Lu PY, Hao ZY, Xing GW, Zhang PF, Liu YS, Li WY, Xu MJ. Improving intraoperative perfusion reliability in anterolateral thigh free flap reconstruction for diabetic foot ulcers. World J Diabetes 2026; 17(6): 118576 [DOI: 10.4239/wjd.118576]
Corresponding Author of This Article
Ming-Jie Xu, MD, Professor, First Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Erqi District, Zhengzhou 450052, Henan Province, China. 65727257@qq.com
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Peng-Yu Lu, Zhuang-Yu Hao, Guang-Wei Xing, Peng-Fei Zhang, Yan-Song Liu, Wen-Yang Li, Ming-Jie Xu, First Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Lu PY contributed to conceptualization, literature review, and writing the original draft; Hao ZY performed the formal analyses and contributed to methodology development and data curation; Xing GW contributed to the investigation, literature screening, and software-assisted data extraction/visualization; Zhang PF contributed to the methodology design, figure/table preparation, and review and editing; Liu YS contributed to the validation, critical revision for important intellectual content, and project administration/coordination; Li WY contributed to resources, supervision support, and critical review of the manuscript; Xu MJ supervised the study and was responsible for visualization oversight, manuscript final editing, and final approval of the version to be published; All authors participated in manuscript preparation and approved the final version of the manuscript.
AI contribution statement: AI-assisted tools, including ChatGPT/DeepL/Grammarly or similar language tools, were used only for language polishing, grammar correction, limited translation assistance, and improvement of readability during the preparation and revision of this manuscript. No portion of the main text of the manuscript, including the abstract, introduction, main body sections, discussion-related interpretation, and conclusion, was generated by AI. The conception of the manuscript, literature selection, evidence synthesis, clinical interpretation, intellectual content, and conclusions were independently completed by the authors. No AI tool was used for data analysis, study design, clinical reasoning, interpretation of results, or formulation of conclusions. All authors have carefully reviewed and verified the accuracy, integrity, and scientific validity of the manuscript and take full responsibility for its entire content. No images, figures, tables, or scientific illustrations in this manuscript were generated by AI.
Supported by the 2023 Henan Provincial Medical Science and Technology Research Program (Joint Co-Construction Project), No. LHGJ20230409.
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Corresponding author: Ming-Jie Xu, MD, Professor, First Department of Orthopedics, The Fifth Affiliated Hospital of Zhengzhou University, No. 3 Kangfuqian Street, Erqi District, Zhengzhou 450052, Henan Province, China. 65727257@qq.com
Received: January 6, 2026 Revised: February 22, 2026 Accepted: April 15, 2026 Published online: June 15, 2026 Processing time: 156 Days and 22.2 Hours
Abstract
Anterolateral thigh free-flap reconstruction remains an important limb-salvage option for patients with diabetic foot ulcers, particularly when complex soft-tissue defects, infection, or exposed deep structures preclude simpler reconstructive approaches. However, intraoperative perfusion insufficiency continues to limit flap reliability and may compromise wound healing, flap survival, and long-term limb salvage. In this setting, flap perfusion should not be regarded as a purely technical consequence of microsurgical anastomosis but rather as the product of a systemic-regional-microcirculatory continuum shaped by distal vascular capacity, diabetes-related microvascular dysfunction, and modifiable host factors. This review summarizes current advances in intraoperative perfusion assessment for anterolateral thigh flap reconstruction in diabetic foot ulcer, with particular emphasis on indocyanine green fluorescence angiography (ICG-FA). We highlight the limitations of relying on static fluorescence intensity alone and argue that quantitative fluorescence-time curve metrics, including wash-in slope, time to maximum intensity, and area under the curve, may provide more robust and reproducible information for intraoperative decision-making. Because diabetes-associated medial arterial calcification and microvascular impairment can confound perfusion interpretation, ICG-FA should be integrated with complementary measures such as toe pressure/toe-brachial index, skin perfusion pressure, and transcutaneous oxygen tension rather than used as a stand-alone tool. We further discuss the importance of preoperative and perioperative optimization of modifiable systemic factors, including glycemic control, anemia, oxygenation and ventilation, and nutritional reserve, all of which influence tissue oxygen delivery and flap viability. Finally, we propose a quantitative, multimodal clinical framework that links preoperative vascular assessment, standardized intraoperative perfusion imaging, and structured postoperative monitoring to clinically meaningful outcomes. Future priorities include harmonization of ICG-FA acquisition and reporting protocols, prospective multicenter validation, and development of registry-based prediction models to improve reproducibility, risk stratification, and implementation of evidence-based limb-salvage strategies in diabetic foot reconstruction.
