近红外自体荧光成像技术在术中甲状旁腺实时导航应用研究进展

蔡畅, 温启烨, 刘振平, 金名亮, 王松

中国实用外科杂志 ›› 2025, Vol. 45 ›› Issue (12) : 1482-1486.

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中国实用外科杂志 ›› 2025, Vol. 45 ›› Issue (12) : 1482-1486. DOI: 10.19538/j.cjps.issn1005-2208.2025.12.24
文献综述

近红外自体荧光成像技术在术中甲状旁腺实时导航应用研究进展

作者信息 +

Research progress on intraoperative real-time navigation using near-infrared autofluorescence imaging for parathyroid glands

Author information +
文章历史 +

摘要

术中甲状旁腺的误切或血运受损,可导致甲状旁腺功能减退及低钙血症,因此,甲状(旁)腺手术中对甲状旁腺的功能定位是甲状腺专科的重点和难点。目前术中辅助定位、识别、保护甲状旁腺的各种光学成像技术的临床应用前景参差不齐,其中近红外自体荧光及其他无标记光学成像技术具有应用简单、高效、安全、实时且具有非侵入性等优点,受到外科医生的青睐。此类技术对于甲状旁腺具有实时保护作用,在甲状(旁)腺手术中展现出明显优势和应用前景。

Abstract

Intraoperative misidentification or vascular damage of the parathyroid glands during thyroid surgery can lead to impaired parathyroid function and hypocalcemia. Therefore, the functional localization of parathyroid glands during thyroid (parathyroid) surgery is a key focus and challenge for thyroid specialists. Currently, the clinical application prospects of various optical imaging techniques for intraoperative localization, identification, and protection of parathyroid glands vary. Among them, near-infrared autogenous fluorescence and other label-free optical imaging techniques have advantages such as simplicity, efficiency, safety, real-time capability, and non-invasiveness, making them favored by surgeons. These techniques provide real-time protection for parathyroid glands and demonstrate significant advantages and application prospects in thyroid (parathyroid) surgery.

关键词

甲状旁腺 / 术中导航 / 无标记光学成像技术 / 自体荧光 / 激光散斑

Key words

parathyroid gland / intraoperative navigation / label-free optical imaging techniques / autofluorescence / laser speckle

引用本文

导出引用
蔡畅, 温启烨, 刘振平, . 近红外自体荧光成像技术在术中甲状旁腺实时导航应用研究进展[J]. 中国实用外科杂志. 2025, 45(12): 1482-1486 https://doi.org/10.19538/j.cjps.issn1005-2208.2025.12.24
CAI Chang, WEN Qi-ye, LIU Zhen-ping, et al. Research progress on intraoperative real-time navigation using near-infrared autofluorescence imaging for parathyroid glands[J]. Chinese Journal of Practical Surgery. 2025, 45(12): 1482-1486 https://doi.org/10.19538/j.cjps.issn1005-2208.2025.12.24
中图分类号: R6   

