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Background Atherosclerosis is a systemic inflammatory disease intertwined with neovascularization. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables the assessment of plaque neovascularization. This study aimed to explore the systemic nature of atherosclerosis by assessing difference in severity of neovascularization as quantified by DCE-MRI of vertebral arteries (VAs) between patients with symptomatic and asymptomatic carotid artery disease. Methods Ten consecutive patients with asymptomatic VA stenosis and concomitant symptomatic carotid artery disease (group 1) and 10 consecutive patients with asymptomatic VA stenosis and concomitant asymptomatic carotid artery disease (group 2) underwent 3-dimensional DCE-MRI of their cervical segment of VAs. A previously validated pharmacokinetic modeling approach was used for DCE-MRI analysis. Ktrans was calculated in the adventitia and plaque as a measure of neovessel permeability. Results Both patient groups were comparable for demographics and comorbidities. Mean luminal stenosis was comparable for both groups (54.4% versus 52.27%, P = .32). Group 1 had higher adventitial Ktrans and plaque Ktrans (.08 ± .01 min−1, .07 ± .01 min−1) compared with Group 2 (.06 ± .01 min−1, .06 ± .01 min−1) (P = .004 and .03, respectively). Good correlation was present among the two image analysts (intraclass correlation coefficient = .78). Conclusions Vertebral Artery atheroma of patients with symptomatic carotid artery disease had increased neovessel permeability compared with the patients with asymptomatic carotid artery disease. These findings are consistent with the hypothesis that atherosclerosis is a systemic inflammatory disease. The VA atherosclerosis is likely to have increased severity of neovascularization if another arterial territory is symptomatic in the same patient cohort.

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.

BACKGROUND: Ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging enables the identification of inflammation within the atheroma, predominantly by USPIO uptake by macrophages present in atherosclerotic tissue. Diabetic patients, however, may have dysfunctional macrophage activity, which may affect utilization of USPIO in identifying plaque inflammation in this patient cohort. METHODS: Fifteen diabetic and fifteen nondiabetic patients underwent USPIO-enhanced carotid MR imaging using 1.5T MR system. Pre- and post-USPIO carotid MR images were manually coregistered. The percentage decrease in the signal intensity after USPIO administration was calculated as a relative measure of the USPIO uptake. RESULTS: Diabetic and nondiabetic patients had comparable demographics and comorbidities. The mean global, maximum quadrant, and maximum slice changes showing change in relative signal intensity as a result of USPIO administration were comparable for the two patient cohorts (P > .05). CONCLUSIONS: USPIO can identify inflammatory burden with carotid atheroma in both diabetic and nondiabetic patients.

Purpose This prospective study evaluated the use of vascular, extracellular and restricted diffusion for cytometry in tumours (VERDICT) MRI to investigate the tissue microstructure in glioma. VERDICT-derived parameters were correlated with both histological features and tumour subtype and were also used to explore the peritumoural region. Methods Fourteen consecutive treatment-naïve patients (43.5 years ± 15.1 years, six males, eight females) with suspected glioma underwent diffusion-weighted imaging including VERDICT modelling. Tumour cell radius and intracellular and combined extracellular/vascular volumes were estimated using a framework based on linearisation and convex optimisation. An experienced neuroradiologist outlined the peritumoural oedema, enhancing tumour and necrosis on T2-weighted imaging and contrast-enhanced T1-weighted imaging. The same regions of interest were applied to the co-registered VERDICT maps to calculate the microstructure parameters. Pathology sections were analysed with semi-automated software to measure cellularity and cell size. Results VERDICT parameters were successfully calculated in all patients. The imaging-derived results showed a larger intracellular volume fraction in high-grade glioma compared to low-grade glioma (0.13 ± 0.07 vs. 0.08 ± 0.02, respectively; p = 0.05) and a trend towards a smaller extracellular/vascular volume fraction (0.88 ± 0.07 vs. 0.92 ± 0.04, respectively; p = 0.10). The conventional apparent diffusion coefficient was higher in low-grade gliomas compared to high-grade gliomas, but this difference was not statistically significant (1.22 ± 0.13 × 10−3 mm2/s vs. 0.98 ± 0.38 × 10−3 mm2/s, respectively; p = 0.18). Conclusion This feasibility study demonstrated that VERDICT MRI can be used to explore the tissue microstructure of glioma using an abbreviated protocol. The VERDICT parameters of tissue structure correlated with those derived on histology. The method shows promise as a potential test for diagnostic stratification and treatment response monitoring in the future. Key Points • VERDICT MRI is an advanced diffusion technique which has been correlated with histopathological findings obtained at surgery from patients with glioma in this study. • The intracellular volume fraction measured with VERDICT was larger in high-grade tumours compared to that in low-grade tumours. • The results were complementary to measurements from conventional diffusion-weighted imaging, and the technique could be performed in a clinically feasible timescale. Electronic supplementary material The online version of this article (10.1007/s00330-019-6011-8) contains supplementary material, which is available to authorized users.

