Carotid Plaque Characterization Using Innovative Ultrasound Techniques

Official title

Tissue and Vascular Microstructure Evaluation for Carotid Plaque Characterization Using Innovative Ultrasound Techniques

Overview

Strokes are the second leading cause of disability and death worldwide (according to World Health Organization in 2019). They are ischemic in origin in 80% of cases. Atheromatous disease, and more specifically carotid stenosis, is responsible for 20% of these ischemic strokes. Current recommendations, based on high levels of evidence, consider only the degree of carotid artery stenosis to define the threshold for surgical treatment. However, it is now accepted that the composition and rate of progression of atherosclerotic plaque are also criteria to be considered when selecting patients at high risk of stroke. The presence of hemorrhage and a lipid core in the atheromatous plaque, both factors of instability, is associated with a greater risk of ipsilateral ischemic events. The presence of intraplaque hemorrhage is therefore a marker of plaque instability. In this context, techniques for in vivo analysis of atherosclerotic plaque composition need to be developed to better target patients for surgery. Ultrafast ultrasound enables imaging rates of several thousand images per second. Ultrasound Localization Microscopy (ULM) gives access to the vascular microstructure of tissues: the localization of injected microbubbles, which enhance the ultrasound signal in vessels, and the tracking of these microbubbles enable the vascularization of the tissue in question to be mapped. Ultrasound spectroscopy qualifies tissue microstructure: this operator- and system-independent technique is based on frequency analysis of ultrasound signals backscattered by tissue, and more specifically on analysis of the backscatter coefficient (BSC). Measuring the BSC is intrinsic to the tissue, and provides quantitative parameters on the scatterers to qualify the tissue. The study hypothesis is that these two ultrasound techniques will provide information on the characteristics of the atherosclerotic plaque: the presence of neovessels and biomarkers linked to its composition, including intraplaque hemorrhage.

Interventions

• Biological blood sampling
  This procedure will take place once during the patient's CARPUS first visit (Croix Rousse hospital (Hospice civils de Lyon). A peripheral venous line of the cathlon 24 G type with tap without tubing will be inserted by a nurse. A blood sample will be taken at the same time to check creatinine levels before the MRI scan and to record the patient's cholesterol levels for the eCRF.
• Device ultrasound imaging exam
  This procedure takes place once immediately after the intervention 1. The patient will first have an ultrasound acquisition with the clinical ultrasound scanner (\~5 minutes) in order to locate the plaque. An acquisition with the research ultrasound scanner and matrix probe will then be performed for measurement for ultrasound spectroscopy (\~5 minutes). An injection of 2.4 ml Sonovue followed by 10 ml saline will be performed during acquisition with the research ultrasound scanner for ultrasou
• Device High resolution MRI plaque exam
  This procedure will take place once during the patient's CARPUS second visit (Pierre Wertheimer hospital (Hospice civils de Lyon)). The patient is greeted in radiology, and his/her identity and absence of contraindications are verified. A peripheral venous line of the cathlon 24 G type with tap without tubing will be inserted by a nurse. Injection of gadolinium and MRI examination of the plaque used in clinical routine.

Primary outcome measures

• Volume of neovessels in carotid atherosclerotic plaques by ULM [Time frame: between 6 and 59 days after inclusion]
• Mean velocity in neovessels in carotid atherosclerotic plaques by ULM [Time frame: between 6 and 59 days after inclusion]
• Location of neovessels in carotid atherosclerotic plaques by ULM [Time frame: between 6 and 59 days after inclusion]

Secondary outcome measures (7)

• Lizzi Feleppa slope (dB/MHz) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques [Time frame: between 6 and 59 days after inclusion]
• Lizzi Feleppa intercept (dB) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques [Time frame: between 6 and 59 days after inclusion]
• Lizzi Feleppa midband (dB) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques [Time frame: between 6 and 59 days after inclusion]
• Integrated backscatter coefficient (BSC) (dB) measured by ultrasound spectroscopy on carotid atherosclerotic plaques [Time frame: between 6 and 59 days after inclusion]
• Acoustic attenuation (dB/mm) measured by ultrasound on carotid atherosclerotic plaques [Time frame: between 6 and 59 days after inclusion]
• Correlation between the volume of neovessels in carotid atherosclerotic plaques, estimated by ULM, and that estimated by anatomopathological analyses [Time frame: between 6 and 59 days after inclusion]
• Correlation between ultrasound parameters of BSC related to intraplaque hemorrhage of carotid atherosclerotic plaques and intraplaque hemorrhage assessed by anatomopathological analyses [Time frame: between 6 and 59 days after inclusion]

Eligibility criteria

Inclusion criteria

• Female or male over 18 years of age
• Patients with asymptomatic or symptomatic carotid plaque (stenosis> 50% NASCET), referred by the Hospices Civils de Lyon (HCL) vascular surgery consultation and for whom a surgical indication has been retained.
• Patient having agreed to participate in the study and signed a written informed consent form
• Patient affiliated to a social security scheme or equivalent.

Exclusion criteria

• Patients with contraindications to Sonovue (right-to-left shunt, severe pulmonary hypertension, allergy to the molecule)
• Patients with unstable cardiovascular pathology (coronary artery disease, stroke / transient ischemic attack, cardiac rhythm disorders)
• Uncontrolled hypertension
• Respiratory distress syndrome
• Patients with contraindications to MRI (claustrophobia, presence of metallic elements, etc.).
• Gadolinium-related contraindications and precautions for use
• Contraindication to dobutamine
• Hypersensitivity to the active substance or to one of the constituents of Gadolinium,
• Renal insufficiency with clearance <30 ml/min/1.73 m²,
• Pregnant or breast-feeding patients
• Patients under guardianship or trusteeship

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

France · 1 center

• Hôpital de la Croix Rousse — Lyon

Identifiers

NCT: NCT06804707 · 69HCL24_0689

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