Core Tip: Intraoperative perfusion remains a key failure point in anterolateral thigh free-flap reconstruction for diabetic foot ulcers. Perfusion is not determined by microsurgical technique alone but reflects a systemic-regional-microcirculatory continuum, often confounded by diabetes-related macrovascular calcification and microvascular dysfunction. We emphasize standardizing indocyanine green fluorescence angiography and shifting from single intensity snapshots to time-intensity kinetics, interpreted alongside toe pressure/toe-brachial index, skin perfusion pressure, and transcutaneous oxygen tension. An actionable perioperative optimization bundle (glycemia, anemia, oxygen delivery, nutrition, monitoring) may improve flap reliability and limb salvage.
Citation: Lu PY, Hao ZY, Xing GW, Zhang PF, Liu YS, Li WY, Xu MJ. Improving intraoperative perfusion reliability in anterolateral thigh free flap reconstruction for diabetic foot ulcers. World J Diabetes 2026; 17(6): 118576
Diabetic foot ulcers (DFUs) remain a major limb-threatening complication of diabetes and frequently require complex soft-tissue reconstruction when deep tissue exposure, infection, or structural defects preclude secondary healing or simple coverage. In this setting, flap-based reconstruction has become an important limb-salvage strategy, with accumulating systematic evidence supporting favorable wound coverage, flap survival, and amputation-sparing outcomes in selected patients[1,2]. Among the available reconstructive options, the anterolateral thigh (ALT) flap has emerged as a workhorse for diabetic foot reconstruction because it provides a long and reliable pedicle, adequate tissue volume, versatile design, and relatively low donor-site morbidity, while also allowing durable coverage of complex defects[3-5].
Despite refinements in microsurgical technique, successful ALT flap reconstruction depends not only on vascular anastomotic patency but also on the adequacy and spatial distribution of tissue perfusion across the transferred flap[6-8]. This issue is especially critical in DFU, where neuropathy, microvascular dysfunction, ischemia, infection, and impaired wound healing frequently coexist and may compromise both flap inset and distal tissue viability[9-11]. Traditional intraoperative assessment based on flap color, capillary refill, temperature, and dermal bleeding remains clinically useful but is inherently subjective. Consequently, objective perfusion-monitoring tools have gained increasing attention, particularly indocyanine green (ICG) fluorescence angiography (FA) and related perfusion-imaging approaches. A systematic review of intraoperative perfusion assessment in free flap surgery identified fluorescence imaging and laser Doppler as the most useful objective methods for intraoperative perfusion evaluation, and a large contemporary series further suggested that ICG angiography can reduce partial flap loss and re-exploration by enabling more accurate intraoperative decision-making[12,13].
Importantly, flap perfusion in diabetic limb reconstruction should not be viewed as a purely technical endpoint. Emerging evidence indicates that intraoperative perfusion is closely linked to the patient’s systemic metabolic and physiologic status. A recent study of ALT flap repair for DFUs identified diabetes duration, glycated hemoglobin, arterial oxygen parameters, and albumin status as independent predictors of intraoperative perfusion, highlighting the integrated influence of metabolic control, oxygen delivery, and nutritional reserve[8]. Consistent with this broader concept, lower preoperative hemoglobin levels, poorer nutritional indices, and hypoalbuminemia have all been associated with higher rates of flap-related complications or failure in microsurgical reconstruction[14-16]. These findings suggest that optimal reconstructive outcomes require not only technical precision at the recipient site but also rigorous perioperative optimization of systemic risk factors.
Against this background, a focused review of intraoperative perfusion reliability in ALT flap reconstruction for DFU is both timely and clinically relevant. This review first summarizes current advances and limitations in objective intraoperative perfusion assessment, with emphasis on ICG-FA quantification and complementary modalities. It then discusses preoperative hemodynamic and systemic determinants of flap viability, including distal perfusion capacity, nutritional status, anemia, and respiratory/oxygenation factors. Next, it outlines a practical multimodal workflow and perioperative optimization pathway for clinical decision-making in ALT free-flap reconstruction. Finally, it highlights priorities for protocol standardization, prospective validation, and registry-based studies to improve flap survival, wound healing, and limb salvage in diabetic foot reconstruction.
