Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging

Abstract

Abstract. There is growing interest in using fluorescence imaging instruments to guide surgery, and the leading options for open-field imaging are reviewed here. While the clinical fluorescence-guided surgery (FGS) field has been focused predominantly on indocyanine green (ICG) imaging, there is accelerated development of more specific molecular tracers. These agents should help advance new indications for which FGS presents a paradigm shift in how molecular information is provided for resection decisions. There has been a steady growth in commercially marketed FGS systems, each with their own differentiated performance characteristics and specifications. A set of desirable criteria is presented to guide the evaluation of instruments, including: (i) real-time overlay of white-light and fluorescence images, (ii) operation within ambient room lighting, (iii) nanomolar-level sensitivity, (iv) quantitative capabilities, (v) simultaneous multiple fluorophore imaging, and (vi) ergonomic utility for open surgery. In this review, United States Food and Drug Administration 510(k) cleared commercial systems and some leading premarket FGS research systems were evaluated to illustrate the continual increase in this performance feature base. Generally, the systems designed for ICG-only imaging have sufficient sensitivity to ICG, but a fraction of the other desired features listed above, with both lower sensitivity and dynamic range. In comparison, the emerging research systems targeted for use with molecular agents have unique capabilities that will be essential for successful clinical imaging studies with low-concentration agents or where superior rejection of ambient light is needed. There is no perfect imaging system, but the feature differences among them are important differentiators in their utility, as outlined in the data and tables here. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Setting Standards for Reporting and Quantification in Fluorescence-Guided Surgery

“…Moreover, various other factors besides sensitivity may play a role in the selection process. Dsouza et al suggest six key features for imaging systems [10]: (1) real-time overlay of white-light reflectance and fluorescence images; (2) fluorescence-mode operation with ambient room lighting present; (3) high sensitivity to tracer of interest; (4) ability to quantify fluorophores in situ; (5) ability to image multiple fluorophores simultaneously; and (6) maximized ergonomic use. Although we focused on the sensitivity point, the other points are equally relevant when deciding on the optimal imaging system for a certain application.…”

“…Phantoms that mimic relevant concentrations of a fluorescent agent in scattering and absorption media can aid in the quantification of the imaging system performance. However, guidance or standard documents describing sensitivity assessment for imaging systems, whether or not including phantoms, is currently lacking [10,11].…”

Bio-inspired imager improves sensitivity in near-infrared fluorescence image-guided surgery

“…Since the NIRF emission is weaker than the visible light reflected from tissue, the exposure time is set to 40 ms to ensure imaging rates of 25 frames/s and acquisition of high-contrast NIR images. This contrasts with current state-of-the-art pixelated NIRF systems that either utilize polymer-based [27] or Fabry–Perot absorptive pixelated spectral filters with low optical density (<1.5) coupled with CMOS sensors (see Tables 1 and 3), allowing only a single exposure time for all pixels, or utilize a multicamera approach, which lacks co-registration accuracy between multimodal images [26]. The multi-exposure capabilities of our CMOS imager, coupled with the high optical density and quantum efficiency of the NIR pixels, enables detection of 100 pM fluorescence concentrations of indocyanine green (ICG) under 60 kLux surgical light illumination ( P < 0.0001), which is a thousand-fold improvement over current state-of-the-art single-exposure pixelated sensors [27] [Fig.…”

“…Hence, the intensity of the NIRF molecular probe, which could be emitted from tumors several centimeters deep in the tissue, is at least 5 orders of magnitude weaker than the intensity of the reflected visible-spectrum light [24,25]. To enable simultaneous color and NIR imaging in the operating room, most FDA-approved instruments work with dimmed surgical illumination, which significantly impedes the surgical workflow: physicians stop the resection, dim the surgical lights, evaluate the surgical margins with NIRF instrumentation, and then continue the surgery under either dim or normal illumination but without NIRF guidance [26]. This significant drawback short-circuits the intrinsic benefits of NIRF, preventing wide acceptance of this technology in the operating room and leading to positive margins and iatrogenic damage.…”

Optical tracer size differences allow quantitation of active pumping rate versus Stokes–Einstein diffusion in lymphatic transport

“…NIRF methods also offer the benefit of high temporal resolution and simultaneous multiagent imaging. 15 However, drug and dye delivery via the lymphatics suffers from issues of high heterogeneity, and intensity-based metrics often need to be considered carefully with appropriate correction for delivery differences. 16 An understanding of tracer lymphatic pharmacokinetics and the influencing factors is also essential for designing appropriate imaging studies and protocols.…”