The paper reports a free-breathing black-blood CINE fast-spin echo (FSE) technique for measuring abdominal aortic wall motion. The free-breathing CINE FSE includes the following MR techniques: (1) variable-density sampling with fast iterative reconstruction; (2) inner-volume imaging; and (3) a blood-suppression preparation pulse. The proposed technique was evaluated in eight healthy subjects. The inner-volume imaging significantly reduced the intraluminal artifacts of respiratory motion (p = 0.015). The quantitative measurements were a diameter of 16.3 ± 2.8 mm and wall distensibility of 2.0 ± 0.4 mm (12.5 ± 3.4%) and 0.7 ± 0.3 mm (4.1 ± 1.0%) for the anterior and posterior walls, respectively. The cyclic cross-sectional distensibility was 35 ± 15% greater in the systolic phase than in the diastolic phase. In conclusion, we developed a feasible CINE FSE method to measure the motion of the abdominal aortic wall, which will enable clinical scientists to study the elasticity of the abdominal aorta.

PURPOSE: This study is to compare the accuracy of four different black-blood T2 mapping sequences in carotid vessel wall. METHODS: Four different black-blood T2 mapping sequences were developed and tested through phantom experiments and 17 healthy volunteers. The four sequences were: 1) double inversion-recovery (DIR) prepared 2D multi-echo spin-echo (MESE); 2) DIR-prepared 2D multi-echo fast spin-echo (MEFSE); 3) improved motion-sensitized driven-equilibrium (iMSDE) prepared 3D FSE and 4) iMSDE prepared 3D fast spoiled gradient echo (FSPGR). The concordance correlation coefficient and Bland-Altman statistics were used to compare the sequences with a gold-standard 2D MESE, without blood suppression in phantom studies. The volunteers were scanned twice to test the repeatability. Mean and standard deviation of vessel wall T2, signal-to-noise (SNR), the coefficient of variance and interclass coefficient (ICC) of the two scans were compared. RESULTS: The phantom study demonstrated that T2 measurements had high concordance with respect to the gold-standard (all r values >0.9). In the volunteer study, the DIR 2D MEFSE had significantly higher T2 values than the other three sequences (P < 0.01). There was no difference in T2 measurements obtained using the other three sequences (P > 0.05). iMSDE 3D FSE had the highest SNR (P < 0.05) compared with the other three sequences. The 2D DIR MESE has the highest repeatability (ICC: 0.96, [95% CI: 0.88-0.99]). CONCLUSION: Although accurate T2 measurements can be achieved in phantom by the four sequences, in vivo vessel wall T2 quantification shows significant differences. The in vivo images can be influenced by multiple factors including black-blood preparation and acquisition method. Therefore, a careful choice of acquisition methods and analysis of the confounding factors are required for accurate in vivo carotid vessel wall T2 measurements. From the settings in this study, the iMSDE prepared 3D FSE is preferred for the future volunteer/patient scans.

