The Value of Super-resolution Ultrasound Imaging for Peripheral Artery Disease

Peripheral artery disease (PAD) is a chronic atherosclerotic disorder characterized by stenosis or occlusion of the extracranial arteries distal to the aortic arch, most commonly affecting the lower extremities. This vascular compromise leads to tissue hypoperfusion, resulting in a spectrum of clinical manifestations ranging from asymptomatic disease to intermittent claudication, critical limb ischemia, and limb loss.

The microvascular system comprises arterioles, capillaries, and post-capillary venules with diameters less than or equal to 100 micrometers. Emerging evidence underscores that microvascular dysfunction (MVD)-defined as structural and functional impairment of this microcirculatory network-plays a pivotal pathophysiological role in PAD progression, contributing to impaired perfusion reserve, endothelial dysfunction, inflammation, and tissue fibrosis, independent of macrovascular stenosis severity.

Super-resolution ultrasound microvascular imaging (SRUMI) is an advanced contrast-enhanced ultrasound technique that leverages the nonlinear acoustic signatures of intravascular microbubble contrast agents (e.g., SonoVue) under ultra-low mechanical index (MI) pulsing schemes. Implemented on the Verasonics Vantage 256 research platform (Verasonics, Inc., Kirkland, WA, USA), SRUMI achieves in vivo visualization of microvascular architecture at sub-diffraction resolution (approximately 10-20 micrometers), surpassing conventional Doppler and contrast-enhanced ultrasound. Key advantages include absence of ionizing radiation, negligible thermal and mechanical bioeffects, real-time capability, portability, and cost-effectiveness. As such, SRUMI represents a promising noninvasive tool to probe microvascular integrity in PAD, enabling mechanistic investigation of MVD's contribution to disease initiation, progression, and therapeutic response.

This study aims to evaluate the diagnostic and prognostic utility of SRUMI for assessing microvascular dysfunction in patients with PAD. The investigators prospectively enrolled patients diagnosed with PAD and admitted to the Department of Interventional Vascular Surgery at Peking University First Hospital. Primary objectives include:

Characterizing lower-limb microvascular density, morphology, and perfusion patterns via SRUMI across PAD subgroups stratified by comorbidities-including diabetes mellitus, current or former smoking, hypertension, and chronic kidney disease;

Assessing the concordance between SRUMI-derived microvascular parameters and established clinical and paraclinical markers, including symptom severity (Rutherford classification), ankle-brachial index (ABI), urinary albumin-to-creatinine ratio (UACR), and retinal microvascular findings on fundoscopy;

Determining the sensitivity, specificity, and predictive value of baseline SRUMI metrics for major adverse limb events (MALE) and cardiovascular outcomes during longitudinal follow-up; and

Comparing the incremental prognostic value of SRUMI against conventional modalities-including ABI, duplex ultrasonography, and clinical risk scores-using multivariable Cox regression and time-dependent receiver operating characteristic (ROC) analyses.

Collectively, this research seeks to establish SRUMI as a quantitative, translatable biomarker of microvascular health in PAD, thereby advancing precision phenotyping, risk stratification, and monitoring of therapeutic efficacy in this high-morbidity population.