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Biomedical subjects

Martin J Graves

Publications and source records attributed to Martin J Graves.

14 recordsLinked to original sources

Assessment of inflammatory burden contralateral to the symptomatic carotid stenosis using high-resolution ultrasmall, superparamagnetic iron oxide-enhanced MRI.

BACKGROUND AND PURPOSE: It is well known that the vulnerable atheromatous plaque has a thin, fibrous cap and large lipid core with associated inflammation. This inflammation can be detected on MRI with use of a contrast medium, Sinerem, an ultrasmall superparamagnetic iron oxide (USPIO). Although the incidence of macrophage activity in asymptomatic disease appears low, we aimed to explore the incidence of MRI-defined inflammation in asymptomatic plaques in patients with known contralateral symptomatic disease. METHODS: Twenty symptomatic patients underwent multisequence MRI before and 36 hours after USPIO infusion. Images were manually segmented into quadrants, and the signal change in each quadrant was calculated after USPIO administration. A mixed mathematical model was developed to compare the mean signal change across all quadrants in the 2 groups. Patients had a mean symptomatic stenosis of 77% compared with 46% on their asymptomatic side, as measured by conventional angiography. RESULTS: There were 11 (55%) men, and the median age was 72 years (range, 53 to 84 years). All patients had risk factors consistent with severe atherosclerotic disease. All symptomatic carotid stenoses had inflammation, as evaluated by USPIO-enhanced imaging. On the contralateral sides, inflammatory activity was found in 19 (95%) patients. Contralaterally, there were 163 quadrants (57%) with a signal loss after USPIO when compared with 217 quadrants (71%) on the symptomatic side (P=0.007). CONCLUSIONS: This study adds weight to the argument that atherosclerosis is a truly systemic disease. It suggests that investigation of the contralateral side in patients with symptomatic carotid stenosis can demonstrate inflammation in 95% of plaques, despite a mean stenosis of only 46%. Thus, inflammatory activity may be a significant risk factor in asymptomatic disease in patients who have known contralateral symptomatic disease. Patients with symptomatic carotid disease should have their contralateral carotid artery followed up.

Aged↗

Identifying inflamed carotid plaques using in vivo USPIO-enhanced MR imaging to label plaque macrophages.

BACKGROUND: Inflammation within atherosclerotic lesions contributes to plaque instability and vulnerability to rupture. We set out to evaluate the use of a macrophage labeling agent to identify carotid plaque inflammation by in vivo magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty patients with symptomatic severe carotid stenosis scheduled for carotid endarterectomy underwent multi-sequence MRI of the carotid bifurcation before and after injection of ultrasmall superparamagnetic particles of iron oxide (USPIOs). USPIO particles accumulated in macrophages in 24 of 30 plaques (80%). Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in 24 of 27 (89%) patients, with an average reduction in signal intensity induced by the USPIO particles of 24% (range, 3.1% to 60.8%). CONCLUSIONS: USPIO-enhanced MRI can identify plaque inflammation in vivo by accumulation of USPIO within macrophages in carotid plaques.

Carotid Stenosis↗

Branch cut surface placement for unwrapping of undersampled three-dimensional phase data: application to magnetic resonance imaging arterial flow mapping.

We demonstrate in both simulated and real cases the effect that undersampling of a three-dimensional (3D) wrapped phase distribution has on the geometry of phase singularity loops and their branch cut surfaces. The more intuitive two-dimensional (2D) problem of setting branch cuts between dipole pairs is taken as a starting point, and then branch cut surfaces in flat and ambiguous 3D loops are discussed. It is shown that the correct 2D branch cuts and 3D branch cut surfaces should be placed where the gradient of the original phase distribution exceeded pi rad voxel(-1). This information, however, is lost owing to undersampling and cannot be recovered from the sampled wrapped phase distribution alone. As a consequence, empirical rules such as finding the surface of minimal area or methods based on the wrapped phase gradient will fail to find the correct branch cut surfaces. We conclude that additional information about the problem under study is therefore needed to produce correct branch cut surfaces that lead to an unwrapped phase distribution with minimum local errors. An example with real data is provided in which downsampled phase contrast magnetic resonance imaging data are successfully unwrapped when the position of the vessel walls and the physical properties of the flowing blood are taken into account.

Algorithms↗

Interactive magnetic resonance cholangiography (MRC) with adaptive averaging.

PURPOSE: To implement and evaluate a technique for adaptively averaging 2D magnetic resonance cholangiography (MRC) images obtained using an interactive imaging system with a view to improving image quality at reduced fields of view (FOVs). MATERIALS AND METHODS: Images were obtained using an interactive implementation of a single-shot half-Fourier rapid acquisition with relaxation enhancement (RARE) technique. Software was developed for adaptively averaging images, and an evaluation was performed in a phantom and a cohort of 10 patients referred for standard MRC. Adaptively averaged and standard single-shot MRC images were evaluated with respect to their ability to demonstrate the common bile duct and main left and right intrahepatic duct branches. RESULTS: In all patient studies there was no difference in the ability of either the adaptive technique or the standard single-shot method to demonstrate the common bile duct and the main left and right intrahepatic duct branches. However, in seven of the 10 patient studies the adaptive technique provided better visualization of the peripheral bile duct system (P = 0.035; sign test). There was no difference in the diagnostic confidence of the two techniques (P = 0.32, Wilcoxon signed-rank test). CONCLUSION: Adaptive averaging of MRC images obtained using an interactive imaging paradigm significantly improves visualization of peripheral intrahepatic ducts.

