Indocyanine Green Angiography Combined With Near-infrared Fluorescence Imaging System To Achieve Intraoperative Navigation Of Perforating Vessels

BackgroundHigh-quality survival of the flap is the premise and basis for the wide application of perforator flap.In order to ensure a good perfusion of the flap,it is crucial to choose an appropriate perforator as the nutrient vessel of the perforator flap.However,perforating vessels have the characteristics of a relatively small caliber,anatomic variations of its course and location,accurate localization of perforating vessels still challenges plastic surgeons.The hand-held Doppler(HHD),color Doppler ultrasound(CDU),computed tomography angiography(CTA),and magnetic resonance angiography(MRA)have been utilized to explore the location and course of perforators.However,the above-mentioned equipment or technologies have some drawbacks,including the inability to localize perforating vessels intraoperatively,a certain false positive rate,and radiation exposure of the patients.Indocyanine green angiography combined with the fluorescence imaging system(ICGA-SPY system)can be effectively used to localize perforators.This study aims to investigate the accuracy of the ICGA-SPY system in detecting the perforating vessels,which includes four parts.Firstly,through animal experimental study,we evaluated the accuracy of the ICGA-SPY system in perforator localization,studied the effects of the perforator diameter,flap thickness,dermis thickness and subcutaneous tissue thickness on the accuracy of the outcomes,and explored the maximum flap thickness and dermis thickness that ICGA-SPY system can accurately localize the perforator.Secondly,to evaluate the advantages of the ICGA-SPY system in terms of accuracy of perforator localization as compared to the results of HHD exploration,a retrospective analysis of all cases in which perforator localization was performed using the ICGA-SPY system,and to analyze the value of the ICGA-SPY system in clinical settings.Finally,we applied the ICGA-SPY system to perforator propeller flap and medial arm flap surgery and evaluated the efficacy of this technique in guiding surgical design,improving surgical outcomes,and reducing complications.In this study,we evaluate the efficacy of the ICGA-SPY system for localizing perforators in the clinic and investigate the accuracy of this system by comparing it with other perforator mapping techniques,as well as explore the relevant factors affecting the accuracy of the technique.By applying the ICGA-SPY system,a real-time and dynamic perforator localization during surgery is achieved to guide the surgery and ensure the safety of perforator flap surgery.ObjectivesPart Ⅰ:Most of the commonly used perforator localization techniques can only explore the location of the perforators preoperatively.Although the ICGA-SPY system enables real-time,dynamic exploration of perforating vessels intraoperatively,however,the accuracy of exploration is not stable.Therefore,we conducted animal studies to investigate the accuracy of the ICGA-SPY system for perforator localization,as well as the factors affecting its accuracy.Part Ⅱ:Perforator flaps have been widely used in the field of reconstructive surgery,however,there is great anatomical variation in the perforators.The ICGA-SPY system enables real-time,dynamic,and repeated intraoperative exploration of perforating vessels.The accuracy and advantages of the ICGA-SPY system for localizing perforators were evaluated by a review of clinical data.Part Ⅲ:Congenital melanocytic nevus(CMN)is a common congenital malformation that severely affects patient appearance,and surgical resection remains the treatment of choice.We used the ICGA-SPY system to explore the location of perforators and evaluated the feasibility of using the perforator propeller flap(PPF)to repair the defect after CMN resection.Part Ⅳ:The medial arm flap is commonly used for cervicofacial defect reconstruction.However,the main drawback is that the upper extremities need to be raised and immobilized with the head and neck during the flap transfer.In appropriate cases,with the assistance of the ICGA-SPY system and tissue expansion technique,the passive position of the upper extremity can be avoided,thus reducing postoperative discomfort or functional damage of the shoulder joint.MethodsPart Ⅰ:The ICGA-SPY system and CTA were applied to detect perforators in 10 Guangxi Bama mini-pigs with 80 sub-observed areas.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of the ICGA-SPY system for perforator localization were calculated.Spearman and Pearson correlation analyses were performed to assess whether perforator caliber,flap thickness,dermal thickness,and subcutaneous tissue thickness affected the accuracy of perforator localization using the ICGA-SPY system.After that,the specific relationship between each factor and the localization accuracy of the ICGA-SPY system was investigated by multiple linear regression analysis.Finally,ROC curves were drawn,and cut-off values were calculated to determine the maximum flap thickness and dermal thickness at which perforators can be accurately detected by the ICGA-SPY system.Part Ⅱ:In this study,we retrospectively analyzed the data of 81 patients who underwent intraoperative real-time perforator localization using the ICGA-SPY system.Pearson Chi-Square test was applied to study the differences between the ICGA-SPY system and HHD in localizing perforators.Sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and effective predictive rate of the flap pedicle were calculated to evaluate the accuracy of perforator localization of the ICGA-SPY system.Factors affecting the accuracy of perforator localization of the ICGA-SPY system were analyzed by multiple linear regression.Part Ⅲ:We reviewed all the clinical information of patients who underwent PPF surgery for defect reconstruction after CMN resection between May 2016 and March 2021.The results of the ICGA-SPY system that was used for