Fluorescence Imaging for Assessing Tissue Perfusion After Revascularization in Peripheral Arterial Disease

Fluorescence Imaging for Assessing Tissue Perfusion After Revascularization in Peripheral Arterial Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Fluorescence Imaging for Assessing Tissue Perfusion After Revascularization in Peripheral Arterial Disease Michaela Kluckner, Philipp H. von Kroge, Anna Duprée, David Wippel, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8621154/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted 13 You are reading this latest preprint version Abstract Purpose Methods for assessing peripheral arterial disease (PAD) include ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO₂) measurements. Fluorescence imaging with indocyanine green (FI) has been proposed as a promising tool for tissue perfusion assessment, despite lack of robust evidence due to small study cohorts or missing comparison of methods. Methods In this prospective study, patients underwent FI, TcPO₂, and ABI measurements before and after revascularization. FI quantification included slope of fluorescence intensity (SFI), background-subtracted peak fluorescence intensity (BSFI), and time to peak (TTP). The primary objective was to assess FI-derived metrics compared to ABI and TcPO₂ after successful revascularization. Results Out of 95 patients 67% showed improved perfusion in FI after revascularization. Worsened perfusion was observed in 18% of patients, characterized by reduced SFI and BSFI and prolonged TTP, while no significant changes were seen in patients with unchanged perfusion. FI-derived parameters showed no correlation with ABI, TcPO₂, or clinical outcomes. Conclusion FI did not reliably detect perfusion improvement despite successful revascularization and showed no association with clinical outcomes or established measures. In contrast, TcPO₂ demonstrated a strong correlation with clinical results. These findings question the reliability of FI for post-procedural perfusion assessment and suggest inferiority compared with TcPO₂. Health sciences/Cardiology Health sciences/Diseases Health sciences/Medical research Arteriosclerosis Indocyanine green tissue perfusion Quantification transcutaneous oxygen pressure measurement Figures Figure 1 Figure 2 Figure 3 Introduction With over 230 million affected people, peripheral artery disease (PAD) is a globally relevant condition [ 1 ]. According to current guidelines, the ankle-brachial index (ABI) remains the diagnostic method of choice for diagnosis of PAD in everyday clinical practice. The ABI is also used for post-interventional evaluation after revascularization to determine the therapeutic success [ 2 – 4 ]. Other, more invasive, diagnostic tools include computed tomography, magnetic resonance imaging, and digital subtraction angiography. All these techniques measure macrovascular differences. However, comorbidities such as diabetes and chronic kidney disease, which are often associated with PAD, decrease the sensitivity of the ABI [ 5 ]. The tissue perfusion can be determined by transcutaneous oxygen pressure (TcPO 2 ) measured by small sensors in areas of interest, an established diagnostic tool in patients with PAD [ 3 ]. While low values are a negative predictor for wound healing, higher values are associated with successful healing [ 6 ]. Nevertheless, the objective assessment of tissue perfusion in patients with PAD remains difficult. Therefore, other methods have been investigated. Among these, fluorescence imaging with indocyanine green (FI) has shown potential. FI, as a diagnostic tool, was initially described in the 1950s for cardiac diagnostics [ 7 ]. Since then, it has been utilized in various medical fields, including ophthalmology, visceral and reconstructive surgery, and has been particularly advertised for evaluating tissue perfusion. Administration via peripheral intravenous route is uncomplicated, however there are contraindications and side effects [ 8 ]. Several clinical studies investigating the role of FI in patients with PAD described promising results [ 9 ]. Different cohorts with pre- and postinterventional quantification of FI using various quantification parameters could demonstrate perfusion improvements after revascularization, however the study cohorts were small, perfusion measurements were only performed at a single time point or no comparison to gold-standard methods was performed [ 10 – 15 ]. The quantification of FI in a region of interest (ROI) using time-dependent fluorescence intensity curves and resulting quantification parameters has been validated in several different non-PAD settings by our group, such as ischemia/reperfusion models in cardiac and mesenteric ischemia as well as gastric tube models [ 16 – 20 ]. In addition, the results could be successfully transferred into clinical applications [ 12 , 21 ]. The present study aimed to investigate whether FI is able to detect the post-procedural change of tissue perfusion in comparison to established and validated tissue perfusion as well as clinical parameters in a prospective PAD cohort. Methods Between October 2022 and February 2025 patients undergoing revascularization for symptomatic PAD (Rutherford categories 3 to 6) were enrolled in a prospective study at a university vascular center. Revascularization techniques included surgical, endovascular, and hybrid procedures. Exclusion criteria were hyperthyroidism, glomerular filtration rate < 30ml/min, iodine allergy, pregnancy, long-term oxygen therapy due to the administration of indocyanine green (ICG) and extensive gangrene of the foot and ulceration at the defined location of perfusion measurements to facilitate TcPO 2 sensor placement. Before revascularization the ABI and TcpO 2 measurements between Os metatarsale I and II as well as FI were performed. The post-procedural measurements were performed one to three days after the revascularization. Clinical follow-up took place three months after revascularization as part of the routine outpatient check-up. Written informed consent was obtained from each patient included in the study. The study was approved by the ethics committee of the Medical University of Innsbruck (EK Nr: 1440/2021), adhered to the declaration of Helsinki and was and registered at ClinicalTrials.gov (NCT05570019, date of registration: 2022-08-29, https://www.clinicaltrials.gov/study/NCT05570019?term=NCT05570019&rank=1 ). The primary objective of the study was to compare the FI perfusion measurements to the ABI and TcPO 2 values in terms of improvement after the technically successful revascularization. In addition, it was analysed whether the allocation to the FI groups was consistent with the results of the ABI and TcPO₂ values. The secondary outcome of the study included the correlation of the tissue perfusion measurements with the clinical status prior revascularization and the improvement afterwards. Fluorescence Imaging EleVisionTM (Medtronic GmbH, Meerbusch, Germany) was used as the technical platform for imaging. Each patient underwent FI before and after the planned intervention. A dosage of 0.1mg/kg body weight ICG (Verdye, Diagnostic Green Limited, Westmeath) was administered via peripheral vein catheter as a bolus, followed by 10 ml of water for injection. The recording was performed in a supine position for 2 minutes after the ICG administration. Further analysis of the FI was performed blinded to the intervention and patient details. A customized software package (Meteroarchive VCL LLS Fluoreszenzangiographie V 1.0, LLS GmbH, Ulm, Germany) was used. The region of interest (ROI) was defined as the area between the metatarsal bones one and two, measuring 80 x 80 pixels, the same location where the TcPO 2 measurement was performed. Explicit care was taken not to measure the signal of the dorsalis pedis artery. A time-dependent fluorescence intensity curve was generated for further calculation of perfusion parameters. Figure 1 shows a pre- and post-interventional fluorescence image with the ROIs marked and the corresponding fluorescence intensity curves. Based on the results of FI, the patient cohort was divided into three different groups. Group 1 (CP) includes patients with a SFI-ratio of 1, indicating constant perfusion, following revascularization. In Group 2 (WP), a ratio > 1 indicated worsened perfusion after the intervention, whereas Group 3 (IP) demonstrated measurable improvement with a ratio < 1. The results of the three groups were compared in terms of changes in ABI, TcPO 2 and a correlation to the clinical outcomes following revascularization was performed. Statistical analysis For statistical analysis, the Statistical Package for the Social Sciences (SPSS) statistical software, version 29.0 (IBM Corp., IBM SPSS Statistics, Armonk, NY), was used. Categorical variables are expressed as numbers (%). A Chi-square test was used for the comparison of categorical variables. Metric values are presented as means with standard deviations (SD). Metric data were tested with a paired t-test. The correlation coefficient was used to describe correlation among ABI, TcPO 2 , and FI parameters. For the comparison of the perfusion measurements between the three groups, a one-sided ANOVA for normally distributed data and a Kruskal-Wallis-test for not normally distributed data was used. A two-sided p-value < 0.05 was considered statistically significant. For post-hoc comparisons between pairs of groups, Mann-Whitney U tests were conducted. To adjust for multiple testing, the Bonferroni correction was applied, resulting in a corrected significance threshold of α = 0.0167. Results A total of 131 patients were included in the study. Due to unsuccessful revascularization/early re-occlusion (n = 10), withdrawal of consent (n = 13) or technical problems with the measurements (n = 13), a total of 95 patients were included in the final analysis. Demographics and cardiovascular risk factors for the overall cohort and the three groups are depicted in Table 1. Table 1 Demographics of the patients. CAD: coronary artery disease; CABG: coronary artery bypass graft; NOAK: new oral anticoagulation; PTCA: percutaneous transluminal coronary angioplasty; VKA: vitamin K antagonist Overall (n = 95) CP (n = 14) WP (n = 17) IP(n = 64) P value Age (median ± s.d) 69 ± 9.4 72 ± 5.7 74 ± 8 67 ± 9.6 0.003 Male 62 (65) 10 (71) 10 (59) 42 (66) 0.760 Diabetes 35 (37) 4 (29) 7 (41) 24 (38) 0.756 Hypertension 73 (77) 13 (93) 12 (71) 48 (75) 0.285 Smoker current 42 (44) 5 (36) 6 (35) 31 (48) 0.491 Smoker former 26 (27) 5 (36) 4 (24) 17 (27) 0.727 Dyslipidemia 54 (57) 7 (50) 5 11 (65) 36 (56) 0.703 CAD 44 (46) 6 (43) 5 (29) 33 (52) 0.255 S.p. PTCA 26 (27) 3 (21) 1 (6) 21 (33) 0.194 S.p. CABG 10 (11) 1 (7) 2 (12) 8 (13) 0.662 Acetylsalicylic acid 71 (76) 11 (79) 10 (59) 50 (78) 0.249 Plavix 27 (28) 4 (29) 5 (29) 18 (28) 0.994 VKA 7 (7) 1 (7) 1 (6) 5 (8) 0.963 NOAK 13 (14) 3 (21) 4 (24) 6 (9) 0.211 Statin 82 (86) 12 (86) 15 (88) 55 (86) 0.968 Metformin 16 (17) 1 (7) 3 (18) 12 (19) 0.756 Patients from the WP-group were significantly older compared to the IP-group (p = 0.003). No other significant difference was detected between the groups. An endovascular revascularization was performed in 54% (n = 51), open surgery in 28% (n = 27) and 18% (n = 17) of patients underwent hybrid procedures with no significant difference between the three groups (p = 0.741). Details on the revascularization procedures are listed in Table 2 . Table 2 Details on the revascularization procedures. PTA: percutaneous transluminal angioplasty Procedure Number (%) Femoro-popliteal bypass 10 (11) Thromboendoarterectomy of the femoral bifurcation 11 (12) Femoro-popliteal thrombectomy 4 (4) Femoro-crural bypass 1 (1) Thromboendoarterectomy of the femoral bifurcation with femoro-popliteal or iliac PTA ± stent 10 (11) Femoro-popliteal thrombectomy with PTA ± stent 7 (7) Femoro-popliteal bypass with proximal or distal PTA ± stent 1 (1) Aorto-iliac PTA 21 (22) PTA of the superficial femoral artery 24 (25) PTA of the popliteal artery 6 (6) Quantification of FI The quantification was successfully conducted in all included cases. Improved perfusion was observed in 64 (67%) patients. In contrast, perfusion remained consistent in 14 (15%) cases, while it worsened in 17 (18%) cases. In the IP-group SFI and BSFI increased while TTP shortened. All changes were statistically significant (p < 0.001). The WP-group showed exactly opposite results. SFI and BSFI decreased, while TTP extended. All changes were statistically significant (p < 0.05). The results of the CP-group showed no statistically significant changes. The quantification results are shown in Table 3 . Table 3 Pre- and post-interventional results of the FA-ICG quantification as means standard deviations). Pre: pre-interventional; post: post-interventional; SFI: slope of fluorescence intensity; BSFI: background-subtracted peak fluorescence intensity; TTP: time to peak; CP: consistent perfusion; WP: worsened perfusion; IP: improved perfusion; ** = p <0.001; * = p<0.05. Numbers are given as median ± standard deviation SFI BSFI TTP Pre Post Pre Post Pre Post IP (n = 64) 0.06 \(\:\pm\:\) 0.04 0.16 \(\:\pm\:\) 0.11** 34.3 \(\:\pm\:\) 18.3 54.0 \(\:\pm\:\) 21.1** 26.9 \(\:\pm\:\) 13.9 20.1 \(\:\pm\:\) 9.8** CP (n = 14) 0.12 \(\:\pm\:\) 0.08 0.12 \(\:\pm\:\) 0.08 53.4 \(\:\pm\:\) 24.6 49.9 \(\:\pm\:\) 10.1 24.4 \(\:\pm\:\) 13.9 21.7 \(\:\pm\:\) 13.4 WP (n = 17) 0.20 \(\:\pm\:\) 0.16 0.07 \(\:\pm\:\) 0.03* 62.6 \(\:\pm\:\) 26.8 38.1 \(\:\pm\:\) 18.1* 24.8 \(\:\pm\:\) 13.1 27.1 \(\:\pm\:\) 11.5* Comparison of perfusion measurements The median ABI prior revascularization was 0.5 ± 0.17, the median TcPO 2 value was 41 ± 21.2 mmHg. After revascularization, the median ABI was 0.82 ± 0.23 with a median improvement of 0.42 ± 0.31 (p < 0.001). The median improvement of the TcPO 2 was 15.6 ± 27.1 mmHg with a median value of 56.6 ± 24.9 mmHg (p < 0.001). No significant correlation between TcPO 2 measurements and the three different FI parameters before and after revascularization was found (pre: SFI: R = 0.08, p = 0.426, BSFI: R=-0.03, p = 0.773, TTP: R=-0.003, p = 0.978; post: SFI: R = 0.02, p = 0.852, BSFI: R=-0.12, p = 0.258, TTP: R=-0.19, p = 0.063). Furthermore, no significant difference was detected in absolute ABI- and TcPO 2 values prior and post revascularization between the three groups (pre: ABI: p = 0.895, TcPO 2 : p = 0.566; post: ABI: p = 0.880, TcPO 2 : p = 0.249). Also, the improvement of TcPO 2 values was not significantly different between the three groups (p = 0.186). In the CP-group, the median improvement was + 2.9 ± 17.1 mmHg, in the WP-group it was + 18.8 ± 37.2 mmHg and IP-group + 17 ± 25.4 mmHg. Clinical outcome Most patients presented with intermittent claudication (n = 65, Rutherford category 3) prior revascularization. Of the CLTI cohort (n = 30), eleven presented with leg ulcerations. Five patients were categorized as WIfI stage 3, whereas 6 patients were staged at WIfI 4. Three months after the revascularization, most patients presented as asymptomatic (Rutherford category 0) at the first scheduled follow-up. Wound healing was achieved within the first three months after revascularization in all 11 patients with tissue loss. Four patients categorized at Rutherford 4 during follow-up suffered from occlusion of their reconstruction within the first 3 months after the procedure. Redo surgery was performed in all 4 patients. Regarding the number of improved Rutherford categories after the revascularization, no significant difference was detected between the CP, IP and WP-groups (p = 0.534). In the CLTI subgroup, significant differences were observed in TcPO₂ values prior to revascularization as well as in the degree of improvement after the procedure. The mean pre-revascularization TcPO₂ was 27 ± 21.7 mmHg in CLTI patients, compared to 47 ± 17.8 mmHg in patients with intermittent claudication (p < 0.001). The CLTI patients showed a median improvement of 28 ± 30.1 mmHg, compared with 10 ± 23.7 mmHg in the non-CLTI patients (p = 0.002). No significant difference was found in post-revascularization TcPO₂ values between those two groups (55 ± 28 mmHg vs. 57 ± 23.5 mmHg, p = 0.564). Regarding the FI measurements, no significant difference could be observed in SFI, BSFI and TTP changes between the two groups (SFI p = 0.857, BSFI p = 0.532, TTP p = 0.873). Furthermore, changes in TcPO₂ values were significantly associated with the degree of improvement in Rutherford categories following revascularization. (p = 0.004). After applying Bonferroni correction for multiple comparisons, only the difference between patients with increasing versus decreasing TcPO₂ values post-revascularization remained statistically significant (p = 0.002, Fig. 3 ). In contrast, the FI results