Use of methylene blue and near-infrared fluorescence in thyroid and parathyroid surgery

Sarah L Hillary,Nicola J Brown,Sabapathy P Balasubramanian,Stephanie Guillermet

doi:10.1007/s00423-017-1641-2

Abstract

PurposeIntraoperative localisation and preservation of parathyroid glands improves outcomes following thyroid and parathyroid surgery. This can be facilitated by fluorescent imaging and methylene blue; a fluorophore is thought to be taken up avidly by parathyroid glands. This preliminary study aims to identify the optimum dose of methylene blue (MB), fluorescent patterns of thyroid and parathyroid glands and develop a protocol for the use of intravenous MB emitted fluorescence to enable parathyroid identification.MethodsThis is a phase 1b, interventional study (NCT02089542) involving 41 patients undergoing thyroid and/or parathyroid surgery. After exposure of the thyroid and/or parathyroid gland(s), intravenous boluses of between 0.05 and 0.5 mg/kg of MB were injected. Fluobeam® (a hand held fluorescence real-time imager) was used to record fluorescence from the operating field prior and up to 10 min following administration.ResultsThe optimum dose of MB to visualise thyroid and parathyroid glands was 0.4 mg/kg body weight. The median time to onset of fluorescence was 23 and 22 s and the median time to peak fluorescence was 41.5 and 40 s, respectively. The peak fluorescence for thyroid and parathyroid glands compared to muscle were 2.6 and 4.3, respectively. Parathyroid auto-fluorescence prior to methylene blue injection was commonly observed.ConclusionsA clinical protocol for detection of fluorescence from MB during thyroid and parathyroid surgery is presented. Parathyroids (especially enlarged glands) fluoresce more intensely than thyroid glands. Auto-fluorescence may aid parathyroid detection, but MB fluorescence is needed to demonstrate viability.

Highlights

Transient and long-term post-surgical hypoparathyroidism due to inadvertent removal, damage or devascularisation of parathyroid glands remains a common problem [1,2,3,4].Sheffield Teaching Hospitals NHS Foundation Trust, c/o Room F25, Royal Hallamshire Hospital, Glossop Road, Sheffield, South Yorkshire S10 2JF, UKDepartment of Oncology and Metabolism, University of Sheffield, Sheffield, UKFluoptics, Grenoble, FranceAccurate identification and differentiation between normal and enlarged parathyroid glands is essential for a good outcome.Parathyroid glands can have a varied position and their small size and soft consistency increases the risk of inaccurate identification and damage at surgery
We have previously investigated the use of methylene blue (MB) and this imaging system in a rabbit model and showed that both thyroid and parathyroid glands fluoresced at low doses (0.025– 3 mg/kg) of MB; the parathyroid glands showed a lower intensity of fluorescence with faster washout when compared to the thyroid gland [24]
The training stage was used to find the approximate dose of MB that would be required by systematically increasing the dose by 0.05 mg/kg until fluorescence was reliably demonstrable in the tissues

Summary

Introduction

Transient and long-term post-surgical hypoparathyroidism due to inadvertent removal, damage or devascularisation of parathyroid glands remains a common problem [1,2,3,4]. Parathyroid glands can have a varied position and their small size and soft consistency increases the risk of inaccurate identification and damage at surgery. These glands may be mistaken for other soft tissues such as lymph nodes or thyroid nodules, or vice versa. Near-infrared fluorescence (NIRF) is one of several novel technologies that may be useful in early identification and preservation of parathyroid glands during surgery. Some emit light outside of the visible spectrum in the near infra-red region (700–900 nm) [5].

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