Early Detection of Vascular Dysfunction Using Biomarkers From Lagrangian Carotid Strain Imaging

University of Wisconsin (UW)

Status: Completed

Conditions: Healthy; Carotid Artery Diseases

Treatments: Device: Pulse Wave Doppler; Device: Magnetic Resonance Imaging (MRI); Device: Transcranial Doppler (TCD); Other: Neurocognitive testing; Device: Ultrasound imaging

Study type: Observational

Funder types: Other; NIH

Identifiers

NCT04632485

2020-0384

2/12/2025 (Other Identifier)

A534800 (Other Identifier)

SMPH/MED PHYSICS (Other Identifier)

1R01HL147866-01A1 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

The purpose of this research is assess imaging and identification of soft plaque that undergoes large deformations or strain will identify plaque vulnerable to rupture which could lead to 'silent strokes'. Validation of current study results with MRI will foster use of real-time ultrasound (US) strain imaging and strain indices as a screening tool for identifying normal human participants susceptible to increased vascular aging and developing plaque prone to rupture or micro-embolization.

Current research will evaluate Lagrangian carotid strain imaging (LCSI) for prediction of vascular health on volunteers. In this study, investigators will evaluate age-related strain variations (due to plaque deposition) in the carotid artery, establishing groundwork that will help identify typical and atypical values for these indices. Investigator's hypothesis is that plaques with higher strain indices (softer plaques) are more prone to rupture than plaques with lower strain indices (stiffer) plaques, thus requiring intervention. Clinical criteria for treatment has focused primarily on the degree of stenosis. Long-term objectives are to provide non-invasive methods for screening participants at risk for vascular aging or plaque rupture in asymptomatic participants, expanding upon current criteria for risk assessments based on focal transient ischemic attack (TIA) or strokes. Variations in vessel strain have been associated with, or are precursors to, plaque deposition, vascular aging, or cerebrovascular diseases. Increased arterial strain and pressure changes have been linked to brain aging using magnetic resonance imaging (MRI) based vascular indices, and memory deficits commonly linked to Alzheimer dementia. Stiffening and thickening of the arterial walls have also been associated with cerebrovascular disease. Investigators hypothesize that strain indices as vascular biomarkers can be utilized for screening possible 'vulnerable participants' validated with MRI, with the potential ability to improve endothelial function and reverse vascular aging. Strain indices may enable differentiating study participants with vascular cognitive impairment (VCI) from other dementias. Cognitive testing is unable to make this differentiation.

Enrollment: 217 patients

Sex: All

Ages: 18 to 89 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

Aim 1 (Ultrasound (US) only):

• Adults at least 18 years
• Are able to provide written informed consent on their own behalf

Aim 2 (US and MRI):

• Participation in the US study (Aim 1)
• Determined by presence of hypoechogenic or echolucent lipid-rich soft plaque during initial ultrasound imaging session
• Adults willing to participate over 5 years

Exclusion criteria

Aim 1 (US only)

• Women that are currently pregnant

• Inability to cooperate with the ultrasound study, in particular those unable to sit without gross movement for the duration the ultrasound study (estimated at 60-90 minutes)

• Open wounds or sores in the anterior neck

• History of cancer treatment, vascular disease, cardiac disease, stroke or TIA

• History of medications that affect vascular wall and plaque

• History of statin medications*

• History of hypertension medications*

• History of anticoagulation, blood thinners

  • These criteria will not be exclusionary for the cohort that is greater than 70 years of age.

Aim 2 (US and MRI):

• Women that are currently pregnant
• Inability to cooperate with the ultrasound study, in particular those unable to sit without gross movement for the duration the ultrasound study (estimated at 60-90 minutes)
• Patients that require intravenous (IV) conscious sedation for imaging are not eligible; patients requiring mild, oral anxiolytics for research imaging will be allowed to participate as long as the following criteria are met:
• The participant has their own prescription for the medication;
• The informed consent process is conducted prior to the self-administration of this medication; and,
• The participant comes to the research visit with a driver
• Contraindications to MR
• Unable to lie in the MRI scanner for 45-60 minutes
• Patients with a contraindication to gadolinium based contrast agents, including allergy or impaired renal function (per University of Wisconsin Health Guidelines)

Trial design

217 participants in 2 patient groups

Aim 1: Ultrasound Only

Description:

Approximately 280 asymptomatic participants will participate in ultrasound (US) studies and blood work.

Treatment:

Device: Ultrasound imaging

Aim 2: Ultrasound and MRI

Description:

A sub-group of 40 at risk volunteers determined from the clinical ultrasound scans and bloodwork from Aim 1 will be asked to participate in a longitudinal US and MRI study. Participants will be selected from a population of individuals that do not have significant atherosclerosis, but present with increased risk due to the presence of soft, lipid rich plaque that are hypoechogenic or echolucent on ultrasound B-mode images. These participants may also satisfy the current clinical guidelines of increased vessel diameter and decreased blood flow velocity with ultrasound that may result in plaque deposition for being in the at risk population. Participants will receive US, strain and shear wave imaging every 2 years after the first scan in Aim 1 and MRI Imaging in Year 1 and Year 5: separated by 4 years

Treatment:

Device: Ultrasound imaging

Other: Neurocognitive testing

Device: Transcranial Doppler (TCD)

Device: Magnetic Resonance Imaging (MRI)

Device: Pulse Wave Doppler