参考文献

[1]
Xia CF, Dong XS, Li H, et al. Cancer statistics in China and United States, 2022:Profiles, trends,and determinants[J]. Chin Med J(Engl), 2022, 135(5):584-590.DOI:10.1097/CM9.0000000000003442.
[2]
Edafe O, Antakia R, Laskar N, et al. Systematic review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia[J]. Br J Surg, 2014, 101(4):307-320.DOI:10.1002/bjs.9384.
Hypocalcaemia is common after thyroidectomy. Accurate prediction and appropriate management may help reduce morbidity and hospital stay. The aim of this study was to perform a systematic literature review and meta-analysis of predictors of post-thyroidectomy hypocalcaemia.A systematic search of PubMed, EMBASE and the Cochrane Library databases was undertaken, and the quality of manuscripts assessed using a modified Newcastle-Ottawa Scale.Some 115 observational studies were included. The median (i.q.r.) incidence of transient and permanent hypocalcaemia was 27 (19-38) and 1 (0-3) per cent respectively. Independent predictors of transient hypocalcaemia included levels of preoperative calcium, perioperative parathyroid hormone (PTH), preoperative 25-hydroxyvitamin D and postoperative magnesium. Clinical predictors included surgery for recurrent goitre and reoperation for bleeding. A calcium level lower than 1·88 mmol/l at 24 h after surgery, identification of fewer than two parathyroid glands (PTGs) at surgery, reoperation for bleeding, Graves' disease and heavier thyroid specimens were identified as independent predictors of permanent hypocalcaemia in multivariable analysis. Factors associated with transient hypocalcaemia in meta-analyses were inadvertent PTG excision (odds ratio (OR) 1·90, 95 per cent confidence interval 1·31 to 2·74), PTG autotransplantation (OR 2·03, 1·44 to 2·86), Graves' disease (OR 1·75, 1·34 to 2·28) and female sex (OR 2·28, 1·53 to 3·40).Perioperative PTH, preoperative vitamin D and postoperative changes in calcium are biochemical predictors of post-thyroidectomy hypocalcaemia. Clinical predictors include female sex, Graves' disease, need for parathyroid autotransplantation and inadvertent excision of PTGs.© 2014 BJS Society Ltd. Published by John Wiley & Sons Ltd.
[3]
穆书奇, 董大山, 施可彬. 无标记光学成像技术[J]. 激光与光电子学进展, 2022, 59(12):11-31.DOI:10.3788/LOP202259.1200001.
[4]
Das K, Stone N, Kendall C, et al. Raman spectroscopy of parathyroid tissue pathology[J]. Lasers Med Sci, 2006, 21(4):192-197.DOI:10.1007/s10103-006-0397-7.
[5]
Paras C, Keller M, White L, et al. Near-infrared autofluorescence for the detection of parathyroid glands[J]. J Biomed Opt, 2011, 16(6):067012.DOI:10.1117/1.3583571.
[6]
McWade MA, Paras C, White LM, et al. A novel optical approach to intraoperative detection of parathyroid glands[J]. Surgery, 2013, 154(6):1371-1377.DOI:10.1016/j.surg.2013.06.046.
[7]
McWade MA, Paras C, White LM, et al. Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging[J]. J Clin Endocrinol Metab, 2014, 99(12):4574-4580.DOI:10.1210/jc.2014-2503.
The inability to accurately localize the parathyroid glands during parathyroidectomy and thyroidectomy procedures can prevent patients from achieving postoperative normocalcemia. There is a critical need for an improved intraoperative method for real-time parathyroid identification.The objective of the study was to test the accuracy of a real-time, label-free technique that uses near-infrared (NIR) autofluorescence imaging to localize the parathyroid.The study was conducted at the Vanderbilt University endocrine surgery center.Patients undergoing parathyroidectomy and/or thyroidectomy were included in this study. To validate the intrinsic fluorescence signal in parathyroid, point measurements from 110 patients were collected using NIR fluorescence spectroscopy. Fluorescence imaging was performed on 6 patients. Imaging contrast is based on a previously unreported intrinsic NIR fluorophore in the parathyroid gland. The accuracy of fluorescence imaging was analyzed in comparison with visual assessment and histological findings.The detection rate of parathyroid glands was measured.The parathyroid glands in 100% of patients measured with fluorescence imaging were successfully detected in real time. Fluorescence images consistently showed 2.4 to 8.5 times higher emission intensity from the parathyroid than surrounding tissue. Histological validation confirmed that the high intrinsic fluorescence signal in the parathyroid gland can be used to localize the parathyroid gland regardless of disease state.NIR fluorescence imaging represents a highly sensitive, real-time, label-free tool for parathyroid localization during surgery. The elegance and effectiveness of NIR autofluorescence imaging of the parathyroid gland makes it highly attractive for clinical application in endocrine surgery.
[8]
Brown EM, MacLeod RJ. Extracellular calcium sensing and extracellular calcium signaling[J]. Physiol Rev, 2001, 81(1):239-297.DOI:10.1152/physrev.2001.81.1.239.