had no significant influence on the degree of improvement in Rutherford categories. Discussion Evaluation of tissue perfusion plays an important role in the diagnosis and prediction of wound healing as well as the risk of limb loss in PAD patients [ 3 , 4 ]. The current prospective study represents one of the largest cohorts investigating the pre- and post-procedural tissue perfusion after successful revascularization in PAD patients. Systematic FI quantification and TcPO 2 were correlated with clinical outcome. FI did not show any significant correlation with established perfusion parameters or clinical outcome. In contrast, TcPO 2 measurements were significantly associated with the degree of improvement in Rutherford categories during follow-up. Based on the SFI-ratio, patients in this study were grouped by consistent, improved, or worsened perfusion. Differences regarding pre- and post-interventional tissue perfusion could be demonstrated in two thirds of patients using FI. Significant changes in all quantification parameters were observed with improved and worsened perfusion, while no differences could be shown in the CP group. However, no correlation was found between FI and TcPO 2 or ABI. While TcPO 2 improvement correlated well with clinical parameters (improvement in Rutherford categories), FI results showed no distinct relationship. Most studies investigating the role of FI in PAD patients included smaller cohorts, performed just one measurement per patient, and rarely attempted a correlation between the FI results and the clinical outcome. A relation between TcPO 2 and intensity after 10 seconds (PDE10) could be demonstrated by Terasaki et al. However, there was no correlation to the time-point at half of the maximum fluorescence intensity [ 10 ]. The results were supported by those of Venermo et al, conducting one of the few studies measuring FI at two different times and comparing the results with ABI, toe pressure (TP) and TcPO 2 values. They showed a weak relation between ABI/TP and TcPO 2 , with stronger but again not significant results in diabetic patients. The only significant correlation between TcPO 2 and the increase of FI intensity during the first 10 seconds of measurements was again found in diabetic patients. No other parameters showed a significant correlation between TcPO 2 and FI [ 22 ]. This is in line with our findings. However, no significant results were found in the diabetic subgroup of our cohort. The number of patients in our study was twice as high with a similar number of diabetic patients (35 in our study vs. 41), providing more robust data. Settembre et al. carried out a quality control assessment with FI in 104 patients undergoing revascularization for Rutherford categories 3 to 5. They concluded that FI provides reliable information about the improvement of perfusion after revascularization. However, no comparison or correlation to other methods was performed. In their study, only 3 patients showed worse FI results after successful revascularization [ 13 ]. In contrast, 18% of the measurements were worse and 15% were consistent to the preoperative measurements in our study. An explanation could be the different ICG devices and softwares analysing the results. All patients with poorer FI values following revascularization demonstrated an improvement in ABI values, accompanied by clinical improvement at the three-month follow-up. In two-thirds of this cohort, TcPO₂ values also showed a significant increase. Regarding time-related parameters our FI results are partially in line with those of Tange et al. In their study, the authors quantified FI using similar parameters in 72 patients. A significantly shortened time to max (Tmax), which corresponds to TTP, could be demonstrated in cases with improved perfusion. In addition, a postinterventional higher ingress rate and an increased maximum intensity (Imax) were shown in patients with clinical improvement. These parameters correspond to the BSFI and SFI, respectively. In contrast to the current study, a clinical correlation with a significant change in ABI was shown [ 23 ]. In addition, Igari et al. demonstrated a significant correlation between the time-dependent parameters of FI quantification and ABI [ 24 ]. Kang et al., on the other hand, were able to detect perfusion differences using FI in their cohort, but these could not be differentiated by the ABI [ 25 ]. This is in line with our data, in which the ABI could not show any significant perfusion differences between the FI groups. This study is limited by the heterogeneity of revascularization methods, the extent and level of revascularization, and the variation in clinical presentations (ranging from claudication to CLTI). Given the restricted use of fluorescent agents in case of renal impairment, which is common in PAD patients, multicentre studies are needed to ensure larger cohorts. Conclusions FI was not able to detect tissue perfusion improvement after successful revascularization in all PAD patients. The FI parameters did not significantly correlate with clinical outcomes or established parameters such as ABI and TcPO 2 . In contrast, TcPO 2 results showed a robust correlation with clinical outcomes, in CLTI as well as intermittent claudication. These findings together with the restricted applicability of FI in patients with impaired kidney function and the need for intravenous administration of ICG challenge the reliability of FI for post-procedural perfusion assessment and suggest inferiority compared with TcPO₂ measurements. Declarations Author contributions statement: Conceptualization, Michaela Kluckner, Florian Enzmann and Sabine Wipper; methodology, Michaela Kluckner and Florian Enzmann.; investigation, Michaela Kluckner, Florian Enzmann, David Wippel, Laura Schönherr.; data curation, Philipp von Kroge, Anna Duprée, Leonhard Gruber ; writing—original draft preparation, Michaela Kluckner, Philipp von Kroge; writing—review and editing, Michaela Kluckner, Philipp von Kroge, Florian Enzmann, David Wippel, Laura Schönherr, Anna Duprée, Leonhard Gruber, Sabine Wipper; funding acquisition, Michaela Kluckner, Florian Enzmann. Additional Information: Competing interests statement: The authors declare no competing interests. Data availability statement: The research data are available from the corresponding author upon request. Funding statement: This work was funded by the scientific grant of the Society of Vascular Surgery Austria. References Criqui, M. H. et al. 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Cite Share Download PDF Status: Published Journal Publication published 03 Apr, 2026 Read the published version in Scientific Reports → Version 1 posted Editorial decision: Revision requested 24 Feb, 2026 Reviews received at journal 24 Feb, 2026 Reviews received at journal 18 Feb, 2026 Reviewers agreed at journal 16 Feb, 2026 Reviews received at journal 15 Feb, 2026 Reviewers agreed at journal 15 Feb, 2026 Reviewers agreed at journal 13 Feb, 2026 Reviewers agreed at journal 03 Feb, 2026 Reviewers invited by journal 29 Jan, 2026 Editor assigned by journal 29 Jan, 2026 Editor invited by journal 28 Jan, 2026 Submission checks completed at journal 24 Jan, 2026 First submitted to journal 24 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8621154","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":582309264,"identity":"8fbfda0f-cce7-4abf-aa75-ebdf427c9c5d","order_by":0,"name":"Michaela Kluckner","email":"","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":false,"prefix":"","firstName":"Michaela","middleName":"","lastName":"Kluckner","suffix":""},{"id":582309265,"identity":"f9e2f80d-fc11-4d19-aff5-30fdbe90d116","order_by":1,"name":"Philipp H. von Kroge","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Philipp","middleName":"H.","lastName":"von Kroge","suffix":""},{"id":582309266,"identity":"58b6ca30-5df2-42b4-a581-7d33c4074535","order_by":2,"name":"Anna Duprée","email":"","orcid":"","institution":"University Medical Center Hamburg-Eppendorf","correspondingAuthor":false,"prefix":"","firstName":"Anna","middleName":"","lastName":"Duprée","suffix":""},{"id":582309267,"identity":"a9cbe2ff-3580-4c9e-bfdd-5b3a1da1f186","order_by":3,"name":"David Wippel","email":"","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Wippel","suffix":""},{"id":582309268,"identity":"71a7ee00-0deb-41de-aa79-f04592568483","order_by":4,"name":"Laura