Novel Applications of Radionuclide Imaging in Peripheral Vascular Disease

Abstract

Peripheral vascular disease (PVD) is a progressive atherosclerotic disease that leads to stenosis or occlusion of blood vessels supplying the lower extremities. Current diagnostic imaging techniques commonly focus on evaluation of anatomy or blood flow at the macrovascular level and do not permit assessment of the underlying pathophysiology associated with disease progression or treatment response. Molecular imaging with radionuclide-based approaches, such as PET and SPECT, can offer novel insight into PVD by providing non-invasive assessment of biological processes such as angiogenesis and atherosclerosis. This review discusses emerging radionuclide-based imaging approaches that have potential clinical applications in the evaluation of PVD progression and treatment.

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

“…Early research studies that applied gamma cameras for the assessment of PAD were primarily accomplished by 2-dimensional scintigraphy or used thallium-201, without assessing regional variability in perfusion within specific 3D vascular territories. 17 However, PAD-focused research in the past decade has begun to use the 99m Tc-labeled perfusion tracers 99m Tc-tetrofosmin and 99m Tc-sestamibi, which has reduced radiation exposure to patients, increased image quality on gamma cameras, and demonstrated clinical utility in the detection of PAD within the calf, 28 , 29 as well as assisted with tracking the response to cell therapy in the foot. 30 – 32 Additionally, recent preclinical research has established and validated methods for assessing serial changes in microvascular perfusion within specific lower extremity muscle groups using SPECT/CT imaging.…”

“…Current clinical imaging tools have limitations related to assessment of microvascular disease in patients with PAD and are commonly restricted to evaluating microvascular perfusion within superficial tissue or only allow for evaluation of major vessel blood flow and morphology. 17 Although magnetic resonance-based approaches, such as blood oxygen level dependent, 18 , 19 arterial spin labeling, 20 , 21 and contrast-enhanced imaging, 22 are capable of quantifying 3D tissue oxygenation and perfusion, these approaches do not allow for assessment of resting foot perfusion and generally require exercise, pharmacological, or reactive hyperemia paradigms to produce quantifiable signals. Radiotracer-based perfusion imaging with single photon emission computed tomography (SPECT)/computed tomography (CT) offers some advantages over conventional imaging techniques by allowing for serial volumetric assessment of regional microvascular perfusion in the lower extremities under resting conditions without the need for iodine- or gadolinium-based contrast agents.…”

Multimodality Imaging Approaches for Evaluating Traumatic Extremity Injuries: Implications for Military Medicine

“…7 SPECT/CT imaging has been applied in the clinical environment for many years for the assessment of myocardial perfusion in patients with coronary artery disease; however, SPECT/CT may also have value in the assessment of extremity trauma through its ability to evaluate skeletal muscle perfusion under conditions of rest or stress. 47 In addition, SPECT/CT imaging has already demonstrated potential for assessing a wide range of other physiological processes, such as bone and tissue infection, [48][49][50][51] heterotrophic ossification, 52 and skeletal muscle angiogenesis, 47 which could be useful in the evaluation of extremity trauma and tracking the response to medical treatment. In the assessment of infection, multiple technetium-99 m ( 99m Tc)-labeled radiotracers have been applied in the extremities.…”

Multimodal and Multiscale Analysis Reveals Distinct Vascular, Metabolic and Inflammatory Components of the Tissue Response to Limb Ischemia

“…Nuclear imaging studies employing dedicated tracers in single photon emission computed tomography (SPECT) or positron emission tomography (PET) combined with x-ray based computed tomography (CT) for anatomical co-localization provide non-invasive tools for the functional evaluation of perfusion, metabolism, angiogenesis and inflammation in ischemic tissues 8, 9. For example, [ 99m Tc]-Sestamibi is a lipophilic cationic isonitrile which distributes in muscular tissue proportionally to the local blood flow which is used clinically in patients with PAD and provides complementary information on ischemic blood flow to Laser-Doppler imaging in animal models 10, 11.…”

“…In contrast, 99m Tc-labeled human serum albumin (HSA) micro-particles given intra-arterially can be used as a marker for arterial vascularization 12, as the particles are trapped in the arterial side of the capillaries. [ 18 F]-Fluorodeoxyglucose (FDG) is a glucose analogue that is taken up by muscle fibers, endothelial cells (EC) and macrophages via glucose transporters and trapped inside the cell, thus imaging glucose metabolism for assessment of inflammation and viability 9, 13, 14. In addition, the combination of perfusion and metabolic studies can detect mismatches between glucose metabolism and perfusion considered the hallmark of myocardial ischemic hibernation 14.…”