PhD student, University of Cambridge
My research uses advanced MRI methods to evaluate carotid plaque vulnerability for preventing stroke
Stroke is one of the leading causes of death and disability worldwide with the majority of ischemic strokes attributed to carotid atherosclerosis.
Magnetic resonance imaging (MRI) showed high sensitivity and specificity in assessing vulnerable carotid plaques at the early stage and has been shown to be able to prevent future stroke. The research that I have been doing is using the most advanced MRI techniques developed in the Department of Radiology, University of Cambridge to evaluate carotid plaque morphological and biological characters. This technique has been tested in healthy volunteers and patients to evaluate the reproducibility and accuracy. In comparison to the conventional MRI techniques, this method provides quantitative analysis of diseased lesion, which gives more objective data and can be used for multi-centre studies for patient screening. The quantitative data could also be used in combination of machine learning to improve the diagnostic accuracy of the carotid disease. The preliminary results from this work have shown that this new technique has high accuracy in identifying high-risk carotid plaque in the early stage.
The abstract about this work has been submitted as an oral presentation at European Society for Magnetic Resonance in Medicine and Biology (ESMRMB) 2017 Congress in October 2017, in Barcelona, Spain. This oral presentation will be in competition for Young Investigator Award at this conference.
Abstract: Computational modelling to calculate the mechanical loading within atherosclerotic plaques has been shown to be complementary to defining anatomical plaque features in determining plaque vulnerability. However, its application has been partially impeded by the lack of comprehensive knowledge about the mechanical properties of various tissues within the plaque. Twenty-one human carotid plaques were collected from endarterectomy. The plaque was cut into rings, and different type of atherosclerotic tissues, including media, fibrous cap (FC), lipid and intraplaque haemorrhage/thrombus (IPH/T) was dissected for uniaxial extension testing. In total, 65 media strips from 17 samples, 59 FC strips from 14 samples, 38 lipid strips from 11 samples, and 21 IPH/T strips from 11 samples were tested successfully. A modified Mooney-Rivlin strain energy density function was used to characterize the stretch-stress relationship. The stiffnesses of media and FC are comparable, as are lipid and IPH/T. However, both media and FC are stiffer than either lipid or IPH/T. The median values of incremental Young's modulus of media, FC, lipid and IPH/T at λ=1 are 290.1, 244.5, 104.4, 52.9, respectively; they increase to 1019.5, 817.4, 220.7 and 176.9 at λ=1.1; and 4302.7, 3335.0, 533.4 and 268.8 at λ=1.15 (unit, kPa; λ, stretch ratio). The material constants of each tissue type are suggested to be: media, c1=0.138kPa, D1=3.833kPa and D2=18.803; FC, c1=0.186kPa, D1=5.769kPa and D2=18.219; lipid, c1=0.046kPa, D1=4.885kPa and D2=5.426; and IPH/T, c1=0.212kPa, D1=4.260kPa and D2=5.312. It is concluded that all soft atherosclerotic tissues are non-linear, and both media and FC are stiffer than either lipid or IPH/T.
Pub.: 10 Sep '14, Pinned: 31 Aug '17
Abstract: Mechanical analysis has been shown to be complementary to luminal stenosis in assessing atherosclerotic plaque vulnerability. However, patient-specific material properties are not available and the effect of material properties variability has not been fully quantified. Media and fibrous cap (FC) strips from carotid endarterectomy samples were classified into hard, intermediate and soft according to their incremental Young's modulus. Lipid and intraplaque haemorrhage/thrombus strips were classified as hard and soft. Idealised geometry-based 3D fluid-structure interaction analyses were performed to assess the impact of material property variability in predicting maximum principal stress (Stress-P1 ) and stretch (Stretch-P1 ). When FC was thick (1000 or 600 µm), Stress-P1 at the shoulder was insensitive to changes in material stiffness, whereas Stress-P1 at mid FC changed significantly. When FC was thin (200 or 65 µm), high stress concentrations shifted from the shoulder region to mid FC, and Stress-P1 became increasingly sensitive to changes in material properties, in particular at mid FC. Regardless of FC thickness, Stretch-P1 at these locations was sensitive to changes in material properties. Variability in tissue material properties influences both the location and overall stress/stretch value. This variability needs to be accounted for when interpreting the results of mechanical modelling.