The cloning of a G protein-coupled extracellular Ca(2+) (Ca(o)(2+))-sensing receptor (CaR) has elucidated the molecular basis for many of the previously recognized effects of Ca(o)(2+) on tissues that maintain systemic Ca(o)(2+) homeostasis, especially parathyroid chief cells and several cells in the kidney. The availability of the cloned CaR enabled the development of DNA and antibody probes for identifying the CaR's mRNA and protein, respectively, within these and other tissues. It also permitted the identification of human diseases resulting from inactivating or activating mutations of the CaR gene and the subsequent generation of mice with targeted disruption of the CaR gene. The characteristic alterations in parathyroid and renal function in these patients and in the mice with "knockout" of the CaR gene have provided valuable information on the CaR's physiological roles in these tissues participating in mineral ion homeostasis. Nevertheless, relatively little is known about how the CaR regulates other tissues involved in systemic Ca(o)(2+) homeostasis, particularly bone and intestine. Moreover, there is evidence that additional Ca(o)(2+) sensors may exist in bone cells that mediate some or even all of the known effects of Ca(o)(2+) on these cells. Even more remains to be learned about the CaR's function in the rapidly growing list of cells that express it but are uninvolved in systemic Ca(o)(2+) metabolism. Available data suggest that the receptor serves numerous roles outside of systemic mineral ion homeostasis, ranging from the regulation of hormonal secretion and the activities of various ion channels to the longer term control of gene expression, programmed cell death (apoptosis), and cellular proliferation. In some cases, the CaR on these "nonhomeostatic" cells responds to local changes in Ca(o)(2+) taking place within compartments of the extracellular fluid (ECF) that communicate with the outside environment (e.g., the gastrointestinal tract). In others, localized changes in Ca(o)(2+) within the ECF can originate from several mechanisms, including fluxes of calcium ions into or out of cellular or extracellular stores or across epithelium that absorb or secrete Ca(2+). In any event, the CaR and other receptors/sensors for Ca(o)(2+) and probably for other extracellular ions represent versatile regulators of numerous cellular functions and may serve as important therapeutic targets.
[9]
Serra C, Serra J, Ferreira Machado IL, et al. Spectroscopic analysis of parathyroid and thyroid tissues by ground-state diffuse reflectance and laser induced luminescence: A preliminary report[J]. J Fluoresc, 2021, 31(5):1235-1239.DOI:10.1007/s10895-021-02783-4.
Intraoperative discrimination of thyroid and parathyroid tissues is fundamental in thyroid surgery. Recent fluorescence studies have shown stronger NIR emission in parathyroid tissue than in thyroid tissue, presenting a potential avenue for the development of a tool for surgical assistance. However, the fluorophore responsible for this emission has not yet been identified. In this work, spectroscopic analysis was performed to ascertain the origin of the emission peaks in parathyroid tissue. Ground-state diffuse reflectance (GSDR) absorption spectroscopy and laser-induced luminescence (LIL) emission spectroscopy were performed in parathyroid, thyroid, and fatty tissue samples and the resulting spectra were compared with the peaks of known fluorophores to identify the origin of each peak. The spectra of the different tissue types were also compared in order to evaluate the wavelength which presents the highest parathyroid emission relative to the emission of the surrounding tissues, representing the ideal wavelength for parathyroid detection. An emission peak in these conditions was observed for both thyroid and parathyroid tissue at 711 nm, with a higher intensity in parathyroid sample, making it suitable for detection applications. These results show a potential avenue for the development of a system allowing parathyroid detection in a surgical setting.© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
[10]
Falco J, Dip F, Quadri P, et al. Increased identification of parathyroid glands using near infrared light during thyroid and parathyroid surgery[J]. Surg Endosc, 2017, 31(9):3737-3742.DOI:10.1007/s00464-017-5424-1.
Parathyroid gland (PG) identification during thyroid and parathyroid surgery is challenging. Accidental parathyroidectomy increases the rate of postoperative hypocalcaemia. Recently, autofluorescence with near infrared light (NIRL) has been described for PG visualization. The aim of this study is to analyze the increased rate of visualization of PGs with the use of NIRL compared to white light (WL).All patients undergoing thyroid and parathyroid surgery were included in this study. PGs were identified with both NIRL and WL by experienced head and neck surgeons. The number of PGs identified with NIRL and WL were compared. The identification of PGs was correlated to age, sex, and histopathological diagnosis.Seventy-four patients were included in the study. The mean age was 48.4 (SD ±13.5) years old. Mean PG fluorescence intensity (47.60) was significantly higher compared to the thyroid gland (22.32) and background (9.27) (p < 0.0001). The mean number of PGs identified with NIRL and WL were 3.7 and 2.5 PG, respectively (p < 0.001). The difference in the number of PGs identified with NIRL and WL and fluorescence intensity was not related to age, sex, or histopathological diagnosis, with the exception of the diagnosis of thyroiditis, in which there was a significant increase in the number of PGs visualized with NIRL (p = 0.026).The use of NIRL for PG visualization significantly increased the number of PGs identified during thyroid and parathyroid surgery, and the differences in fluorescent intensity among PGs, thyroid glands, and background were not affected by age, sex, and histopathological diagnosis.
[11]
Kwaśny M, Bombalska A. Applications of laser-induced fluorescence in medicine[J]. Sensors, 2022, 22(8):2956.DOI:10.3390/s22082956.
