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Emerging Imaging Technologies for Parathyroid Gland Identification and Vascular Assessment in Thyroid SurgeryA Review From the American Head and Neck Society Endocrine Surgery Section

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Importance  Identification and preservation of parathyroid glands (PGs) remain challenging despite advances in surgical techniques. Considerable morbidity and even mortality result from hypoparathyroidism caused by devascularization or inadvertent removal of PGs. Emerging imaging technologies hold promise to improve identification and preservation of PGs during thyroid surgery.

Observation  This narrative review (1) comprehensively reviews PG identification and vascular assessment using near-infrared autofluorescence (NIRAF)—both label free and in combination with indocyanine green—based on a comprehensive literature review and (2) offers a manual for possible implementation these emerging technologies in thyroid surgery.

Conclusions and Relevance  Emerging technologies hold promise to improve PG identification and preservation during thyroidectomy. Future research should address variables affecting the degree of fluorescence in NIRAF, standardization of signal quantification, definitions and standardization of parameters of indocyanine green injection that correlate with postoperative PG function, the financial effect of these emerging technologies on near-term and longer-term costs, the adoption learning curve and effect on surgical training, and long-term outcomes of key quality metrics in adequately powered randomized clinical trials evaluating PG preservation.

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Article Information

Accepted for Publication: November 15, 2022.

Published Online: January 12, 2023. doi:10.1001/jamaoto.2022.4421

Corresponding Author: Amanda L. Silver Karcioglu, MD, Division of Otolaryngology–Head and Neck Surgery, Department of Surgery, NorthShore University HealthSystem, 9669 Kenton Ave, Ste 206, Skokie, IL 60076 (amandalsilver@gmail.com).

Conflict of Interest Disclosures: Dr Triponez reported personal fees (consulting fees paid to institution) from Medtronic, Fluoptics, and Stryker during the conduct of the study. Dr Almquist reported grants from IPSEN and Medtronic outside the submitted work. Dr Benmiloud reported personal fees from Fluoptics (consulting) outside the submitted work. Dr Berber reported personal fees from Aesculap, Medtronic, Johnson & Johnson, and Intuitive outside the submitted work. Dr Cha reported grants from Children’s National Hospital (NIH 2 R44 EB030874-02) during the conduct of the study; grants from Optosurgical (NIH 2 R44 EB030874-02) outside the submitted work; a patent for US17/854,084 pending; and is the founder and scientific advisor for Optosurgical and has a financial interest with the company. Dr Mahadevan-Jansen reported grants from Medtronic (in-kind) during the conduct of the study; in addition, Dr Mahadevan-Jansen has a patent for NIRAF for parathyroid detection that is licensed by her institution to Medtronic. Dr Mannstadt reported grants from Takeda and Calcilytix and personal fees from Amolyt outside the submitted work. Dr Singer is a consultant for Medtronic outside the submitted work. Dr Thomas reported affiliation with Vanderbilt University, which has a licensing agreement for PTeye with Ai Biomed (now officially acquired by Medtronic). Dr Randolph reported grants (research support) from Fluoptics, Medtronic, and Eisai during the conduct of the study; Dr Randolph also reported serving as the president of the International Thyroid Oncology Group and the World Congress on Thyroid Cancer, chair of the Administrative Division of the American Head and Neck Society, and American College of Surgeons Otolaryngology Governor. No other disclosures were reported.

Additional Contributions: We thank Garyfallia Pagonis, BFA, BS (Massachusetts Eye and Ear Infirmary), for her assistance in the preparation of tables and figures, as well as Louise Collins, DVM, MSLIS (Massachusetts Eye and Ear Infirmary), for her assistance with building the search strategy of the literature review. They were not compensated for their contributions. Dr Randolph would like to acknowledge the ongoing support of Mike and Eliz Ruane and of John and Claire Bertucci for his research efforts.

Disclaimer: Dr Davies is an Associate Editor of JAMA Otolaryngology–Head & Neck Surgery but was not involved in any of the decisions regarding review of the manuscript or its acceptance.

