Contemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the... Show moreContemporary quality control methods are often insufficient in predicting clinical outcomes after revascularization in lower extremity arterial disease (LEAD) patients. This study evaluates the potential of near-infrared fluorescence imaging with indocyanine green to predict the clinical outcome following revascularization. Near-infrared fluorescence imaging was performed before and within 5 days following the revascularization procedure. Clinical improvement was defined as substantial improvement of pain free walking distance, reduction of rest- and/or nocturnal pain, or tendency toward wound healing. Time-intensity curves and 8 perfusion parameters were extracted from the dorsum of the treated foot. The quantified postinterventional perfusion improvement was compared within the clinical outcome groups. Successful near-infrared fluorescence imaging was performed in 72 patients (76 limbs, 52.6% claudication, 47.4% chronic limb-threatening ischemia) including 40 endovascular- and 36 surgical/hybrid revascularizations. Clinical improvement was observed in 61 patients. All perfusion parameters showed a significant postinterventional difference in the clinical improvement group (P-values <.001), while no significant differences were seen in the group without clinical improvement (P-values .168-.929). Four parameters demonstrated significant differences in percentage improvement comparing the outcome groups (P-values within .002-.006). Near-infrared fluorescence imaging has promising additional value besides clinical parameters for predicting the clinical outcome of revascularized LEAD patients. Show less
Tange, F.P.; Ferrari, B.R.; Hoven, P. van den; Schaik, J. van; Schepers, A.; Rijswijk, C.S.P. van; ... ; Vorst, J.R. van der 2023
Background: The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization (DR) is... Show moreBackground: The angiosome concept is defined as the anatomical territory of a source artery within all tissue layers. When applying this theory in vascular surgery, direct revascularization (DR) is preferred to achieve increased blood flow toward the targeted angiosome of the foot in patients with lower extremity arterial disease (LEAD). This study evaluates the applicability of the angiosome concept using quantified near-infrared (NIR) fluorescence imaging with indocMethods: This study included patients undergoing an endovascular- or surgical revascularization of the leg between January 2019 and December 2021. Preinterventional and postinterventional ICG NIR fluorescence imaging was performed. Three angiosomes on the dorsum of the foot were determined: the posterior tibial artery (hallux), the anterior tibial artery (dorsum of the foot) and the combined angiosome (second to fifth digit). The angiosomes were classified from the electronic patient records and the degree of collateralization was classified based on preprocedural computed tomography angiography and/or X-ray angiography. Fluorescence intensity was quantified in all angiosomes. A subgroup analysis based on endovascular or surgical revascularized angiosomes, and within critical limb threatening ischemia (CLTI) patients was performed. Results: ICG NIR fluorescence measurements were obtained in 52 patients (54 limbs) including a total of 157 angiosomes (121 DR and 36 indirect revascularizations [IR]). A significant improvement of all perfusion parameters in both the directly and indirectly revascularized angiosomes was found (P-values between <0.001e0.007). Within the indirectly revascularized angiosomes, 90.6% of the scored collaterals were classified as significant. When comparing the percentual change in perfusion parameters between the directly and indirectly revascularized angiosomes, no significant difference was seen in all perfusion parameters (P-values between 0.253 and 0.881). Similar results were shown in the CLTI patients subgroup analysis, displaying a significant improvement of perfusion parameters in both the direct and indirect angiosome groups (P-values between <0.001 and 0.007), and no significant difference when comparing the percentual parameter improvement between both angiosome groups (P-values between 0.134 and 0.359). Furthermore, no significant differences were observed when comparing Show less
Hoven, P. van den; Osterkamp, J.; Nerup, N.; Svendsen, M.B.S.; Vahrmeijer, A.; Vorst, J.R. van der; Achiam, M.P. 2023
PurposeIncorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a... Show morePurposeIncorrect assessment of tissue perfusion carries a significant risk of complications in surgery. The use of near-infrared (NIR) fluorescence imaging with Indocyanine Green (ICG) presents a possible solution. However, only through quantification of the fluorescence signal can an objective and reproducible evaluation of tissue perfusion be obtained. This narrative review aims to provide an overview of the available quantification methods for perfusion assessment using ICG NIR fluorescence imaging and to present an overview of current clinically utilized software implementations.MethodsPubMed was searched for clinical studies on the quantification of ICG NIR fluorescence imaging to assess tissue perfusion. Data on the utilized camera systems