Schönherr","email":"","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":false,"prefix":"","firstName":"Laura","middleName":"","lastName":"Schönherr","suffix":""},{"id":582309269,"identity":"74991250-58e1-4859-b35e-a911b3520be5","order_by":5,"name":"Leonhard Gruber","email":"","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":false,"prefix":"","firstName":"Leonhard","middleName":"","lastName":"Gruber","suffix":""},{"id":582309270,"identity":"c03af1ce-e255-4edc-bb66-2366c55a5f78","order_by":6,"name":"Florian K. Enzmann","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIie2PMUvDQBSAnxxcBi9kTSn2/kJCd/tX7gg0U3dBwYBwnezcIT+iIlTHwoO4CK4J7RAoZmqhkyiieBWEUC5x7XDf8OCO++7jAVgsR4gz1kPULnp0P1mLwvBA6dcU0qzUkcm/CiHZrrxagdcdv84+HlfxBE5luYFzDs7LwqzQaCqyCjrpYljcPlcjBe59mEIUJiwyVgaE9UFQhCAXWe4qHCm+nXcZEL2gWWG/yjfCIJeq+FIYU3AfPhlcC/DWzYpUuuJHdKkrQitzwgAF+E0VGoGcIPPzIV2eKQz3u3TS4ClU/jowKs4Nnry/Yc+bxlWxVch54t7tNheX3PNkacz8qQdn/T9te2+xWCyWVn4A2VdVVil3U+EAAAAASUVORK5CYII=","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":true,"prefix":"","firstName":"Florian","middleName":"K.","lastName":"Enzmann","suffix":""},{"id":582309271,"identity":"81364b08-fca3-470c-b59f-d808ef8ff5de","order_by":7,"name":"Sabine Wipper","email":"","orcid":"","institution":"Innsbruck Medical University","correspondingAuthor":false,"prefix":"","firstName":"Sabine","middleName":"","lastName":"Wipper","suffix":""}],"badges":[],"createdAt":"2026-01-16 17:08:39","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8621154/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8621154/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-026-47505-7","type":"published","date":"2026-04-03T15:59:54+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101654097,"identity":"7f4d376b-1dfa-4815-9643-701c7e7ad7f8","added_by":"auto","created_at":"2026-02-02 09:42:59","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102675,"visible":true,"origin":"","legend":"\u003cp\u003eThe left image shows a patient’s foot with a marked region of interest (white square) between metatarsal bones one and twoduring FI. The right image shows the identical foot post-interventional, with subjectively better perfusion indicated by a homogenous and more intense fluorescence pattern. The fluorescence intensity curves calculated from the corresponding region of interest differ in slope and absolute increase of fluorescence intensity with objectively impaired perfusion pre-interventional.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8621154/v1/a77ef24b572816fed98b3835.jpg"},{"id":101654025,"identity":"bb23470e-ca4b-4d58-8620-f693966dc481","added_by":"auto","created_at":"2026-02-02 09:42:55","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":52495,"visible":true,"origin":"","legend":"\u003cp\u003eThe image displays a time-dependent fluorescence intensity curve, along with a schematic calculation of the quantification parameters: SFI, the slope of fluorescence intensity; BSFI, the background-subtracted peak fluorescence intensity; and TTP, the time to peak.\u003c/p\u003e","description":"","filename":"Fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8621154/v1/8e3f76d2df637c4fedf4d065.jpg"},{"id":101654188,"identity":"26480d2c-ff08-49b5-8e69-04224ff9d4a2","added_by":"auto","created_at":"2026-02-02 09:43:10","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":564541,"visible":true,"origin":"","legend":"\u003cp\u003eNumber of Rutherford categories improved after successful revascularization, stratified by whether the post-interventional TcPO₂ value increased or decreased.\u003c/p\u003e","description":"","filename":"Fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8621154/v1/efb5590acc4aacb1140775cd.jpg"},{"id":106343604,"identity":"5e7fb8f6-aaff-4faa-9af9-315c1ef7b5b5","added_by":"auto","created_at":"2026-04-07 16:07:04","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1387289,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8621154/v1/1af5e853-900b-444b-8793-3c5358affb86.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Fluorescence Imaging for Assessing Tissue Perfusion After Revascularization in Peripheral Arterial Disease","fulltext":[{"header":"Introduction","content":"\u003cp\u003eWith over 230\u0026nbsp;million affected people, peripheral artery disease (PAD) is a globally relevant condition [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to current guidelines, the ankle-brachial index (ABI) remains the diagnostic method of choice for diagnosis of PAD in everyday clinical practice. The ABI is also used for post-interventional evaluation after revascularization to determine the therapeutic success [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Other, more invasive, diagnostic tools include computed tomography, magnetic resonance imaging, and digital subtraction angiography. All these techniques measure macrovascular differences. However, comorbidities such as diabetes and chronic kidney disease, which are often associated with PAD, decrease the sensitivity of the ABI [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe tissue perfusion can be determined by transcutaneous oxygen pressure (TcPO\u003csub\u003e2\u003c/sub\u003e) measured by small sensors in areas of interest, an established diagnostic tool in patients with PAD [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. While low values are a negative predictor for wound healing, higher values are associated with successful healing [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Nevertheless, the objective assessment of tissue perfusion in patients with PAD remains difficult. Therefore, other methods have been investigated. Among these, fluorescence imaging with indocyanine green (FI) has shown potential. FI, as a diagnostic tool, was initially described in the 1950s for cardiac diagnostics [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Since then, it has been utilized in various medical fields, including ophthalmology, visceral and reconstructive surgery, and has been particularly advertised for evaluating tissue perfusion. Administration via peripheral intravenous route is uncomplicated, however there are contraindications and side effects [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSeveral clinical studies investigating the role of FI in patients with PAD described promising results [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Different cohorts with pre- and postinterventional quantification of FI using various quantification parameters could demonstrate perfusion improvements after revascularization, however the study cohorts were small, perfusion measurements were only performed at a single time point or no comparison to gold-standard methods was performed [\u003cspan additionalcitationids=\"CR11 CR12 CR13 CR14\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe quantification of FI in a region of interest (ROI) using time-dependent fluorescence intensity curves and resulting quantification parameters has been validated in several different non-PAD settings by our group, such as ischemia/reperfusion models in cardiac and mesenteric ischemia as well as gastric tube models [\u003cspan additionalcitationids=\"CR17 CR18 CR19\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In addition, the results could be successfully transferred into clinical applications [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe present study aimed to investigate whether FI is able to detect the post-procedural change of tissue perfusion in comparison to established and validated tissue perfusion as well as clinical parameters in a prospective PAD cohort.