Pub.: 06 May '15, Pinned: 31 Aug '17
Abstract: Calculating high stress concentration within carotid atherosclerotic plaques has been shown to be complementary to anatomical features in assessing vulnerability. Reliability of stress calculation may depend on the constitutive laws/strain energy density functions (SEDFs) used to characterize tissue material properties. Different SEDFs, including neo-Hookean, one-/two-term Ogden, Yeoh, 5-parameter Mooney-Rivlin, Demiray and modified Mooney-Rivlin, have been used to describe atherosclerotic tissue behavior. However, the capacity of SEDFs to fit experimental data and the difference in the stress calculation remains unexplored. In this study, seven SEDFs were used to fit the stress-stretch data points of media, fibrous cap, lipid and intraplaque hemorrhage/thrombus obtained from 21 human carotid plaques. Semi-analytic solution, 2D structure-only and 3D fully coupled fluid-structure interaction (FSI) analyses were used to quantify stress using different SEDFs and the related material stability examined. Results show that, except for neo-Hookean, all other six SEDFs fitted the experimental points well, with vessel stress distribution in the circumferential and radial directions being similar. 2D structural-only analysis was successful for all seven SEDFs, but 3D FSI were only possible with neo-Hookean, Demiray and modified Mooney-Rivlin models. Stresses calculated using Demiray and modified Mooney-Rivlin models were nearly identical. Further analyses indicated that the energy contours of one-/two-term Ogden and 5-parameter Mooney-Rivlin models were not strictly convex and the material stability indictors under homogeneous deformations were not always positive. In conclusion, considering the capacity in characterizing material properties and stabilities, Demiray and modified Mooney-Rivlin SEDF appear practical choices for mechanical analyses to predict the critical mechanical conditions within carotid atherosclerotic plaques.
Pub.: 17 Oct '15, Pinned: 31 Aug '17
Abstract: Improved motion-sensitized driven-equilibrium (iMSDE) preparations have been successfully used in carotid artery wall imaging to achieve blood suppression, but it causes notable signal loss, mostly due to inherent T2 decay, eddy current effects and B1 + inhomogeneity. In this study, we investigate the signal to noise ratio (SNR) and blood suppression performance of iMSDE using composite RF pulses and sinusoidal gradients. Optimized first moment (m1) values for iMSDE prepared T1- and T2- weighted (T1- and T2-w) imaging are presented.Twelve healthy volunteers and six patients with carotid artery disease underwent iMSDE and double inversion recovery (DIR) prepared T1- and T2-w fast spin echo (FSE) MRI of the carotid arteries. Modified iMSDE module using composite RF pulses and sinusoidal gradients were evaluated with a range of m1. SNR of adjacent muscle, vessel wall and the lumen were reported. The optimized iMSDE module was also tested in a 3D variable flip angle FSE (CUBE) acquisition.The SNR of muscle was highest using sinusoidal gradients, and the relative improvement over the trapezoidal gradient increased with higher m1 (p<0.001). Optimal SNR was observed using an iMSDE preparation scheme containing two 180° composite pulses and standard 90° and -90° pulses (p=0.151). iMSDE produced better blood suppression relative to DIR preparations even with a small m1 of 487 mT*ms2/m (p<0.001). In T1-w iMSDE, there was a SNR decrease and an increased T2 weighting with increasing m1. In T2-w iMSDE, by matching the effective echo time (TE), the SNR was equivalent when m1 was <= 1518 mT*ms2/m, however, higher m1 values (2278 - 3108 mT*ms2/m) reduced the SNR. In the patient study, iMSDE improved blood suppression but reduced vessel wall CNR efficiency in both T1-w and T2-w imaging. iMSDE also effectively suppressed residual flow artifacts in the CUBE acquisition.iMSDE preparation achieved better blood suppression than DIR preparation with reduced vessel wall CNR efficiency in T1-w and T2-w images. The optimized m1s are 487 mT*ms2/m for T1-w imaging and 1518 mT*ms2/m for T2-w imaging. Composite 180° refocusing pulses and sinusoidal gradients improve SNR performance. iMSDE further improves the inherent blood suppression of CUBE.