INTRAOPERATIVE FLAP PERFUSION ASSESSMENT: ICG ANGIOGRAPHY AND BEYOND
Current applications of ICG-FA in flap reconstruction
ICG-FA/ICG near-infrared has been widely adopted in microsurgical reconstruction, particularly in free flap procedures, as a real-time tool for assessing intraoperative perfusion status. In their review, Van't Hof et al[17] emphasized that ICG FA provides an intraoperative visual “perfusion map,” facilitating the identification of regions at risk for hypoperfusion and guiding decisions regarding resection of poorly perfused margins or the need for supercharging.
In recent years, efforts toward quantitative analysis have shifted from relying solely on absolute or relative fluorescence intensity to evaluating fluorescence-time curves. Key dynamic parameters - such as wash-in slope, time-to-maximum intensity (Tmax), maximum fluorescence intensity, and area under the curve (AUC) - have been introduced to reduce variability related to device settings, gain, and ICG dosage, thereby improving inter-study comparability[18,19].
For instance, Dalli et al[20] investigated the quantitative potential of ICG-FA under varying operative conditions, noting that “time-dependent parameters are more robust than static intensity parameters,” while acknowledging the lack of large-scale validation. Similarly, Andersen’s narrative review highlighted that most existing studies still rely on intensity-based metrics, which are highly sensitive to illumination and gain settings; by contrast, time-dynamic parameters (e.g., slope, Tmax) theoretically offer greater resistance to systematic bias[19].
Additionally, several studies have explored ICG dilution strategies to optimize the dynamic range and contrast of fluorescence signals. Atmodiwirjo et al[18] compared ICG concentrations of 5 mg/mL, 2.5 mg/mL, and 0.5 mg/mL, finding that a 2.5 mg/mL solution yielded the highest grayscale (fluorescence) values - suggesting that lower concentrations may be preferable intraoperatively to avoid signal saturation, artifacts, or pooling effects.
In summary, ICG-FA in free flap surgery is evolving from empirical application toward a more quantitative and standardized methodology. However, substantial heterogeneity persists across studies in terms of ICG dosage, region-of-interest selection, normalization methods, device gain settings, and injection rates, underscoring the need for a unified protocol. Repeated ICG-FA within the same procedure may be useful after corrective maneuvers; however, routine repeated injections without clinical indication are not recommended due to cumulative dosing considerations and limited additional decision yield.
Limitations in the context of diabetic foot
In patients with DFU, ICG-FA visualizes superficial microcirculation in real time. However, its interpretation is affected by tissue thickness, edema, temperature, injection dose, imaging distance, and device settings. In addition, diabetes-related microvascular dysfunction may create the misleading appearance of “normal brightness” despite impaired exchange efficiency. This underscores that perfusion assessment based solely on fluorescence intensity or perfused area ratio is inadequate, and greater emphasis should be placed on time-dependent dynamic parameters and multimodal validation[21-23].
In addition, medial arterial calcification, which is common in diabetes, can reduce the reliability of macrocirculatory bedside assessments such as ankle-brachial index (ABI) and may yield falsely elevated or discordant pressure-based results[24-26]. Because ICG-FA primarily provides real-time information on tissue perfusion rather than a complete assessment of macrovascular inflow and hemodynamics, it should not be interpreted as a stand-alone substitute for macrocirculatory evaluation or as an isolated predictor of longer-term outcomes[27-29]. Therefore, ICG-FA findings are best interpreted together with toe pressure/toe-brachial index (TBI), skin perfusion pressure (SPP), and transcutaneous oxygen tension (TcPO2), and correlated with postoperative endpoints such as partial or total flap necrosis and limb salvage rate[13,30].
Authoritative guidelines likewise recommend that, in diabetic foot populations, comprehensive vascular assessment and healing prediction should incorporate Toe pressure/TBI, SPP, and TcPO2, recognizing that even an ABI > 0.9 does not exclude peripheral arterial disease. In certain cases, revascularization and objective reassessment are warranted. Collectively, these considerations indicate that ICG-FA should serve as a component within an integrated perfusion assessment framework rather than as a standalone decision-making tool[19,31,32]. Collectively, these considerations support a systemic-regional-microcirculatory continuum for DFU reconstruction, underscoring the need to interpret standardized quantitative ICG-FA kinetics in the context of systemic status and distal perfusion metrics (Figure 1).
Figure 1 Improving anterolateral thigh free-flap perfusion reliability in diabetic foot ulcers.