Atherosclerotic plaque rupture occurs when mechanical loading exceeds its material strength. Mechanical analysis has been shown to be complementary to the morphology and composition for assessing vulnerability. However, strength and stretch thresholds for mechanics-based assessment are currently lacking. This study aims to quantify the ultimate material strength and extreme extensibility of atherosclerotic components from human carotid plaques. Tissue strips of fibrous cap, media, lipid core and intraplaque hemorrhage/thrombus were obtained from 21 carotid endarterectomy samples of symptomatic patients. Uni-extension test with tissue strips was performed until they broke or slid. The Cauchy stress and stretch ratio at the peak loading of strips broken about 2mm away from the clamp were used to characterize their ultimate strength and extensibility. Results obtained indicated that ultimate strength of fibrous cap and media were 158.3 [72.1, 259.3] kPa (Median [Inter quartile range]) and 247.6 [169.0, 419.9] kPa, respectively; those of lipid and intraplaque hemorrhage/thrombus were 68.8 [48.5, 86.6] kPa and 83.0 [52.1, 124.9] kPa, respectively. The extensibility of each tissue type were: fibrous cap – 1.18 [1.10, 1.27]; media – 1.21 [1.17, 1.32]; lipid – 1.25 [1.11, 1.30] and intraplaque hemorrhage/thrombus – 1.20 [1.17, 1.44]. Overall, the strength of fibrous cap and media were comparable and so were lipid and intraplaque hemorrhage/thrombus. Both fibrous cap and media were significantly stronger than either lipid or intraplaque hemorrhage/thrombus. All atherosclerotic components had similar extensibility. Moreover, fibrous cap strength in the proximal region (closer to the heart) was lower than that of the distal. These results are helpful in understanding the material behavior of atherosclerotic plaques.

Purpose To develop and optimise a 3D black-blood R2* mapping sequence for imaging the carotid artery wall, using optimal blood suppression and k-space view ordering. Methods Two different blood suppression preparation methods were used; Delay Alternating with Nutation for Tailored Excitation (DANTE) and improved Motion Sensitive Driven Equilibrium (iMSDE) were each combined with a three-dimensional (3D) multi-echo Fast Spoiled GRadient echo (ME-FSPGR) readout. Three different k-space view-order designs: Radial Fan-beam Encoding Ordering (RFEO), Distance-Determined Encoding Ordering (DDEO) and Centric Phase Encoding Order (CPEO) were investigated. The sequences were evaluated through Bloch simulation and in a cohort of twenty volunteers. The vessel wall Signal-to-Noise Ratio (SNR), Contrast-to-Noise Ratio (CNR) and R2*, and the sternocleidomastoid muscle R2* were measured and compared. Different numbers of acquisitions-per-shot (APS) were evaluated to further optimise the effectiveness of blood suppression. Results All sequences resulted in comparable R2* measurements to a conventional, i.e. non-blood suppressed sequence in the sternocleidomastoid muscle of the volunteers. Both Bloch simulations and volunteer data showed that DANTE has a higher signal intensity and results in a higher image SNR than iMSDE. Blood suppression efficiency was not significantly different when using different k-space view orders. Smaller APS achieved better blood suppression. Conclusion The use of blood-suppression preparation methods does not affect the measurement of R2*. DANTE prepared ME-FSPGR sequence with a small number of acquisitions-per-shot can provide high quality black-blood R2* measurements of the carotid vessel wall.

Accurate segmentation of carotid artery plaque in MR images is not only a key part but also an essential step for in vivo plaque analysis. Due to the indistinct MR images, it is very difficult to implement the automatic segmentation. Two kinds of classification models, that is, Bayes clustering and SSVM, are introduced in this paper to segment the internal lumen wall of carotid artery. The comparative experimental results show the segmentation performance of SSVM is better than Bayes.

Stroke remains a major cause of death and disability worldwide, with approximately one-third of ischaemic strokes being a consequence of carotid atherosclerotic plaque rupture. Thus, diagnostic strategies that could identify those patients at highest risk of events are of critical importance.

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.

