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Initial application of near-infrared fluorescence imaging using indocyanine green in urethral reconstructive surgery
Abstract
Introduction
Near-infrared fluorescence (NIRF) imaging using indocyanine green (ICG) is increasingly being explored in various urological procedures, including urethral reconstructive surgery. This real-time technology assists surgeons in the visualization of critical anatomical structures, thereby potentially improving surgical precision and patient outcomes.
Objective
This study aimed to report our preliminary experience using ICG technology in urethral reconstructive surgery using the SPY system by Novadaq.
Materials and Methods
ICG technology was adopted in seven urethral reconstructive procedures performed in Saiful Anwar Hospital over 1 month in 2018. The procedures were performed by two surgeons, consisting of five excisions and primary anastomosis (EPA) and two substitution urethroplasties with real-time evaluation of ICG expression in corpus spongiosum intraoperatively.
Result
The ICG solution was injected intravenously in all urethral reconstructive procedures. The ICG injection was allowed to visualize the corpus spongiosum in a matter of 30–60 s. The dosage of ICG used was 5 mg diluted in 10 mL of normal saline. One procedure had been converted from EPA to vascular-sparring anastomotic urethroplasty because of poor perfusion of the corpus spongiosum. All the procedures had good outcomes. No adverse and allergic reactions to ICG and other complications occurred postoperatively.
Conclusion
Our preliminary experience confirmed the safety and efficacy of ICG technology in urethral reconstructive surgery. The main advantage of using NIRF imaging is allowing the surgeon to real-time evaluate corpus spongiosum qualitatively and quantitatively. The limitation is specific equipment needed like the SPY system by Novadaq.
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The inspection of the urethra in patients with documented or suspected urethral stricture should be carried out with small caliber ureteroscope of 6/7.5Ch. Different from flexible cystoscope (16Ch) or resectoscope (26Ch), small caliber ureteroscope allows a comprehensive evaluation of the stricture, including its length and the status of the mucosa in its proximity, without injuring or overstretching the urethra. With a small caliber ureteroscope it is also possible to cross the stricture, allowing the evaluation of the proximal urethra, the external urethral sphincter, and the bladder. A 6/7.5Ch ureteroscope also allows estimation of the real caliber of the stricture, providing a useful landmark for further treatment decisions.
(1) Background: Near-infrared fluorescence imaging is a technique capable of assessing tissue perfusion and has been adopted in various fields including plastic surgery, vascular surgery, coronary arterial disease, and gastrointestinal surgery. While the usefulness of this technique has been broadly explored, there is a large variety in the calculation of perfusion parameters. In this systematic review, we aim to provide a detailed overview of current perfusion parameters, and determine the perfusion parameters with the most potential for application in near-infrared fluorescence imaging. (2) Methods: A comprehensive search of the literature was performed in Pubmed, Embase, Medline, and Cochrane Review. We included all clinical studies referencing near-infrared perfusion parameters. (3) Results: A total of 1511 articles were found, of which, 113 were suitable for review, with a final selection of 59 articles. Near-infrared fluorescence imaging parameters are heterogeneous in their correlation to perfusion. Time-related parameters appear superior to absolute intensity parameters in a clinical setting. (4) Conclusions: This literature review demonstrates the variety of parameters selected for the quantification of perfusion in near-infrared fluorescence imaging.
Objective:
The use of methylene blue dye (MB) to highlight anatomical structures in urology has been well-established. Urethral stricture may extend about a centimeter beyond the abnormal area seen on urethrogram. Although the current literature suggests a tension-free and end- to- end anastomosis after excision of the strictured urethral segment with spongiofibrosis and surrounding corpus spongiosum in short bulbar strictures, some centers dealing with urethroplasty prefer anastomosis for short bulbar strictures while others prefer augmentation. With this study, use of MB for delineating stricture line and assessing spongiofibrosis in the diagnosis of urethral stricture was evaluated.
Material and methods:
Five cc MB including 10 mg/mL is diluted with 10 cc saline. In the first scenario, MB is gently injected into urethra via the meatus before the urethroplasty procedure. Meanwhile, the extent of urethral segment stained by MB is noted. In the second scenario (MB spongiosography) in short bulbar stricture, insulin needles are inserted in spongiosa of the stricture site distally and proximally. MB is gently injected with distal needle. The two remaining needles are then observed. Presence of MB efflux in proximal needle implies deficiency of significant spongiofibrosis, so buccal augmentation is performed. Absence of efflux of MB implies significant spongiofibrosis and anastomotik site excised.
