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L. Baldari et al.
Table1.3 reports some of the most widely adopted devices both for conventional and minimally invasive/robotic surgery (Table1.3).
Table 1.3 Some of the most widely adopted NIR imaging systems both for conventional and minimally invasive/robotic uorescence-guided surgery
Imaging system
Stryker 1688
advanced imaging modalities
Pinpoint with SPY-PHI
Karl Storz 1 S™
Arthrex Synergy ID
Da Vinci Surgical System (Intuitive)
Image 1S™ HD xenon
Image 1S™ Rubina™
System
Firey camera system integrated into Da Vinci Si and Xi
Image resolution Use
4k Laparoscopic – Green overlay
Full HD Open – Green overlay
Laparoscopic – Optical light source
4k and 3D Laparoscopic – Overlay mode
Laser-free LED light source
4k Laparoscopic – Overlay mode
3D Robotic – Normal imaging
LED light – No overlay
Visualization mode
mode – SPY-ENV mode – SPY-contrast – IRIS
mode – Color-
segmented
uorescence
mode – SPY-
uorescence
mode
illumination and
contrast-
enhanced
modality – No overlay
mode
– Intensity map
– Monochromatic
– Monochromatic
and uorescent
modes
mode
1 History andScience ofImmunouorescence
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Conclusion
In conclusion, since its rst clinical application in surgery, uo­rescence underwent huge development and spread among special­ties. Among all the uorophores, indocyanine green is the most diffused, thanks to its peculiar features that promote its wide­spread. Many probes are currently under clinical development and will be on the market soon.
A growing number of companies are developing systems for uorescence-guided surgery. This imaging system is in constant evolution with many features like overlay visualization and the second near-infrared window (1000–1700 nm), enhancing the power and increasing applications of this technology.
References
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20. Khutsishili TS, Milaeva MA.The use of the uorescent method for deter­mining the degree of revascularization of the heart in the surgical treat­ment of experimental cardiac ischemia. Grudn Khir. 1965;7(6):11–2. Russian.
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22. Zhang RR, Schroeder AB, Grudzinski JJ, Rosenthal EL, Warram JM, Pinchuk AN, etal. Beyond the margins: real-time detection of cancer using targeted uorophores. Nat Rev Clin Oncol. 2017;14(6):347–64.
23. Mordon S, Devoisselle JM, Soulie-Begu S, Desmettre T. Indocyanine green: physicochemical factors affecting its uorescence in vivo. Microvasc Res. 1998;55:146–52.
24. Desmettre T, Devoisselle JM, Mordon S. Fluorescence properties and metabolic features of indocyanine green (ICG) as related to angiography. Surv Ophthalmol. 2000;45:15–27.
25. Valeur B, Berberan-Santos MN.Molecular uorescence: principles and applications. Weinheim: Wiley-VCH; 2012. ISBN: 978-3-527-32837-6.
26. Lakowicz JR.Principles of uorescence spectroscopy. New York, NY: Springer; 2010. ISBN: 978-1-4615-7658-7.
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27. Azzopardi EA, Owens SE, Murison M, Rees D, Anne Sawhney M, Francis LW, et al. Chromophores in operative surgery: current practice and rationalized development. J Control Release. 2017;249:123–30.
28. Rashid A, Warnakulasuriya S. The use of light-based (optical) detection systems as adjuncts in the detection of oral cancer and oral potentially malignant disorders: a systematic review. J Oral Pathol Med. 2015;44(5):307–28.
29. de Boer E, Harlaar NJ, Taruttis A, Nagengast WB, Rosenthal EL, Ntziachristos V, van Dam GM.Optical innovations in surgery. Br J Surg. 2015;102(2):e56–72.
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31. Mondal SB, et al. Real-time uorescence image-guided oncologic sur­gery. Adv Cancer Res. 2014;124:171–211.
32. Marmorstein AD, Marmorstein LY, Sakaguchi H, Hollyeld JG.Spectral proling of autouorescence associated with lipofuscin, Bruch’s mem­brane, and sub-RPE deposits in normal and AMD eyes. Invest Ophthalmol Vis Sci. 2002;43(7):2435–41.
33. Shin D, Vigneswaran N, Gillenwater A, Richards-Kortum R.Advances in uorescence imaging techniques to detect oral cancer and its precursors. Future Oncol. 2010;6:1143–54.
34. Selvam S, Sarkar I.Bile salt induced solubilization of methylene blue: study on methylene blue uorescence properties and molecular mechan­ics calculation. J Pharm Anal. 2017;7:71–5.
35. Matsui A, Tanaka E, Choi HS, Kianzad V, Gioux S, Lomnes SJ, Frangioni JV. Real-time, near-infrared, uorescence-guided identication of the ureters using methylene blue. Surgery. 2010;148:78–86.