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eBetween October 2022 and February 2025 patients undergoing revascularization for symptomatic PAD (Rutherford categories 3 to 6) were enrolled in a prospective study at a university vascular center. Revascularization techniques included surgical, endovascular, and hybrid procedures. Exclusion criteria were hyperthyroidism, glomerular filtration rate \u0026lt;\u0026thinsp;30ml/min, iodine allergy, pregnancy, long-term oxygen therapy due to the administration of indocyanine green (ICG) and extensive gangrene of the foot and ulceration at the defined location of perfusion measurements to facilitate TcPO\u003csub\u003e2\u003c/sub\u003e sensor placement. Before revascularization the ABI and TcpO\u003csub\u003e2\u003c/sub\u003e measurements between Os metatarsale I and II as well as FI were performed. The post-procedural measurements were performed one to three days after the revascularization. Clinical follow-up took place three months after revascularization as part of the routine outpatient check-up. Written informed consent was obtained from each patient included in the study. The study was approved by the ethics committee of the Medical University of Innsbruck (EK Nr: 1440/2021), adhered to the declaration of Helsinki and was and registered at ClinicalTrials.gov (NCT05570019, date of registration: 2022-08-29, \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.clinicaltrials.gov/study/NCT05570019?term=NCT05570019\u0026amp;rank=1\u003c/span\u003e\u003cspan address=\"https://www.clinicaltrials.gov/study/NCT05570019?term=NCT05570019\u0026amp;rank=1\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe primary objective of the study was to compare the FI perfusion measurements to the ABI and TcPO\u003csub\u003e2\u003c/sub\u003e values in terms of improvement after the technically successful revascularization. In addition, it was analysed whether the allocation to the FI groups was consistent with the results of the ABI and TcPO₂ values. The secondary outcome of the study included the correlation of the tissue perfusion measurements with the clinical status prior revascularization and the improvement afterwards.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eFluorescence Imaging\u003c/h2\u003e \u003cp\u003eEleVisionTM (Medtronic GmbH, Meerbusch, Germany) was used as the technical platform for imaging. Each patient underwent FI before and after the planned intervention. A dosage of 0.1mg/kg body weight ICG (Verdye, Diagnostic Green Limited, Westmeath) was administered via peripheral vein catheter as a bolus, followed by 10 ml of water for injection. The recording was performed in a supine position for 2 minutes after the ICG administration.\u003c/p\u003e \u003cp\u003eFurther analysis of the FI was performed blinded to the intervention and patient details. A customized software package (Meteroarchive VCL LLS Fluoreszenzangiographie V 1.0, LLS GmbH, Ulm, Germany) was used. The region of interest (ROI) was defined as the area between the metatarsal bones one and two, measuring 80 x 80 pixels, the same location where the TcPO\u003csub\u003e2\u003c/sub\u003e measurement was performed. Explicit care was taken not to measure the signal of the dorsalis pedis artery. A time-dependent fluorescence intensity curve was generated for further calculation of perfusion parameters. Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows a pre- and post-interventional fluorescence image with the ROIs marked and the corresponding fluorescence intensity curves.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBased on the results of FI, the patient cohort was divided into three different groups. Group 1 (CP) includes patients with a SFI-ratio of 1, indicating constant perfusion, following revascularization. In Group 2 (WP), a ratio\u0026thinsp;\u0026gt;\u0026thinsp;1 indicated worsened perfusion after the intervention, whereas Group 3 (IP) demonstrated measurable improvement with a ratio\u0026thinsp;\u0026lt;\u0026thinsp;1. The results of the three groups were compared in terms of changes in ABI, TcPO\u003csub\u003e2\u003c/sub\u003e and a correlation to the clinical outcomes following revascularization was performed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eFor statistical analysis, the Statistical Package for the Social Sciences (SPSS) statistical software, version 29.0 (IBM Corp., IBM SPSS Statistics, Armonk, NY), was used.\u003c/p\u003e \u003cp\u003eCategorical variables are expressed as numbers (%). A Chi-square test was used for the comparison of categorical variables. Metric values are presented as means with standard deviations (SD). Metric data were tested with a paired t-test. The correlation coefficient was used to describe correlation among ABI, TcPO\u003csub\u003e2\u003c/sub\u003e, and FI parameters. For the comparison of the perfusion measurements between the three groups, a one-sided ANOVA for normally distributed data and a Kruskal-Wallis-test for not normally distributed data was used. A two-sided p-value\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant. For post-hoc comparisons between pairs of groups, Mann-Whitney U tests were conducted. To adjust for multiple testing, the Bonferroni correction was applied, resulting in a corrected significance threshold of α\u0026thinsp;=\u0026thinsp;0.0167.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 131 patients were included in the study. Due to unsuccessful revascularization/early re-occlusion (n\u0026thinsp;=\u0026thinsp;10), withdrawal of consent (n\u0026thinsp;=\u0026thinsp;13) or technical problems with the measurements (n\u0026thinsp;=\u0026thinsp;13), a total of 95 patients were included in the final analysis. Demographics and cardiovascular risk factors for the overall cohort and the three groups are depicted in \u003cb\u003eTable\u0026nbsp;1.\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 1\u003c/strong\u003e Demographics of the patients. CAD: coronary artery disease; CABG: coronary artery bypass graft; NOAK: new oral anticoagulation; PTCA: percutaneous transluminal coronary angioplasty; VKA: vitamin K antagonist\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Taba\" border=\"1\"\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOverall (n\u0026thinsp;=\u0026thinsp;95)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eCP (n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWP (n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eIP(n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (median\u0026thinsp;\u0026plusmn;\u0026thinsp;s.d)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69\u0026thinsp;\u0026plusmn;\u0026thinsp;9.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67\u0026thinsp;\u0026plusmn;\u0026thinsp;9.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42 (66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.760\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24 (38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e73 (77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48 (75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoker current\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (44)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e31 (48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.491\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSmoker former\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.727\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDyslipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e54 (57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 11 (65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36 (56)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.703\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCAD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33 (52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.255\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS.p. PTCA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21 (33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.194\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eS.p. CABG\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcetylsalicylic acid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71 (76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10 (59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50 (78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlavix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e18 (28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.994\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVKA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.963\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNOAK\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.211\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStatin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e82 (86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15 (88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55 (86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.968\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMetformin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12 (19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.756\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003ePatients from the WP-group were significantly older compared to the IP-group (p\u0026thinsp;=\u0026thinsp;0.003). No other significant difference was detected between the groups.