Parathyroid gland accounts for calcium regulation. Due to its special appearance and the anatomical adjacency to thyroid, the identification and protection of parathyroid glands is a key process in the thyroidectomy procedure. Unintentional removal or injury of the parathyroid glands during thyroidectomy may lead to temporary or permanent hypoparathyroidism and hypocalcemia, and lead to numbness in the hands and feet, even tetany. The incidence of permanent hypocalcemia after total thyroidectomy is about 0-3.8%[20]. This clinical problem would eventually lead to fatal convulsions, cardiac arrhythmia, heart failure and chronic renal failure[3, 21]. For patients with thyroid carcinoma, if the lymph node were mistaken as parathyroid gland, it would give rise to the risk of cancer residual and increase recurrence rate. So, a noninvasive and timely procedure is indispensable during thyroidectomy so as to identify the parathyroid glands accurately.
In the present study, we present that NIR fluorescence spectroscopy can accurately identify normal parathyroid glands without additional injury to its function. Each sample was validated by histologic result. Moreover, we designed a Fisher’s linear discriminant model which provided reliable verification for the data of NIR auto-fluorescence. Fisher’s linear discriminant analysis is a useful model for the distinction of objects that belong to different classes. It extracts descriptive characteristics, and is used to reduce the dimensionality of a space, to generate a discriminant space with a lower dimension, keeping useful information to discriminate among classes[22-24]. In the present study, we used Fisher's linear discriminant is to discriminate auto-fluorescence spectra from parathyroid glands and other cervical tissues and achieved an accuracy about 90%. To our knowledge, this is the first report of Fisher's linear discriminant model used for predicting parathyroid glands by detection data and reveals high accuracy. The results indicate that NIR fluorescence spectroscopy can provide real-time, reliable and repeatable help for surgeon during thyroidectomies. Additionally, the combination of optical metrology model with NIR technique provides the potential for transforming it to an artificial intelligent detection instrument, making this technique easier and faster for practical use.
NIR fluorescence spectroscopy is a novel and promising method for intraoperative detection of parathyroid gland during thyroidectomy. Compared with other parathyroid identifying methods, especially biopsy or fine-needle aspiration with intact PTH, the greatest advantages of the tool using intrinsic NIR auto-fluorescence are noninvasive and time-saving. It does no extra injury to the parathyroid glands and thus provides protection for the parathyroid function. The whole detection procedure just takes a few minutes without affecting the duration of surgery.
The tool uses intrinsic NIR auto-fluorescence to distinguish different tissues. However, the underlying molecular basis is still not clear. Primary hypothesis considers tissue specific fluorophore, the extracellular Calcium-sensing Receptor (CaSR). The CaSR is a G-protein-coupled receptor mainly expressed in tissues participating Ca2+ regulation, including parathyroid chief cells, thyroidal C-cells, kidney, bone and intestinal cells at different levels but not present in other neck tissues[25, 26]. The tissue specific distribution and expression level of CaSR fluorophore make it possible that parathyroid emits higher intensity of NIR auto-fluorescence when exited by certain length of NIR laser. McWade and colleagues detected the same peak fluorescence signal in human kidney and colon when exited as parathyroid and thyroid[15]. Furthermore, the intensity of the fluorescence was consistent with the CaSR expression level. This provides primary evidence for the candidate role of CaSR in parathyroid NIR auto-fluorescence. Further cellular and spectroscopic studies will probably provide interpretation.
A potential restriction of the tool is that the detection depth is limited, because of the limitation of near infrared light penetration. When the parathyroid gland is covered by overlying layer of fat tissue, it may influence the accuracy of detection[27]. Another defect is the current NIR technique cannot estimate blood perfusion of parathyroid glands[18, 28]. Furthermore, the detection procedure requires turning off the operation lights[15, 29]. Further improving in the technology is still needed. The study of the underlying molecules and chemical construction, together with the use of artificial intelligent model, will provide the possibility.
In previous studies, Constantine Paras and colleagues have detected the near-infrared autofluorescence of pathologic parathyroid glands. When stimulated by 785-nm excitation, parathyroid fluorescence was several times stronger than that of the thyroid tissues with peak fluorescence occurring at 820 to 830 nm regardless of disease state. The results indicated that the near-infrared autofluorescence from pathologic parathyroid glands is similar to that from normal parathyroid glands[13, 14]. In the other hand, in patients with parathyroid diseases, such as parathyroid hyperplasia and parathyroid adenoma, the parathyroid glands usually become larger in size, round in shape, and increase in hardness. Thus, it is usually very easy to find out and identify the pathologic parathyroid glands without the need for extra tools in endocrine surgeries. The difficulty in clinical practice is the identification of normal parathyroid glands because of its small size and similarity in appearance to the surrounding tissues[8]. Based on the facts above, we focused on normal parathyroid glands identification and detection, and did not included patients with parathyroid diseases.
Overall, our study presents a practical technique tool and a predicting optical metrology model which would provide real-time help in detecting and protecting parathyroid glands in endocrine surgeries. We just did validation in twenty patients. The increase of sample amount will improve the efficacy of both the detection method and the metrology model. We believe that a portable and intelligent NIR instrument will decrease postoperative hypoparathyroidism and hypocalcemia, and improve patient outcome.