Brandi  ML , Bilezikian  JP , Shoback  D ,  et al.  Management of hypoparathyroidism: summary statement and guidelines.   J Clin Endocrinol Metab. 2016;101(6):2273-2283. doi:10.1210/jc.2015-3907PubMedGoogle ScholarCrossref
Annebäck  M , Hedberg  J , Almquist  M , Stålberg  P , Norlén  O .  Risk of permanent hypoparathyroidism after total thyroidectomy for benign disease: a nationwide population-based cohort study from Sweden.   Ann Surg. 2021;274(6):e1202-e1208. doi:10.1097/SLA.0000000000003800PubMedGoogle ScholarCrossref
Almquist  M , Ivarsson  K , Nordenström  E , Bergenfelz  A .  Mortality in patients with permanent hypoparathyroidism after total thyroidectomy.   Br J Surg. 2018;105(10):1313-1318. doi:10.1002/bjs.10843PubMedGoogle ScholarCrossref
Demarchi  MS , Seeliger  B , Lifante  JC , Alesina  PF , Triponez  F .  Fluorescence image-guided surgery for thyroid cancer: utility for preventing hypoparathyroidism.   Cancers (Basel). 2021;13(15):3792. doi:10.3390/cancers13153792PubMedGoogle ScholarCrossref
Edafe  O , Sandler  LM , Beasley  N , Balasubramanian  SP .  Systematic review of incidence, risk factors, prevention and treatment of post-laryngectomy hypoparathyroidism.   Eur Arch Otorhinolaryngol. 2021;278(5):1337-1344. doi:10.1007/s00405-020-06213-2PubMedGoogle ScholarCrossref
Bergenfelz  A , Nordenström  E , Almquist  M .  Morbidity in patients with permanent hypoparathyroidism after total thyroidectomy.   Surgery. 2020;167(1):124-128. doi:10.1016/j.surg.2019.06.056PubMedGoogle ScholarCrossref
Underbjerg  L , Sikjaer  T , Mosekilde  L , Rejnmark  L .  Cardiovascular and renal complications to postsurgical hypoparathyroidism: a Danish nationwide controlled historic follow-up study.   J Bone Miner Res. 2013;28(11):2277-2285. doi:10.1002/jbmr.1979PubMedGoogle ScholarCrossref
Gosmanova  EO , Houillier  P , Rejnmark  L , Marelli  C , Bilezikian  JP .  Renal complications in patients with chronic hypoparathyroidism on conventional therapy: a systematic literature review: renal disease in chronic hypoparathyroidism.   Rev Endocr Metab Disord. 2021;22(2):297-316. doi:10.1007/s11154-020-09613-1PubMedGoogle ScholarCrossref
Stack  BCJ  Jr , Bimston  DN , Bodenner  DL ,  et al.  American Association of Clinical Endocrinologists and American College of Endocrinology disease state clinical review: postoperative hypoparathyroidism—definitions and management.   Endocr Pract. 2015;21(6):674-685. doi:10.4158/EP14462.DSCPubMedGoogle ScholarCrossref
Orloff  LA , Wiseman  SM , Bernet  VJ ,  et al.  American Thyroid Association statement on postoperative hypoparathyroidism: diagnosis, prevention, and management in adults.   Thyroid. 2018;28(7):830-841. doi:10.1089/thy.2017.0309PubMedGoogle ScholarCrossref
Hartogsohn  EAR , Khan  AA , Kjaersulf  LU , Sikjaer  T , Hussain  S , Rejnmark  L .  Changes in treatment needs of hypoparathyroidism during pregnancy and lactation: a case series.   Clin Endocrinol (Oxf). 2020;93(3):261-268. doi:10.1111/cen.14212PubMedGoogle ScholarCrossref
Corbeels  K , Steenackers  N , Lannoo  M ,  et al.  Reversal of Roux-en-Y gastric bypass fails to facilitate the management of recalcitrant hypocalcaemia caused by primary hypoparathyroidism.   Obes Surg. 2020;30(12):5150-5152. doi:10.1007/s11695-020-04903-8PubMedGoogle ScholarCrossref
Zaarour  M , Zaharia  R , Bretault  M ,  et al.  Laparoscopic revision of bariatric surgeries in two patients with severe resistant hypocalcemia after endocrine cervical surgery.   Obes Surg. 2020;30(4):1616-1620. doi:10.1007/s11695-019-04132-8PubMedGoogle ScholarCrossref
US Food and Drug Administration. FDA permits marketing of two devices that detect parathyroid tissue in real-time during surgery. News release. November 2, 2018. Accessed November 30, 2018. https://www.fda.gov/news-events/press-announcements/fda-permits-marketing-two-devices-detect-parathyroid-tissue-real-time-during-surgery
