Fluorescence guided surgery and tracer-dose, fact or fiction?

Abstract

Introduction: Fluorescence guidance is an upcoming methodology to improve surgical accuracy. Challenging herein is the identification of the minimum dose at which the tracer can be detected with a clinical-grade fluorescence camera. Using a hybrid tracer such as indocyanine green (ICG)-(99m)Tc-nanocolloid, it has become possible to determine the accumulation of tracer and correlate this to intraoperative fluorescence-based identification rates. In the current study, we determined the lower detection limit of tracer at which intraoperative fluorescence guidance was still feasible.

Methods: Size exclusion chromatography (SEC) provided a laboratory set-up to analyze the chemical content and to simulate the migratory behavior of ICG-nanocolloid in tissue. Tracer accumulation and intraoperative fluorescence detection findings were derived from a retrospective analysis of 20 head-and-neck melanoma patients, 40 penile and 20 prostate cancer patients scheduled for sentinel node (SN) biopsy using ICG-(99m)Tc-nanocolloid. In these patients, following tracer injection, single photon emission computed tomography fused with computed tomography (SPECT/CT) was used to identify the SN(s). The percentage injected dose (% ID), the amount of ICG (in nmol), and the concentration of ICG in the SNs (in μM) was assessed for SNs detected on SPECT/CT and correlated with the intraoperative fluorescence imaging findings.

Results: SEC determined that in the hybrid tracer formulation, 41 % (standard deviation: 12 %) of ICG was present in nanocolloid-bound form. In the SNs detected using fluorescence guidance a median of 0.88 % ID was present, compared to a median of 0.25 % ID in the non-fluorescent SNs (p-value < 0.001). The % ID values could be correlated to the amount ICG in a SN (range: 0.003-10.8 nmol) and the concentration of ICG in a SN (range: 0.006-64.6 μM).

Discussion: The ability to provide intraoperative fluorescence guidance is dependent on the amount and concentration of the fluorescent dye accumulated in the lesion(s) of interest. Our findings indicate that intraoperative fluorescence detection with ICG is possible above a μM concentration.

Keywords: Fluorescence-guided surgery; Microdosing; Multimodal; SPECT/CT; Sentinel node.

Fig. 1

Schematic overview of the size exclusion chromatography experiments. Phantom set-up to mimic the in vivo drainage of the hybrid tracer (a). Size exclusion chromatography of the prepared hybrid tracer results in an ICG-nanocolloid fraction and a fraction of stacked ICG that accumulated on the column (b). Absorption spectra of ICG dissolved in saline, and of ICG-nanocolloid before and after size exclusion chromatography (c)

Fig. 2

Typical examples of the sentinel node biopsy procedure when using the hybrid approach. In the first row a head-and-neck melanoma case is illustrated, in the second row a penile cancer case is illustrated and in the third row a prostate cancer case is illustrated. From left to right a) lymphoscintigram with the location of the SN(s) (arrows); b) a 3D volume rendering of the SPECT/CT (arrows); c) white light imaging of the SN in vivo; and d) in vivo fluorescence imaging of the SN. Fluorescence imaging with the PDE generates a black-and-white image, the fluorescence laparoscope shows the fluorescence signal in the SN in blue

Fig. 3

Boxplots of intraoperative fluorescence detection versus % ID, amount of ICG in nmol and the concentration indocyanine green in the sentinel nodes. a % ID in relation to the intraoperative fluorescence detection; b The amount of ICG (nmol) in relation to the intraoperative fluorescence detection; and c The concentration of ICG (μM) in relation to the fluorescence detection