\u003c/p\u003e \u003cp\u003eAn endovascular revascularization was performed in 54% (n\u0026thinsp;=\u0026thinsp;51), open surgery in 28% (n\u0026thinsp;=\u0026thinsp;27) and 18% (n\u0026thinsp;=\u0026thinsp;17) of patients underwent hybrid procedures with no significant difference between the three groups (p\u0026thinsp;=\u0026thinsp;0.741). Details on the revascularization procedures are listed in \u003cb\u003eTable\u0026nbsp;2\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 2\u003c/strong\u003e Details on the revascularization procedures. PTA: percutaneous transluminal angioplasty\u003c/p\u003e\u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabb\" border=\"1\"\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProcedure\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNumber (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoro-popliteal bypass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThromboendoarterectomy of the femoral bifurcation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoro-popliteal thrombectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoro-crural bypass\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThromboendoarterectomy of the femoral bifurcation with femoro-popliteal or iliac PTA\u0026thinsp;\u0026plusmn;\u0026thinsp;stent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoro-popliteal thrombectomy with PTA\u0026thinsp;\u0026plusmn;\u0026thinsp;stent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemoro-popliteal bypass with proximal or distal PTA\u0026thinsp;\u0026plusmn;\u0026thinsp;stent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAorto-iliac PTA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21 (22)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTA of the superficial femoral artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePTA of the popliteal artery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eQuantification of FI\u003c/h3\u003e\n\u003cp\u003eThe quantification was successfully conducted in all included cases. Improved perfusion was observed in 64 (67%) patients. In contrast, perfusion remained consistent in 14 (15%) cases, while it worsened in 17 (18%) cases.\u003c/p\u003e \u003cp\u003eIn the IP-group SFI and BSFI increased while TTP shortened. All changes were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The WP-group showed exactly opposite results. SFI and BSFI decreased, while TTP extended. All changes were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). The results of the CP-group showed no statistically significant changes. The quantification results are shown in \u003cb\u003eTable\u0026nbsp;3\u003c/b\u003e.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eTable 3\u003c/strong\u003e Pre- and post-interventional results of the FA-ICG quantification as means\u0026nbsp;\u0026nbsp;\u0026nbsp;standard deviations). Pre: pre-interventional; post: post-interventional; SFI: slope of fluorescence intensity; BSFI: background-subtracted peak fluorescence intensity; TTP: time to peak;\u003cem\u003e\u0026nbsp;\u003c/em\u003eCP: consistent perfusion; WP: worsened perfusion; IP: improved perfusion; ** = p \u0026lt;0.001; * = p\u0026lt;0.05. Numbers are given as median \u0026plusmn; standard deviation\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"No\" id=\"Tabc\" border=\"1\"\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003eSFI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003eBSFI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e \u003cp\u003eTTP\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u003cem\u003ePre\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ePost\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003ePre\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ePost\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003ePre\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ePost\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIP (n\u0026thinsp;=\u0026thinsp;64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.06 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.04\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.16 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.11**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34.3 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 18.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e54.0 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 21.1**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e26.9 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e20.1 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 9.8**\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.12 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.12 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.08\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.4 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 24.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e49.9 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 10.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.4 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 13.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e21.7 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 13.4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWP\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.20 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.07 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 0.03*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e62.6 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 26.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.1 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 18.1*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.8 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 13.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e27.1 \u003cspan class=\"InlineEquation\"\u003e\u003cspan class=\"mathinline\"\u003e\\(\\:\\pm\\:\\)\u003c/span\u003e\u003c/span\u003e 11.5*\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eComparison of perfusion measurements\u003c/h3\u003e\n\u003cp\u003eThe median ABI prior revascularization was 0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;0.17, the median TcPO\u003csub\u003e2\u003c/sub\u003e value was 41\u0026thinsp;\u0026plusmn;\u0026thinsp;21.2 mmHg. After revascularization, the median ABI was 0.82\u0026thinsp;\u0026plusmn;\u0026thinsp;0.23 with a median improvement of 0.42\u0026thinsp;\u0026plusmn;\u0026thinsp;0.31 (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The median improvement of the TcPO\u003csub\u003e2\u003c/sub\u003e was 15.6\u0026thinsp;\u0026plusmn;\u0026thinsp;27.1 mmHg with a median value of 56.6\u0026thinsp;\u0026plusmn;\u0026thinsp;24.9 mmHg (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant correlation between TcPO\u003csub\u003e2\u003c/sub\u003e measurements and the three different FI parameters before and after revascularization was found (pre: SFI: R\u0026thinsp;=\u0026thinsp;0.08, p\u0026thinsp;=\u0026thinsp;0.426, BSFI: R=-0.03, p\u0026thinsp;=\u0026thinsp;0.773, TTP: R=-0.003, p\u0026thinsp;=\u0026thinsp;0.978; post: SFI: R\u0026thinsp;=\u0026thinsp;0.02, p\u0026thinsp;=\u0026thinsp;0.852, BSFI: R=-0.12, p\u0026thinsp;=\u0026thinsp;0.258, TTP: R=-0.19, p\u0026thinsp;=\u0026thinsp;0.063). Furthermore, no significant difference was detected in absolute ABI- and TcPO\u003csub\u003e2\u003c/sub\u003e values prior and post revascularization between the three groups (pre: ABI: p\u0026thinsp;=\u0026thinsp;0.895, TcPO\u003csub\u003e2\u003c/sub\u003e: p\u0026thinsp;=\u0026thinsp;0.566; post: ABI: p\u0026thinsp;=\u0026thinsp;0.880, TcPO\u003csub\u003e2\u003c/sub\u003e: p\u0026thinsp;=\u0026thinsp;0.249). Also, the improvement of TcPO\u003csub\u003e2\u003c/sub\u003e values was not significantly different between the three groups (p\u0026thinsp;=\u0026thinsp;0.186). In the CP-group, the median improvement was +\u0026thinsp;2.9\u0026thinsp;\u0026plusmn;\u0026thinsp;17.1 mmHg, in the WP-group it was +\u0026thinsp;18.8\u0026thinsp;\u0026plusmn;\u0026thinsp;37.2 mmHg and IP-group\u0026thinsp;+\u0026thinsp;17\u0026thinsp;\u0026plusmn;\u0026thinsp;25.4 mmHg.