This schematic frames anterolateral thigh (ALT) free-flap perfusion in diabetic foot ulcer (DFU) as an integrated continuum linking systemic modifiable physiology - glycemic status [hemoglobin A1c (HbA1c)/perioperative glucose], anemia/iron status, respiration and oxygen delivery (DO2) [arterial partial pressure of carbon dioxide/oxygen (PaCO2/PaO2), ventilation], and nutritional reserve (albumin/prealbumin) - to regional vascular capacity in the setting of diabetes-related medial arterial calcification (MAC), where ankle-brachial index (ABI) may be misleading, and distal perfusion should be characterized using toe pressure/toe-brachial index (TBI), skin perfusion pressure (SPP), and transcutaneous oxygen tension (TcPO2), with revascularization when indicated. These layers converge with microcirculatory dysfunction and impaired capillary recruitment at the flap and recipient-site level (conceptual note: “Brightness ≠ exchange efficiency”). The central intraoperative quantitative perfusion decision hub integrates systemic status, distal perfusion context, and standardized indocyanine green fluorescence angiography (ICG-FA) acquisition, emphasizing fluorescence-time curve kinetics [wash-in slope, time to maximum intensity, maximum fluorescence intensity, area under the curve (AUC)] rather than single intensity snapshots. Outputs are actionable intraoperative strategies (revise anastomosis, trim hypoperfused margins, supercharging/additional venous outflow, proceed vs delay/optimize) to reduce partial/total necrosis and reoperation and improve limb salvage. ROI: Region of interest.
Other feasible tools and their complementarity
To improve clarity and reduce redundancy, the major adjunct perfusion modalities are summarized in Table 1, which consolidates their physiological targets, quantitative readouts, strengths, and limitations within an integrated workflow.
Table 1 Multimodal perfusion assessment toolbox for patients with diabetic foot ulcer undergoing anterolateral thigh free-flap reconstruction.
Laser doppler flowmetry/imaging: This technique enables noninvasive quantification of microvascular blood flow in skin tissue (expressed in perfusion units) and is suitable for continuous monitoring of perfusion trends. Spectral analyses of blood flow in diabetic foot patients have demonstrated its ability to reveal microcirculatory vasomotor dysfunction, including altered responses to thermal stimulation and changes in amplitude spectra[33]. However, the limitations of laser Doppler flowmetry/imaging include a small probe coverage area, high sensitivity to motion artifacts, and limited penetration depth, making it less responsive to deep tissue perfusion.
Near-infrared spectroscopy/tissue oximetry: Near-infrared spectroscopy/tissue oximetry (NIRS) measures local tissue hemoglobin oxygen saturation as an indirect indicator of oxygenation status. Systematic reviews have reported that NIRS demonstrates good early-warning capability in flap monitoring, detecting perfusion abnormalities before visual changes occur[34]. Nonetheless, variability across devices and probes remains a major issue, and standardized threshold criteria for intervention have not yet been established.
TcPO2: TcPO2 is a classic tool for assessing tissue oxygenation, widely applied in lower-limb ischemia and wound healing. Its predictive value for DFU healing has been confirmed in multiple studies. For example, one study identified TcPO2 ≥ 25 mmHg as an optimal threshold for wound healing prediction, with an AUC of approximately 0.84[35]. Another review also affirmed the clinical utility of TcPO2 in assessing oxygenation status in patients with DFU[36]. However, TcPO2 measurement is highly sensitive to probe placement, temperature control, and skin thickness, and it suffers from response delay and limited real-time feedback[36].
Additionally, emerging studies have explored the combination of infrared thermography with TcPO2 for lower-limb perfusion assessment, showing promising preliminary results in diabetic foot and vascular reconstruction settings[37]. A consolidated comparison of these modalities, including their quantitative readouts, strengths/Limitations, and recommended clinical roles, is provided in Table 1.
PREOPERATIVE PREDICTORS OF PERFUSION SUCCESS: FROM ABI TO SYSTEMIC INDICATORS
Reliability of ABI, TBI, and SPP/ TcPO2 in diabetic populations
In patients with DFU, the ABI is often affected by medial arterial calcification, which may lead to falsely normal or elevated values and thus weak predictive performance for wound healing. The 2023 International Working Group on the Diabetic Foot/European Society for Vascular Surgery (ESVS)/Society for Vascular Surgery joint guidelines clearly state that ABI/ankle pressure serves only as a weak predictor of healing and amputation risk. In contrast, toe pressure and the TBI better reflect distal microcirculation. Specifically, toe pressure ≥ 30 mmHg increases the pre-test probability of wound healing by approximately 30%, whereas toe pressure < 30 mmHg markedly elevates the risk of major amputation.