Although recent developments in imaging biomarkers have revolutionized the diagnosis of Alzheimer's disease at early stages, the utility of most of these techniques in clinical setting remains unclear. The aim of this review is to provide a clear stepwise algorithm on using multitier imaging biomarkers for the diagnosis of Alzheimer's disease to be used by clinicians and radiologists for day-to-day practice. We summarized the role of most common imaging techniques and their appropriate clinical use based on current consensus guidelines and recommendations with brief sections on acquisition and analysis techniques for each imaging modality. Structural imaging, preferably MRI or alternatively high resolution CT, is the essential first tier of imaging. It improves the accuracy of clinical diagnosis and excludes other potential pathologies. When the results of clinical examination and structural imaging, assessed by dementia expert, are still inconclusive, functional imaging can be used as a more advanced option. PET with ligands such as amyloid tracers and 18F-fluorodeoxyglucose can improve the sensitivity and specificity of diagnosis particularly at the early stages of the disease. There are, however, limitations in using these techniques in wider community due to a combination of lack of facilities and expertise to interpret the findings. The role of some of the more recent imaging techniques including tau imaging, functional MRI, or diffusion tensor imaging in clinical practice, remains to be established in the ongoing and future studies.

BACKGROUND: Multiple overlapping uncovered stents (MOUS) system has shown potentials in managing complex aortic aneurysms with side branches involvement. It promotes the development of thrombus by modulating local flow pattern that reduces the wall tension, while maintaining patency of side branches. However the modulation of local hemodynamic parameters depends on various factors that have not been assessed comprehensively. METHODS: Aneurysm 3D geometry was reconstructed based on CT images. One-way fluid-structure interaction analysis was performed to quantify structural stress concentration in the wall, and changes of blood velocity, wall shear stress (WSS), oscillatory shear index (OSI), relative residence time (RRT) and pressure in the sac due to the stent deployment. RESULTS: High structural stress concentration due to stent deployment was found in the landing zone and it increased linearly with the number of stents deployed. The wall tension in the sac was unaffected by the stent deployment. Stress within the wall was insensitive to the different overlapping pattern. After one stent was deployed, the mean flow velocity in the sac reduced by 36.4%. The deployment of the 2nd stent further reduced the mean sac velocity by 10%. WSS decreased while both OSI and RRT increased after stent deployment, however pressure in the sac remained nearly unchanged. Except for the cases with complete stents struts alignment, different overlapping pattern had little effect on flow parameters. CONCLUSIONS: Mechanical parameters modulated by the MOUS are insensitive to different overlapping pattern suggesting that endovascular procedure can be performed with less attention to the overlapping pattern.

PURPOSE: To develop a 3D black-blood T2 mapping sequence with a combination of compressed sensing (CS) and parallel imaging (PI) for carotid wall imaging. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

PURPOSE: Multi-slice ungated double inversion recovery has been proposed as an alternative time-efficient and effective sequence for black-blood carotid imaging. The purpose of this study is to evaluate the comparative repeatability of this multi-contrast sequence with respect to a single slice double inversion recovery prepared gated sequence. MATERIALS AND METHODS: Ten healthy volunteers and three patients with Doppler ultrasound defined carotid artery stenosis >30% were recruited. T₁-weighted (T₁W) and T₂W fast spin-echo (FSE) images were acquired centered at the carotid bifurcation with and without cardiac gating. Repeat imaging was performed without patient repositioning to determine the variations in vessel wall measurement and signal intensity due to gating, while negating variations as a result of slice misalignment and anatomical displacement relative to the receiver coil. The distributions and the repeatability of lumen area, vessel wall area, signal and contrast-to-noise ratio (SNR/CNR) of the vessel wall and adjacent muscle were reported. RESULTS: The T₁W ungated sequence generally had comparable wall SNR/CNR with respect to the gated sequence, however the muscle SNR was lower (P = 0.013). The T₂W ungated multi-slice sequence had lower SNR/CNR than the gated single slice sequence (P < 0.001), but with equivalent effective wall CNR (P = 0.735). Vessel area measurements using the gated/ungated sequences were equivalent. Ungated sequences had better repeatability in SNR/CNR than the gated sequences with borderline and statistically significant differences. The repeatability of T₂W wall area measurement was better using the ungated sequences (P = 0.02), and the repeatability of the remaining vessel area measurements were equivalent. CONCLUSIONS: Ungated sequences can achieve comparable SNR/CNR and equivalent carotid vessel area measurements than gated sequences with improved repeatability of SNR/CNR. Ungated sequences are good alternatives of gated sequences for vessel area measurement and plaque composition quantification.

