Date of Award


Document Type

Open Access Thesis

Degree Name

Medical Doctor (MD)



First Advisor

Mitchel Stacy

Second Advisor

Albert Sinusas



Jessica L. Buckley, Albert J. Sinusas, Mitchel R. Stacy. Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT.

Impaired lower extremity perfusion is a hallmark of peripheral arterial disease (PAD) and is particularly problematic in diabetic patients, who suffer from high rates of PAD, ulceration, and lower extremity amputation. The ability to non-invasively detect deficits in microvascular perfusion within vascular territories, or angiosomes, of the feet may provide information related to tissue viability and guide therapeutic interventions. In this study, we sought to apply single photon emission computed tomography (SPECT)/CT imaging to quantify volumetric microvascular perfusion within specific angiosomes containing non-healing foot ulcers in diabetic patients with critical limb ischemia (CLI). Additionally, we sought to assess the value of SPECT/CT perfusion imaging for predicting limb salvage in CLI patients undergoing lower extremity endovascular revascularization.

Forty-one diabetic patients (mean age, 66±12 yrs) with non-healing ulcers and nine healthy control subjects (mean age, 50±10 yrs) underwent SPECT/CT imaging of the feet following a resting injection of technetium-99m (99mTc)-tetrofosmin (dose, 550.6 ± 37 Mbq). CT images of diabetic feet were segmented into five angiosomes and used for quantifying relative radiotracer uptake, expressed as standardized uptake values (SUVs). SUVs were assessed for each CLI patient in the angiosome containing the non-healing ulcers, while average whole foot perfusion was assessed for healthy control subjects. Percent change in SPECT SUVs of ulcerated angiosomes was quantified following endovascular revascularization in patients, and 3-, 6-, and 12-month limb salvage outcomes were assessed.

SPECT/CT imaging allowed for visualization of perfusion deficits under resting conditions. 99mTc-tetrofosmin SPECT/CT imaging of angiosome foot perfusion demonstrated a significant difference in baseline perfusion values (SUVs) between diabetic patients with CLI and healthy control subjects (p = 0.02). Analysis of baseline SPECT/CT imaging and ankle-brachial index (ABI) measurements in CLI patients and healthy control subjects demonstrated a significant and positive relationship between SPECT/CT angiosome perfusion and ABI (p = 0.01; r = 0.41). Serial evaluation of relative changes in SPECT angiosome foot perfusion following revascularization revealed significant quantitative changes in perfusion after treatment, whereas ABI measurements did not demonstrate significant changes after revascularization. Changes in SPECT/CT-derived angiosome perfusion significantly differed between patients with and patients without amputation in the 3 (p = 0.01), 6 (p = 0.03), and 12 (p = 0.03) months following revascularization.

SPECT/CT imaging provides a useful non-invasive tool for evaluating microvascular perfusion within specific angiosomes of the foot under resting conditions. SPECT/CT imaging also allows for serial assessment of sensitive changes in angiosome microvascular perfusion following revascularization that are undetected by ABI. Perfusion imaging with SPECT/CT offers a novel quantitative imaging approach for assessing the efficacy of revascularization strategies targeted at restoring perfusion to non-healing wounds of the foot and may assist with predicting limb salvage outcomes in CLI patients undergoing revascularization. Future application of SPECT/CT perfusion imaging may provide additional value for detection and targeting of ischemic tissue for therapeutic interventions in the PAD patient population.


This is an Open Access Thesis.

Open Access

This Article is Open Access