De Leeuw  F , Breuskin  I , Abbaci  M ,  et al.  Intraoperative near-infrared imaging for parathyroid gland identification by auto-fluorescence: a feasibility study.   World J Surg. 2016;40(9):2131-2138. doi:10.1007/s00268-016-3571-5PubMedGoogle ScholarCrossref
Kahramangil  B , Dip  F , Benmiloud  F ,  et al.  Detection of parathyroid autofluorescence using near-infrared imaging: a multicenter analysis of concordance between different surgeons.   Ann Surg Oncol. 2018;25(4):957-962. doi:10.1245/s10434-018-6364-2PubMedGoogle ScholarCrossref
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 Am Coll Surg. 2019;228(5):744-751. doi:10.1016/j.jamcollsurg.2018.12.044PubMedGoogle ScholarCrossref
McWade  MA , Sanders  ME , Broome  JT , Solórzano  CC , Mahadevan-Jansen  A .  Establishing the clinical utility of autofluorescence spectroscopy for parathyroid detection.   Surgery. 2016;159(1):193-202. doi:10.1016/j.surg.2015.06.047PubMedGoogle ScholarCrossref
Thomas  G , Squires  MH , Metcalf  T , Mahadevan-Jansen  A , Phay  JE .  Imaging or fiber probe-based approach? assessing different methods to detect near infrared autofluorescence for intraoperative parathyroid identification.   J Am Coll Surg. 2019;229(6):596-608.e3. doi:10.1016/j.jamcollsurg.2019.09.003PubMedGoogle ScholarCrossref
Thomas  G , McWade  MA , Nguyen  JQ ,  et al.  Innovative surgical guidance for label-free real-time parathyroid identification.   Surgery. 2019;165(1):114-123. doi:10.1016/j.surg.2018.04.079PubMedGoogle ScholarCrossref
Ladurner  R , Al Arabi  N , Guendogar  U , Hallfeldt  K , Stepp  H , Gallwas  J .  Near-infrared autofluorescence imaging to detect parathyroid glands in thyroid surgery.   Ann R Coll Surg Engl. 2018;100(1):33-36. doi:10.1308/rcsann.2017.0102PubMedGoogle ScholarCrossref
Kahramangil  B , Berber  E .  Comparison of indocyanine green fluorescence and parathyroid autofluorescence imaging in the identification of parathyroid glands during thyroidectomy.   Gland Surg. 2017;6(6):644-648. doi:10.21037/gs.2017.09.04PubMedGoogle ScholarCrossref
Kim  SW , Song  SH , Lee  HS ,  et al.  Intraoperative real-time localization of normal parathyroid glands with autofluorescence imaging.   J Clin Endocrinol Metab. 2016;101(12):4646-4652. doi:10.1210/jc.2016-2558PubMedGoogle ScholarCrossref
Kose  E , Rudin  AV , Kahramangil  B ,  et al.  Autofluorescence imaging of parathyroid glands: an assessment of potential indications.   Surgery. 2020;167(1):173-179. doi:10.1016/j.surg.2019.04.072PubMedGoogle ScholarCrossref
DiMarco  A , Chotalia  R , Bloxham  R , McIntyre  C , Tolley  N , Palazzo  FF .  Autofluorescence in parathyroidectomy: signal intensity correlates with serum calcium and parathyroid hormone but routine clinical use is not justified.   World J Surg. 2019;43(6):1532-1537. doi:10.1007/s00268-019-04929-9PubMedGoogle ScholarCrossref
McWade  MA , Paras  C , White  LM ,  et al.  Label-free intraoperative parathyroid localization with near-infrared autofluorescence imaging.   J Clin Endocrinol Metab. 2014;99(12):4574-4580. doi:10.1210/jc.2014-2503PubMedGoogle ScholarCrossref
Kim  SW , Lee  HS , Ahn  YC ,  et al.  Near-infrared autofluorescence image-guided parathyroid gland mapping in thyroidectomy.   J Am Coll Surg. 2018;226(2):165-172. doi:10.1016/j.jamcollsurg.2017.10.015PubMedGoogle ScholarCrossref
Kim  Y , Kim  SW , Lee  KD , Ahn  YC .  Video-assisted parathyroid gland mapping with autofocusing.   J Biophotonics. 2019;12(12):e201900017. doi:10.1002/jbio.201900017PubMedGoogle ScholarCrossref
Wang  B , Zhu  CR , Liu  H , Yao  XM , Wu  J .  The accuracy of near infrared autofluorescence in identifying parathyroid gland during thyroid and parathyroid surgery: a meta-analysis.   Front Endocrinol (Lausanne). 2021;12:701253. doi:10.3389/fendo.2021.701253PubMedGoogle ScholarCrossref
