Extrahepatic biliary tract visualization using near-infrared fluorescence imaging with indocyanine green: optimization of dose and dosing time

Abstract Background The dose and dosing time of indocyanine green (ICG) vary among fluorescence cholangiography (FC) studies. The purpose of this prospective, randomized, exploratory clinical trial was to optimize the dose and dosing time of ICG. Methods PubMed was searched to determine the optimal dose. To optimize the dosing time of ICG, a clinical trial was designed with two parts. The first part included patients with T tubes for more than 1 month. After the patient was injected with ICG, bile was collected at 10 time points to explore the change and trends of bile fluorescence intensity (FI). In addition, the results of the first experiment were used to setup a randomized controlled trial (RCT) that aimed to find the optimal dosing timing for ICG injections for laparoscopic cholecystectomy (LC). During surgery, imaging data were collected for analysis. Results After performing a systematic review, the ICG injection dose for each patient in the clinical trial was 10 mg. Five patients were included in the first part of the study. Bile collected 8 h after ICG injection had a higher FI than bile collected at other time points (p < 0.05), and the FI of bile collected 20 h after ICG injection was nearly zero. In the second part of the experiment, 4 groups of patients (6 patients per group) were injected with 10 mg ICG at 8, 10, 12 and 14 h prior to surgery. The distribution of bile duct FI (p = 0.001), liver FI (p < 0.001), and common bile duct (CBD)-to-liver contrast (p = 0.001) were not the same in each group. Further analysis with the Bonferroni method revealed the following: (1) the FI of the CBD in the 8 h group was significantly different from that in the 14 h group (adjusted p < 0.001); (2) the liver FI of the 8 h group was higher than that of the 10 h group (adjusted p = 0.042) and the 14 h group (adjusted p < 0.001); and (3) the CBD-to-liver contrast of the 8 h group was lower than that of the 10 h group (adjusted p = 0.013) and the 14 h group (adjusted p = 0.001). Conclusion ICG FC enables the real-time identification of extrahepatic bile ducts. The optimal effect of FC can be achieved by performing 10 mg ICG injections 10 to 12 h prior to surgery.

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P11: NEAR INFRARED FLUORESCENT CHOLANGIOGRAPHY IN LAPAROSCOPIC CHOLECYSTECTOMY: A SINGLE CENTRE FEASIBILITY STUDY. THE OPTIMUM DOSING REGIME, LIMITATIONS AND WHERE NEXT?

British Journal of Surgery ◽

10.1093/bjs/znab117.096 ◽

2021 ◽

Vol 108 (Supplement_1) ◽

Author(s):

G Armstrong ◽

G Toogood ◽

DG Jayne ◽

AM Smith

Keyword(s):

Laparoscopic Cholecystectomy ◽

Bile Duct ◽

Indocyanine Green ◽

Feasibility Study ◽

Near Infrared ◽

Intravenous Dose ◽

Structure Identification ◽

Dosing Regimen ◽

Single Centre ◽

Fluorescent Cholangiography

Abstract Introduction This study explored near-infrared fluorescent cholangiography (NIRFC) with Indocyanine Green (ICG) during laparoscopic cholecystectomy (LC) surgery in a tertiary referral hepatobiliary unit. ICG binds to albumin and is excreted in bile. NIRFC utilises the fluorescent and excretory properties of ICG to provide dynamic extrahepatic bile duct mapping during LC. Method Non-randomised single centre feasibility study. Twenty-two participants were sequentially allocated to four dosing subgroups prior to NIRFC assisted LC. Each received a single intravenous dose of ICG prior to LC with the Stryker Novadaq NIR laparoscope. The biliary anatomy was assessed with NIRFC at three time-points, detection was compared to radiological cholangiogram where available and surgeon satisfaction was assessed. Result Eight participants received 2.5mg ICG 20-40min before surgery, four 0.25mg/kg 20-40min, five 90min – 180min and five 12 – 36 hour pre-operatively. Average age 50 years (S.D±15), BMI 27.5m2 (S.D±3.6), 6/22 were acute LC procedures. The prolonged dosing interval produced increased extrahepatic biliary structure identification (p = 0.016), reduced noise to signal ratio and was consistently preferred by the operating surgeon. NIRFC was inferior to radiological cholangiogram (n = 10) (p = 0.014) for bile duct mapping. We observed iatrogenic bile spillage saturating the field and obscuring structure differentiation and peri-hilar inflammation impeding fluorescent detection in acute LC. Conclusion The dosing regimen 0.25mg/kg ICG 12 to 36 hours prior to surgery provides optimum NIRFC structure visualisation. Fluorescent tissue penetrance is limited in acute peri-hilar inflammation. More research in to the efficiency of NIRFC in emergency LC is required. Take-home message An intravenous dose of 0.25mg/kg of Indocyanine Green 12 to 36 hours before surgery is the optimum dosing regimen for increased extra-hepatic bile duct structures with near infrared fluorescent cholangiography. The role of NIRFC in acute laparoscopic cholecystectomy surgery remains ill-defined.