The rupture of an atherosclerotic plaque in the coronary circulation remains the main cause of heart attack. As a fiber-oriented structure, the fiber structure, in particular in the fibrous cap (FC), may affect both loading and material strength in the plaque. However, the role of fiber orientation and dispersion in plaque rupture is unclear. Local orientation and dispersion of fibers were calculated for the shoulder regions, mid FC, and regions with intimal thickening (IT) from histological images of 16 human coronary atherosclerotic lesions. Finite element analysis was performed to assess the effect of these properties on mechanical conditions. Fibers in shoulder regions had markedly reduced alignment (Median [interquartile range] 12.9° [6.6, 18.0], $p$, This research is supported by HRUK (RG2638/14/ 16), NSERC (6799-427538-2012), the WD Armstrong Trust, and the NIHR Cambridge Biomedical Research Centre.

Objectives The aim of this study was to identify the determinants of plaque structural stress (PSS) and the relationship between PSS and plaques with rupture. Background Plaque rupture is the most common cause of myocardial infarction, occurring particularly in higher risk lesions such as fibroatheromas. However, prospective intravascular ultrasound–virtual histology studies indicate that 135 kPa was a good predictor of rupture in higher risk regions. Conclusions PSS is determined by plaque composition, plaque architecture, and lumen geometry. PSS and PSS variability are increased in plaques with rupture, particularly at proximal segments. Incorporating PSS into plaque assessment may improve identification of rupture-prone plaques., Graphical abstract

BACKGROUND: Abdominal aortic aneurysm (AAA) wall inflammation and mechanical structural stress may influence AAA expansion and lead to rupture. We hypothesized a positive correlation between structural stress and fluorine-18-labeled 2-deoxy-2-fluoro-d-glucose (18F-FDG) positron emission tomography-defined inflammation. We also explored the influence of computed tomography-derived aneurysm morphology and composition, including intraluminal thrombus, on both variables. METHODS AND RESULTS: Twenty-one patients (19 males) with AAAs below surgical threshold (AAA size was 4.10±0.54 cm) underwent 18F-FDG positron emission tomography and contrast-enhanced computed tomography imaging. Structural stresses were calculated using finite element analysis. The relationship between maximum aneurysm 18F-FDG standardized uptake value within aortic wall and wall structural stress, patient clinical characteristics, aneurysm morphology, and compositions was explored using a hierarchical linear mixed-effects model. On univariate analysis, local aneurysm diameter, thrombus burden, extent of calcification, and structural stress were all associated with 18F-FDG uptake (P

Background— Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound. Methods and Results— Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5–30.6; P 2 (hazard ratio: 6.6; 95% confidence interval, 2.1–20.1; P =0.036), although absolute event rates for high-risk lesions remained P P =0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P =0.003) and minimal luminal area ≤4 mm 2 ( P =0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS ( P Conclusions— Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.

BACKGROUND: Functional magnetic resonance (MR) imaging of atheroma using contrast media enables assessment of the systemic severity of atherosclerosis in different arterial beds. Whether black-blood imaging has similar ability remains widely unexplored. In this study, we evaluate whether black-blood imaging can differentiate carotid plaques of patients with and without coronary artery disease (CAD) in terms of morphological and biomechanical features of plaque vulnerability, thereby allowing assessment of the systemic severity nature of atherosclerosis in different arterial beds. METHODS: Forty-one patients with CAD and 59 patients without CAD underwent carotid black-blood MR imaging. Plaque components were segmented to identify large lipid core (LC), ruptured fibrous cap (FC), and plaque hemorrhage (PH). These segmented contours of plaque components were used to quantify maximum structural biomechanical stress. RESULTS: Patients with CAD and without CAD had comparable demographics and comorbidities. Both groups had comparable prevalence of morphological features of plaque vulnerability (FC rupture, 44% versus 41%, P = .90; PH, 58% versus 47%, P = .78; large LC, 32% versus 47%, P = .17), respectively. The maximum biomechanical stress was not significantly different for both groups (241versus 278 kPa, P = .14) respectively. CONCLUSIONS: Black-blood imaging does not appear to have the ability to differentiate between the morphological and biomechanical features of plaque vulnerability when comparing patients with and without symptomatic atherosclerotic disease in a distant arterial territory such as coronary artery.