When toe pressure cannot be measured, the guidelines recommend assessing healing potential using TcPO2 and SPP, with TcPO2 ≥ 25 mmHg and SPP ≥ 40 mmHg both associated with higher likelihoods of healing. The document also highlights the physiological rationale for misleading pressure measurements in the presence of diabetic vascular calcification and advocates for a combined interpretation of ABI, TBI/toe pressure, and Doppler waveform morphology to grade ischemia severity and determine revascularization indications[38].
Consistent with these recommendations, multiple systematic reviews and cohort studies have proposed operational thresholds: Toe pressure ≥ 30 mmHg correlates with wound healing, and SPP ≥ 40 mmHg demonstrates good sensitivity and specificity (approximately 75% and 83%, respectively) for predicting 1-month healing outcomes. In contrast, ABI alone shows limited discriminative ability for DFU healing and is prone to distortion by medial arterial calcification; therefore, integrated interpretation with TBI/toe pressure, TcPO2/SPP, and revascularization data is strongly advised[39].
Systemic “modifiable” indicators: Nutrition and gas exchange
In surgical populations with DFUs, hypoalbuminemia is strongly associated with poor postoperative healing and increased amputation risk. A retrospective study of DFU surgical patients demonstrated that a preoperative albumin level < 3.5 g/dL significantly predicted non-healing within 28 days, with a receiver operating characteristic cutoff of approximately 3.44 g/dL. Similarly, a 2024 meta-analysis confirmed a robust association between low albumin and amputation events. Evidence from head and neck microsurgical free flap reconstruction also indicates that low prealbumin (reflecting acute nutritional status) correlates with higher rates of flap failure and postoperative complications, supporting its value as a rapid perioperative nutritional marker across surgical specialties. Collectively, these findings underscore that perioperative nutritional optimization - targeting albumin ≥ approximately 3.5 g/dL and providing protein supplementation when necessary - may help reduce wound complications and flap-related risks[40].
Gas exchange [partial pressure of arterial oxygen (PaO2)/partial pressure of arterial carbon dioxide (PaCO2)] and tissue oxygen delivery: Flap survival depends on adequate oxygen delivery and microcirculatory perfusion. Anesthesiology reviews emphasize maintaining oxygenation, intravascular volume, and hemoglobin concentration to ensure sufficient perfusion and oxygen supply. Physiologic and clinical studies have shown that mild hypercapnia can enhance peripheral tissue oxygen tension by increasing cardiac output and peripheral blood flow, suggesting potential benefits for marginally perfused tissues[41]. Moreover, studies on free flap monitoring have demonstrated that transcutaneous partial pressure of carbon dioxide can serve as a dynamic indicator of local perfusion, with tissue hypercapnia and arterial-tissue PaCO2 decoupling occurring when local blood flow declines[42-44].
Accordingly, in microsurgical reconstruction for DFU, respiratory management should balance adequate oxygenation (to avoid hypoxemia) with controlled ventilation that avoids excessive hypocapnia, while incorporating transcutaneous partial pressure of carbon dioxide intensity or NIRS monitoring when feasible to detect microcirculatory alterations in real time.
Taken together, these findings indicate that while ICG-FA provides real-time intraoperative assessment of perfusion, its interpretation is modulated by both systemic and local factors. Preoperative hemodynamic indices such as TBI, toe pressure, SPP, and TcPO2 reflect distal vascular capacity, whereas systemic indicators including albumin and PaO2/PaCO2 determine the efficiency of oxygen delivery and tissue repair potential. Integrating preoperative perfusion metrics, systemic physiological status, and intraoperative ICG-FA data may enhance the accuracy of perfusion assessment and improve postoperative outcome prediction[24].
PRACTICAL IMPLEMENTATION AND FREQUENCY STRATEGY OF ICG-FA WITHIN A MULTIMODAL WORKFLOW
A practical workflow may involve an initial ICG-FA run after reperfusion, followed by selective repeat imaging after corrective maneuvers. We typically perform an initial ICG-FA run immediately after flap anastomosis and reperfusion to evaluate global inflow patterns and detect gross hypoperfusion. When borderline zones are identified, a second run is performed after corrective measures (e.g., warming, vasodilator application, or minor anastomotic adjustment) to reassess fluorescence-time kinetics. Preoperatively, ICG-FA findings are interpreted in conjunction with toe pressure/TBI and TcPO2. For patients with marginal distal perfusion (e.g., toe pressure 25-30 mmHg), we emphasize careful intraoperative kinetic interpretation and adopt a lower threshold for margin trimming or venous augmentation. Postoperatively, routine repetition of ICG-FA is not standard practice; instead, we rely on structured clinical monitoring supplemented by NIRS or TcPO2 when perfusion is equivocal. Repeated ICG-FA is reserved for suspected vascular compromise or re-exploration scenarios. This experience reinforces that ICG-FA is most effective when embedded within a multimodal and physiology-aware workflow rather than applied in isolation.