36. Alander JT, Kaartinen I, Laakso A, Pätilä T, Spillmann T, Tuchin VV, etal. A review of indocyanine green uorescent imaging in surgery. Int J Biomed Imaging. 2012;2012:940585.
37. Schaafsma BE, Mieog JS, Hutteman M, vad der Vorst JR, Kuppen PJ, Lowik CW, etal. The clinical use of indocyanine green as a near-infrared uorescent contrast agent for image-guided oncologic surgery. J Surg Oncol. 2011;104:323–32.
38. Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. Fluorescence-guided surgery with 5-aminolevulinic acid for resec­tion of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol. 2006;7(5):392–401.
39. Staderini M, Megia-Fernandez A, Dhaliwal K, Bradley M.Peptides for optical medical imaging and steps towards therapy. Bioorg Med Chem. 2018;26:2816–26.
40. Hoogstins CES, Boogerd LSF, Sibinga Mulder BG, Mieog JSD, Swijnenburg RJ, van de Velde CJH, et al. Image-guided surgery in patients with pancreatic cancer: rst results of a clinical trial using SGM-
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101, a novel carcinoembryonic antigen-targeting, near-infrared uores­cent agent. Ann Surg Oncol. 2018;25:3350–7.
41. Patil CG, Walker DG, Miller DM, Butte P, Morrison B, Kittle DS, etal. Phase 1 safety, pharmacokinetics, and uorescence imaging study of Tozuleristide (BLZ-100) in adults with newly diagnosed or recurrent gliomas. Neurosurgery. 2019;85:E641–9.
42. Randall LM, Wenham RM, Low PS, Dowdy SC, Tanyi JL.A phase II, multicenter, open-label trial of OTL38 injection for the intra-operative imaging of folate receptor-alpha positive ovarian cancer. Gynecol Oncol. 2019;155:63–8.
43. Luo S, Zhang E, Su Y, Cheng T, Shi C.A review of NIR dyes in cancer targeting and imaging. Biomaterials. 2011;32:7127–38.
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org/10.1007/978- 1- 62703- 649- 8.
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Current Fluorescence- Guided
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Platforms andDevices
DonovanHui, KevinCarroll, ChristinaSanders, andDavidPechman
Introduction
Fluorescence-guided surgery (FGS) enables clinicians to visu­alize uorescence-enhanced images in real time to assist in sur­gical procedures. Its use has transformed the way surgeons visualize structures that may not be apparent under visible light alone [1]. The wavelength of visible light is between 380 and 780 nm. Near- infrared (NIR) extends from a wavelength of 780–2500 nm with penetration of tissues ranging from 5 to
D. Hui Department of Surgery, New York Medical College Metropolitan Hospital Center, New York, NY, USA
K. Carroll Department of Surgery, Northwell Health—South Shore University Hospital, Bay Shore, NY, USA
C. Sanders Department of Surgery, Jacobs School of Medicine and Biomedical Sciences, State University of NewYork at Buffalo, Buffalo, NY, USA e-mail: cs328@buffalo.edu
D. Pechman (*) Department of Surgery, Zucker School of Medicine at Hofstra, Northwell Health—South Shore University Hospital, Bay Shore, NY, USA
2
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 N. Szoka et al. (eds.), The SAGES Manual of Fluorescence-Guided Surgery, https://doi.org/10.1007/978-3-031-40685-0_2
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D. Hui et al.
8mm [2, 3]. The depth of penetration and the working distance of each device determine which structures can be identied with uorescence imaging.
FGS utilizes a specialized camera with an NIR detector to relay images in real time. An excitation light source is used to activate uorophores within target tissue [4, 5]. Excitation and emission wavelengths are specic for each device. These wave­lengths are generally within a similar range and are limited by clinically available uorophores [2, 3, 6, 7].
Fluorescence imaging requires a uorophore or an NIR- emitting LED to create near-infrared images. Fluorophores are compounds that release light with excitation and are the primary means for visualizing key structures in FGS.In 2021, available uorophores include uorescein, methylene blue (MB), 5- aminolevulinic acid (5-ALA), and indocyanine green (ICG) [8]. ICG is the most fre­quently used uorophore due to its ease of use and low side effect prole. It is easy to mix and administer intravenously in the pre-op or intraoperative setting. Its emission wavelength does not overlap with visible light; this minimizes scattering effect and background noise that may obscure visualization [810].
Fluorescein has an excitation wavelength of 495nm and an emission wavelength of 519nm. MB has an excitation wavelength of 668nm and an emission wavelength of 688nm. 5-ALA has an excitation wavelength of 380–440 and an emission wavelength of 620–634nm, depending on the acidity of its solution. Fluorescein, MB, and 5-ALA have emission wavelengths within the visible light wavelength and are therefore not ideal uorophores for FGS.The excitation and emission wavelengths of ICG are 740– 900 and 800–860nm ranges, respectively, and are ideal for use with NIR cameras [1113].