Fluorescence is the most sensitive spectroscopic method of analysis and fluorescence methods. However, classical analysis requires sampling. There are new needs for real-time analyses of biological materials, without the need for sampling. This article presents examples of proprietary applications of laser-induced fluorescence (LIF) in medicine with such methods. A classic example is the analysis of photosensitizers using the photodynamic treatment method (PDT). The level and kinetics of accumulation and excretion of sensitizers in the body are examined, as well as the optimal exposure time after the application of compounds. The LIF method is also used to analyze endogenous fluorophores; it has been used to detect neoplasms, e.g., lung cancer or gynecological and dermatological diseases. Furthermore, it is used for the diagnosis of early stages of tooth decay or detection of fungi. The article will present the construction of sensors based on the LIF method—fiber laser spectrometers and investigated fluorescence spectra in individual applications. Examples of fluorescence imaging, e.g., dermatological, and dental diagnostics and measuring systems will be presented. The advantage of the method is it has greater sensitivity and easily detects lesions early compared to the methods used in observing the material in reflected light.
[12]
Tabei I, Fuke A, Fushimi A, et al. Determination of the optimum excitation wavelength for the parathyroid gland using a near-infrared camera[J]. Front Surg, 2021, 7:619859.DOI:10.3389/fsurg.2020.619859.
When performing thyroid/parathyroid surgery, difficulty detecting the parathyroid gland is a common experience because it is frequently mistaken with surrounding structures, including the thyroid gland, lymph nodes, and fat. To obtain successful surgical results, the auto fluorescent property of the parathyroid gland occurring at 820–830 nm has been used. Intraoperative visualization and detection by fluorescence enable protection of the gland from damage and unintended removal. Use of a near-infrared (NIR) camera has been proposed to indicate the parathyroid gland, but the devices and success rates have varied. This study aimed to define optimum excitation wavelength (EWL) by measuring the EWL of the parathyroid gland for its autofluorescence. Glands were exposed to EWL at 10-nm intervals from 670–790 nm with a light-emitting diode monochromator; autofluorescence intensity was recorded with a conventional NIR video camera. Autofluorescence intensity curves of three normal parathyroid glands were depicted; the optimum EWL was measured as 760–770 nm. Also, the illumination of the surrounding structures were compared at the optimum EWL. The auto fluorescent intensity of the parathyroid gland was 2-fold greater than for surrounding structures. This difference in fluorescence intensity should enable distinction of the parathyroid gland from surrounding structures. The clarification of the optimum EWL can guide refinements of the NIR camera for better surgical outcomes by improving detection of the parathyroid glands. Also, an understanding of optimum EWL should lead to developments for microscopic devices to unravel the still unknown mechanisms of the intrinsic autofluorescence of the parathyroid gland.
[13]
Liu Y, Zhang L, Hu N, et al. An optogenetic approach for regulating human parathyroid hormone secretion[J]. Nat Commun, 2022, 13(1):771.DOI:10.1038/s41467-022-28472-9.
Parathyroid hormone (PTH) plays crucial role in maintaining calcium and phosphorus homeostasis. In the progression of secondary hyperparathyroidism (SHPT), expression of calcium-sensing receptors (CaSR) in the parathyroid gland decreases, which leads to persistent hypersecretion of PTH. How to precisely manipulate PTH secretion in parathyroid tissue and underlying molecular mechanism is not clear. Here, we establish an optogenetic approach that bypasses CaSR to inhibit PTH secretion in human hyperplastic parathyroid cells. We found that optogenetic stimulation elevates intracellular calcium, inhibits both PTH synthesis and secretion in human parathyroid cells. Long-term pulsatile PTH secretion induced by light stimulation prevented hyperplastic parathyroid tissue-induced bone loss by influencing the bone remodeling in mice. The effects are mediated by light stimulation of opsin expressing parathyroid cells and other type of cells in parathyroid tissue. Our study provides a strategy to regulate release of PTH and associated bone loss of SHPT through an optogenetic approach.© 2022. The Author(s).
[14]
陈志达, 郗洪庆, 刘培发, 等. 近红外自体荧光显像技术在甲状腺肿瘤手术中辅助识别甲状旁腺有效性分析[J]. 中国实用外科杂志, 2021, 41(8):882-885.DOI:10.19538/j.cjps.issn1005-2208.2021.08.11.
[15]
柳桢, 殷德涛, 王涛, 等. 近红外荧光系统对甲状腺术中甲状旁腺识别临床应用研究[J]. 中国实用外科杂志, 2020, 40(2):230-234.DOI:10.19538/j.cjps.issn1005-2208.2020.02.020.
[16]
张颖超, 陈承坤, 伍波, 等. 近红外自体荧光成像对术中甲状旁腺实时识别的初步研究[J]. 临床外科杂志, 2021, 29(7):646-651.DOI:10.3969/j.issn.1005-6483.2021.07.016.
[17]
Dip F, Falco J, Verna S, et al. Randomized controlled trial comparing white light with near-infrared autofluorescence for parathyroid gland identification during total thyroidectomy[J]. J Am Coll Surg, 2019, 228(5):744-751.DOI:10.1016/j.jamcollsurg.2018.12.044.
[18]
Benmiloud F, Godiris-Petit G, Gras R, et al. Association of autofluorescence-based detection of the parathyroid glands during total thyroidectomy with postoperative hypocalcemia risk: Results of the parafluo multicenter randomized clinical trial[J]. JAMA Surg, 2020, 155(2):106-112.DOI:10.1001/jamasurg.2019.4613.