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Real-time identification of hepatoblastoma using a near infrared imaging with indocyanine green

Journal of Pediatric Surgery Case Reports ◽

10.1016/j.epsc.2014.03.008 ◽

2014 ◽

Vol 2 (4) ◽

pp. 180-183 ◽

Cited By ~ 1

Author(s):

Yasuyuki Mitani ◽

Akio Kubota ◽

Masaki Ueno ◽

Katsunari Takifuji ◽

Takashi Watanabe ◽

...

Keyword(s):

Indocyanine Green ◽

Real Time ◽

Near Infrared ◽

Infrared Imaging ◽

Near Infrared Imaging ◽

Real Time Identification

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A phase II randomized clinical trial on cerebral near-infrared spectroscopy plus a treatment guideline versus treatment as usual for extremely preterm infants during the first three days of life (SafeBoosC): study protocol for a randomized controlled trial

Trials ◽

10.1186/1745-6215-14-120 ◽

2013 ◽

Vol 14 (1) ◽

pp. 120 ◽

Cited By ~ 26

Author(s):

Simon Hyttel-Sorensen ◽

Topun Austin ◽

Frank van Bel ◽

Manon Benders ◽

Olivier Claris ◽

...

Keyword(s):

Clinical Trial ◽

Randomized Controlled Trial ◽

Near Infrared ◽

Controlled Trial ◽

Treatment Guideline ◽

Treatment As Usual ◽

Randomized Controlled ◽

Extremely Preterm ◽

Extremely Preterm Infants ◽

Versus Treatment

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INDOCYANINE GREEN NEAR-INFRARED FLUORESCENCE CHOLANGIOGRAM DURING PURE LAPAROSCOPIC LIVING DONOR HEPATECTOMY FOR OPTIMAL BILE DUCT DIVISION

Transplantation Journal ◽

10.1097/01.tp.0000701176.11375.93 ◽

2020 ◽

Vol 104 (S3) ◽

pp. S498-S498

Author(s):

Ja Ryung Han ◽

Young Seok Han ◽

Jae Min Chun ◽

Yoon Jin Hwang

Keyword(s):

Bile Duct ◽

Indocyanine Green ◽

Living Donor ◽

Near Infrared ◽

Near Infrared Fluorescence ◽

Donor Hepatectomy ◽

Living Donor Hepatectomy

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Application of near-infrared fluorescent cholangiography using indocyanine green in laparoscopic cholecystectomy

Journal of International Medical Research ◽

10.1177/0300060520979224 ◽

2020 ◽

Vol 48 (12) ◽

pp. 030006052097922

Author(s):

Chusi Wang ◽

Wenguang Peng ◽

Jiarui Yang ◽

Yuxuan Li ◽

Jiawei Yang ◽

...

Keyword(s):

Laparoscopic Cholecystectomy ◽

Bile Duct ◽

Postoperative Complications ◽

Blood Loss ◽

Near Infrared ◽

Hepatic Duct ◽

Operation Time ◽

Common Hepatic Duct ◽

Intraoperative Blood Loss ◽

Real Time Identification

Objective Near-infrared fluorescence cholangiography (NIRF-C) can help to identify the bile duct during laparoscopic cholecystectomy. This retrospective study was performed to investigate the effect of NIRF-C in laparoscopic cholecystectomy. Methods Consecutive patients who underwent NIRF-C-assisted laparoscopic cholecystectomy (n = 34) or conventional laparoscopic cholecystectomy (n = 36) were enrolled in this study. Identification of biliary structures, the operation time, intraoperative blood loss, and postoperative complications were analyzed. Results Laparoscopic cholecystectomy was completed in all patients without conversion to laparotomy. The median operation time and intraoperative blood loss were not significantly different between the two groups. No intraoperative injuries or postoperative complications occurred in either group. In the NIRF-C group, the visualization rate of the cystic duct, common bile duct, and common hepatic duct prior to dissection was 91%, 79%, and 53%, respectively. The success rate of cholangiography was 100% in the NIRF-C group. NIRF-C was more effective for visualizing biliary structures in patients with a BMI of <25 than >25 kg/m2. Conclusions NIRF-C is a safe and effective technique that enables real-time identification of the biliary anatomy during laparoscopic cholecystectomy. NIRF-C helps to improve the efficiency of dissection.

