Fluorescence imaging in surgery

Abstract

Although the modern surgical era is highlighted by multiple technological advances and innovations, one area that has remained constant is the dependence of the surgeon's vision on white-light reflectance. This renders different body tissues in a limited palette of various shades of pink and red, thereby limiting the visual contrast available to the operating surgeon. Healthy tissue, anatomic variations, and diseased states are seen as slight discolorations relative to each other and differences are inherently limited in dynamic range. In the upcoming years, surgery will undergo a paradigm shift with the use of targeted fluorescence imaging probes aimed at augmenting the surgical armamentarium by expanding the "visible" spectrum available to surgeons. Such fluorescent "smart probes" will provide real-time, intraoperative, pseudo-color, high-contrast delineation of both normal and pathologic tissues. Fluorescent surgical molecular guidance promises another major leap forward to improve patient safety and clinical outcomes, and to reduce overall healthcare costs. This review provides an overview of current and future surgical applications of fluorescence imaging in diseased and nondiseased tissues and focus on the innovative fields of image processing and instrumentation.

Fig. 1

Nerves, vessels and muscles are not easily differentiated from one another with white light reflectance imaging. Intraoperative view of a lymph node dissection in a patient's neck, showing that large blood vessels and nerve structures arc difficult to differentiate from surrounding muscle with white-light reflectance alone (A). The carotid artery (red), jugular vein (blue) and vagus nerve (yellow) are highlighted in the schematic (B). The vagus nerve is a few millimeters across and represents the largest scale nerve that surgeons identify. The smallest nerves that surgeons must identify are less than a millimeter in diameter.

Fig. 2

Fine nerve structures can be obscured by overlying tissue. White light reflectance image showing a facial nerve in a mouse nerve (A). Much greater detail regarding nerve location and branching even under overlying non-nerve structures (compare arrows between A and B) is seen in the fluorescence image following systemic injection of a nerve labeling marker (NP41) (B).

Fig. 3

Cancer margins are not easily discernible with white light inspection. Color photograph showing a patient with a tongue cancer. The surface of the tumor is seen as a whitish growth, with a red-pink background of tongue mucosa (A). Beneath the surface, cancer growth extends in an unpredictable pattern (B: schematic, green line). The green line represents deep tumor growth. In order to achieve complete resection, the surgeon must estimate the tumor extent when making cuts around the cancer (B: schematic, blue line). Depending on the actual tumor spread, the cut edges can be variably close to cancer cells, and there is a risk of having a positive margin.

Fig. 4

Fluorescent labeling of tumor aids removal. In a mouse model of cancer, no residual tumor on the sciatic nerve is apparent to the human eye using white light reflectance (A). (B) With fluorescence imaging following injection of a molecularly targeted probe (activatable cell penetrating peptide, ACPP), it is clear that there is residual cancer tissue (arrow). (C) Pseudocolor overlay of the fluorescence image on top of the white light reflectance image shows the surgical view that retains anatomical details of standard surgery while adding the molecular details of the fluorescently labeled probe.