Because inadvertent damage of parathyroid glands can lead to postoperative hypocalcemia, their identification and preservation, which can be challenging, are pivotal during total thyroidectomy.To determine if intraoperative imaging systems using near-infrared autofluorescence (NIRAF) light to identify parathyroid glands could improve parathyroid preservation and reduce postoperative hypocalcemia.This randomized clinical trial was conducted from September 2016 to October 2018, with a 6-month follow-up at 3 referral hospitals in France. Adult patients who met eligibility criteria and underwent total thyroidectomy were randomized. The exclusion criteria were preexisting parathyroid diseases.Use of intraoperative NIRAF imaging system during total thyroidectomy.The primary outcome was the rate of postoperative hypocalcemia (a corrected calcium <8.0 mg/dL [to convert to mmol/L, multiply by 0.25] at postoperative day 1 or 2). The main secondary outcomes were the rates of parathyroid gland autotransplantation and inadvertent parathyroid gland resection.A total of 245 of 529 eligible patients underwent randomization. Overall, 241 patients were analyzed for the primary outcome (mean [SD] age, 53.6 [13.6] years; 191 women [79.3%]): 121 who underwent NIRAF-assisted thyroidectomy and 120 who underwent conventional thyroidectomy (control group). The temporary postoperative hypocalcemia rate was 9.1% (11 of 121 patients) in the NIRAF group and 21.7% (26 of 120 patients) in the control group (between-group difference, 12.6% [95% CI, 5.0%-20.1%]; P = .007). There was no significant difference in permanent hypocalcemia rates (0% in the NIRAF group and 1.6% [2 of 120 patients] in the control group). Multivariate analyses accounting for center and surgeon heterogeneity and adjusting for confounders, found that use of NIRAF reduced the risk of hypocalcemia with an odds ratio of 0.35 (95% CI, 0.15-0.83; P = .02). Analysis of secondary outcomes showed that fewer patients experienced parathyroid autotransplantation in the NIRAF group than in the control group: respectively, 4 patients (3.3% [95% CI, 0.1%-6.6%) vs 16 patients (13.3% [95% CI, 7.3%-19.4%]; P = .009). The number of inadvertently resected parathyroid glands was significantly lower in the NIRAF group than in the control group: 3 patients (2.5% [95% CI, 0.0%-5.2%]) vs 14 patients (11.7% [95% CI, 5.9%-17.4%], respectively; P = .006).The use of NIRAF for the identification of the parathyroid glands may help improve the early postoperative hypocalcemia rate significantly and increase parathyroid preservation after total thyroidectomy.ClinicalTrials.gov Identifier: NCT02892253.
[19]
Takahashi T, Yamazaki K, Ota H, et al. Near-infrared fluorescence imaging in the identification of parathyroid glands in thyroidectomy[J]. Laryngoscope, 2021, 131(5):1188-1193.DOI:10.1002/lary.29163.
To assess the ability of near‐infrared fluorescence imaging (NIFI) to identify parathyroid glands (PGs) among histologically proven PG/non‐PG specimens compared with a surgeon's visual acumen, and to determine NIFI sensitivity in detecting incidentally resected PGs from thyroidectomy specimens, compared to the surgeon's visual inspection.
[20]
Barbieri D, Indelicato P, Vinciguerra A, et al. The impact of near-infrared autofluorescence on postoperative hypoparathyroidism during total thyroidectomy: A case-control study[J]. Endocrine, 2023, 79(2):392-399.DOI:10.1007/s12020-022-03222-5.
[21]
Pastoricchio M, Bernardi S, Bortul M, et al. Autofluorescence of parathyroid glands during endocrine surgery with minimally invasive technique[J]. J Endocrinol Invest, 2022, 45(7):1393-1403.DOI:10.1007/s40618-022-01774-x.
Accidental injury to the parathyroid glands (PTGs) is common during thyroid and parathyroid surgery. To overcome the limitation of naked eye in identifying the PTGs, intraoperative autofluorescence imaging has been embraced by an increasing number of surgeons. The aim of our study was to describe the technique and assess its utility in clinical practice.Near-infrared (NIR) autofluorescence imaging was carried out during open parathyroid and thyroid surgery in 25 patients (NIR group), while other 26 patients underwent traditional PTG detection based on naked eye alone (NO-NIR group). Primary variables assessed for correlation between traditional approach and autofluorescence were number of PTGs identified and incidence of postoperative hypoparathyroidism (hypoPT).81.9% of PTGs were detected by means of fluorescence imaging and 74.5% with visual inspection alone, with an average of 2.72 PTGs visualized per patient using NIR imaging versus approximately 2.4 per patient using naked eye (p = 0.38). Considering only the more complex total thyroidectomies (TTs), the difference was almost statistically significant (p = 0.06). Although not statistically significant, the observed postoperative hypoPT rate was lower in the NIR group.Despite the limitations and technical aspects still to be investigated, fluorescence seems to reduce this complication rate by improving the intraoperative detection of the PTGs.© 2022. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).
[22]
Takeuchi M, Takahashi T, Shodo R, et al. Comparison of autofluorescence with near-infrared fluorescence imaging between primary and secondary hyperparathyroidism[J]. Laryngoscope, 2021, 131(6):E2097-E2104.DOI:10.1002/lary.29310.
[23]
Berber E, Akbulut S, Avci S, et al. Comparison of parathyroid autofluorescence signals in different types of hyperparathyroidism[J]. World J Surg, 2022, 46(4):807-812.DOI:10.1007/s00268-021-06422-8.
