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

The Predictive Value of Super-resolution Ultrasound Microvascular Imaging for the Prognosis of 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.

Study Overview

• Status: Recruiting
• Conditions: Peripheral Artery Disease

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Min Yang, M.D.; Phone Number: 01083572622; Email: dryangmin@gmail.com

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100034
      • Recruiting
      • Peking University First Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

**Study Population Description:** Participants will be recruited from the Department of Interventional Vascular Surgery at Peking University First Hospital. The cohort comprises two parallel groups: (i) patients hospitalized with a confirmed diagnosis of PAD, and (ii) control participants without PAD (i.e., non-atherosclerotic controls), matched for age and sex where feasible. Enrollment adheres strictly to the prespecified inclusion and exclusion criteria above.

**Sampling Method:** Convenience sampling (a form of non-probability sampling), reflecting real-world clinical recruitment within a single tertiary academic medical center.

Description

*Inclusion Criteria:*

1. Adults aged ≥18 years and ≤100 years;
2. Diagnosis of peripheral artery disease (PAD) confirmed by comprehensive clinical assessment-including characteristic symptoms (e.g., intermittent claudication, rest pain), physical findings (e.g., diminished or absent distal pulses, bruits), ankle-brachial index (ABI) < 0.9, and corroborating vascular imaging (e.g., duplex ultrasonography, CTA, or MRA);
3. Alternatively, healthy adults without PAD (i.e., ABI ≥ 0.9, absence of suggestive symptoms or signs, and no history of atherosclerotic cardiovascular disease) who meet all other eligibility requirements;
4. Willing and able to provide written informed consent.

*Exclusion Criteria:*

1. Inability to complete study procedures due to:

   1. Severe involuntary movement disorders (e.g., advanced Parkinson's disease or cerebellar ataxia) interfering with image acquisition;
   2. Contraindication to contrast-enhanced ultrasound (e.g., documented hypersensitivity to sulfur hexafluoride microbubble contrast agent [SonoVue®]);
   3. Active lower-limb infection (e.g., diabetic foot infection with systemic signs or osteomyelitis), which precludes safe or interpretable data collection;
2. Cognitive impairment or legal incapacity precluding autonomous informed consent;
3. Refusal-by the participant or their legally authorized representative-to provide informed consent.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy People
PAD Patients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
microvascular density	Baseline; Perioperative(before endovascular surgery)

Collaborators and Investigators

• Sponsor: Peking University First Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 8, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: January 12, 2026
• First Submitted That Met QC Criteria: January 24, 2026
• First Posted (Actual): January 29, 2026

Study Record Updates

• Last Update Posted (Actual): May 18, 2026
• Last Update Submitted That Met QC Criteria: May 14, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Atherosclerosis; Arteriosclerosis; Arterial Occlusive Diseases; Peripheral Vascular Diseases; Peripheral Arterial Disease
• Other Study ID Numbers: 2025R0004

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No