Indocyanine Green Angiography for the Diagnosis of Peripheral Arterial Disease with Isolated Infrapopliteal Lesions

doi:10.1016/j.avsg.2014.03.024

Annals of Vascular Surgery

Volume 28, Issue 6, August 2014, Pages 1479-1484

https://doi.org/10.1016/j.avsg.2014.03.024 Get rights and content

Background

In this study, we evaluated the accuracy of the indocyanine green angiography (ICGA) test to diagnose peripheral arterial disease (PAD) with isolated infrapopliteal lesions.

Methods

This study was undertaken from a retrospective review of PAD patients with isolated infrapopliteal lesions who underwent ICGA between November 2012 and July 2013. We calculated the ICGA parameters while comparing the findings with the ankle-brachial index (ABI) and toe-brachial index (TBI) in patients with infrapopliteal lesions.

Results

Twenty-three limbs with isolated infrapopliteal lesions in 14 PAD patients and 15 limbs without arterial lesions in 9 control patients were examined using ABI, TBI, and ICGA. The Td 90% (the time elapsed from the maximum intensity to 90% of the maximum intensity) correlated most significantly with the ABI value. A cutoff value of Td 90% >25 sec also significantly correlated with the presence of PAD (sensitivity, 82.6%).

Conclusions

ICGA might therefore be useful for assessing the peripheral perfusion quantitatively, even in PAD patients with isolated infrapopliteal lesions. The use of Td 90% on ICGA may also be effective for accurately estimating the presence of PAD.

Introduction

Peripheral arterial disease (PAD) induces a broad spectrum of clinical conditions ranging from asymptomatic disease to critical limb ischemia.¹ Although PAD commonly occurs in patients with diabetes, it nevertheless remains greatly underdiagnosed.² The presentation of PAD in patients with diabetes exhibits specific characteristics. Arteriopathy in diabetic patients is known to more frequently involve the distal arteries than the proximal arteries. The primary vessels affected are the popliteal artery, anterior tibioperoneal trunk, and posterior tibial and dorsalis pedis arteries.³ Moreover, a strong association is observed between diabetes and medial artery calcification,⁴ which causes arterial wall stiffness and results in an artificially high ankle pressure.

PAD screening may be performed to prevent the progression of PAD or future cardiovascular disease in general. Therefore, several noninvasive and invasive tests have been designed to detect PAD in clinical practice. These tests include computed tomographic angiography (CTA), magnetic resonance angiography (MRA), duplex ultrasound sonography (DUS), and the ankle-brachial index (ABI). Among these tests, measuring the ABI is the most simple and inexpensive. According to Inter-Society Consensus guidelines,⁵ PAD is diagnosed based on the detection of an ABI of ≦0.90 or a toe-brachial index (TBI) of <0.70. In patients with media calcification, the ankle pressure can be either falsely elevated or within the normal limits. Therefore, the ABI has been shown to underestimate the presence of PAD, especially in patients with media calcification. The reported sensitivity of an ABI of <0.90 in detecting ≧50% stenosis in the lower extremities using digital subtraction angiography ranges from 15% to 79%, with a specificity of 83–100%.⁶ On the other hand, the toe vessels are less susceptible to vessel stiffness, which makes the TBI more useful than the ABI.⁷ Williams et al.⁸ reported that a TBI of <0.75 detected the presence of PAD with diabetes with a sensitivity ranging from 91% to 100% and a specificity ranging from 61% to 65%. Although several guidelines and reviews of PAD diagnostics5, 7 recommend a TBI of 0.70 as the cutoff, this recommendation is not strictly evidence based, and several TBI values, such as <0.75,⁸ <0.65,⁹ and <0.60,¹⁰ are therefore currently used as the cutoff points.

For screening PAD, it is necessary to identify more accurate parameters than the ABI. In this study, we evaluated the accuracy of the indocyanine green (ICG) angiography (ICGA) test to diagnose the PAD with isolated infrapopliteal lesions that can easily mask the patient's symptoms, thus resulting in a misdiagnosis. ICG is clinically used as a near infrared fluorophore for intravital imaging, a marker of the liver function,¹¹ and as a sensitizer for photodynamic therapy. Following intravenous administration, ICG is distributed throughout the intravascular space, where it thereafter rapidly binds to major serum proteins, particularly albumin.¹² ICGA rapidly provides excellent and informative images of tissue perfusion, thus making it possible to accurately estimate the degree of tissue perfusion.¹³ Therefore, we quantitatively assessed the peripheral circulation using ICGA tests while comparing the findings with the ABI values.