There are scant data in the literature regarding whether parathyroid autofluorescence (AF) signal patterns vary based on the etiology of hyperparathyroidism. The aim of this study was to compare AF signals of parathyroid glands across different etiologies of hyperparathyroidism.As a prospective institutional review board-approved study between 2016 and 2019, AF intensities and heterogeneity indexes (HIs) of parathyroid glands in patients who underwent parathyroidectomy using AF were calculated and compared using Chi-square, Kruskal Wallis, Mann Whitney U, and logistic regression tests.Of the total of 183 patients, 127 patients had sporadic classic primary hyperparathyroidism, 30 patients had sporadic normohormonal primary hyperparathyroidism, 10 patients had sporadic normocalcemic primary hyperparathyroidism, 12 patients had tertiary hyperparathyroidism, and 4 patients had familial primary hyperparathyroidism related to multiple endocrine neoplasia (MEN) 2A. There were no statistical differences in AF signals of abnormal parathyroid glands in classic, normohormonal or normocalcemic sporadic hyperparathyroidism. Parathyroid glands in patients with tertiary hyperparathyroidism were similar in intensity, but more homogenous compared to those in sporadic primary hyperparathyroidism.The pattern of AF exhibited by abnormal parathyroid glands was similar across different spectrums of primary hyperparathyroidism, in accordance with observations in the literature. However, parathyroid glands in tertiary hyperparathyroidism were more homogeneous, despite exhibiting a similar intensity of AF compared to those in sporadic primary hyperparathyroidism. These differences should be kept in mind when using the AF pattern as an adjunct to visual assessment in parathyroid exploration.© 2021. The Author(s) under exclusive licence to Société Internationale de Chirurgie.
[24]
Merrill AL, Sims SS, Dedhia PH, et al. Near-infrared autofluorescence features of parathyroid carcinoma[J]. J Endocr Soc, 2022, 6(8):bvac090.DOI:10.1210/jendso/bvac090.
[25]
Lang BH, Wong CK, Hung HT, et al. Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy[J]. Surgery, 2017, 161(1):87-95.DOI:10.1016/j.surg.2016.03.037.
[26]
Ladurner R, Sommerey S, Arabi NA, et al. Intraoperative near-infrared autofluorescence imaging of parathyroid glands[J]. Surg Endosc, 2017, 31(8):3140-3145.DOI:10.1007/s00464-016-5338-3.
To identify parathyroid glands intraoperatively by exposing their autofluorescence using near-infrared light.Fluorescence imaging was carried out during minimally invasive and open parathyroid and thyroid surgery. After identification, the parathyroid glands as well as the surrounding tissue were exposed to near-infrared (NIR) light with a wavelength of 690-770 nm using a modified Karl Storz near-infrared/indocyanine green (NIR/ICG) endoscopic system. Parathyroid tissue was expected to show near-infrared autofluorescence, captured in the blue channel of the camera. Whenever possible the visual identification of parathyroid tissue was confirmed histologically.In preliminary investigations, using the original NIR/ICG endoscopic system we noticed considerable interference of light in the blue channel overlying the autofluorescence. Therefore, we modified the light source by interposing additional filters. In a second series, we investigated 35 parathyroid glands from 25 patients. Twenty-seven glands were identified correctly based on NIR autofluorescence. Regarding the extent of autofluorescence, there were no noticeable differences between parathyroid adenomas, hyperplasia and normal parathyroid glands. In contrast, thyroid tissue, lymph nodes and adipose tissue revealed no substantial autofluorescence.Parathyroid tissue is characterized by showing autofluorescence in the near-infrared spectrum. This effect can be used to distinguish parathyroid glands from other cervical tissue entities.
[27]
Mannoh EA, Thomas G, Solórzano CC, et al. Intraoperative assessment of parathyroid viability using laser speckle contrast imaging[J]. Sci Rep, 2017, 7(1):14798.DOI:10.1038/s41598-017-14941-5.
Post-surgical hypoparathyroidism and hypocalcemia are known to occur after nearly 50% of all thyroid surgeries as a result of accidental disruption of blood supply to healthy parathyroid glands, which are responsible for regulating calcium. However, there are currently no clinical methods for accurately identifying compromised glands and the surgeon relies on visual assessment alone to determine if any gland(s) should be excised and auto-transplanted. Here, we present Laser Speckle Contrast Imaging (LSCI) for real-time assessment of parathyroid viability. Taking an experienced surgeon's visual assessment as the gold standard, LSCI can be used to distinguish between well vascularized (n = 32) and compromised (n = 27) parathyroid glands during thyroid surgery with an accuracy of 91.5%. Ability to detect vascular compromise with LSCI was validated in parathyroidectomies. Results showed that this technique is able to detect parathyroid gland devascularization before it is visually apparent to the surgeon. Measurements can be performed in real-time and without the need to turn off operating room lights. LSCI shows promise as a real-time, contrast-free, objective method for helping reduce hypoparathyroidism after thyroid surgery.
[28]
Mannoh EA, Thomas G, Baregamian N, et al. Assessing intraoperative laser speckle contrast imaging of parathyroid glands in relation to total thyroidectomy patient outcomes[J]. Thyroid, 2021, 31(10):1558-1565.DOI:10.1089/thy.2021.0093.
[29]
Mannoh EA, Parker LB, Thomas G, et al. Development of an imaging device for label-free parathyroid gland identification and vascularity assessment[J]. J Biophotonics, 2021, 14(6):e202100008.DOI:10.1002/jbio.202100008.