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Abstract LB-025: Fluorescence-guided surgery using the fluorescence in near-infrared II window of indocyanine green for resection of glioma: A randomized controlled trial

10.1158/1538-7445.am2020-lb-025 ◽

2020 ◽

Author(s):

Zhenhua Hu ◽

Xiaojing Shi ◽

Zhe Zhang ◽

Zeyu Zhang ◽

Caiguang Cao ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Indocyanine Green ◽

Near Infrared ◽

Controlled Trial ◽

Guided Surgery ◽

Randomized Controlled ◽

Fluorescence Guided Surgery

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Fluorescent Imaging With Indocyanine Green During Laparoscopic Cholecystectomy in Patients at Increased Risk of Bile Duct Injury

Surgical Innovation ◽

10.1177/1553350617690309 ◽

2017 ◽

Vol 24 (3) ◽

pp. 245-252 ◽

Cited By ~ 21

Author(s):

Marjolein Ankersmit ◽

Dieuwertje A. van Dam ◽

Anne-Sophie van Rijswijk ◽

Baukje van den Heuvel ◽

Jurriaan B. Tuynman ◽

...

Keyword(s):

Laparoscopic Cholecystectomy ◽

Bile Duct ◽

Indocyanine Green ◽

Bile Duct Injury ◽

Near Infrared ◽

Fluorescent Imaging ◽

Added Value ◽

Optimal Dosage ◽

Nir Light ◽

Increased Risk

Background. Although rare, injury to the common bile duct (CBD) during laparoscopic cholecystectomy (LC) can be reduced by better intraoperative visualization of the cystic duct (CD) and CBD. The aim of this study was to establish the efficacy of early visualization of the CD and the added value of CBD identification, using near-infrared (NIR) light and the fluorescent agent indocyanine green (ICG), in patients at increased risk of bile duct injury. Materials and Methods. Patients diagnosed with complicated cholecystitis and scheduled for LC were included. The CBD and CD were visualized with NIR light before and during dissection of the liver hilus and at critical view of safety (CVS). Results. Of the 20 patients originally included, 2 were later excluded due to conversion. In 6 of 18 patients, the CD was visualized early during dissection and prior to imaging with conventional white light. The CBD was additionally visualized with ICG-NIR in 7 of 18 patients. In 1 patient, conversion was prevented due to detection of the CD and CBD with ICG-NIR. Conclusions. Early visualization of the CD or additional identification of the CBD using ICG-NIR in patients with complicated cholecystolithiasis can be helpful in preventing CBD injury. Future studies should attempt to establish the optimal dosage and time frame for ICG administration and bile duct visualization with respect to different gallbladder pathologies.

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NurOwn, phase 2, randomized, clinical trial in patients with ALS

Neurology ◽

10.1212/wnl.0000000000008620 ◽

2019 ◽

Vol 93 (24) ◽

pp. e2294-e2305 ◽

Cited By ~ 9

Author(s):

James D. Berry ◽

Merit E. Cudkowicz ◽

Anthony J. Windebank ◽

Nathan P. Staff ◽

Margaret Owegi ◽

...

Keyword(s):

Clinical Trial ◽

Disease Progression ◽

Randomized Clinical Trial ◽

Rating Scale ◽

Controlled Trial ◽

Early Time ◽

Phase 2 ◽

Post Transplantation ◽

Monocyte Chemoattractant Protein 1 ◽

Time Points

ObjectiveTo determine the safety and efficacy of mesenchymal stem cell (MSC)-neurotrophic factor (NTF) cells (NurOwn®, autologous bone marrow-derived MSCs, induced to secrete NTFs) delivered by combined intrathecal and intramuscular administration to participants with amyotrophic lateral sclerosis (ALS) in a phase 2 randomized controlled trial.MethodsThe study enrolled 48 participants randomized 3:1 (treatment: placebo). After a 3-month pretransplant period, participants received 1 dose of MSC-NTF cells (n = 36) or placebo (n = 12) and were followed for 6 months. CSF was collected before and 2 weeks after transplantation.ResultsThe study met its primary safety endpoint. The rate of disease progression (Revised ALS Functional Rating Scale [ALSFRS-R] slope change) in the overall study population was similar in treated and placebo participants. In a prespecified rapid progressor subgroup (n = 21), rate of disease progression was improved at early time points (p < 0.05). To address heterogeneity, a responder analysis showed that a higher proportion of treated participants experienced ≥1.5 points/month ALSFRS-R slope improvement compared to placebo at all time points, and was significant in rapid progressors at 4 and 12 weeks (p = 0.004 and 0.046, respectively). CSF neurotrophic factors increased and CSF inflammatory biomarkers decreased in treated participants (p < 0.05) post-transplantation. CSF monocyte chemoattractant protein-1 levels correlated with ALSFRS-R slope improvement up to 24 weeks (p < 0.05).ConclusionA single-dose transplantation of MSC-NTF cells is safe and demonstrated early promising signs of efficacy. This establishes a clear path forward for a multidose randomized clinical trial of intrathecal autologous MSC-NTF cell transplantation in ALS.Classification of evidenceThis phase II study provides Class I evidence.

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