Section snippets

Patients

All protocols, surveys, and consent forms were approved by the Institutional Review Board of Tokyo Medical and Dental University Hospital. Written informed consent was obtained from all subjects. In this study, we performed ICGA in 14 established PAD patients with isolated infrapopliteal lesions. We diagnosed PAD using CTA, MRA, DUS, and/or digital subtraction angiography based on the presence of >50% vessel stenosis due to the infrapopliteal lesions. Patients with aortoiliac lesions and/or

Patient Characteristics

During the study period, a total of 38 ICGA examinations were performed. Among the patients with PAD, the average patient age was 69.8 years (range: 61–82) and 10 patients (10 of 14 = 71%) were men. Among group B, the average patient age was 76.3 years (range: 58–86) and 3 patients (3 of 9 = 33%) were men; therefore, the group B was older than the group A. The documented comorbidities were diabetes mellitus (82% and 0%), hypertension (78% and 87%), dyslipidemia (30% and 67%), coronary artery

Discussion

PAD patients with diabetes exhibit macrovascular angiopathy primarily in association with infrapopliteal lesions.¹⁸ Diagnosing PAD in patients with diabetes is often difficult because of the absence of clinical symptoms. The diagnostic efficacy of ABI as a screening test may be limited in diabetic patients with elevated cardiovascular risks, neuropathy, and foot lesions because of its weak sensitivity and the high rate of biased normal values. In our study, the sensitivity of the ABI fell to

References (24)

C. Hoyer et al.
Randomised diagnostic accuracy study of a fully automated portable device for diagnosing peripheral arterial disease by measuring the toe-brachial index
Eur J Vasc Endovasc Surg
(2013)
T.W. Rooke et al.
2011 ACCF/AHA focused update of the guideline for the management of patients with peripheral artery disease (updating the 2005 Guideline). A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
J Am Coll Cardiol
(2011)
V. Suominen et al.
Prevalence and risk factors of PAD among patients with elevated ABI
Eur J Vasc Endovasc Surg
(2008)
U. Schmidt-Erfurth et al.
Time course and morphology of vascular effects associated with photodynamic therapy
Ophthalmology
(2005)
K. Igari et al.
Quantitative evaluation of the outcomes of revascularization procedures for peripheral arterial disease using indocyanine green angiography
Eur J Vasc Endovasc Surg
(2013)
L. Potier et al.
Use and utility of ankle brachial index in patients with diabetes
Eur J Vasc Endovasc Surg
(2011)
F. Schroder et al.
A modified calculation of ankle-brachial pressure index is far more sensitive in the detection of peripheral arterial disease
J Vasc Surg
(2006)
B.H. Gray et al.
The impact of isolated tibial disease on outcomes in the critical limb ischemic population
Ann Vasc Surg
(2010)
J.D. Braun et al.
Early quantitative evaluation of indocyanine green angiography in patients with critical limb ischemia
J Vasc Surg
(2013)
A.T. Hirsch et al.
Peripheral arterial disease detection, awareness, and treatment in primary care
JAMA
(2001)

E.B. Jude et al.

Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome

Diabetes Care

(2001)

P.D. Reaven et al.

Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes

Diabetologia

(2005)