Results:
Four hundred and ninety-two consecutive cases prospectively evaluated between 2010 and 2014. Precise staining of stricture was successfully observed in 464 (94%) patients. Grossly normal appearing urothelium remained pink. Histopathology confirmed that the stained urethra had a stricture. Of the 22 short bulbar idiopathic strictures, in 18 (82%) MB was seen across the stricture and urethral transection was avoided. Anastomosis was performed in 4 (18%) cases where no MB went across the primary excision. There were no known allergic complications.
Conclusion:
MB aids in delineating the urethral lumen and exact site of stricture that needs augmentation. MB Spongiography in short bulbar strictures could be used as a beneficial guide in relation to the type of urethral repair to be performed in terms of augmentation versus excision and anastomosis.
The purpose of this paper is to give an overview of
the recent surgical intraoperational applications of indocyanine
green fluorescence imaging methods, the basics of the technology,
and instrumentation used. Well over 200 papers describing this
technique in clinical setting are reviewed. In addition to the surgical
applications, other recent medical applications of ICG are briefly
examined.
Background
Urethral injury is a dreaded complication during laparoscopic, perineal and transanal surgery and is mainly a result of a failed visualization of the urethra. The aim of this systematic review is to provide an overview of the available literature on the near-infrared fluorescence (NIRF) imaging technique using contrast agents for the intra-operative visualization of the urethra.
Material and methods
A systematic review of the literature was conducted including studies on NIRF imaging using contrast agents to visualize the urethra. All studies describing a NIRF imaging technique and demonstrating visual findings of the urethra were included.
Results
Five studies were identified. Four studies examined indocyanine green, one of which also studied the IRDye® 800BK agent and one examined the CP-IRT dye. All studies showed that the NIRF imaging technique was feasible for an early identification of the urethra. No complications related to NIRF imaging were reported.
Conclusion
We conclude that the use of a NIRF imaging technique is feasible and that it can contribute to prevent iatrogenic injury to the urethra. However, based on the limited available data, no solid conclusion can yet be drawn and further translation to the clinical practice is necessary.
Background
Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) has been recently adopted in pediatric minimally invasive surgery (MIS) in order to improve intra-operative visualization of anatomic structures and facilitate surgery.
Objective
This study aimed to report our preliminary experience using ICG technology in pediatric urology using laparoscopy and robotics.
Study Design
ICG technology was adopted in 57 laparoscopic or robotic urological procedures performed in our unit over a 24-month period: 41 (38 laparoscopic - 3 robotic) left varicocele repairs with intra-operative lymphography and 16 renal procedures (12 laparoscopic - 4 robotic) including 9 partial nephrectomies, 3 nephrectomies and 4 renal cyst deroofings.
Results
The ICG solution was injected intravenously in renal procedures or into the testis body in case of varicocele repair. Regarding the timing of the administration, the ICG injection was performed intra-operatively in all cases and allowed the visualization of the anatomic structures in a matter of 30-60 seconds. The dosage of ICG was 0.3 mg/ml/kg in all indications. All procedures were completed laparoscopically or robotically without conversions. No adverse and allergic reactions to ICG and other complications occurred postoperatively.
Discussion
This paper describes for the first time in pediatric urology that ICG-guided NIRF imaging may be helpful in laparoscopic and robotic procedures. In case of varicocele repair, ICG-enhanced fluorescence allowed to perform a lymphatic-sparing procedure and avoid the risk of postoperative hydrocele. In case of partial nephrectomy, ICG-guided NIRF was helpful to visualize the vascularization of the non-functioning moiety, identify the dissection plane between the two moieties (Figure 1) and check the perfusion of the residual parenchyma after resection of the non-functioning pole. In case of renal cyst deroofing, ICG-guided NIRF aided to identify the avascular cyst dome and to guide its resection. No real benefits of using ICG-enhanced fluorescence were observed during nephrectomy.
Conclusion
Our preliminary experience confirmed the safety and efficacy of ICG technology in pediatric urology and highlighted its potential advantages as adjunctive surgical technology in patients undergoing laparoscopic or robotic urological procedures. Use of NIRF was also cost-effective as no added costs were required except for the ICG dye (cost 40 eur per bottle). The most common and useful applications in pediatric urology included varicocele repair, partial nephrectomy ad renal cyst deroofing. The main limitation is the specific equipment needed in laparoscopy, that is not available in all centers whereas the robot is equipped with the Firefly® software for NIRF.
Introduction
Near-infrared fluorescence (NIRF) imaging, using contrast agents with fluorescent characteristics in the near-infrared (NIR: 700–900 nm) window, is considered to possess great potential for clinical practice in the future of minimally invasive surgery (MIS), given its capacity for intraoperative, real-time anatomical navigation, and identification. The aim of this review is to provide an overview of the literature concerning the current and potential future applications of fluorescence imaging in supporting anatomical guidance during MIS, and thereby guiding future research.
Methods
A systematic literature search was performed in the PubMed and Embase databases. All identified articles were screened and checked for eligibility by two authors. In addition, literature was sought by screening references of eligible articles.
