The use of Near-Infrared Fluorescence Imaging in parathyroid visualization during Thyroid Surgery: a pilot study

Surgical procedures involving the thyroid gland require identification of the
parathyroid glands. However, these glands are small and can be difficult to
distinguish from normal fat tissue and lymph nodes around the thyroid gland.
Identification of the parathyroid glands therefore, takes considerable surgical
time. Despite the efforts of endocrine surgeons to preserve the parathyroid
glands, iatrogenic hypoparathyroidism is a common complication following
thyroidectomy, occurring in up to 15% of patients. Hypoparathyroidism can
result in hypocalcemia. Severe hypocalcemia can result in cardiac arrhythmias
and tetany, increased morbidity, prolonged duration of hospitalization and
death. Identification of the parathyroid glands during thyroid surgery may
prevent their inadvertent surgical removal and thus provide a better
postoperative outcome and quality of life. Recently, a case report and earlier
a dog study is published which both show promising results in the use of NIRF
for identification of the parathyroid glands.

Another desire is to not only recognize the parathyroid gland during surgery,
but also knowing whether the function of the parathyroid gland is appropriate.
The functioning of the preserved parathyroid glands seems to be dependent on
the vascularization of the glands. ICG angiography is used already in
anastomotic bowel surgery and to visualize the cystic artery. Fortunity et al
investigated the applicability of NIRF with ICG in the assessment of the
perfusion of the parathyroid gland. The results of this article are promising.

Our hypothesis is, that the use of ICG-based fluorescence imaging during
thyroid surgery will provide a real-time intraoperative visualization of the
parathyroid glands. This will improve patient safety by avoiding complications
related to misidentification of the parathyroid glands, and might decrease
surgical time. Furthermore, ICG based fluorescence angiography after thyroid
removal can be a used as a reassurance whether the (vascularization of) the
parathyroid is still intact.

The main goal of this pilot study is to investigate the feasibility of the
identification of the parathyroid glands by means of the present commercially
available near infrared fluorescence imaging system during thyroid surgery: is
it possible to obtain real-time clearer and earlier identification of the
parathyroid glands in comparison to conventional surgery without the use of ICG?

A second objective is to investigate the use of fluorescence angiography of the
parathyroid after thyroid removal: does it predict the postoperative outcome
concerning parathyroid hormone?

A prospective feasibility study
The study will be conducted in the Maastricht University Medical Center (MUMC)
The surgery will be performed by or under supervision of experienced
endocrine-surgeons.
Video recordings will be made during the procedure after ICG injection:
1. During identification of the parathyroid glands
2. After resection of the thyroid to visualize the perfusion

After surgery the NIRF technique will be assessed using the intraoperative
registration form (See attachment) and visual recordings will be analyzed.
Additionally, on postoperative day 1 and 2 and after two weeks calcium levels
will be determined, together with TSH level after two weeks in patients after
total thyroidectomy as in standard care.

The VITOM Fluorescence exoscope will be used during surgery. and in 30 patients
simultaneously the Quest Spectrum Platform.
For this, a dose of 7.5 mg ICG will be administered intravenously at least two
times at the following moments:
- during the resection of the thyroid for identification of the parathyroid
glands
- after resection of the thyroid for assessment of the perfusion of the
parathyroid glands.


As in standard care, postoperatively on day 1 and 2 and after two weeks blood
levels of calcium are measured, together wit TSH after two weeks.

Compared with standard care, patients will undergo the following extra
procedures:
- The VITOM exoscope will be used during surgery and in 30 patients
simultaneously the Quest Spectrum Platform.
- At least two times as dose of 7.5mg will be administered intravenously

The outer outcomeparamters will be obtained from the patients medical dosier
(pathology report concerning presence of parathyroidglands in resected thyroid
(part) and postoperative calcium levels and TSH levels as determined in
standard care).

It is known that injection of ICG preparations, in very rare cases, can cause
nausea and anaphylactoid or anaphylactic reactions (<1:10,000). Patients with
terminal renal insufficiency seem to be more prone for such an anaphylactic
reaction.

The VITOM NIRF exoscope and Quest Spectrum Platform are both not related to
additional risk for the patient.

Initially, patients participating in this study will not benefit from the
application of NIRF during the surgical procedure.

We have a small sample size of 30 as it is expected that the outcome of this
first feasibility study in this applicability of NIRF will be of great
importance for the further application of this technique, and can therefore be
the basis for future research qualifying the possible advantages of the
technique.