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Pedal Acceleration Time (PAT): A Novel Predictor of Limb Salvage
2021, Annals of Vascular Surgery
Citation Excerpt :
However, in patients with extensive foot wound and/or edema, direct measurement of TCPO2 can be difficult to obtain and provide false readings.2 Indocyanine green angiography (ICGA) is also being used to help determine perfusion, but is invasive, results can be subjective, and costly and not readily portable.10 Our previous study revealed that PAT is highly correlative with ankle-brachial indices in evaluating patients with compressible vessels.
In the setting of Peripheral Arterial Disease (PAD), pedal arch interrogation by ultrasound has not been well described. Patients with noncompressible vessels and/or open wounds of the foot may preclude the use of ankle-brachial indices, toe pressure measurements, or TcPO2, respectively. We propose that pedal artery interrogations with Pedal Acceleration Time (PAT) can be a predictor for limb salvage in patients with Chronic Limb-Threatening Ischemia (CLTI).
A retrospective review of a prospectively kept database was performed from 2018 to 2019. Patients with pending amputation due to severe infection (WIFI infection class 2 and 3) were excluded from the study. We identified 73 limbs with CLTI that fit the inclusion criteria. Data included WIFI classification, age, gender, cardiovascular risk factors, PAT, ABI, and TBI when reliable, were collected. PAT measurements were categorized into 4 classifications; 1 (40–120 msec), 2 (121–180 msec), 3 (181–224 msec), and 4 (Greater than 225 msec). Statistical analyses were performed.
Seventy-three limbs with CLTI were included in our study. All patients underwent arterial revascularization with either percutaneous technique or arterial bypass. Limb salvage was achieved in 59 (81%) of the 73 limbs. All 59 limbs had a 2-classification improvement in their PAT following interventions. A total of 14 (19%) limbs without improvement in their PAT underwent above ankle level amputations. An improvement in PAT classes to class 1 or 2 is associated with limb salvage.
Patients with noncompressible ankle pressures or nonobtainable toe pressures poses a challenge in the complete assessment of WIFI classification. Our group has shown that PAT can be used in the scoring system for severity of ischemia in conjunction with current WIFI classification. Our data suggests that limb salvage correlates with post procedure PAT in category 1 and 2. Therefore we propose that PAT be added as part of the WIFI classification.
The accuracy of toe brachial index and ankle brachial index in the diagnosis of lower limb peripheral arterial disease: A systematic review and meta-analysis
2020, Atherosclerosis
We aimed to compare the diagnostic accuracy of ankle brachial index (ABI) and toe brachial index (TBI) for peripheral arterial disease (PAD) in a wide spectrum of PAD populations and reference standard tests, and to examine variables influencing heterogeneity in the estimates.
Systematic searches in EMBASE, MEDLINE, Web of Science and the Cochrane Library databases were performed, from inception to January 2020. Hierarchical summary receiver operating characteristic curves (HSROC) were used to summarize the pooled test performance.
Thirty five (patient-level: 1318 patients, limb-level: 5637 limbs) and nine studies (patient-level: 294 patients, limb-level: 826 limbs) were included in ABI and TBI meta-analyses, respectively. The QUADAS-2 tool identified many studies with high risk of bias, especially in the “patient selection” domain. Pooled estimates for ABI in detecting 50% or greater stenosis were sensitivity = 61% (95% CI: 55–69), specificity = 92% (95% CI: 89–95) and dOR = 16.5 (95% CI: 11.5–23.6). Similarly, TBI yielded sensitivity = 81% (95% CI: 70–94), specificity = 77% (95% CI: 66–90) and dOR = 13.1 (95% CI: 7.0–24.8). In a direct comparison of seven studies jointly analyzing ABI and TBI, TBI showed better overall diagnostic accuracy (16.4 vs 11.0 in dOR) at the expense of sensitivity (82% vs 52%), while specificity (77% vs 94%) performed worse in TBI than ABI. Heterogeneity was large in sensitivity for ABI, with variables as different reference standard tests, smoking habit and PAD prevalence accounting for such variability. Similarly, gender, different index test cut-offs and sample size influenced the heterogeneity in TBI specificity.
Though ABI and TBI showed similar diagnostic performance to diagnose PAD, TBI showed far better sensitivity than ABI, especially in “challenging populations”, as those exhibiting calcification.
Vascular Assessment of the Lower Extremity with a Chronic Wound
2020, Surgical Clinics of North America
A systematic review of the use of near-infrared fluorescence imaging in patients with peripheral artery disease
2019, Journal of Vascular Surgery
Citation Excerpt :
Furthermore, this review shows the heterogeneity in ROIs that are used and the variety of parameters for quantitative assessment of perfusion. As stated by Igari et al,25 time-related parameters appear to have greater diagnostic accuracy than fluorescence intensity, especially because fluorescence intensity alone is influenced by multiple factors.9 This statement is supported by this review, which shows that highest diagnostic accuracies are found with use of time-related parameters, such as T½, PDE10, and Td90%.