and performed methods of quantification were collected.ResultsEleven software programs for quantifying tissue perfusion using ICG NIR fluorescence imaging were identified. Five of the 11 programs have been described in three or more clinical studies, including Flow (R) 800, ROIs Software, IC Calc, SPY-Q (TM), and the Quest Research Framework (R). In addition, applying normalization to fluorescence intensity analysis was described for two software programs.ConclusionSeveral systems or software solutions provide a quantification of ICG fluorescence; however, intraoperative applications are scarce and quantification methods vary abundantly. In the widespread search for reliable quantification of perfusion with ICG NIR fluorescence imaging, standardization of quantification methods and data acquisition is essential. Show less
Hoven, P. van den; Verduijn, P.S.; Capelle, L. van; Tange, F.P.; Michi, M.; Corion, L.U.M.; ... ; Vorst, J.R. van der 2022
Background: One of the complications of free flap breast reconstruction is the oc-currence of skin and fat necrosis. Intra-operative use of near-infrared (NIR) fluorescence imag-ing with... Show moreBackground: One of the complications of free flap breast reconstruction is the oc-currence of skin and fat necrosis. Intra-operative use of near-infrared (NIR) fluorescence imag-ing with Indocyanine Green (ICG) has the potential to predict these complications. In this study, the quantification of the fluorescence intensity measured in free flap breast reconstruction was performed to gain insight into the perfusion patterns observed with ICG NIR fluorescence imag-ing.Methods: ICG NIR fluorescence imaging was performed in patients undergoing free flap breast reconstruction following mastectomy. After completion of the arterial and venous anastomosis, 7.5 mg ICG was administered intravenously. The fluorescence intensity over time was recorded using the Quest Spectrum Platform (R). Four regions of interest (ROI) were selected based on location and interpretation of the NIR fluorescence signal: (1) The perforator, (2) normal per -fusion, (3) questionable perfusion, and (4) low perfusion. Time-intensity curves were analyzed, and two parameters were extracted: Tmax and Tmax slopes.Results: Successful ICG NIR fluorescence imaging was performed in 13 patients undergoing 17 free flap procedures. Region selection included 16 perforators, 17 normal perfusions, 8 ques-tionable perfusions, and 5 low perfusion ROIs. Time-intensity curves of the perforator ROIs were comparable to the ROIs of normal perfusion and demonstrated a fast inflow. No outflow was observed for the ROIs with questionable and low perfusion.Conclusion: This study provides insight into the perfusion patterns observed with ICG NIR flu-orescence imaging in free flap breast reconstruction. Future studies should correlate quantita-tive parameters with clinical perfusion assessment and outcome.(c) 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Pub-lished by Elsevier Ltd. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ) Show less
Near-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable... Show moreNear-infrared (NIR) fluorescence imaging with indocyanine green (ICG) is a promising imaging technique for the assessment of tissue perfusion. This thesis describes the quest for valid and reliable quantitative assessment of tissue perfusion using this technique, predominantly in patients with lower extremity arterial disease. Two systematic reviews were performed, describing the experience with ICG NIR fluorescence imaging within various surgical fields. In three original studies, perfusion patterns were described in various groups, including lower extremity arterial disease, healthy controls and in patients undergoing free flap reconstructive breast surgery. By applying normalization to the quantitative assessment, an increased validity and reliability was seen. To describe potential clinical applications, the use of ICG NIR fluorescence imaging was described for two indications. In patients undergoing unilateral revascularization, quantitative assessment showed an increase of inflow parameters, whilst parameters in the untreated side remained unchanged. In a cohort of patients undergoing amputation surgery, ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Future use of ICG NIR fluorescence imaging should focus on improving validity and reliability of quantitative perfusion assessment. Show less
Hoven, P. van den; Tange, F.; Valk, J. van der; Nerup, N.; Putter, H.; Rijswijk, C. van; ... ; Vorst, J. van der 2022