SummaryCarotid atherosclerotic plaques are a major cause of ischaemic stroke. The biomechanical environment to which the arterial wall and plaque is subjected to plays an important role in the initiation, progression and rupture of carotid plaques. MRI is frequently used to characterize the morphology of a carotid plaque, but new developments in MRI enable more functional assessment of carotid plaques. In this review, MRI based biomechanical parameters are evaluated on their current status, clinical applicability, and future developments. Blood flow related biomechanical parameters, including endothelial wall shear stress and oscillatory shear index, have been shown to be related to plaque formation. Deriving these parameters directly from MRI flow measurements is feasible and has great potential for future carotid plaque development prediction. Blood pressure induced stresses in a plaque may exceed the tissue strength, potentially leading to plaque rupture. Multi-contrast MRI based stress calculations in combination with tissue strength assessment based on MRI inflammation imaging may provide a plaque stress-strength balance that can be used to assess the plaque rupture risk potential. Direct plaque strain analysis based on dynamic MRI is already able to identify local plaque displacement during the cardiac cycle. However, clinical evidence linking MRI strain to plaque vulnerability is still lacking. MRI based biomechanical parameters may lead to improved assessment of carotid plaque development and rupture risk. However, better MRI systems and faster sequences are required to improve the spatial and temporal resolution, as well as increase the image contrast and signal-to-noise ratio.

Atherosclerosis remains a major cause of morbidity and mortality worldwide, and a thorough understanding of the underlying pathophysiological mechanisms is crucial for the development of new therapeutic strategies. Although atherosclerosis is a systemic inflammatory disease, coronary atherosclerotic plaques are not uniformly distributed in the vascular tree. Experimental and clinical data highlight that biomechanical forces, including wall shear stress (WSS) and plaque structural stress (PSS), have an important role in the natural history of coronary atherosclerosis. Endothelial cell function is heavily influenced by changes in WSS, and longitudinal animal and human studies have shown that coronary regions with low WSS undergo increased plaque growth compared with high WSS regions. Local alterations in WSS might also promote transformation of stable to unstable plaque subtypes. Plaque rupture is determined by the balance between PSS and material strength, with plaque composition having a profound effect on PSS. Prospective clinical studies are required to ascertain whether integrating mechanical parameters with medical imaging can improve our ability to identify patients at highest risk of rapid disease progression or sudden cardiac events.

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.

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. © 2015 The Authors. International Journal for Numerical Methods in Biomedical Engineering published by John Wiley & Sons Ltd.

Background Atherosclerotic plaque is subjected to a repetitive deformation due to arterial pulsatility during each cardiac cycle and damage may be accumulated over a time period causing fibrous cap (FC) fatigue, which may ultimately lead to rupture. In this study, we investigate the fatigue process in human carotid plaques using in vivo carotid magnetic resonance (MR) imaging. Method Twenty seven patients with atherosclerotic carotid artery disease were included in this study. Multi-sequence, high-resolution MR imaging was performed to depict the plaque structure. Twenty patients were found with ruptured FC or ulceration and 7 without. Modified Paris law was used to govern crack propagation and the propagation direction was perpendicular to the maximum principal stress at the element node located at the vulnerable site. Results The predicted crack initiations from 20 patients with FC defect all matched with the locations of the in vivo observed FC defect. Crack length increased rapidly with numerical steps. The natural logarithm of fatigue life decreased linearly with the local FC thickness (R2 = 0.67). Plaques (n=7) without FC defect had a longer fatigue life compared with those with FC defect (p = 0.03). Conclusion Fatigue process seems to explain the development of cracks in FC, which ultimately lead to plaque rupture.