Fluoroscopic devices have become increasingly prevalent in the opening room since the Food and Drug Administration (FDA) approved the Novadaq SPY imaging system in 2005 [6, 12]. FGS has shown utility in a wide range of procedures, including intra­operative angiography, perfusion assessment, tissue plane identi­cation, biliary structure identication, and lymphangiography [5, 14]. As the technology to uorescently label specic tissues continues to advance, FGS devices will become increasingly more commonplace in the operative suite[8, 9].
2 Current Fluorescence-Guided Platforms andDevices
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Indocyanine Green (ICG) Dye
Indocyanine green (ICG) was developed in 1955 by Kodak Research Laboratory for NIR photography. It was approved for clinical use in 1959 for assessment of cardiac output. It was later found to be excreted exclusively by the liver with uptake by hepa­tocytes and excretion via bile which prompted its use in the assess­ment of hepatic function [15]. ICG was found to be useful in the assessment of choroidal blood ow and has since been utilized in an increasing number of angiographic and lymphangiographic modalities [11]. Use of ICG is heavily favored for uorescence­guided surgery as it is a water-soluble dye with emission wave­length of approximately 800 nm. The autouorescence at this wavelength in normal tissue is low which increases the signal-to­noise ratio and improves sensitivity of visualized target anatomy following excitation. ICG has a relatively low toxicity prole with a half-life at approximately 3min. It readily binds lipoproteins in the blood without systemic effects and is very well tolerated by patients [16, 17]. It is non-nephrotoxic and has a low side effect prole. It can be used multiple times during the same surgery. ICG requires fresh preparation with 6h of viable use.
Contraindication for use of ICG is anaphylaxis. Recommended dosing, mode of administration, timing for administration, and timing for visualization are per manufacturer recommendations [17]. General recommendations are as follows:
• Angiographic perfusion: 2.5 mg given intravenously during
surgery with visualization in less than 1min.
• Biliary assessment: 5 mg given intravenously up to 1–7 h
before surgery with direct visualization.
• Lymph node mapping: 2.5mg given directly around target tis-
sue during surgery with visualization in 15–30min.
Fluorescence-Guided Systems andDevices
The rst FDA-approved system for FGS is the Novadaq SPY system developed in 2005. Many of the rst FGS systems were used in open surgery via a cart-based platform that contained
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an excitation laser and imager to capture NIR light. These cart­based systems have largely been replaced by handheld devices and have been adapted to laparoscopic, robotic, and micro­scopic systems. As FGS continues to advance, devices may integrate with augmented reality systems and wearable tech­nology.
D. Hui et al.
Open Surgical Systems
The two categories of open FGS systems are cart-based and hand­held devices. Cart-based systems offer visualization of key struc­tures while freeing the surgeon’s hands to manipulate tissue and operate while assessing in real time. The working distance for such devices is xed, but offers a wide area of visualization in assessing overall perfusion in reconstructive procedures. Handheld devices also offer visualization of key structures in real time with some systems having the option for mounting the imager on an adjustable securing arm. The size and convenience of handheld devices offer a greater degree of freedom and maneuverability with a exible working distance [1, 3, 6].
Cart-Based Platform
SPY Elite System [Spy Elite Intraoperative Perfusion Assessment System (LC3000, SP 3000)]—Stryker, Kalamazoo,
Michigan, USA
The SPY Elite System (Fig.2.1a) is the updated version of the rst clinically available FGS platform, the SPY System. The SPY Elite System consists of a mounted imaging head that can be posi­tioned above the surgical eld in order to obtain NIR images.
SPY Elite System Components
The system includes the following: imaging console (radiation source and mage detector), dual display (1080p resolution),
bc
2 Current Fluorescence-Guided Platforms andDevices
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a
Fig. 2.1 (a) SPY Elite cart-based uorescence system—Photo courtesy of Stryker. (b) SPY Elite uorescence image—Photo courtesy of Stryker. (c) SPY-Q image captured for qualitative assessment of tissue perfusion—Photo courtesy of Stryker
CINEVAQ Software, sterile drape, and SPY AGENT GREEN (ICG)—25mg vials.
For use, the SPY Elite System should be positioned in the operating room to provide optimal visualization of the monitor located on the cart. The imaging console is sterilely draped, using the included clear drapes, and positioned over the surgical eld. The imaging console is attached to a exible arm mount con­nected directly to the cart system, which can be easily positioned and removed from the operative eld while maintaining sterility. The working distance of the imaging console is 30cm and is the ideal distance from the target anatomy to obtain accurate uores­cence images. SPY mode uorescence is activated from the cart or the “laser on” button on the left side of the imaging console. The radiation source is a class 3R laser that activates a uoro­phore to produce emission wavelengths between 825 and 850nm. NIR images are captured through a charge-coupled device camera and relay real-time images on the display attached to the system cart. The preferred uorophore with SPY Elite System is SPY AGENT GREEN (ICG), and its timing for use depends on the indication for use [18, 19].
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