Radiotracer Imaging Allows for Noninvasive Detection and Quantification of Abnormalities in Angiosome Foot Perfusion in Diabetic Patients With Critical Limb Ischemia and Nonhealing Wounds

Abstract

Background: Single photon emission computed tomography (SPECT)/computed tomography (CT) imaging allows for assessment of skeletal muscle microvascular perfusion but has not been quantitatively assessed in angiosomes, or 3-dimensional vascular territories, of the foot. This study assessed and compared resting angiosome foot perfusion between healthy subjects and diabetic patients with critical limb ischemia (CLI). Additionally, the relationship between SPECT/CT imaging and the ankle-brachial index-a standard tool for evaluating peripheral artery disease-was assessed.

Methods and results: Healthy subjects (n=9) and diabetic patients with CLI and nonhealing ulcers (n=42) underwent SPECT/CT perfusion imaging of the feet. CT images were segmented into angiosomes for quantification of relative radiotracer uptake, expressed as standardized uptake values. Standardized uptake values were assessed in ulcerated angiosomes of patients with CLI and compared with whole-foot standardized uptake values in healthy subjects. Serial SPECT/CT imaging was performed to assess uptake kinetics of technetium-99m-tetrofosmin. The relationship between angiosome perfusion and ankle-brachial index was assessed via correlational analysis. Resting perfusion was significantly lower in CLI versus healthy subjects (P=0.0007). Intraclass correlation coefficients of 0.95 (healthy) and 0.93 (CLI) demonstrated excellent agreement between serial perfusion measurements. Correlational analysis, including healthy and CLI subjects, demonstrated a significant relationship between ankle-brachial index and SPECT/CT (P=0.01); however, this relationship was not significant for diabetic CLI patients only (P=0.2).

Conclusions: SPECT/CT imaging assesses regional foot perfusion and detects abnormalities in microvascular perfusion that may be undetectable by conventional ankle-brachial index in patients with diabetes mellitus. SPECT/CT may provide a novel approach for evaluating responses to targeted therapies.

Keywords: diabetes mellitus; ischemia; perfusion imaging; peripheral artery disease.

Figure 1.

Volume rendered foot angiosomes overlaid on X-ray computed tomography attenuation images acquired in a patient with critical limb ischemia. A, Medial, (B) lateral, and (C) posterior views display the medial heel (orange), lateral heel (yellow), dorsal foot (green), medial plantar (blue), and lateral plantar (red) angiosomes.

Figure 2.

Serial registration of x-ray computed tomography foot images for assessing test–retest reliability of single photon emission computed tomography/CT perfusion imaging. Registration was achieved using points from outer skin surfaces. Pictured are lateral and posterior views of rendered surfaces from 2 separate imaging studies (green, scan 1 foot position; and red, scan 2 foot position) at the (A) starting position before registration, (B) after global rigid registration, and (C) after nonrigid registration.

Figure 3.

Resting ^99mTc-tetrofosmin single photon emission computed tomography (SPECT)/computed tomography (CT) perfusion imaging in a critical limb ischemia patient with a nonh ealing foot ulcer. A, Coronal, (B) axial, and (C) sagittal views of fused SPECT/CT images reveal a relative perfusion defect (denoted by white arrows) located in the (D) region of the nonhealing wound (denoted by yellow arrow) that extends along the plantar aspect of the foot.

Figure 4.

Comparison of resting single photon emission computed tomography (SPECT)/computed tomography (CT) perfusion imaging in healthy and critical limb ischemia (CLI) subjects. A, Axial, (B) coronal, and (C) sagittal views of ^99mTc-tetrofosmin SPECT/CT imaging demonstrate visual differences in foot perfusion under resting conditions. D, Quantitative image analysis reveals significant differences in resting foot perfusion (standardized uptake values) between healthy subjects and patients with CLI.

Figure 5.

Evaluation of ^99mTc-tetrofosmin uptake kinetics in the feet of healthy subjects and patients with critical limb ischemia (CLI). The Bland–Altman plot collectively displays perfusion values for each angiosome in healthy and CLI subjects. Intraclass correlation coefficients of 0.95 (healthy subjects) and 0.93 (patients with CLI) demonstrated excellent agreement level between measurements acquired at 15 and 45 min post-radiotracer injection. n=8 healthy subjects, and n=6 patients with CLI. SPECT indicates single photon emission computed tomography; and SUV, standardized uptake value.

Figure 6.

Evaluation of the relationship between single photon emission computed tomography (SPECT)-derived angiosome perfusion and ankle–brachial index (ABI). A, Correlational analysis of both healthy and critical limb ischemia (CLI) subjects demonstrated a significant relationship between ABI and SPECT angiosome perfusion; however, this relationship was not significant in (B) correlational analysis of patients with CLI only. n=30 patients with CLI, and n=9 healthy subjects.