RISK STRATIFICATION AND OPTIMIZATION BUNDLE: TOWARD AN ACTIONABLE CLINICAL PATHWAY
In practical implementation, the proposed quantitative and multimodal pathway is most effectively operationalized within a coordinated “plastic-vascular-anesthesia” collaborative framework that reflects the systemic-regional-microcirculatory continuum underlying flap perfusion. Within this model, vascular surgeons stratify distal perfusion capacity and determine revascularization needs; plastic and microsurgeons interpret intraoperative ICG-FA kinetics and perform targeted corrective maneuvers; anesthesiologists maintain systemic determinants of oxygen delivery - including hemoglobin concentration, oxygenation, and ventilation strategy - that directly influence fluorescence dynamics and tissue perfusion. Embedding standardized data capture and parameter reporting within a shared perioperative protocol or institutional registry may further enhance reproducibility and outcome linkage.
Within this coordinated structure, optimization bundles integrating metabolic control, nutritional support, vascular intervention, and oxygenation management are implemented to enhance reconstructive outcomes. A consistent body of evidence demonstrates that poor perioperative nutritional status is closely associated with delayed wound healing, higher complication rates, and prolonged hospitalization, whereas early preoperative supplementation with protein and calories significantly accelerates postoperative recovery[45-47]. Retrospective analyses and guideline-based literature on free flap and extensive reconstructive surgery further identify nutritional optimization as a key element of preparation, with correction of hypoalbuminemia shown to reduce the risk of flap-related complications[48-50].
In the context of diabetic foot reconstruction, optimization of vascular inflow is particularly crucial[24,51]. For patients with severe distal ischemia, successful flap perfusion and durable limb salvage are often difficult to achieve without prior revascularization or bypass procedures[52,53]. Consequently, multidisciplinary plastic-vascular collaboration has gained increasing attention, emphasizing vascular intervention before flap transfer to establish a more reliable perfusion bed for reconstruction[24,54]. Such interventions improve distal perfusion and wound-bed oxygenation and are associated with better wound healing and improved limb salvage outcomes[30,54,55].
Building upon these principles, a practical and integrated clinical workflow can be established for patients undergoing ALT free flap reconstruction. Comprehensive preoperative evaluation should encompass nutritional status (albumin, prealbumin, body mass index, and muscle mass), metabolic control, oxygenation and ventilatory function, and distal perfusion indices such as TBI, toe pressure, SPP, and TcPO2. Patients identified as nutritionally at risk should begin high-protein nutritional supplementation (oral or enteral) 7-14 days before surgery to improve protein reserves and immune competence. Those with evidence of distal ischemia - manifested by reduced toe pressure, TcPO2, or SPP - should undergo preoperative vascular intervention or bypass reconstruction, followed by reassessment of perfusion indices to confirm improvement. Anemia correction should be initiated early with iron or erythropoiesis-stimulating agents, while intravenous iron is preferred when the surgical window is short. For patients with impaired respiratory function or obstructive sleep apnea/chronic obstructive pulmonary disease, preoperative respiratory optimization is recommended to ensure stable intraoperative and postoperative oxygenation and ventilation. Surgery should proceed only after all optimization goals have been met and reconfirmed[56-58]. Based on the above considerations, we propose a quantitative, multimodal clinical pathway for ALT free-flap reconstruction in DFU, integrating preoperative optimization, standardized intraoperative ICG-FA kinetics, and structured postoperative monitoring (Figure 2).
Figure 2 Quantitative, multimodal pathway for anterolateral thigh flap perfusion in diabetic foot ulcer.