Kim  DH , Lee  S , Jung  J , Kim  S , Kim  SW , Hwang  SH .  Near-infrared autofluorescence-based parathyroid glands identification in the thyroidectomy or parathyroidectomy: a systematic review and meta-analysis.   Langenbecks Arch Surg. 2022;407(2):491-499. doi:10.1007/s00423-021-02269-8PubMedGoogle ScholarCrossref
Ladurner  R , Sommerey  S , Arabi  NA , Hallfeldt  KKJ , Stepp  H , Gallwas  JKS .  Intraoperative near-infrared autofluorescence imaging of parathyroid glands.   Surg Endosc. 2017;31(8):3140-3145. doi:10.1007/s00464-016-5338-3PubMedGoogle ScholarCrossref
Falco  J , Dip  F , Quadri  P , de la Fuente  M , Prunello  M , Rosenthal  RJ .  Increased identification of parathyroid glands using near infrared light during thyroid and parathyroid surgery.   Surg Endosc. 2017;31(9):3737-3742. doi:10.1007/s00464-017-5424-1PubMedGoogle ScholarCrossref
DiMarco  A , Chotalia  R , Bloxham  R , McIntyre  C , Tolley  N , Palazzo  FF .  Does fluoroscopy prevent inadvertent parathyroidectomy in thyroid surgery?   Ann R Coll Surg Engl. 2019;101(7):508-513. doi:10.1308/rcsann.2019.0065PubMedGoogle ScholarCrossref
Kim  YS , Erten  O , Kahramangil  B , Aydin  H , Donmez  M , Berber  E .  The impact of near infrared fluorescence imaging on parathyroid function after total thyroidectomy.   J Surg Oncol. 2020;122(5):973-979. doi:10.1002/jso.26098PubMedGoogle ScholarCrossref
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.   JAMA Surg. 2020;155(2):106-112. doi:10.1001/jamasurg.2019.4613PubMedGoogle ScholarCrossref
Van Slycke  S , Van Den Heede  K , Brusselaers  N , Vermeersch  H .  Feasibility of autofluorescence for parathyroid glands during thyroid surgery and the risk of hypocalcemia: first results in Belgium and review of the literature.   Surg Innov. 2021;28(4):409-418. doi:10.1177/1553350620980263PubMedGoogle ScholarCrossref
Papavramidis  TS , Chorti  A , Tzikos  G ,  et al.  The effect of intraoperative autofluorescence monitoring on unintentional parathyroid gland excision rates and postoperative PTH concentrations-a single-blind randomized-controlled trial.   Endocrine. 2021;72(2):546-552. doi:10.1007/s12020-020-02599-5PubMedGoogle ScholarCrossref
Solórzano  CC , Thomas  G , Baregamian  N , Mahadevan-Jansen  A .  Detecting the near infrared autofluorescence of the human parathyroid: hype or opportunity?   Ann Surg. 2020;272(6):973-985. doi:10.1097/SLA.0000000000003700PubMedGoogle ScholarCrossref
Alesina  PF , Meier  B , Hinrichs  J , Mohmand  W , Walz  MK .  Enhanced visualization of parathyroid glands during video-assisted neck surgery.   Langenbecks Arch Surg. 2018;403(3):395-401. doi:10.1007/s00423-018-1665-2PubMedGoogle ScholarCrossref
Yu  HW , Chung  JW , Yi  JW ,  et al.  Intraoperative localization of the parathyroid glands with indocyanine green and Firefly(R) technology during BABA robotic thyroidectomy.   Surg Endosc. 2017;31(7):3020-3027. doi:10.1007/s00464-016-5330-yPubMedGoogle ScholarCrossref
Kahramangil  B , Berber  E .  The use of near-infrared fluorescence imaging in endocrine surgical procedures.   J Surg Oncol. 2017;115(7):848-855. doi:10.1002/jso.24583PubMedGoogle ScholarCrossref
Spartalis  E , Ntokos  G , Georgiou  K ,  et al.  Intraoperative indocyanine green (ICG) angiography for the identification of the parathyroid glands: current evidence and future perspectives.   In Vivo. 2020;34(1):23-32. doi:10.21873/invivo.11741PubMedGoogle ScholarCrossref
Abbaci  M , De Leeuw  F , Breuskin  I ,  et al.  Parathyroid gland management using optical technologies during thyroidectomy or parathyroidectomy: a systematic review.   Oral Oncol. 2018;87:186-196. doi:10.1016/j.oraloncology.2018.11.011PubMedGoogle ScholarCrossref