Background Carotid plaque rupture, characterized by ruptured fibrous cap (FC), is associated with subsequent cerebrovascular events. However, ruptured FC may heal following stroke and convey decreased risk of future events. This study aims to characterize the healing process of ruptured FC by assessing the lumen conditions, quantified by the lumen curvature and roughness, using in vivo carotid cardiovascular magnetic resonance (CMR). Methods Patients suffering from transient ischemic attack underwent high resolution carotid MR imaging within 72 hours of the acute cerebrovascular ischemic event. CMR imaging was repeated at 3 and 12 months in 26 patients, in whom FC rupture/erosion was observed on baseline images and subsequent cerebrovascular events were recorded during the follow-up period. Lumen curvature and roughness were quantified from carotid CMR images and changes in these values were monitored on follow-up imaging. Results Healing of ruptured plaque was observed in patients (23 out of 26) without any ischemic symptom recurrence as shown by the lumen surface becoming smoother during the follow-up period, characterized by decreasing maximum lumen curvature (p < 0.05), increasing minimum lumen curvature (p < 0.05) and decreasing lumen roughness (p < 0.05) during the one year follow-up period. Conclusions Carotid plaque healing can be assessed by quantification of the lumen curvature and roughness and the incidence of recurrent cerebrovascular events may be high in plaques that do not heal with time. The assessment of plaque healing may facilitate risk stratification of recent stroke patients on the basis of CMR results.

Inflammation is a recognized risk factor for the vulnerable atherosclerotic plaque. USPIO-enhanced MRI imaging is a promising non-invasive method to identify high-risk atheromatous plaque inflammation in vivo in humans, in which areas of focal signal loss on MR images have been shown to correspond to the location of activated macrophages, typically at the shoulder regions of the plaque. This is the first report in humans describing simultaneous USPIO uptake within atheroma in two different arterial territories and again emphasises that atherosclerosis is a truly systemic disease. With further work, USPIO-enhanced MR imaging may be useful in identifying inflamed vulnerable atheromatous plaques in vivo, so refining patient selection for intervention and allowing appropriate early aggressive pharmacotherapy to prevent plaque rupture.

Background and Purpose— MR is widely used to depict still ischemic but viable tissue in acute stroke. However, the relationship between the apparent diffusion coefficient (ADC) and energy failure from reduced oxygen supply are unknown in man. Methods— Acute carotid-territory stroke patients were studied prospectively with both diffusion tensor–imaging and back-to-back steady-state 15 O-PET. Substantial numbers of voxels with oxygen extraction fraction >0.70 (ie, significant ongoing hypoxia) were identified in 3 patients (imaged at 7, 16 and 21 hours after stroke onset). In this voxel population, the quantitative relationships between the ADC and cerebral metabolic rate of oxygen (CMRO 2 ), and ADC and cerebral blood flow (CBF), were assessed. Results— The ADC remained essentially unchanged until CBF reached values ≈20 mls/100g per min, beyond which it declined linearly. In contrast, except when severely reduced, the ADC was a poorer predictor of CMRO 2 . For both CBF and CMRO 2 , however, the relationship with ADC became steeper with longer times since onset, ie, the same ADC reflected lower perfusion and CMRO 2 with elapsed time. Conclusions— Despite the small sample and late times from stroke onset, the findings indicate that the degree of restricted water diffusion reliably reflects the severity of oxygen deprivation below the penumbral threshold but is less strongly related to metabolic disruption, which may explain why the ADC does not reliably predict tissue outcome. However, the same degree of diffusion restriction may correspond to greater severity of tissue disruption with elapsing time, which has relevance for stroke therapy. Time elapsed since stroke onset should be taken into account when interpreting ADC declines and in voxel-based infarct prediction models.

Endovascular stenting has been successfully employed in the management of aortic aneurysms; however, its use in managing peripheral arterial conditions remains questionable. We review the utility of endovascular technique in the management of peripheral arterial conditions like aneurysms, pseudoaneurysms and arterio-venous fistulas in the emergency setting. Though long term data about graft patency rates is not yet available, the endovascular approach appears to be a useful minimally invasive technique in situations where open repair is either difficult or not feasible.