Research

Background

Transport of oxygen and nutrients is crucial for functioning of our organs. This is mainly maintained by the blood flow. However, deviations from normal blood flow can lead to events. Cerebrovascular accidents (i.e. strokes) are the second leading cause of death and disability worldwide with an annual incidence of 13.7 million people. A stroke is a blockage of the blood flow which can be caused by an obstruction in the carotid artery by so-called atherosclerotic plaques. To prevent (recurrent) ischemic strokes, a carotid endarterectomy (CEA) could be performed. Clinical risk stratification in these patients is mainly based on the stenosis degree (geometry, maximum blood velocity) caused by the atherosclerotic plaque and clinical risk factors, such as hypertension and hyperlipidemia. However, it is known that blood flow profiles are not only related to plaque built up but also might be a direct indication of the severity and rupture risk of the stenosis. Therefore, detailed information of the blood flow pattern might be of great value for treatment-planning in patients with carotid plaques.

What has been done
Techniques to study the blood velocity are already available in commercial ultrasound machines but these techniques are based on the Doppler principle, which implies that only the velocity component parallel to the ultrasound direction can be estimated. Thus, true blood velocity vector and complex blood flow phenomena often present in our cardiovascular system cannot be captured. To accurately estimate the blood velocity in the carotid artery we are developing ultrafast flow techniques.

Our research aim

Our current research aims are:

• to further develop and evaluate 2D flow imaging techniques in patients with atherosclerotic diseases and show the association between flow-related measures and cardiovascular events to establish new prognostic markers.
• to characterize the obtained 2D blood flow in terms of vorticity, complexity, and induced shear stress in order to facilitate patient specific treatment and provide parameters that can be used as new prognostic markers.
• to extend the already developed 2D flow quantification technique (i.e. ultrafast flow) to a 3D technique to get the full 3D velocity profile in the stenotic artery. 

Methods

In- and ex-vivo clinical studies are being performed in order to validate the performance of the developed 2D technique in patients and to link the flow measures to the cardiovascular risk profile of patients. To circumvent the angular dependence of conventional Doppler-based blood flow imaging techniques, the velocity vector is estimated by 2D (speckle) tracking. However, this technique requires high frame rates. To achieve this, plane wave transmission (one transmission over an entire region instead of multiple focused ultrasound pulses) with displacement compounding is used to measure flow profiles with a high frame rate and sufficient image quality.

The 2D flow imaging technique is further extended with coded excitations (link naar ‘Cascaded plane wave imaging’) to facilitate velocity vector imaging in more challenging situations, for example, a deep lying vessel. Cascaded dual-polarity waves are used to improve the image quality and enhance velocity vector imaging.

Furthermore, the 2D velocity vector imaging technique is evaluated in two ongoing explorative clinical studies, where the association between flow and flow-related parameters with atherosclerotic plaque progression and rupture risk is evaluated (link naar ‘First explorative clinical studies’)

Finally, the 2D velocity vector imaging techniques are extended to 3D by using ultrafast ultrasound transmission sequences combined with dedicated (sparse) matrix arrays. 

Results

It has been shown that using the flow techniques complex flow patterns could be visualized in healthy and diseased carotid arteries and quantified using a vector complexity measure that increased with increasing wall irregularity (Saris, 2019).

Temporal evolution of the velocity vector fields in the carotid artery of a patient after endarterectomy and patch placement. From: Saris et al. 2019

Simulations, experiments and initial in vivo evaluation of Cascaded dual-polarity waves (CDW) show increased signal power and feasibility of velocity vector imaging (VVI) using CDW. As a result CDW based velocity vector imaging (VVI) outperforms conventional plane wave VVI in low signal to noise conditions.

In one of the ongoing explorative clinical studies, 2D velocity vector imaging is acquired in patients who are planned for surgical plaque removal. First results show a clear feasibility of visualizing complex and recirculating flow patterns in patients after surgery (movie X). In both clinical trials, multiple flow-derived parameters, i.e. vector complexity, vortex identification and wall shear stress, will be estimated to quantify and distinguish complex from normal flow patterns. 

Funding

• Ultrafast imaging, the next level of cardiovascular diagnosis (VICI grant of the Netherlands Organisation for Scientific Research NWO and the Dutch Technology Foundation STW, finished)
• ULTRA-X-TREME: Ultrafast Ultrasound Imaging for Extended Diagnosis and Treatment of Vascular Disease (NWO Perspectief grant, active).
• VORTECS: Ultrafast ultrasound blood flow quantification for diagnosis and treatment of vascular diseases ('Connecting Innovators', Open Technology Program of the Netherlands Organization for Scientific Research (NWO), 2019, active).
• Regional Research Project 2020, Radboudumc-Rijnstate Initiative