This workflow summarizes a stepwise, bundle-based algorithm for diabetic foot ulcer (DFU) candidates undergoing anterolateral thigh (ALT) free-flap reconstruction. Step 1 (preoperative evaluation) integrates distal perfusion testing [toe pressure/toe-brachial index (TBI), skin perfusion pressure (SPP), transcutaneous oxygen tension (TcPO2)], systemic optimization targets [glucose control, hemoglobin (Hb), oxygenation/ventilation, nutritional reserve], and comorbidity risk flags [peripheral artery disease (PAD), medial arterial calcification (MAC), edema/inflammation]. If perfusion and optimization targets are not met, an optimization/revascularization bundle is initiated and reassessed before proceeding. Step 2 (intraoperative perfusion imaging) applies indocyanine green fluorescence angiography (ICG-FA) under a standardized acquisition protocol and prioritizes fluorescence-time curve quantification [e.g., wash-in slope, time-to-peak, area under the curve (AUC)] to avoid intensity-only snapshots. Step 3 (multimodal validation) cross-checks ICG-FA kinetics against distal perfusion metrics and optional monitoring tools (near-infrared spectroscopy [NIRS]/tissue oximetry and laser Doppler perfusion) to adjudicate marginal perfusion. When quantitative kinetics suggest borderline perfusion, targeted intraoperative corrective actions (trim hypoperfused margins, revise anastomosis, supercharging) are implemented; otherwise, the surgeon proceeds to inset/closure. Step 4 (postoperative monitoring and endpoints) emphasizes structured surveillance (clinical assessment with optional near-infrared spectroscopy/TcPO2) and links the pathway to clinically meaningful outcomes, including partial/total necrosis, wound healing, and limb salvage. Tmax: Time to maximum fluorescence intensity; StO2: Tissue oxygen saturation; PU: Perfusion units.
Quantitatively, preoperative distal perfusion should reach at least toe pressure ≥ 30 mmHg, SPP ≥ 40 mmHg, and TcPO2 ≥ 25 mmHg; patients not meeting these criteria should undergo vascular optimization first. According to European Society for Clinical Nutrition and Metabolism surgical nutrition guidelines, perioperative nutritional support should target 1.2-1.5 g/kg/day of protein and ≥ 25 kcal/kg/day of energy intake when organ function permits. In line with American Diabetes Association Standards of Care, elective procedures should ideally be performed when hemoglobin A1c is < 8%, with perioperative glucose maintained between 100-180 mg/dL. Anemia management should aim to restore hemoglobin toward the normal range prior to elective reconstruction, consistent with perioperative optimization principles[24]. For elective cases, these optimization measures should ideally begin 2-4 weeks prior to surgery to allow measurable physiological stabilization, with reassessment of distal perfusion indices before proceeding to flap transfer.
FUTURE DIRECTIONS: INTEGRATION, STANDARDIZATION, AND CLINICAL TRIALS
Future research should advance measurement standardization, evidence-generation frameworks, and clinical implementation in parallel to bridge the gap between experimental perfusion assessment and real-world reconstructive outcomes. In terms of measurement standardization, establishing a reproducible, cross-center reporting framework for ICG-FA is imperative. Key methodological variables - including ICG dosage (mg/kg) and injection rate, timing of image acquisition (initial and repeat intervals), camera and gain settings, region-of-interest delineation rules, and the extraction of dynamic fluorescence-time curve parameters such as wash-in slope, Tmax, and AUC - should be uniformly defined, with explicit reporting of parameter derivation and validation. Current consensus papers and narrative reviews in surgical and fluorescence-guided imaging consistently identify inconsistent quantitative definitions as a major barrier to clinical adoption. Thus, developing a standardized imaging protocol and parameter set through Delphi or expert consensus, accompanied by cross-platform calibration charts and quality-control workflows, is strongly recommended to ensure reproducibility across institutions and imaging systems[59]. Accordingly, Table 2 outlines a minimum reporting set that can serve as a practical template for protocol harmonization and future clinical trials.
Table 2 Proposed minimum reporting set for standardized quantitative indocyanine green fluorescence angiography in diabetic foot ulcer anterolateral thigh free-flap reconstruction.
Reporting domain
Minimum items to report (recommended)
Why it matters
Outcome anchoring
Patient and limb ischemia phenotype
Diabetes duration/type; PAD history; prior revascularization (type, timing); ulcer location/angiosome; infection status
Baseline heterogeneity strongly shapes perfusion signals and failure risk
Stratify analyses by ischemia phenotype and revascularization status
Distal perfusion capacity (pre-op baseline)
Toe pressure/TBI, SPP, TcPO2 (site, temperature settings, timing); Doppler waveform
Interprets ICG-FA within a “distal capacity ceiling”; mitigates ABI distortion in medial calcification
Use clinically meaningful thresholds and report proportion meeting targets
Equally important is the harmonization of vascular assessment criteria. In diabetic populations, existing guidelines emphasize that ABI frequently yields falsely normal values due to medial arterial calcification and should not be used alone to assess distal perfusion. Instead, TBI/toe pressure, SPP, and TcPO2 should be prioritized or applied in combination, with clearly defined thresholds and interpretation algorithms, while ABI should remain a screening tool for peripheral arterial disease detection and stratification (e.g., ≤ 0.9 as an abnormal cutoff). Future studies should align with International Working Group on the Diabetic Foot/ESVS/Society for Vascular Surgery and ESVS 2024 guidelines, consistently collecting and reporting TBI/toe pressure, SPP, and TcPO2, and integrating these with ICG-FA dynamic parameters as shared baselines for study inclusion, outcome assessment, and inter-trial comparability[24].
