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

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.

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. 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. 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. 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.