During thyroid surgeries, it is important for surgeons to accurately identify healthy parathyroid glands and assess their vascularity to preserve their function postoperatively, thus preventing hypoparathyroidism and hypocalcemia. Near infrared autofluorescence detection enables parathyroid identification, while laser speckle contrast imaging allows assessment of parathyroid vascularity. Here, we present an imaging system combining the two techniques to perform both functions, simultaneously and label‐free. An algorithm to automate the segmentation of a parathyroid gland in the fluorescence image to determine its average speckle contrast is also presented, reducing a barrier to clinical translation. Results from imaging ex vivo tissue samples show that the algorithm is equivalent to manual segmentation. Intraoperative images from representative procedures are presented showing successful implementation of the device to identify and assess vascularity of healthy and diseased parathyroid glands.
[30]
Oh E, Lee HC, Kim Y, et al. A pilot feasibility study to assess vascularity and perfusion of parathyroid glands using a portable hand-held imager[J]. Lasers Surg Med, 2022, 54(3):399-406.DOI:10.1002/lsm.23478.
Intraoperative localization and preservation of parathyroid glands (PGs) are challenging during thyroid surgery. A new noninvasive technique of combined near‐infrared PG autofluorescence detection and dye‐free imaging angiography that allows intraoperative feedback has recently been introduced. The objective of this study was to evaluate this technique in real‐time.
[31]
Oh E, Kim Y, Ning B, et al. Development of a non-invasive,dual-sensor handheld imager for intraoperative preservation of parathyroid glands[J]. Annu Int Conf IEEE Eng Med Biol Soc, 2021, 2021:7408-7411.DOI:10.1109/EMBC46164.2021.9630503.
[32]
Lin H, Cheng J. Computational coherent Raman scattering imaging: Breaking physical barriers by fusion of advanced instrumentation and data science[J]. eLight, 2023, 3(6):1-19. DOI:10.1186/s43593-023-00062-4.
[33]
Avci SN, Isiktas G, Berber E. A visual deep learning model to localize parathyroid-specific autofluorescence on near-infrared imaging: Localization of parathyroid autofluorescence with deep learning[J]. Ann Surg Oncol,2022 Mar 28.Online ahead of print. DOI:10.1245/s10434-022-11632-y.
[34]
Avci SN, Isiktas G, Ergun O, et al. A visual deep learning model to predict abnormal versus normal parathyroid glands using intraoperative autofluorescence signals[J]. J Surg Oncol, 2022, 126(2):263-267.DOI:10.1002/jso.26884.
Previous work demonstrated that abnormal versus normal parathyroid glands (PGs) exhibit different patterns of autofluorescence, with former appearing darker and more heterogenous. Our objective was to develop a visual artificial intelligence model using intraoperative autofluorescence signals to predict whether a PG is abnormal (hypersecreting and/or hypercellular) or normal before excision during surgical exploration for primary hyperparathyroidism.
[35]
Kim Y, Kim SW, Lee KD, et al. Real-time localization of the parathyroid gland in surgical field using Raspberry Pi during thyroidectomy: A preliminary report[J]. Biomed Opt Express, 2018, 9(7):3391-3398.DOI:10.1364/BOE.9.003391.
We created an auto-para viewer, an autofluorescence imaging device, to localize the parathyroid glands during thyroidectomy using an inexpensive Raspberry Pi. A special emission filter in the auto-para viewer was designed to pass 1/100 of visible light and nearly all infrared light longer than 808 nm. With this emission filter, we simultaneously acquired an autofluorescence image of the parathyroid and a visible light image of the surrounding surgical field. The auto-para viewer displayed four times brighter autofluorescence of the parathyroid glands compared to the background tissues without operating room light. Additionally, it showed two times brighter autofluorescence than the background tissues simultaneously showing the surgical field illuminated by the visible light from the operating room light. The NOIR camera, using the auto-para viewer, could reduce the camera's exposure time so the parathyroid glands to be viewed in real-time, which is expected to prevent unintentional damage to the parathyroid gland during thyroidectomy.
[36]
McWade MA, Thomas G, Nguyen JQ, et al. Enhancing parathyroid gland visualization using a near infrared fluorescence-based overlay imaging system[J]. J Am Coll Surg, 2019, 228(5):730-743.DOI:10.1016/j.jamcollsurg.2019.01.017.
[37]
Akbulut S, Erten O, Gokceimam M, et al. Intraoperative near-infrared imaging of parathyroid glands: A comparison of first- and second-generation technologies[J]. J Surg Oncol, 2021, 123(4):866-871.DOI:10.1002/jso.26336.
Intraoperative near‐infrared imaging (NIFI) of parathyroid glands (PG) by first‐generation technology had limited image quality and depth penetration. Second‐generation NIFI has recently been introduced. Our aim was to compare (1) capability to detect PG and (2) image quality between older and newer technologies.
[38]
Chen W, Ma X, Shao P, et al. Autofluorescence detection and co-axial projection for intraoperative localization of parathyroid gland[J]. Biomed Eng Online, 2022, 21(1):37.DOI:10.1186/s12938-022-01004-8.
Near-infrared (NIR) autofluorescence detection is an effective method for identifying parathyroid glands (PGs) in thyroidectomy or parathyroidectomy. Fiber optical probes provide quantitative autofluorescence measurements for PG detection owing to its high sensitivity and high excitation light cut-off efficiency at a fixed detection distance. However, an optical fiber probe lacks the imaging capability and cannot map the autofluorescence distribution on top of normal tissue background. Therefore, there is a need for intraoperative mapping of PGs with high sensitivity and imaging resolution.We have developed a fluorescence scanning and projection (FSP) system that combines a scanning probe and a co-axial projector for intraoperative localization and in situ display of PGs. Some of the key performance characteristics, including spatial resolution and sensitivity for detection, spatial resolution for imaging, dynamic time latency, and PG localization capability, are characterized and verified by benchtop experiments. Clinical utility of the system is simulated by a fluorescence-guided PG localization surgery on a tissue-simulating phantom and validated in an ex vivo experiment.The system is able to detect indocyanine green (ICG) solution of 5 pM at a high signal-to-noise ratio (SNR). Additionally, it has a maximal projection error of 0.92 mm, an averaged projection error of 0.5 ± 0.23 mm, and an imaging resolution of 748 μm at a working distance ranging from 35 to 55 cm. The dynamic testing yields a short latency of 153 ± 54 ms, allowing for intraoperative scanning on target tissue during a surgical intervention. The simulated fluorescence-guided PG localization surgery has validated the system's capability to locate PG phantom with operating room ambient light interference. The simulation experiment on the PG phantom yields a position detection bias of 0.36 ± 0.17 mm, and an area intersection over unit (IoU) of 76.6% ± 6.4%. Fluorescence intensity attenuates exponentially with the thickness of covered tissue over the PG phantom, indicating the need to remove surrounding tissue in order to reveal the weak autofluorescence signal from PGs. The ex vivo experiment demonstrates the technical feasibility of the FSP system for intraoperative PG localization with accuracy.We have developed a novel probe-based imaging and navigation system with high sensitivity for fluorescence detection, capability for fluorescence image reconstruction, multimodal image fusion and in situ PG display function. Our studies have demonstrated its clinical potential for intraoperative localization and in situ display of PGs in thyroidectomy or parathyroidectomy.© 2022. The Author(s).
[39]
Duan Y, Wang CL, Geng XH, et al. A highly sensitive optical fiber based near-infrared laser induced fluorescence detector(LIF)for parathyroid gland detection[J]. Sens Actuators B: Chem, 2022, 364:131879. DOI:10.1016/j.snb.2022.131879.
[40]
Maktabi M, Köhler H, Ivanova M, et al. Classification of hyperspectral endocrine tissue images using support vector machines[J]. Int J Med Robot, 2020, 16(5):1-10.DOI:10.1002/rcs.2121.
Thyroidectomy is one of the most commonly performed surgical procedures. The region of the neck has a very complex structural organization. It would be beneficial to introduce a tool that can assist the surgeon in tissue discrimination during the procedure. One such solution is the noninvasive and contactless technique, called hyperspectral imaging (HSI).
[41]
Marsden M, Weaver SS, Marcu L, et al. Intraoperative mapping of parathyroid glands using fluorescence lifetime imaging[J]. J Surg Res, 2021, 265:42-48.DOI:10.1016/j.jss.2021.03.023.
Hypoparathyroidism is a common complication following thyroidectomy. There is a need for technology to aid surgeons in identifying the parathyroid glands. In contrast to near infrared technologies, fluorescence lifetime imaging (FLIm) is not affected by ambient light and may be valuable in identifying parathyroid tissue, but has never been evaluated in this capacity.We used FLIm to measure the UV induced (355 nm) time-resolved autofluorescence signatures (average lifetimes in 3 spectral emission channels) of thyroid, parathyroid, lymphoid and adipose tissue in 21 patients undergoing thyroid and parathyroid surgery. The Mann-Whitney U test was used to assess the ability of FLIm to discriminate normocellular parathyroid from each of the other tissues. Various machine learning classifiers (random forests, neural network, support vector machine) were then evaluated to recognize parathyroid through a leave-one-out cross-validation.Statistically significant differences in average lifetime were observed between parathyroid and each of the other tissue types in spectral channels 2 and 3 respectively. The largest change was observed between adipose tissue and parathyroid (P < 0.001), while less pronounced but still significant changes were observed when comparing parathyroid with lymphoid tissue (P < 0.05) and thyroid (P < 0.01). A random forest classifier trained on average lifetimes was found to detect parathyroid tissue with 100% sensitivity and 93% specificity at the acquisition run level.We found that FLIm derived parameters can distinguish the parathyroid glands and other adjacent tissue types and has promise in scanning the surgical field to identify parathyroid tissue in real-time.Published by Elsevier Inc.
[42]
Rubinstein M, Hu AC, Chung PS, et al. Intraoperative use of optical coherence tomography to differentiate normal and diseased thyroid and parathyroid tissues from lymph node and fat[J]. Lasers Med Sci, 2021, 36(2):269-278.DOI:10.1007/s10103-020-03024-z.

基金

国家自然科学基金青年科学基金项目(62004070)
国家级大学生创新创业项目(202310570015)
广东省省级临床重点专科建设项目(粤卫医函[2023]2号)
教育部产学合作协同育人项目(230902331264216)
广州市教育局高校科研面上科研项目(2024312260)

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