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. 2014 Jun;36(6):853-8.
doi: 10.1002/hed.23384. Epub 2013 Oct 4.

Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue

Joost R van der Vorst  1 , Boudewijn E Schaafsma, Floris P R Verbeek, Rutger-Jan Swijnenburg, Quirijn R J G Tummers, Merlijn Hutteman, Jaap F Hamming, Job Kievit, John V Frangioni, Cornelis J H van de Velde, Alexander L Vahrmeijer
Affiliations

Intraoperative near-infrared fluorescence imaging of parathyroid adenomas with use of low-dose methylene blue

Joost R van der Vorst et al. Head Neck. 2014 Jun.

Abstract

Background: Intraoperative identification of parathyroid adenomas can be challenging. We hypothesized that low-doses methylene blue (MB) and near-infrared fluorescence (NIRF) imaging could be used to identify parathyroid adenomas intraoperatively.

Methods: MB was injected intravenously after exploration at a dose of 0.5 mg/kg into 12 patients who underwent parathyroid surgery. NIRF imaging was performed using the Mini-FLARE imaging system.

Results: In 10 of 12 patients, histology confirmed a parathyroid adenoma. In 9 of these patients, NIRF could clearly identify the parathyroid adenoma during surgery. Seven of these 9 patients had a positive preoperative (99m) Tc-sestamibi single photon emission CT (SPECT) scan. Importantly, in 2 patients, parathyroid adenomas could be identified only using NIRF.

Conclusion: This is the first study to show that low-dose MB can be used as NIRF tracer for identification of parathyroid adenomas, and suggests a correlation with preoperative (99m) Tc-sestamibi SPECT scanning.

Keywords: hyperparathyroidism; image-guided surgery; methylene blue; near-infrared fluorescence imaging; parathyroid adenoma.

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Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

Joost R. van der Vorst, M.D.: Nothing to declare

Boudewijn E. Schaafsma, M.D.: Nothing to declare

Floris P.R. Verbeek: Nothing to declare

Rutger-Jan Swijnenburg, M.D., Ph.D.: Nothing to declare

Quirijn Tummers, M.D.: Nothing to declare

Merlijn Hutteman, Ph.D.: Nothing to declare

Jaap F. Hamming, M.D., Ph.D.: Nothing to declare

Cornelis J.H. van de Velde, M.D., Ph.D.: Nothing to declare

J. Kievit, M.D., Ph.D.: Nothing to declare

FLARE™ technology is owned by Beth Israel Deaconess Medical Center, a teaching hospital of Harvard Medical School. It has been licensed to the FLARE™ Foundation, a non-profit organization focused on promoting the dissemination of medical imaging technology for research and clinical use. Dr. Frangioni is the founder and chairman of the FLARE™ Foundation. The Beth Israel Deaconess Medical Center will receive royalties for sale of FLARE™ Technology. Dr. Frangioni has elected to surrender post-market royalties to which he would otherwise be entitled as inventor, and has elected to donate pre-market proceeds to the FLARE™ Foundation.

Alexander L. Vahrmeijer, M.D., Ph.D.: Nothing to declare

Figures

Figure 1
Figure 1. Preoperative surgical planning and intraoperative NIR fluorescence-guided resection of a parathyroid adenoma located in the neck
A: 3D SPECT-CT image 2 h postinjection of 99mTc-sestamibi with visualization of a parathyroid adenoma located at the right side of the neck (arrow). B: During minimally-invasive parathyroid surgery, a parathyroid adenoma is identified using NIR fluorescence imaging, 5 and 10 minutes postinjection of 0.5 mg/kg MB. T= thyroid tissue.
Figure 2
Figure 2. Preoperative surgical planning and intraoperative NIR fluorescence-guided resection of a parathyroid adenoma located in the mediastinum
A: 3D SPECT-CT image 2 h postinjection of 99mTc-sestamibi with visualization of a parathyroid adenoma located paratracheally in the mediastinum (arrow). B: A parathyroid adenoma located paratracheally in the mediastinum is identified using NIR fluorescence imaging, 10 minutes postinjection of 0.5 mg/kg MB.
Figure 3
Figure 3. Schematic overview of parathyroid adenoma location and corresponding detection methods
Shown is the location of all parathyroid adenomas (N = 10) and one parathyroid carcinoma (N = 1, Asterix) and corresponding imaging modalities with which they were identified. The patient with parathyromatosis was excluded from this scheme.
Figure 4
Figure 4. Histopathological evaluation and fluorescence microscopy
Shown are 40X H&E staining (left) of the resected specimen, which shows oncocytic cells with monotone round nuclei surrounding a blood vessel. The right image shows the same section stained with 4′,6-diamidino-2-phenylindole (DAPI) nuclear staining (blue), with the 700 nm NIR fluorescence from MB pseudo-colored in yellow. The NIR fluorescent signal is located in the oncocytic cells.
See this image and copyright information in PMC

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