Current and Future Applications of Fluorescence Guidance in Orthopaedic Surgery

Abstract

Fluorescence-guided surgery (FGS) is an evolving field that seeks to identify important anatomic structures or physiologic phenomena with helpful relevance to the execution of surgical procedures. Fluorescence labeling occurs generally via the administration of fluorescent reporters that may be molecularly targeted, enzyme-activated, or untargeted, vascular probes. Fluorescence guidance has substantially changed care strategies in numerous surgical fields; however, investigation and adoption in orthopaedic surgery have lagged. FGS shows the potential for improving patient care in orthopaedics via several applications including disease diagnosis, perfusion-based tissue healing capacity assessment, infection/tumor eradication, and anatomic structure identification. This review highlights current and future applications of fluorescence guidance in orthopaedics and identifies key challenges to translation and potential solutions.

Keywords: Fluorescence-guided surgery; Indocyanine green imaging; Meniscus tear; Necrotizing soft tissue infection; Nerve imaging; Tissue-simulating phantoms; Tumor imaging.

Fig. 1

Overview of the three general applications of fluorescence guidance in orthopaedic surgery discussed in this review article: tissue infection management, perfusion-based assessment of tissue healing capacity and joint repairs, and nerve and tumor tissue identification.

Fig. 2

Representative patient presenting with confirmed necrotizing fasciitis (NF) in the lower leg. a White light color image shows minimal contrast to disease extent. b Wide-field ICG image at two-min post-injection reveals approximate extent of disease (yellow dashed line) with disease represented by ICG signal void; quantitative fluorescence standard (QUEL Imaging, White River Junction, VT) is shown on left; regions of interest depict deep NF-affected tissue (red), near-boarder NF-affected tissue (blue), and unaffected tissue (yellow). c Time-resolved fluorescence kinetic curve parameterization yields four features: max intensity (Imax), time-to-peak (TTP), ingress slope (IS), and egress slope (ES). d Kinetic curves extracted from the three regions of interest defined in (B). e Imax parameter map. f TTP parameter map. g IS parameter map. h ES parameter map. Scale bar in a also applies to b, e–h.

Fig. 3

Two representative knee joints imaged using the Image1 S RU Rubina OPAL 1 arthroscope (Karl Storz, Tuttlingen, Germany). a ICG signal intensity enables high-contrast visualization of joint microvascular (white arrows). b ICG signal visualizes well-perfused synovial tissue and highlights regions of low and potentially jeopardized perfusion corresponding to fluorescence signal voids. The 5-mm scale bar in a also applies to b.

Fig. 4

Preliminary data of shoulder arthroplasty tendon perfusion assessment in six patients using dynamic, contrast-enhanced ICG imaging. a The peak fluorescence intensity pre- and post-procedure for each of six study patients. b Distribution of fluorescence intensities extracted from a region of interest delineating the exposed sub-scapularis tendon, before and after the procedure. c Mean region of interest fluorescence intensity curves for each patient during ICG wash-in and wash-out, before and after the procedure.

Fig. 5

Resected (i.e., ex vivo) benign-aggressive bone lesion tissue (white dashed line) exhibits increased ICG fluorescence relative to healthy resected tissues (white arrows). Quantitative fluorescence standard is shown on the left (QUEL Imaging, White River Junction, VT). Surgery and imaging performed 24 h post-injection.

Fig. 6

Representative fluorescence images demonstrating positive contrast using the nerve-specific, NIR fluorophore LGW16-03 in a human limb perfusion model. a Fluorescence highlights in vivo deep peroneal nerve surrounded by adipose tissue; the intensity profile (red dashed line) is plotted in b. c Ex vivo tissues imaged highlight common peroneal nerve fluorescence relative to muscle tissue.

Fig. 7

Gelatin-based, tissue-simulating phantom for assessing conventional medical imaging (i.e., CT and MRI) and fluorescence imaging for surgical guidance. a White light image of a representative phantom. b Volumetric rendering of the same phantom showing tumor-simulating MRI contrast agent inclusion (red). Scale bar in a also applies to b.