In the diagnosis of peripheral artery disease (PAD), the ankle-brachial index plays an important role. However, results of the ankle-brachial index are unreliable in patients with severe media sclerosis. Near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) can provide information about tissue perfusion and has already been studied in oncologic, reconstructive, and cardiac surgery. For patients with PAD, this technique might give insight into skin perfusion and thereby guide treatment. We performed a systematic review of the literature on the use of NIR fluorescence imaging in patients with PAD.
PubMed, MEDLINE, Embase, and Cochrane were searched for articles and abstracts on the application of NIR fluorescence imaging using ICG as fluorescent dye in patients with PAD. Our search strategy combined the terms “fluorescence,” “ICG,” or synonyms and “peripheral artery disease” or synonyms. The extracted data included fluorescence parameters and test characteristics for diagnosis of PAD.
Twenty-three articles were found eligible for this review using 18 different parameters for evaluation of the fluorescence signal intensity. NIR fluorescence imaging was used for four main indications: diagnosis, quality control in revascularization, guidance in amputation surgery, and visualization of vascular structures. For the diagnosis of PAD, NIR fluorescence imaging yields a sensitivity ranging from 67% to 100% and a specificity varying between 72% and 100%. Significant increases in multiple fluorescence parameters were found in comparing patients before and after revascularization.
NIR fluorescence imaging can be used for several indications in patients with PAD. NIR fluorescence imaging seems promising in diagnosis of PAD and guidance of surgeons in treatment, especially in patients in whom current diagnostic methods are not applicable. Further standardization is needed to reliably use this modality in patients with PAD.
Perfusion Assessment and Treatment in the Diabetic Patient
2019, Clinics in Podiatric Medicine and Surgery
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Given the challenge of correlating angiosomes- and nonangiosomes-based perfusion assessment with clinical outcomes, the use of indocyanine green angiography (ICGA) has also emerged as perfusion assessment tool. ICGA has been studied extensively in free flap creation and has been shown to provide perfusion information that predicts tissue survival in assessing flap viability.20–22 ICG is administered intravascularly and binds to serum proteins.
Microcirculation Evaluated by Intraoperative Fluorescence Angiography after Tibial Bypass Surgery
2017, Annals of Vascular Surgery
Citation Excerpt :
Therefore, we tried to evaluate this technique in the setting of tibial bypass surgery and compared our findings afterward with the clinical outcome. In recent years, a number of studies emphasized the relevance of the assessment of the microcirculation to achieve a sufficient wound healing especially in CLI patients with Rutherford categories V and VI.13,14,26–28 Most patients with tibial artery calcification show an additional involvement of the plantar and dorsal foot arteries and a complete pedal arch is rarely observed.29,30
Intact microperfusion of the foot in the critical ischemic limb remains a crucial condition for ulcer healing. Aim of this clinical study was to evaluate the immediate effect of tibial bypass surgery on the microcirculation by usage of fluorescence angiography.
Prospective analysis of 33 patients presenting with critical limb ischemia (Rutherford IV–VI) undergoing tibial bypass surgery was performed. Macroperfusion was investigated by measurement of ankle-brachial index. For assessment of microperfusion, intraoperative fluorescence angiography (SPY Elite, NOVADAQ) was undertaken during general anesthesia immediately before and after operation. For each investigation, a fluorescence dye (Indocyanine green) with an amount of 0.1 mg/kg was administered intravenously. Follow-up investigations were performed to assess the clinical outcome.
The mean follow-up time was 8.28 (±4.46) months. The parameters Ingress (IN) and Ingress rate (InR) of the fluorescence dye representing the microcirculation showed a significant improvement to preoperative values and correlated with the ankle-brachial index significantly. Furthermore, a significant difference between the individual improvement of the microcirculation parameters (preoperative–postoperative) between patients with postoperative clinical improvement (wound healing, absence of rest pain) and those without could be demonstrated (InR: P = 0.039, IN: P = 0.036).
The parameters IN and InR significantly reproduced the postoperative improvement of the microcirculation. An increased ankle-brachial index significantly correlated with increased microcirculation parameters. A better clinical outcome was found in those patients who had a higher relative improvement of microcirculation postoperatively.

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Clinical ResearchIndocyanine Green Angiography for the Diagnosis of Peripheral Arterial Disease with Isolated Infrapopliteal Lesions

Background

Methods

Results

Conclusions

Introduction

Section snippets

Patients

Patient Characteristics

Discussion

Eur J Vasc Endovasc Surg

J Am Coll Cardiol

Eur J Vasc Endovasc Surg

Ophthalmology

Eur J Vasc Endovasc Surg

Eur J Vasc Endovasc Surg

J Vasc Surg

Ann Vasc Surg

J Vasc Surg

Peripheral arterial disease detection, awareness, and treatment in primary care

JAMA

Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome

Diabetes Care

Coronary artery and abdominal aortic calcification are associated with cardiovascular disease in type 2 diabetes

Diabetologia

Clinical Research
Indocyanine Green Angiography for the Diagnosis of Peripheral Arterial Disease with Isolated Infrapopliteal Lesions