Pub.: 28 Aug '14, Pinned: 31 Aug '17
Abstract: The purpose of this work is to evaluate the repeatability of a compressed sensing (CS) accelerated multi-contrast carotid protocol at 3 T.Twelve volunteers and eight patients with carotid disease were scanned on a 3 T MRI scanner using a CS accelerated 3-D black-blood multi-contrast protocol which comprises T 1w, T 2w and PDw without CS, and with a CS factor of 1.5 and 2.0. The volunteers were scanned twice, the lumen/wall area and wall thickness were measured for each scan. Eight patients were scanned once, the inter/intra-observer reproducibility of the measurements was calculated.In the repeated volunteer scans, the interclass correlation coefficient (ICC) for the wall area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.95, 0.81, and 0.97, respectively. The ICC for lumen area measurement using a CS factor of 1.5 in PDw, T 1w and T 2w were 0.96, 0.92, and 0.96, respectively. In patients, the ICC for inter/intra-observer measurements of lumen/wall area, and wall thickness were all above 0.81 in all sequences.The results show a CS accelerated 3-D black-blood multi-contrast protocol is a robust and reproducible method for carotid imaging. Future protocol design could use CS to reduce the scanning time.
Pub.: 28 Jun '17, Pinned: 31 Aug '17
Abstract: Atherosclerosis remains the leading cause of long-term mortality and morbidity worldwide, despite remarkable advancement in its management. Vulnerable atherosclerotic plaques are principally responsible for thromboembolic events in various arterial territories such as carotid, coronary, and lower limb vessels. Carotid plaque ulceration is one of the key features associated with plaque vulnerability and is considered a notable indicator of previous plaque rupture and possible future cerebrovascular events. Multiple imaging modalities have been used to assess the degree of carotid plaque ulceration for diagnostic and research purposes. Early diagnosis and management of carotid artery disease could prevent further cerebrovascular events. In this review, we highlight the merits and limitations of various imaging techniques for identifying plaque ulceration.
Pub.: 23 Dec '16, Pinned: 29 Jun '17
Abstract: To develop a 3D black-blood T2 mapping sequence with a combination of compressed sensing (CS) and parallel imaging (PI) for carotid wall imaging.A 3D black-blood fast-spin-echo (FSE) sequence for T2 mapping with CS and PI was developed and validated. Phantom experiments were performed to assess T2 accuracy using a Eurospin Test Object, with different combination of CS and PI acceleration factors. A 2D multi-echo FSE sequence was used as a reference to evaluate the accuracy. The concordance correlation coefficient and Bland-Altman statistics were calculated. Twelve volunteers were scanned twice to determine the repeatability of the sequence and the intraclass correlation coefficient (ICC) was reported. Wall-lumen sharpness was calculated for different CS and PI combinations. Six patients with carotid stenosis >50% were scanned with optimised sequence. The T2 maps were compared with multi-contrast images.Phantom scans showed good correlation in T2 measurement between current and reference sequence (r=0.991). No significant difference was found between different combination of CS and PI accelerations (p=0.999). Volunteer scans showed good repeatability of T2 measurement (ICC: 0.93, 95% CI 0.84-0.97). The mean T2 of the healthy wall was 48.0±9.5ms. Overall plaque T2 values from patients were 54.9±12.2ms. Recent intraplaque haemorrhage and fibrous tissue have higher T2 values than the mean plaque T2 values (88.1±6.8ms and 62.7±9.3ms, respectively).This study demonstrates the feasibility of combining CS and PI for accelerating 3D T2 mapping in the carotid artery, with accurate T2 measurements and good repeatability.
Pub.: 27 Nov '16, Pinned: 29 Jun '17
Abstract: This study aims to explore the relationship between plaque surface morphology and neovascularization using a high temporal and spatial resolution 4D contrast-enhanced MRI/MRA sequence.Twenty one patients with either recent symptoms or a carotid artery stenosis ≥40% were recruited in this study. Plaque surface morphology and luminal stenosis were determined from the arterial phase MRA images. Carotid neovascularization was evaluated by a previously validated pharmacokinetic (PK) modeling approach. K (trans) (transfer constant) and v p (partial plasma volume) were calculated in both the adventitia and plaque.Image acquisition and analysis was successfully performed in 28 arteries. Mean luminal stenosis was 44% (range 11-82%). Both adventitial and plaque K (trans) in ulcerated/irregular plaques were significantly higher than smooth plaques (0.079 ± 0.018 vs. 0.064 ± 0.011 min(-1), p = 0.02; 0.065 ± 0.013 vs. 0.055 ± 0.010 min(-1), p = 0.03, respectively). Positive correlations between adventitial K (trans) and v p against stenosis were observed (r = 0.44, p = 0.02; r = 0.55, p = 0.01, respectively).This study demonstrates the feasibility of using a single sequence to acquire both high resolution 4D CE-MRA and DCE-MRI to evaluate both plaque surface morphology and function. The results demonstrate significant relationships between lumen surface morphology and neovascularization.
Pub.: 30 Apr '17, Pinned: 29 Jun '17