Purpose: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower... Show morePurpose: Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) is gaining popularity for the quantification of tissue perfusion, including foot perfusion in patients with lower extremity arterial disease (LEAD). However, the absolute fluorescence intensity is influenced by patient-and system-related factors limiting reliable and valid quantification. To enhance the quality of quantitative perfusion assessment using ICG NIR fluorescence imaging, normalization of the measured time-intensity curves seems useful. Materials and Methods: In this cohort study, the effect of normalization on 2 aspects of ICG NIR fluorescence imaging in assessment of foot perfusion was measured: the repeatability and the region selection. Following intravenous administration of ICG, the NIR fluorescence intensity in both feet was recorded for 10 mins using the Quest Spectrum platform(R). The effect of normalization on repeatability was measured in the nontreated foot in patients undergoing unilateral revascularization preprocedural and postprocedural (repeatability group). The effect of normalization on region selection was performed in patients without LEAD (region selection group). Absolute and normalized time-intensity curves were compared. Results: Successful ICG NIR fluorescence imaging was performed in 54 patients (repeatability group, n = 38; region selection group, n = 16). For the repeatability group, normalization of the time-intensity curves displayed a comparable inflow pattern for repeated measurements. For the region selection group, the maximum fluorescence intensity (Imax) demonstrated significant differences between the 3 measured regions of the foot (P = .002). Following normalization, the time-intensity curves in both feet were comparable for all 3 regions. Conclusion: This study shows the effect of normalization of time-intensity curves on both the repeatability and region selection in ICG NIR fluorescence imaging. The significant difference between absolute parameters in various regions of the foot demonstrates the limitation of absolute intensity in interpreting tissue perfusion. Therefore, normalization and standardization of camera settings are essential steps toward reliable and valid quantification of tissue perfusion using ICG NIR fluorescence imaging. Show less
Hoven, P. van den; Berg, S.D. van den; Valk, J.P. van der; Krogt, H. van der; Doorn, L.P. van; Bogt, K.E.A. van de; ... ; Vorst, J.R. van der 2022
Background: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is... Show moreBackground: Patients with chronic limb threatening ischemia have a risk of undergoing a major amputation within 1 year of nearly 30% with a substantial risk of re-amputation since wound healing is often impaired. Quantitative assessment of regional tissue viability following amputation surgery can identify patients at risk for impaired wound healing. In quantification of regional tissue perfusion, near-infrared (NIR) fluorescence imaging using Indocyanine Green (ICG) seems promising. Methods: This pilot study included adult patients undergoing lower extremity amputation surgery due to peripheral artery disease or diabetes mellitus. ICG NIR fluorescence imaging was performed within 5 days following amputation surgery using the Quest Spectrum Platform (R). Following intravenous administration of ICG, the NIR fluorescence intensity of the amputation wound was recorded for 10 minutes. The NIR fluorescence intensity videos were analyzed and if a fluorescence deficit was observed, this region was marked as "low fluorescence." All other regions were marked as "normal fluorescence." Results: Successful ICG NIR fluorescence imaging was performed in 10 patients undergoing a total of 15 amputations. No "low fluorescence" regions were observed in 11 out of 15 amputation wounds. In 10 out of these 11 amputations, no wound healing problems occurred during followup. Regions with "low fluorescence" were observed in 4 amputation wounds. Impaired wound healing corresponding to these regions was observed in all wounds and a re-amputation was necessary in 3 out of 4. When observing time-related parameters, regions with low fluorescence had a significantly longer time to maximum intensity (113 seconds vs. 32 seconds, P = 0.003) and a significantly lesser decline in outflow after five minutes (80.3% vs. 57.0%, P = 0.003). Conclusions: ICG NIR fluorescence imaging was able to predict postoperative skin necrosis in all four cases. Quantitative assessment of regional perfusion remains challenging due to influencing factors on the NIR fluorescence intensity signal, including camera angle, camera distance and ICG dosage. This was also observed in this study, contributing to a large variety in fluorescence intensity parameters among patients. To provide surgeons with reliable NIR fluorescence cut-off values for prediction of wound healing, prospective studies on the intraoperative use of this technique are required. The potential prediction of wound healing using ICG NIR fluorescence imaging will have a huge impact on patient mortality, morbidity as well as the burden of amputation surgery on health care. Show less
Hoven, P. van den; Goncalves, L.N.; Quax, P.H.A.; Rijswijk, C.S.P. van; Schaik, J. van; Schepers, A.; ... ; Vorst, J.R. van der 2021
In assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current... Show moreIn assessing the severity of lower extremity arterial disease (LEAD), physicians rely on clinical judgements supported by conventional measurements of macrovascular blood flow. However, current diagnostic techniques provide no information about regional tissue perfusion and are of limited value in patients with chronic limb-threatening ischemia (CLTI). Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has been used extensively in perfusion studies and is a possible modality for tissue perfusion measurement in patients with CLTI. In this prospective cohort study, ICG NIR fluorescence imaging was performed in patients with CLTI and control patients using the Quest Spectrum Platform(R) (Middenmeer, The Netherlands). The time-intensity curves were analyzed using the Quest Research Framework. Fourteen parameters were extracted. Successful ICG NIR fluorescence imaging was performed in 19 patients with CLTI and in 16 control patients. The time to maximum intensity (seconds) was lower for CLTI patients (90.5 vs. 143.3, p = 0.002). For the inflow parameters, the maximum slope, the normalized maximum slope and the ingress rate were all significantly higher in the CLTI group. The inflow parameters observed in patients with CLTI were superior to the control group. Possible explanations for the increased inflow include damage to the regulatory mechanisms of the microcirculation, arterial stiffness, and transcapillary leakage. Show less
Hoven, P. van den; Weller, F.S.; Bent, M. van de; Goncalves, L.N.; Ruig, M.; Berg, S.D. van den; ... ; Vorst, J.R. van der 2021
Objectives Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR)... Show moreObjectives Current diagnostic modalities for patients with peripheral artery disease (PAD) mainly focus on the macrovascular level. For assessment of tissue perfusion, near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) seems promising. In this prospective cohort study, ICG NIR fluorescence imaging was performed pre- and post-revascularization to assess changes in foot perfusion. Methods ICG NIR fluorescence imaging was performed in 36 patients with PAD pre- and post-intervention. After intravenous bolus injection of 0.1 mg/kg ICG, the camera registered the NIR fluorescence intensity over time on the dorsum of the feet for 15 min using the Quest Spectrum Platform (R). Time-intensity curves were plotted for three regions of interest (ROI): (1) the dorsum of the foot, (2) the forefoot, and (3) the hallux. Time-intensity curves were normalized for maximum fluorescence intensity. Extracted parameters were the maximum slope, area under the curve (AUC) for the ingress, and the AUC for the egress. The non-treated contralateral leg was used as a control group. Results Successful revascularization was performed in 32 patients. There was a significant increase for the maximum slope and AUC egress in all three ROIs. The most significant difference was seen for the maximum slope in ROI 3 (3.7%/s to 6.6%/s, p < 0.001). In the control group, no significant differences were seen for the maximum slope and AUC egress in all ROIs. Conclusions This study shows the potential of ICG NIR fluorescence imaging in assessing the effect of revascularization procedures on foot perfusion. Future studies should focus on the use of this technique in predicting favorable outcome of revascularization procedures. Show less
Goncalves, L.N.; Hoven, P. van den; Schaik, J. van; Leeuwenburgh, L.; Hendricks, C.H.F.; Verduijn, P.S.; ... ; Vorst, J.R. van der 2021
(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... Show more(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. Show less
Hoven, P. van den; Ooms, S.; Manen, L. van; Bogt, K.E.A. van der; Schaik, J. van; Hamming, J.F.; ... ; Mieog, J.S.D. 2019
Objective: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe... Show moreObjective: In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe media sclerosis. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) can provide information about tissue perfusion and has already been studied in oncologic, reconstructive, and cardiac surgery. For patients with PAD, this technique might give insight into skin perfusion and thereby guide treatment. We performed a systematic review of the literature on the use of NIR fluorescence imaging in patients with PAD.Methods: PubMed, MEDLINE, Embase, and Cochrane were searched for articles and abstracts on the application of NIR fluorescence imaging using ICG as fluorescent dye in patients with PAD. Our search strategy combined the terms "fluorescence," "ICG," or synonyms and "peripheral artery disease" or synonyms. The extracted data included fluorescence parameters and test characteristics for diagnosis of PAD.Results: Twenty-three articles were found eligible for this review using 18 different parameters for evaluation of the fluorescence signal intensity. NIR fluorescence imaging was used for four main indications: diagnosis, quality control in revascularization, guidance in amputation surgery, and visualization of vascular structures. For the diagnosis of PAD, NIR fluorescence imaging yields a sensitivity ranging from 67% to 100% and a specificity varying between 72% and 100%. Significant increases in multiple fluorescence parameters were found in comparing patients before and after revascularization.Conclusions: NIR fluorescence imaging can be used for several indications in patients with PAD. NIR fluorescence imaging seems promising in diagnosis of PAD and guidance of surgeons in treatment, especially in patients in whom current diagnostic methods are not applicable. Further standardization is needed to reliably use this modality in patients with PAD. Show less
Hulle, T. van der; Exter, P.L. den; Hoven, P. van den; Hoeven, J.J. van der; Meer, F.J.M. van der; Eikenboom, J.; ... ; Klok, F.A. 2016
