracers, they may not be effective for nodular goiter or giant nodular thyroid tumors.

The technique of nano carbon parathyroid negative imaging is safe and effective. The nano carbon parathyroid negative imaging protection technology does not increase the operation time, intraoperative blood loss and hospital stay of patients, and the position and number of parathyroid glands can be determined during the operation through negative imaging. The clinical application of nano carbon also has limitations: (1) The price is expensive, increasing the economic burden of patients; (2) The parathyroid glands, which are moved down by gravity and located differently in the neck and upper mediastinum, are difficult to distinguish by tissue color contrast; (3) If the nano-carbon is accidentally leaked out during the injection process, the surgical field will be stained, making the anatomical structure unclear and easy to damage blood vessels and nerves; and (4) For patients undergoing secondary surgery, the integrity of the cervical lymphatic system may be damaged due to previous surgical trauma, and there may be leakage of nano-carbon, resulting in contamination of the surgical field[6].

ICG fluorescence imaging technology in intraoperative parathyroid gland imaging

In recent years, with the rise of precision medicine, optical molecular imaging has been increasingly applied in the field of biomedical research due to its non-invasive and high-resolution characteristics. Conventional imaging methods for parathyroid gland imaging include radioactive isotope imaging and imaging of the blood supply to the parathyroid neck region, but these methods have limitations and potential side effects. ICG fluorescence imaging technology provides a new option for parathyroid gland imaging.

Initially, ICG was mainly used for sentinel lymph node tracing in diseases such as breast cancer, gastric cancer, and colorectal cancer. By injecting ICG at the boundary between the tumor and normal tissue, and then using a fluorescence detector, lymph nodes can be quickly identified under imaging guidance. In 2016, Vidal Fortuny et al[7] applied ICG to normal human parathyroid glands, and approximately 83% of patients could detect at least one parathyroid gland using ICG fluorescence imaging. Razavi et al[8] observed patients with thyroid cancer who underwent total thyroidectomy and central lymph node dissection. Indolyanine green was used by the surgeon to identify the vascular network of the parathyroid gland and determine the blood supply of the parathyroid gland, thus providing assistance for autologous transplantation. However, no statistically significant difference was observed in the incidence of postoperative hypoparathyroidism between the non-ICG group and the ICG group (7.9% vs 3.9%, P = 0.37). Zhang et al[6] observed the use of ICG fluorescence tracer and nano-carbon in total thyroidectomy and central region dissection under areolar endoscopy, and found that the incidence of hypoparathyroidism in the ICG group was lower than that in the nano-carbon group (4.3% vs 28.0%), and the number of lymph nodes detected in the ICG group was higher than that in the nano-carbon group (4.6% vs 3.8%). It was found that ICG can identify parathyroid glands well, suggesting that ICG tracer may have a certain application prospect in endoscopic thyroid surgery. Some studies have shown that ICG fluorescence imaging technology may have false negatives in identifying normal parathyroid glands, which may be related to the dosage of ICG and blood supply, but there is currently a lack of unified standards.

In recent years, researchers have discovered that ICG fluorescence imaging technology can be used to assess the blood supply to the parathyroid glands during surgery[7,8]. Using this technology can effectively reduce the occurrence of temporary parathyroid gland dysfunction after surgery, but it requires the surgeon to have rich experience in intraoperative assessment. ICG fluorescence imaging technology has high accuracy, visibility, safety, and real-time imaging in parathyroid gland imaging, which can help doctors accurately locate and protect the parathyroid tissue. However, this technology is still in the development stage and further research and clinical validation are needed for better application in parathyroid surgery.

Near-infrared imaging technology in intraoperative parathyroid gland imaging

In recent years, near-infrared (NIR) imaging technology has received increasing attention from surgeons due to its strong tissue penetration and minimal biological sample photodamage. In 2014, McWade et al[9] first reported the use of NIR fluorescence imaging technology for intraoperative parathyroid gland imaging in patients undergoing thyroidectomy. NIR imaging technology is a technique that utilizes light within the NIR spectrum for imaging. NIR light is located between visible light and infrared light, with a wavelength range typically from 700 nm to 2500 nm. NIR imaging technology utilizes the characteristics of NIR light to provide non-invasive, real-time imaging information by measuring and analyzing the absorption, scattering, transmission, and reflection behaviors of light.

The principle of NIR imaging technology is based on the differences in absorption and scattering characteristics of tissues and substances to NIR light. Different tissues and substances have varying degrees of absorption and scattering of NIR light. Therefore, by measuring the transmission and reflection of NIR light in tissues, information about the structure, function, and metabolic state of tissues can be obtained.

