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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
BASIC_SCIENCE
Masking
NONE
Enrollment
17
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.
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 ultrasound localization imaging measurement (\~10 minutes). The patient must remain under observation (in the waiting room) for 30 minutes after the examination.
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.
Hôpital de la Croix Rousse
Lyon, France
Volume of neovessels in carotid atherosclerotic plaques by ULM
From the vascularization cartography obtained by ULM, the volume of vascularization of the plaque will be estimated (number of pixels with vascularization compared with the number of pixels in the plaque x100). Plaques can then be described by neovessel volume distribution.
Time frame: between 6 and 59 days after inclusion
Mean velocity in neovessels in carotid atherosclerotic plaques by ULM
From the vascularization cartography obtained by ULM, the mean velocity (mm/s) in all the neovessels will be estimated.
Time frame: between 6 and 59 days after inclusion
Location of neovessels in carotid atherosclerotic plaques by ULM
The main location of vessels will also be described according to their topography in the plaque (e.g. central, peripheral, both).
Time frame: between 6 and 59 days after inclusion
Lizzi Feleppa slope (dB/MHz) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques
In ultrasound signals, the plaque is divided into regions of interest and ultrasound spectroscopy is applied. This will enable us to obtain the backscatter coefficient (BSC) for each region of interest. From the backscatter coefficient, parameters derived from the BSC will be evaluated. One of these parameters is: \- Lizzi-Feleppa slope: slope of the linear fit of the BSC as a function of frequency. This parameter in the different regions of interest on the plaque will be averaged for each plaque.
Time frame: between 6 and 59 days after inclusion
Lizzi Feleppa intercept (dB) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques
In ultrasound signals, the plaque is divided into regions of interest and ultrasound spectroscopy is applied. This will enable us to obtain the backscatter coefficient (BSC) for each region of interest. From the backscatter coefficient, parameters derived from the BSC will be evaluated. One of these parameters is: \- Lizzi-Feleppa intercept: intercept of the linear fit of the BSC as a function of frequency. This parameter in the different regions of interest on the plaque will be averaged for each plaque.
Time frame: between 6 and 59 days after inclusion
Lizzi Feleppa midband (dB) derived from BSC measured by ultrasound spectroscopy on carotid atherosclerotic plaques
In ultrasound signals, the plaque is divided into regions of interest and ultrasound spectroscopy is applied. This will enable us to obtain the backscatter coefficient (BSC) for each region of interest. From the backscatter coefficient, parameters derived from the BSC will be evaluated. One of these parameters is: \- Lizzi-Feleppa midband: midband of the linear fit of the BSC as a function of frequency. This parameter in the different regions of interest on the plaque will be averaged for each plaque.
Time frame: between 6 and 59 days after inclusion
Integrated backscatter coefficient (BSC) (dB) measured by ultrasound spectroscopy on carotid atherosclerotic plaques
In ultrasound signals, the plaque is divided into regions of interest and ultrasound spectroscopy is applied. This will enable us to obtain the backscatter coefficient (BSC) for each region of interest. From the backscatter coefficient, parameters derived from the BSC will be evaluated. One of these parameters is: \- integrated BSC: Integrated BSC on the -6 dB frequency bandwidth. This parameter in the different regions of interest on the plaque will be averaged for each plaque.
Time frame: between 6 and 59 days after inclusion
Acoustic attenuation (dB/mm) measured by ultrasound on carotid atherosclerotic plaques
In ultrasound signals, the plaque is divided into regions of interest and ultrasound spectroscopy is applied. This will enable us to obtain the backscatter coefficient (BSC) for each region of interest. From the backscatter coefficient, parameters derived from the BSC will be evaluated. One of these parameters is: \- acoustic attenuation. This parameter in the different regions of interest on the plaque will be averaged for each plaque.
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
For each plaque, histological analysis will give the stage of intraplaque haemorrhage according to Derksen's grading scale if intraplaque haemorrhage is present. A semi-quantitative grading denoting the quantity of neovessels (score between 0 and 3) will also be performed. The correlation between these grades and the volume of neovessels originating from the ULM will be studied.
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
Histological analysis will give the stage of intraplaque haemorrhage according to Derksen's grading scale if intraplaque haemorrhage is present. A semi-quantitative scale denoting the ratio of the area of intraplaque hemorrhage to the total area of the plaque (score 0 if ratio between 0 and 25%, score 1 if ratio between 25 and 50%, score 2 if ratio between 50 and 75% and score 3 if ratio between 75 and 100%). The thresholds for the BSC parameters need to be calibrated to determine the thresholds corresponding to intraplaque hemorrhage. For this step, areas of intraplaque hemorrhage will be localized using plaque MRI. This will enable us to determine which BSC parameter or combination of parameters best characterizes intraplaque hemorrhage, and then to estimate for each plaque a relative volume of region of interest containing intraplaque hemorrhage. The correlation between these grades and the volume of intraplaque hemorrhage derived from ultrasound measurements will be studied.
Time frame: between 6 and 59 days after inclusion
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