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Title: The evaluation of shear wave elastography ultrasound in the early detection and diagnosis of vascular disease
Author: Alsaadi, Mohammed Jayez
ISNI:       0000 0004 9356 7144
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2018
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Introduction: It is estimated that cardiovascular diseases (CVDs) are responsible for over 17.3 million deaths per year and are the leading causes of death and disability in the world. In one hand, atherosclerotic disease of the carotid arteries has been associated with the development of cerebrovascular events due to rupture of carotid plaques. Determining plaque vulnerability is critical when selecting the most suitable treatment for patients with carotid stenosis. On the other hand, venous thrombus diagnosis and ageing is critically important in allowing physicians to introduce an appropriate treatment plan. The decision whether or not to perform a thrombectomy or thrombolysis is dependent upon the age of the blood clot. Currently, clinical non-invasive ultrasound-based methods for plaque characterization are limited to visual assessment of plaque morphology and thrombus ageing and new quantitative methods are needed. The aim of this research is to evaluate the utility of Shear Wave Elastography Ultrasound (SWEU) in characterising and ageing the status of atherothromboembolism disease. The current gold standard method to provide more detail about atherothromboembolism status is histopathology. Other modalities such as Magnetic Resonance Imaging (MRI), Computed Tomography Angiography (CTA) are available for diagnosis. MRI is considered the superior imaging modality regarding the atherothromboembolism status, but it has some limitations. SWEU is a novel imaging modality. SWEU is currently used to characterize and stage liver fibrosis and provide more details about the type of breast tumours; it is a new technology that may offer a better method to characterise plaques morphology in patient with cardiovascular disease and to determine the age of venous thrombus. SWEU is a non-invasive imaging technique that works with the B-mode ultrasound to provide more detail about mechanical properties and tissue stiffness of the internal structure. This technique uses high-intensity pulses that are transmitted throughout the tissue to produce shear waves. These waves can be tracked to calculate the shear velocity and tissue stiffness, and the resulting data provides plaque characterization information and thrombus ageing. Our hypothesis is that SWEU can characterize age of the thrombus, provide information about the plaque composition and arterial stiffness, which will be similar to histological finding. Our goal was to (1) estimate the carotid plaque stiffness and characterization in comparison with histopathology. (2) To assess the arterial stiffness in the arterial wall of patient with coronary artery disease and haemodialysis patients using SWE. (3) To determine whether Shear Wave Elastography (SWE) can differentiate and age the thrombus in an experimental model of vascular tissue and thrombosed arteriovenous fistula (AVF) patients. Material and Methods: three different prospective analytical studies were conducted to achieve the goals of this project. Patient with cardiovascular disease, DM, and those undergoing carotid endarterectomy had carotid scan. This study involved three experimental and one control group. Arterial stiffness was calculated using SWE proximal to carotid bifurcation or proximal to plaque when it is present at bifurcation. Another prospective in- vivo study was performed in human vascular tissue. Long saphenous veins and mammary arteries leftover after CABG surgery were used for this study. These saphenous veins segment were infused with human blood from a volunteer who was not on any anticoagulation. These segments were allowed to thrombus and sequentially scanned using SWE to assess the age of thrombus for a period of 14 days. In order to further validate the findings of this in-vivo experiment, arteriovenous patients who present with acute thrombus or DVT in the upper limb veins were recruited. The data that acquired from various parts of the thrombus using SWE was compared with histology. The third study was carried out in patients with existing AVF and a second set who were booked for AVF creation. The patients were divided into three groups Group-A: ESRD patient with AVF and diabetes, Group-B: ESRD with AVF but no diabetes, and Group C: ESRD with no AVF and no diabetes. These groups were divided into further subgroups according to maturation period of AVF. Wall stiffness were measured where the intimal media thicken. Result: The first study findings revealed that stiffness in all the segments in subject having diabetes with carotid plaques was significantly higher as compared to controls (P=0.04, P=0.01 and P =0.02 in segment 1, 2and 3 respectively). The carotid wall stiffness was almost similar in all segments whether adjacent or away from plaque. Moreover, the SWE investigation demonstrated increased stiffness of normal IMT in patients with CAD, the mean stiffness was 80+/- 20KPa compared with 85+/-25KPa for thicken IMT with CAD, P<0.05. Although the IMT thickness was lower in one group but the stiffness had significantly increased in the group with normal IMT, implying that stiffness precedes thickness. The venous thrombus ageing study showed that SWE values of thrombus elasticity were ranged between 8-12 kPa in the first three days. This correlated with the histological findings, which demonstrated a marked increase in fibroblast and collagen production in the clots during this time. The thrombus Elasticity become harder from day 12 and onward, SWE values ranged from 40-60kPa. Calibration curves for thrombus aging over a period of time were created to demonstrate the increase of SWE values of thrombus over a period of time. The third study revealed that the comorbidities such as hypertension and diabetes showed insignificant effect on the venous stiffness (p > 0.05). However, venous stiffness showed a significant increase with the maturation of AVF (p < 0.05). The mean values of elasticity showed that there was a large increase in the stiffness of venous wall in patients with AVF (47.44 kPa) compared to patients without AVF (21.29 kPa) and healthy subjects (17.11 kPa). Conclusion: Arterial stiffness values quantified by shear wave elastography are reproducible. Higher arterial stiffness is associated with plaque formation. SWE can predict and detect subclinical changes in the arterial and venous wall. SWE was able to age thrombus in experimental and clinical cases. SWE can be used to predict the maturation rate of AVF and can also help to detect venous thinning especially in venous aneurysm, associated with AVF, so the potential rupture and leakage can be minimised. SWE can incorporated as an integral modality into routine scanning of vascular patients. This will provide additional pathological information similar to histology. Thereby, help with better management of patients with cardiovascular diseases.
Supervisor: Aslam, Mohammed ; Standfield, Nigel Sponsor: Prince Sattam Bin Abdulaziz University
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral