Prognostic Value of Radiotracer-Based Perfusion Imaging in Critical Limb Ischemia Patients Undergoing Lower Extremity Revascularization

Abstract

Objectives: The purpose of this study was to evaluate the prognostic value of single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging of angiosome foot perfusion for predicting amputation outcomes in patients with critical limb ischemia (CLI) and diabetes mellitus (DM).

Background: Radiotracer imaging can assess microvascular foot perfusion and identify regional perfusion abnormalities in patients with critical limb ischemia CLI and DM, but the relationship between perfusion response to revascularization and subsequent clinical outcomes has not been evaluated.

Methods: Patients with CLI, DM, and nonhealing foot ulcers (n = 25) were prospectively enrolled for SPECT/CT perfusion imaging of the feet before and after revascularization. CT images were used to segment angiosomes (i.e., 3-dimensional vascular territories) of the foot. Relative changes in radiotracer uptake after revascularization were evaluated within the ulcerated angiosome. Incidence of amputation was assessed at 3 and 12 months after revascularization.

Results: SPECT/CT detected a significantly lower microvascular perfusion response for patients who underwent amputation compared with those who remained amputation free at 3 (p = 0.01) and 12 (p = 0.01) months after revascularization. The cutoff percent change in perfusion for predicting amputation at 3 months was 7.55%, and 11.56% at 12 months. The area under the curve based on the amputation outcome was 0.799 at 3 months and 0.833 at 12 months. The probability of amputation-free survival was significantly higher at 3 (p = 0.002) and 12 months (p = 0.03) for high-perfusion responders than low-perfusion responders to revascularization.

Conclusions: SPECT/CT imaging detects regional perfusion responses to lower extremity revascularization and provides prognostic value in patients with CLI (Radiotracer-Based Perfusion Imaging of Patients With Peripheral Arterial Disease; NCT03622359).

Keywords: critical limb ischemia; diabetes; perfusion imaging; revascularization; single-photon emission computed tomography.

Conflict of interest statement

Funding Support and Author Disclosures Dr. Stacy has received funding from National Institutes of Health grant R01 HL135103. All other authors have reported that they have no relationships relevant to the content of this paper to disclose.

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1.. Comparison of SPECT/CT imaging-derived changes in angiosome perfusion in response to lower extremity revascularization between patients who remained amputation free versus patients who received an amputation.

SPECT/CT perfusion imaging detected significantly lower percent change in angiosome perfusion for patients who received an amputation in the initial (A) 3 and (B) 12 months after revascularization.

Figure 2.. Receiver-operating characteristic curve analysis for determining the cutoff for percent change in angiosome perfusion value based on the occurrence of lower extremity amputation or death at 3 and 12 months after revascularization.

(A) At 3 months after revascularization, the cutoff value for percent change in perfusion that predicted amputation-free survival was 7.5% and the area under the ROC was 0.799. (B) At 12 months after revascularization, the cutoff value for percent change in perfusion was 9.94%, and the area under the ROC curve was 0.833.

Figure 3.. Kaplan-Meier plots for amputation-free survival based on revascularization-induced change in angiosome perfusion.

Amputation-free survival in the high perfusion responder patient group was significantly higher than in the low perfusion responder group at (A) 3 months (log-rank test, p = 0.002) and (B) 12 months (p = 0.03) after lower extremity revascularization.

Figure 4.. Forest plot of hazard ratios (HR) for lower extremity amputation in patients with CLI during the first 12 months after endovascular revascularization.

HR calculations are based on univariate Cox proportional hazards regression models.

Figure 5.. Assessment of the test-retest reliability of SPECT/CT perfusion measurements.

Bland-Altman plot revealed a mean difference of 0.0007 with 95% agreement limits of −0.020 to 0.021 for perfusion measures acquired in the contralateral untreated foot before and after revascularization, which demonstrated excellent agreement level between serial SPECT/CT imaging perfusion measurements. n=19 patients.

Central Illustration.. SPECT/CT perfusion imaging of perfusion response to lower extremity revascularization in the setting of DM and CLI.

Pictured is (A) a patient who demonstrated a low perfusion response to revascularization (i.e. 5%) and underwent eventual minor amputation in the first month, and (B) a patient who alternatively demonstrated a high perfusion response (i.e. 29%) and did not receive an amputation in the 12 months after revascularization.