Results
After administration of a fluorescent dye (e.g., indocyanine green), NIRF imaging can be helpful to improve the visualization of vital anatomical structures during MIS. Extra-hepatic bile ducts, arteries, ureters, sentinel lymph nodes, and lymph vessels have successfully been identified using NIRF imaging. A uniform approach regarding timing and route of dye administration has not yet been established. Optimization of both imaging systems and fluorescent dyes is needed to improve current shortcomings. New preclinical dyes are considered for optimization of NIRF imaging.
Conclusion
Future implementation of new intraoperative optical methods, such as NIRF, could significantly contribute to intraoperative anatomy navigation and facilitate critical decision-making in MIS. Further research (i.e., large multi-center randomized controlled trials) is needed to establish the true value of this innovative optical imaging technique in standard clinical practice.
Near-infrared fluorescence (NIRF) molecular imaging holds great promise as a new "point-of-care" medical imaging modality that can potentially provide the sensitivity of nuclear medicine techniques, but without the radioactivity that can otherwise place limitations of usage. Recently, NIRF imaging devices of a variety of designs have emerged on the market and in investigational clinical studies using indocyanine green (ICG) as a non-targeting NIRF contrast agent to demark the blood and lymphatic vasculatures both non-invasively and intraoperatively. Approved in the US since 1956 for intravenous administration, ICG has been more recently used off-label in intradermal or subcutaneous administrations for fluorescence imaging of the lymphatic vasculature and lymph nodes. Herein, we summarize the devices of a variety of designs, summarize their performance in lymphatic imaging in a tabular format, and comment on necessary efforts to develop standards for device performance to compare and use these emerging devices in future, NIRF molecular imaging studies.
Background:
Better postoperative results can be expected in nerve reconstruction when vascularized nerve grafts are used. Previous studies reported reconstruction with flaps including "vascularized" nerves; however, few have evaluated blood supply to these nerves. The aim of this study was to quantitatively assess blood perfusion to nerves included in anterolateral thigh (ALT) flaps by indocyanine green (ICG) fluorescence angiography.
Patients and methods:
Participants comprised eight patients who underwent reconstructive surgery with nerve defects using free ALT flaps, including the vastus lateralis motor nerve and/or femoral cutaneous nerve. Intraoperative ICG fluorescent angiography was performed. Time after the drug injection and the intensity of fluorescence in these nerves were analyzed as time-intensity curves. Maximum intensity (Imax), time to Imax (Tmax), and time at the beginning of intensity elevation (Te) were measured at three points: Point C, the central portion of the flap-attached region of the nerve; Point P, 2 cm from the proximal flap-attached edge; and Point D, 2 cm from the distal edge.
Results:
Imax and Te at point C and Imax/Tmax-Te at point P were significantly different between these two nerves (p = 0.03125, p = 0.02895, p = 0.03125, respectively). Fluorescence in the vastus lateralis motor nerve was slightly quicker and stronger than that in the femoral cutaneous nerve, and also exhibited an axial pattern of fluorescence.
Conclusion:
Intraoperative ICG fluorescent angiography can be used to determine which nerve is better for nerve reconstruction. The indexes of Imax, Te, and Imax/Tmax-Te may be the suitable criteria for decision making regarding donor nerve selection.
To evaluate the safety of near infrared fluorescence (NIRF) of intravenously injected indocyanine green (ICG) during open partial nephrectomy, and to demonstrate the feasibility of this technology to identify the renal vasculature and distinguish renal cortical tumors from normal parenchyma.
Patients undergoing open partial nephrectomy provided written informed consent for inclusion in this institutional review board-approved study. Perirenal fat was removed to allow visualization of the renal parenchyma and lesions to be excised. The patients received intravenous injections of ICG, and NIRF imaging was performed using the SPY system. Intraoperative NIRF video images were evaluated for differentiation of tumor from normal parenchyma and for renal vasculature identification.
A total of 15 patients underwent 16 open partial nephrectomies. The mean cold ischemia time was 26.6 minutes (range 20-33). All 14 malignant lesions were afluorescent or hypofluorescent compared with the surrounding normal renal parenchyma. NIRF imaging of intravenously injected ICG clearly identified the renal hilar vessels and guided selective arterial clamping in 3 patients. No adverse reactions to ICG were noted, and all surgical margins were negative on final pathologic examination.
The intravenous use of ICG combined with NIRF is safe during open renal surgery. This technology allows the surgeon to distinguish renal cortical tumors from normal tissue and highlights the renal vasculature, with the potential to maximize oncologic control and nephron sparing during open partial nephrectomy. Additional study is needed to determine whether this imaging technique will help improve the outcomes during open partial nephrectomy.