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eClinical outcome\u003c/h2\u003e \u003cp\u003eMost patients presented with intermittent claudication (n\u0026thinsp;=\u0026thinsp;65, Rutherford category 3) prior revascularization. Of the CLTI cohort (n\u0026thinsp;=\u0026thinsp;30), eleven presented with leg ulcerations. Five patients were categorized as WIfI stage 3, whereas 6 patients were staged at WIfI 4. Three months after the revascularization, most patients presented as asymptomatic (Rutherford category 0) at the first scheduled follow-up. Wound healing was achieved within the first three months after revascularization in all 11 patients with tissue loss. Four patients categorized at Rutherford 4 during follow-up suffered from occlusion of their reconstruction within the first 3 months after the procedure. Redo surgery was performed in all 4 patients. Regarding the number of improved Rutherford categories after the revascularization, no significant difference was detected between the CP, IP and WP-groups (p\u0026thinsp;=\u0026thinsp;0.534).\u003c/p\u003e \u003cp\u003eIn the CLTI subgroup, significant differences were observed in TcPO₂ values prior to revascularization as well as in the degree of improvement after the procedure. The mean pre-revascularization TcPO₂ was 27\u0026thinsp;\u0026plusmn;\u0026thinsp;21.7 mmHg in CLTI patients, compared to 47\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8 mmHg in patients with intermittent claudication (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The CLTI patients showed a median improvement of 28\u0026thinsp;\u0026plusmn;\u0026thinsp;30.1 mmHg, compared with 10\u0026thinsp;\u0026plusmn;\u0026thinsp;23.7 mmHg in the non-CLTI patients (p\u0026thinsp;=\u0026thinsp;0.002). No significant difference was found in post-revascularization TcPO₂ values between those two groups (55\u0026thinsp;\u0026plusmn;\u0026thinsp;28 mmHg vs. 57\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5 mmHg, p\u0026thinsp;=\u0026thinsp;0.564). Regarding the FI measurements, no significant difference could be observed in SFI, BSFI and TTP changes between the two groups (SFI p\u0026thinsp;=\u0026thinsp;0.857, BSFI p\u0026thinsp;=\u0026thinsp;0.532, TTP p\u0026thinsp;=\u0026thinsp;0.873).\u003c/p\u003e \u003cp\u003eFurthermore, changes in TcPO₂ values were significantly associated with the degree of improvement in Rutherford categories following revascularization. (p\u0026thinsp;=\u0026thinsp;0.004). After applying Bonferroni correction for multiple comparisons, only the difference between patients with increasing versus decreasing TcPO₂ values post-revascularization remained statistically significant (p\u0026thinsp;=\u0026thinsp;0.002, Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e3\u003c/span\u003e). In contrast, the FI results had no significant influence on the degree of improvement in Rutherford categories.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eEvaluation of tissue perfusion plays an important role in the diagnosis and prediction of wound healing as well as the risk of limb loss in PAD patients [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The current prospective study represents one of the largest cohorts investigating the pre- and post-procedural tissue perfusion after successful revascularization in PAD patients. Systematic FI quantification and TcPO\u003csub\u003e2\u003c/sub\u003e were correlated with clinical outcome. FI did not show any significant correlation with established perfusion parameters or clinical outcome. In contrast, TcPO\u003csub\u003e2\u003c/sub\u003e measurements were significantly associated with the degree of improvement in Rutherford categories during follow-up.\u003c/p\u003e \u003cp\u003eBased on the SFI-ratio, patients in this study were grouped by consistent, improved, or worsened perfusion. Differences regarding pre- and post-interventional tissue perfusion could be demonstrated in two thirds of patients using FI. Significant changes in all quantification parameters were observed with improved and worsened perfusion, while no differences could be shown in the CP group. However, no correlation was found between FI and TcPO\u003csub\u003e2\u003c/sub\u003e or ABI. While TcPO\u003csub\u003e2\u003c/sub\u003e improvement correlated well with clinical parameters (improvement in Rutherford categories), FI results showed no distinct relationship.\u003c/p\u003e \u003cp\u003eMost studies investigating the role of FI in PAD patients included smaller cohorts, performed just one measurement per patient, and rarely attempted a correlation between the FI results and the clinical outcome. A relation between TcPO\u003csub\u003e2\u003c/sub\u003e and intensity after 10 seconds (PDE10) could be demonstrated by Terasaki et al. However, there was no correlation to the time-point at half of the maximum fluorescence intensity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. The results were supported by those of Venermo et al, conducting one of the few studies measuring FI at two different times and comparing the results with ABI, toe pressure (TP) and TcPO\u003csub\u003e2\u003c/sub\u003e values. They showed a weak relation between ABI/TP and TcPO\u003csub\u003e2\u003c/sub\u003e, with stronger but again not significant results in diabetic patients. The only significant correlation between TcPO\u003csub\u003e2\u003c/sub\u003e and the increase of FI intensity during the first 10 seconds of measurements was again found in diabetic patients. No other parameters showed a significant correlation between TcPO\u003csub\u003e2\u003c/sub\u003e and FI [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. This is in line with our findings. However, no significant results were found in the diabetic subgroup of our cohort. The number of patients in our study was twice as high with a similar number of diabetic patients (35 in our study vs. 41), providing more robust data. Settembre et al. carried out a quality control assessment with FI in 104 patients undergoing revascularization for Rutherford categories 3 to 5. They concluded that FI provides reliable information about the improvement of perfusion after revascularization. However, no comparison or correlation to other methods was performed. In their study, only 3 patients showed worse FI results after successful revascularization [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In contrast, 18% of the measurements were worse and 15% were consistent to the preoperative measurements in our study. An explanation could be the different ICG devices and softwares analysing the results. All patients with poorer FI values following revascularization demonstrated an improvement in ABI values, accompanied by clinical improvement at the three-month follow-up. In two-thirds of this cohort, TcPO₂ values also showed a significant increase.\u003c/p\u003e \u003cp\u003eRegarding time-related parameters our FI results are partially in line with those of Tange et al. In their study, the authors quantified FI using similar parameters in 72 patients. A significantly shortened time to max (Tmax), which corresponds to TTP, could be demonstrated in cases with improved perfusion. In addition, a postinterventional higher ingress rate and an increased maximum intensity (Imax) were shown in patients with clinical improvement. These parameters correspond to the BSFI and SFI, respectively. In contrast to the current study, a clinical correlation with a significant change in ABI was shown [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In addition, Igari et al. demonstrated a significant correlation between the time-dependent parameters of FI quantification and ABI [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Kang et al., on the other hand, were able to detect perfusion differences using FI in their cohort, but these could not be differentiated by the ABI [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. This is in line with our data, in which the ABI could not show any significant perfusion differences between the FI groups.\u003c/p\u003e \u003cp\u003eThis study is limited by the heterogeneity of revascularization methods, the extent and level of revascularization, and the variation in clinical presentations (ranging from claudication to CLTI). Given the restricted use of fluorescent agents in case of renal impairment, which is common in PAD patients, multicentre studies are needed to ensure larger cohorts.