Its principle is based on the strong tissue penetration and biocompatibility of ICG. Typically, ICG accumulates in the parathyroid gland, with its fluorescence intensity being higher than that of surrounding tissues, usually from 2.4 times to 8.5 times higher. In practical applications, only a preoperative intravenous injection of ICG is needed, and the overlaid fluorescence image of the parathyroid gland on the white light image in the surgical area can clearly distinguish the parathyroid gland from surrounding tissues. This makes ICG an ideal NIR probe for the parathyroid gland. Firstly, NIR imaging technology can be used for the evaluation of thyroid nodules. By irradiating the thyroid region with NIR light and utilizing the absorption and scattering characteristics of light, NIR imaging technology can display the blood perfusion of thyroid nodules. This is of great significance for distinguishing between benign and malignant nodules, providing more accurate nodule assessment and classification, and assisting doctors in formulating more rational treatment plans.

Furthermore, the application of NIR imaging technology in thyroid surgery is increasing. In thyroid surgery, it is important to preserve thyroid function while removing thyroid cancer tissue as thoroughly as possible. NIR imaging technology can help doctors accurately locate and remove thyroid cancer tissue by injecting NIR fluorescent dyes that emit specific fluorescence signals in NIR light, thereby improving the accuracy and success rate of the surgery. Additionally, NIR imaging technology can also be used for the evaluation of thyroid function. Thyroid dysfunction is often associated with blood supply. By using NIR imaging technology, the blood oxygen saturation and hemodynamic information in the thyroid region can be observed, allowing for the assessment of thyroid function. This provides important references for the early diagnosis and treatment of thyroid dysfunction[10]. NIR imaging technology has broad prospects in the field of thyroid diseases. It can provide non-invasive, real-time imaging information to assist doctors in early diagnosis and treatment monitoring. In thyroid surgery, NIR imaging technology can improve the accuracy and success rate of the surgery. With the continuous development and improvement of the technology, it is believed that NIR imaging technology will play an increasingly important role in the diagnosis and treatment of thyroid diseases.

Technetium-99m methoxyisobutylisonitrile imaging combined with a gamma detector for intraoperative parathyroid imaging

Technetium-99m methoxyisobutylisonitrile (99mTc-MIBI) imaging is a commonly used method for parathyroid imaging, often combined with a gamma detector for detection. 99mTc-MIBI is a radioactive isotope with a long half-life and suitable radioactive decay characteristics. In parathyroid imaging, 99mTc-MIBI is injected into the patient’s body and subsequently circulates through the bloodstream to the parathyroid gland region. The parathyroid tissue has a high uptake and retention capacity for 99mTc-MIBI, making it an ideal imaging agent. During the imaging process, a gamma detector is used to measure the radioactive signal from the isotope. The gamma detector generates images by detecting the gamma rays emitted by the radioactive isotope, providing information about the location, morphology, and function of the parathyroid gland. Doctors can use the gamma images to locate parathyroid tissue and perform surgical operations or other treatment measures [11,12].

The combination of 99mTc-MIBI imaging and a gamma detector in parathyroid imaging offers several advantages. Firstly, 99mTc-MIBI is a safe and reliable imaging agent that is widely used in clinical practice. Secondly, the gamma detector provides high-resolution radioactive images, allowing doctors to accurately locate and assess parathyroid tissue. Additionally, the real-time and non-invasive nature of 99mTc-MIBI imaging combined with a gamma detector allows for immediate imaging results without significant trauma to the patient’s body[13].

However, it is important to note that there are also limitations to the use of 99mTc-MIBI imaging combined with a gamma detector in parathyroid imaging. For example, the uptake and retention capacity of the imaging agent can be influenced by various factors, leading to variability in imaging results[14]. Additionally, the use of radioactive isotopes carries a certain radiation risk, so the benefits and risks should be weighed and appropriate safety measures should be taken based on the specific situation.

In summary, 99mTc-MIBI imaging combined with a gamma detector is a commonly used method for parathyroid imaging, providing important information about the location and function of the parathyroid gland[15]. However, the specific application and results may vary due to individual differences and other factors, so it is important to follow the guidance and judgment of healthcare professionals when using this technique.

CONCLUSION

Currently, the most commonly used preoperative localization techniques for parathyroid surgery include 99mTc-MIBI imaging, ultrasound, and computed tomography. Preoperative localization of the parathyroid glands is important to avoid damage to other structures[16]. However, these techniques have several drawbacks, such as high cost, complexity of operation, and the difficulty for surgeons to obtain direct and intuitive localization information during surgery. In clinical practice, various imaging techniques are relied upon to protect the parathyroid glands and their blood supply. Nano-carbon negative imaging protection technology is safe and effective and is widely used in clinical practice, although it is expensive and cannot display the blood supply of the parathyroid glands. Methylene blue is limited in clinical application due to safety concerns, but it can be used for secondary thyroid surgery and parathyroid lesions with adequate communication with the patient and strict control of dosage and infusion rate. ICG, as a fluorescent dye, is safe, feasible, and cost-effective. It has significant advantages in determining the blood supply of the parathyroid glands and predicting postoperative parathyroid function. It is believed that it will have broad development prospects in the field of thyroid surgery in the future[17,18].