Goldenberg  D , Ferris  RL , Shindo  ML , Shaha  A , Stack  B , Tufano  RP .  Thyroidectomy in patients who have undergone gastric bypass surgery.   Head Neck. 2018;40(6):1237-1244. doi:10.1002/hed.25098PubMedGoogle ScholarCrossref
Vidal Fortuny  J , Sadowski  SM , Belfontali  V ,  et al.  Randomized clinical trial of intraoperative parathyroid gland angiography with indocyanine green fluorescence predicting parathyroid function after thyroid surgery.   Br J Surg. 2018;105(4):350-357. doi:10.1002/bjs.10783PubMedGoogle ScholarCrossref
Vidal Fortuny  J , Belfontali  V , Sadowski  SM , Karenovics  W , Guigard  S , Triponez  F .  Parathyroid gland angiography with indocyanine green fluorescence to predict parathyroid function after thyroid surgery.   Br J Surg. 2016;103(5):537-543. doi:10.1002/bjs.10101PubMedGoogle ScholarCrossref
Zaidi  N , Bucak  E , Yazici  P ,  et al.  The feasibility of indocyanine green fluorescence imaging for identifying and assessing the perfusion of parathyroid glands during total thyroidectomy.   J Surg Oncol. 2016;113(7):775-778. doi:10.1002/jso.24237PubMedGoogle ScholarCrossref
Demarchi  MS , Baccaro  M , Karenovics  W , Bédat  B , Triponez  F .  Is the indocyanine green score an accurate predictor of postoperative parathyroid hormone level?   Surgery. 2022;171(6):1526-1534. doi:10.1016/j.surg.2021.12.036PubMedGoogle ScholarCrossref
Vidal Fortuny  J , Sadowski  SM , Belfontali  V , Karenovics  W , Guigard  S , Triponez  F .  Indocyanine green angiography in subtotal parathyroidectomy: technique for the function of the parathyroid remnant.   J Am Coll Surg. 2016;223(5):e43-e49. doi:10.1016/j.jamcollsurg.2016.08.540PubMedGoogle ScholarCrossref
Lang  BHH , Wong  CKH , Hung  HT , Wong  KP , Mak  KL , Au  KB .  Indocyanine green fluorescence angiography for quantitative evaluation of in situ parathyroid gland perfusion and function after total thyroidectomy.   Surgery. 2017;161(1):87-95. doi:10.1016/j.surg.2016.03.037PubMedGoogle ScholarCrossref
Jin  H , Dong  Q , He  Z , Fan  J , Liao  K , Cui  M .  Research on indocyanine green angiography for predicting postoperative hypoparathyroidism.   Clin Endocrinol (Oxf). 2019;90(3):487-493. doi:10.1111/cen.13925PubMedGoogle ScholarCrossref
van den Bos  J , van Kooten  L , Engelen  SME , Lubbers  T , Stassen  LPS , Bouvy  ND .  Feasibility of indocyanine green fluorescence imaging for intraoperative identification of parathyroid glands during thyroid surgery.   Head Neck. 2019;41(2):340-348. doi:10.1002/hed.25451PubMedGoogle ScholarCrossref
Razavi  AC , Ibraheem  K , Haddad  A ,  et al.  Efficacy of indocyanine green fluorescence in predicting parathyroid vascularization during thyroid surgery.   Head Neck. 2019;41(9):3276-3281. doi:10.1002/hed.25837PubMedGoogle ScholarCrossref
Rudin  AV , McKenzie  TJ , Thompson  GB , Farley  DR , Lyden  ML .  Evaluation of parathyroid glands with indocyanine green fluorescence angiography after thyroidectomy.   World J Surg. 2019;43(6):1538-1543. doi:10.1007/s00268-019-04909-zPubMedGoogle ScholarCrossref
Llorente  PM , Francos Martínez  JM , Barrasa  AG .  Intraoperative parathyroid hormone measurement vs indocyanine green angiography of parathyroid glands in prediction of early postthyroidectomy hypocalcemia.   JAMA Surg. 2020;155(1):84-85. doi:10.1001/jamasurg.2019.3652PubMedGoogle ScholarCrossref
Papavramidis  TS , Anagnostis  P , Chorti  A ,  et al.  Do near-infrared intra-operative findings obtained using indocyanine green correlate with post-thyroidectomy parathyroid function? the Icgpredict study.   Endocr Pract. 2020;26(9):967-973. doi:10.4158/EP-2020-0119PubMedGoogle ScholarCrossref
Barbieri  D , Indelicato  P , Vinciguerra  A ,  et al.  Autofluorescence and indocyanine green in thyroid surgery: a systematic review and meta-analysis.   Laryngoscope. 2021;131(7):1683-1692. doi:10.1002/lary.29297PubMedGoogle ScholarCrossref
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