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eFI was not able to detect tissue perfusion improvement after successful revascularization in all PAD patients. The FI parameters did not significantly correlate with clinical outcomes or established parameters such as ABI and TcPO\u003csub\u003e2\u003c/sub\u003e. In contrast, TcPO\u003csub\u003e2\u003c/sub\u003e results showed a robust correlation with clinical outcomes, in CLTI as well as intermittent claudication. These findings together with the restricted applicability of FI in patients with impaired kidney function and the need for intravenous administration of ICG challenge the reliability of FI for post-procedural perfusion assessment and suggest inferiority compared with TcPO₂ measurements.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAuthor contributions statement:\u0026nbsp;\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualization, Michaela Kluckner, Florian Enzmann and Sabine Wipper; methodology, Michaela Kluckner and Florian Enzmann.; investigation, Michaela Kluckner, Florian Enzmann, David Wippel, Laura Schönherr.; data curation, Philipp von Kroge, Anna Duprée, Leonhard Gruber ; writing—original draft preparation, Michaela Kluckner, Philipp von Kroge; writing—review and editing, Michaela Kluckner, Philipp von Kroge, Florian Enzmann, David Wippel, Laura Schönherr, Anna Duprée, Leonhard Gruber, Sabine Wipper; funding acquisition, Michaela Kluckner, Florian Enzmann.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eAdditional Information:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests statement:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability statement:\u003c/strong\u003e The research data are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cu\u003eFunding statement:\u003c/u\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis work was funded by the scientific grant of the Society of Vascular Surgery Austria.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCriqui, M. H. et al. Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement from the American Heart Association. \u003cem\u003eCirculation\u003c/em\u003e \u003cb\u003e144\u003c/b\u003e, E171\u0026ndash;E191 (2021).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVenermo, M. et al. (eds) \u0026rsquo;s Choice \u0026ndash; Follow-up of Patients After Revascularisation for Peripheral Arterial Diseases: A Consensus Document From the European Society of Cardiology Working Group on Aorta and Peripheral Vascular Diseases and the European Society for Vascular Su. Eur J Vasc Endovasc Surg. ; 58: 641\u0026ndash;653. (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eConte, M. S. et al. Global Vascular Guidelines on the Management of Chronic Limb-Threatening Ischemia. \u003cem\u003eEur. J. Vasc Endovasc Surg.\u003c/em\u003e \u003cb\u003e58\u003c/b\u003e, S1\u0026ndash;S109e33 (2019).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFitridge, R. et al. The intersocietal IWGDF, ESVS, SVS guidelines on peripheral artery disease in people with diabetes mellitus and a foot ulcer. \u003cem\u003eJ. Vasc Surg.\u003c/em\u003e \u003cb\u003e78\u003c/b\u003e, 1101\u0026ndash;1131 (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAboyans, V. et al. 2017 ESC Guidelines on the Diagnosis and Treatment of Peripheral Arterial Diseases, in collaboration with the European Society for Vascular Surgery (ESVS). \u003cem\u003eEur. Heart J.\u003c/em\u003e \u003cb\u003e39\u003c/b\u003e, 763\u0026ndash;816 (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWoo, Y. et al. TcPO2 Value Can Predict Wound Healing Time in Clinical Practice of CLTI Patints. \u003cem\u003eAnn. 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Dynamic fluorescence imaging of indocyanine green for reliable and sensitive diagnosis of peripheral vascular insufficiency. \u003cem\u003eMicrovasc Res.\u003c/em\u003e \u003cb\u003e80\u003c/b\u003e, 552\u0026ndash;555 (2010).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Arteriosclerosis, Indocyanine green, tissue perfusion, Quantification, transcutaneous oxygen pressure measurement","lastPublishedDoi":"10.21203/rs.3.rs-8621154/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8621154/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cu\u003ePurpose\u003c/u\u003e\u003cbr\u003e\nMethods for assessing peripheral arterial disease (PAD) include ankle-brachial index (ABI) and transcutaneous oxygen pressure (TcPO₂) measurements. Fluorescence imaging with indocyanine green (FI) has been proposed as a promising tool for tissue perfusion assessment, despite lack of robust evidence due to small study cohorts or missing comparison of methods.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eMethods\u003c/u\u003e\u003cbr\u003e\nIn this prospective study, patients underwent FI, TcPO₂, and ABI measurements before and after revascularization. FI quantification included slope of fluorescence intensity (SFI), background-subtracted peak fluorescence intensity (BSFI), and time to peak (TTP). The primary objective was to assess FI-derived metrics compared to ABI and TcPO₂ after successful revascularization.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eResults\u003c/u\u003e\u003cbr\u003e\nOut of 95 patients 67% showed improved perfusion in FI after revascularization. Worsened perfusion was observed in 18% of patients, characterized by reduced SFI and BSFI and prolonged TTP, while no significant changes were seen in patients with unchanged perfusion. FI-derived parameters showed no correlation with ABI, TcPO₂, or clinical outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cu\u003eConclusion\u003c/u\u003e\u003cbr\u003e\nFI did not reliably detect perfusion improvement despite successful revascularization and showed no association with clinical outcomes or established measures. In contrast, TcPO₂ demonstrated a strong correlation with clinical results. These findings question the reliability of FI for post-procedural perfusion assessment and suggest inferiority compared with TcPO₂.\u003c/p\u003e","manuscriptTitle":"Fluorescence Imaging for Assessing Tissue Perfusion After Revascularization in Peripheral Arterial Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-02 09:41:28","doi":"10.21203/rs.3.rs-8621154/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-24T08:01:45+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-24T06:55:58+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-18T13:38:33+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"94490651627663002605455665862768061424","date":"2026-02-16T13:44:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-15T18:40:45+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"266004748192842950309675116150538762672","date":"2026-02-15T16:57:27+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"49789830509598359784704534002434205950","date":"2026-02-13T11:07:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"321760855108192411910658624284254992488","date":"2026-02-03T11:13:17+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-29T08:53:10+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-29T08:50:37+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-01-28T17:53:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-24T17:29:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2026-01-24T17:23:17+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"83acdb76-4ca2-4c5a-88bb-d84c8107a925","owner":[],"postedDate":"February 2nd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":61949983,"name":"Health sciences/Cardiology"},{"id":61949984,"name":"Health sciences/Diseases"},{"id":61949985,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2026-04-07T16:03:27+00:00","versionOfRecord":{"articleIdentity":"rs-8621154","link":"https://doi.org/10.1038/s41598-026-47505-7","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2026-04-03 15:59:54","publishedOnDateReadable":"April 3rd, 2026"},"versionCreatedAt":"2026-02-02 09:41:28","video":"","vorDoi":"10.1038/s41598-026-47505-7","vorDoiUrl":"https://doi.org/10.1038/s41598-026-47505-7","workflowStages":[]},"version":"v1","identity":"rs-8621154","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8621154","identity":"rs-8621154","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}