perforator localization and flap perfusion assessment were summarized and analyzed,as well as the causes of related complications.Part Ⅳ:This retrospective study was performed using data from 14 patients who underwent cervicofacial reconstruction using the pre-expanded medial arm flap.The ICGA-SPY system was used to locate perforators and evaluate the flap perfusion.The possibility of avoiding passive immobilization posture of the upper extremity during flap transfer was also discussed.ResultsPart Ⅰ:The ICGA-SPY system and CTA were used to localize perforators in 80 sub-observed areas,and 184 and 190 perforators were detected,respectively.The sensitivity,specificity,positive predictive value,negative predictive value,and accuracy of the ICGA-SPY system were 67.76%,55.68%,78.80%,41.53%and 64.24%,respectively.Spearman correlation analysis showed that the accuracy of the perforator localization by the ICGA-SPY system was weakly correlated with the perforator vessel caliber(r=-0.207,P<0.05),but strongly correlated with the thickness of the flap,dermis,and subcutaneous tissue(r=-0.561,P<0.05;r=-0.445,P<0.05;r=-0.473,P<0.05)after analysis by Pearson correlation.Multi-factor linear regression analysis revealed that flap thickness(X1)and dermis thickness(X2)were the main factors influencing the accuracy(Y)of the ICGA-SPY system for perforator localization,with a regression model relationship of Y=1.512-0.635 X1-0.652 X2.The ROC curve analysis revealed a cutoff value of 1.06 cm for flap thickness and 0.32 cm for dermal layer thickness for accurate perforator localization with the ICGA-SPY system.Part Ⅱ:Eighty-one patients and 84 flaps were included in the retrospective study.Sixty-one and 147 perforators were detected using the HHD and ICGA-SPY system,respectively.Pearson’s chi square test indicated that the HHD and ICGA-SPY system differed significantly in the localization of perforators(x2=58.14;P<0.05).The sensitivity,specificity,positive predictive value,negative predictive value,accuracy,and effective predictive rate of flap pedicles by the ICGA-SPY system were 78.26%,48.78%,85.71%,36.36%,72.28%,and 62.59%,respectively.Multiple linear regression analysis showed that both gender and location of the perforator exploration significantly affected the effective prediction rate of the flap pedicle when the ICGA-SPY system was used for perforator localization.Part Ⅲ:A total of 36 PPFs were used to reconstruct defects after nevi resection,of which 23 PPFs were used to reconstruct the defects in one stage and 13 flaps were preexpanded before reconstruction.The flap size ranged from 7.5 cm2 to 437 cm2.The ICGASPY system localized a total of 70 perforators,and the position of 39 perforators were consistent with the intraoperative exploration findings.Intraoperatively,hypoperfusion were found in the distal part of three flaps.One of the poor perfused areas of the flap was directly excised intraoperatively,and the other two poor perfused areas were trimmed into full-thickness skin graft with subdermal vascular network.Another three flaps suffered from temporary venous congestion and all of them was relieved by conservative management.All flaps survived without any major complications.The patients were satisfied with the outcomes at a mean follow-up period of 8.1 months.Part IV:A total of 15 full-length medial arm flaps with a mean flap area of 203.9cm2 and a flap length of 20-28cm were included.All perforators identified by the ICGA-SPY system could be found during the surgery.The ICGA-SPY system showed the presence of poor perfusion in the distal parts of four flaps.The aforementioned hypoperfused areas were removed in combination with the reconstructive needs.Donor sites were primarily closed or repaired by using an additional flap.All flaps survived without any major complications.The patients and their families were satisfied with the outcomes between 1 to 22 months of follow-up.ConclusionsPart Ⅰ:The ICGA-SPY system can be used for intraoperative perforator localization,however the accuracy of localization correlates with flap thickness as well as with dermal thickness.The accuracy of localization decreased with the increase of the thickness of flap and dermis.When the flap thickness is greater than 1.06 cm or dermal thickness is greater than 0.32 cm,the location of the perforator cannot be accurately detected by the ICGASPY system.Therefore,the ICGA-SPY system is more suitable for localizing perforators of thinner flaps.The ICGA-SPY system can be used to explore the perforator path at the superficial level of the flap,assess the corresponding perforasome and flap perfusion in areas with a thicker flap or with a thick dermal layer.Part Ⅱ:The ICGA-SPY system allows accurate intraoperative real-time localization of the perforating vessels,but the accuracy of prediction of the vascular pedicle of the flap is affected by gender and the region explored.In thinner areas of skin such as the medial arm,the ICGA-SPY system can accurately localize the perforator intraoperatively;however,in thicker skin areas such as the thigh,the accuracy of perforator localization decreases.In these sites,perforator mapping with the ICGA-SPY system alone is not recommended and can be combined with other preoperative perforator mapping methods such as CTA to improve the accuracy and reliability of perforator exploration.In addition,the ICGA-SPY system has a higher accuracy in predicting the flap pedicle in female patients compared with male patients.Part Ⅲ:Assisted by the ICGA-SPY system,the PPF can be used to reconstruct defects following resection of the CMN.The ICGA-SPY system allows accurate localization of the perforator of the PPF and accurate assessment of the flap perfusion.Part Ⅳ:With the assistance of the ICGA-SPY system and tissue expansion technique,the pre-expanded medial arm flap can be used to reconstruct cervicofacial defects,and for strictly selected patients,passive posture of the upper extremity can be avoided during the flap transfer.