From the standpoint of evidence generation, the establishment of prospective, multicenter registry cohorts represents a critical next step. Such registries should utilize a unified data dictionary and standardized measurement standard operating procedures, ensuring synchronized collection of ICG-FA parameters, macro- and microcirculatory indices, and systemic variables including glycemic control, nutritional status, anemia, and respiratory function. Longitudinal outcomes - such as partial or total flap necrosis, reoperation rate, hospitalization duration, and limb salvage - should be systematically tracked. Within these registries, embedded randomized sub-studies could assess the causal effects of a comprehensive optimization bundle (revascularization, metabolic control, nutritional support, and oxygenation management) on both ICG-FA readouts and clinical outcomes. This registry-based trial design aligns closely with recent multidisciplinary consensus statements emphasizing the urgent need for high-quality prospective and interventional studies in this field[60].
For translation into clinically actionable prediction and optimization tools, future modeling efforts should follow the updated transparent reporting of a multivariable prediction model for individual prognosis or diagnosis + artificial intelligence guidelines for transparent development and reporting. Predictive models should be constructed using penalized regression or machine learning algorithms, incorporate resampling-based internal validation, and report full discrimination and calibration performance. After external validation, models should provide intuitive visualization interfaces (e.g., nomograms or online calculators) and include decision-curve analyses to evaluate threshold-dependent clinical utility. Input variables should encompass TBI/toe pressure, SPP, TcPO2, and ICG-FA dynamic indices, integrated with systemic parameters such as hemoglobin A1c, albumin/prealbumin, hemoglobin, and oxygenation/ventilation metrics, thereby reflecting the systemic-regional-microcirculatory continuum underlying perfusion dynamics. All predictive modeling and clinical evaluation studies should comply with transparent reporting of a multivariable prediction model for individual prognosis or diagnosis + artificial intelligence reproducibility and transparency standards to facilitate cross-institutional verification and iterative refinement[61].
In summary, the standardization of ICG-FA quantification and harmonization of distal perfusion metrics will establish a foundation for cross-study comparability; registry-based multicenter cohorts with embedded randomized trials will yield high-quality causal evidence; and rigorously developed predictive models and optimization bundles will enable the translation of intraoperative perfusion imaging into evidence-based, executable perioperative strategies with demonstrable clinical benefit.
CONCLUSION
ALT free-flap reconstruction in DFUs requires more than technical precision - it demands standardized perfusion assessment and systemic optimization. Surgeons should: (1) Interpret ICG-FA using dynamic fluorescence-time kinetics rather than static intensity alone; (2) Contextualize intraoperative findings with distal perfusion metrics such as toe pressure, SPP, and TcPO2; and (3) Optimize modifiable systemic factors - including nutrition, anemia, oxygenation, and glycemic control - before flap transfer. Establishing standardized ICG-FA reporting protocols and integrating systemic variables into prospective registries will be essential to translate perfusion imaging into reproducible, evidence-based limb salvage strategies.
ACKNOWLEDGEMENTS
The authors gratefully acknowledge Zhejiang Luming Biotechnology Co., Ltd. (2nd Floor, 113-1 to 113-5 Nanliu Road, Chashan Street, Ouhai District, Wenzhou, Zhejiang Province, China) for their technical support and assistance in scientific figure preparation, formatting optimization, and related manuscript support for this work. The authors are solely responsible for the scientific content, interpretations, and conclusions of this manuscript.
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Footnotes
Peer review: Externally peer reviewed.
Peer-review model: Single blind
Specialty type: Endocrinology and metabolism
Country of origin: China
Peer-review report’s classification
Scientific quality: Grade A, Grade B, Grade C
Novelty: Grade B, Grade B, Grade B
Creativity or innovation: Grade A, Grade B, Grade B
Scientific significance: Grade A, Grade B, Grade B
P-Reviewer: Khurram MF, MD, PhD, Professor, India; Septrina R, PhD, Assistant Professor, Consultant, Researcher, Indonesia S-Editor: Hu XY L-Editor: Filipodia P-Editor: Yang YQ