Adolescent↗

Ultrafast magnetic resonance imaging protocols in stroke.

Stroke is the third leading cause of death and morbidity in the Western world. Ever since the publication of the major randomized trials showing the benefit of thrombolysis in early acute stroke, there has been growing impetus for the diagnosis of acute stroke to become a medical emergency. Currently, computed tomography (CT) remains the diagnostic method of choice in the assessment of acute strokes. It is practical, rapid, and widely available and, as used in these trials, can robustly exclude acute hemorrhage before potential thrombolysis. Although magnetic resonance imaging (MRI) has a number of advantages over unenhanced CT, the practicalities of performing MRI in the acute setting have hampered its widespread use. There are several reasons why speed of imaging is paramount in acute strokes. Firstly, such patients are often unwell and agitated and, as such, require close monitoring. Moreover, because of the short window within which intravenous thrombolysis can be given, time-consuming imaging studies decrease the therapeutic options available and likelihood of successful intervention. This review summarizes the latest developments in ultrafast imaging protocols that have the potential to improve practical feasibility, and thus propel MRI back to the forefront of acute stroke imaging.

Diffusion Magnetic Resonance Imaging↗

Identification of culprit lesions after transient ischemic attack by combined 18F fluorodeoxyglucose positron-emission tomography and high-resolution magnetic resonance imaging.

BACKGROUND AND PURPOSE: Carotid endarterectomy is currently guided by angiographic appearance on the assumption that the most stenotic lesion visible at angiography is likely to be the lesion from which future embolic events will arise. However, risk of plaque rupture, the most common cause of atherosclerosis-related thromboembolism, is dictated by the composition of the plaque, in particular the degree of inflammation. Angiography may, therefore, be an unreliable method of identifying vulnerable plaques. In this study, plaque inflammation was quantified before endarterectomy using the combination of 18F fluorodeoxyglucose positron (FDG)-emission tomography (PET) and high-resolution MRI (HRMRI). METHODS: Twelve patients, all of whom had suffered a recent transient ischemic attack, had a severe stenosis in the ipsilateral carotid artery, and were awaiting carotid endarterectomy underwent FDG-PET and HRMRI scanning. A semiquantitative estimate of plaque inflammation was calculated for all of the lesions identified on HRMRI. RESULTS: In 7 of 12 patients (58%), high FDG uptake was seen in the lesion targeted for endarterectomy. In the remaining 5 patients, FDG uptake in the targeted lesion was low. In these 5 patients, 3 had nonstenotic lesions identified on HRMRI that exhibited a high level of FDG uptake. All 3 of the highly inflamed nonstenotic lesions were located in a vascular territory compatible with the patients' presenting symptoms. CONCLUSIONS: Our data suggest that angiography may not always identify the culprit lesion. Combined FDG-PET and HRMRI can assess the degree of inflammation in stenotic and nonstenotic plaques and could potentially be used to identify lesions responsible for embolic events.

Aged↗

Stress analysis of carotid plaque rupture based on in vivo high resolution MRI.

Atheromatous carotid plaque rupture is responsible for the majority of ischaemic strokes in the developed world. Plaque rupture has been associated with plaque morphology, plaque components' properties, inflammation and local stress concentration. High resolution multi-spectral magnetic resonance imaging (MRI) has allowed the plaque components to be visualized in vivo. This study combined the recent advances in finite element analysis (FEA) and MRI, and performed stress analysis of five vulnerable carotid plaques based on the geometry derived from in vivo MRI. Image segmentation was based on multi-spectral MRI and co-registered with histology for plaque characterization. Plaque fibrous cap, lipid pool and vessel wall were modelled as isotropic, incompressible hyperelastic materials undergoing large deformation under pulse pressure loading. High stress concentrations were predicted at the shoulders and the thinnest fibrous cap regions of the plaque, and the mean maximal stresses were found to be higher in the ruptured plaques (683.3 kPa) than those in the unruptured plaques (226.9 kPa). The effect of the relative stiffness of fibrous cap to lipid pool on the stress within the cap itself was studied. It was shown that larger relative stiffness of fibrous cap to lipid pool resulted in higher stress within the cap. Thus, it is likely that high stress concentrations in vulnerable plaque may cause plaque rupture and lead to acute ischaemic sequelae. A combination of in vivo high resolution MRI and FEA could potentially act as a useful tool to assess plaque vulnerability and risk stratify patients with carotid atheroma.

Aged↗

Cost-effectiveness of diagnostic strategies prior to carotid endarterectomy.

The main objective of this study was to assess the long-term cost-effectiveness of five alternative diagnostic strategies for identification of severe carotid stenosis in recently symptomatic patients. A decision-analytical model with Markov transition states was constructed. Data sources included a prospective study involving 167 patients who had screening Doppler ultrasound (DUS), confirmatory contrast-enhanced magnetic resonance angiography (CEMRA) and confirmatory digital subtraction angiography (DSA), individual patient data from the European Carotid Surgery Trial and other published clinical and cost data. A "selective" strategy, whereby all patients receive DUS and CEMRA (only proceeding to DSA if the CEMRA is positive and the DUS is negative), was most cost-effective. This was both the cheapest imaging and treatment strategy (35,205 dollars per patient) and yielded 6.1590 quality-adjusted life years (QALYs), higher than three alternative imaging strategies. Probabilistic sensitivity analysis demonstrated that there was less than a 10% probability that imaging with either DUS or DSA alone are cost-effective at the conventional 50,000 dollars/QALY threshold. In conclusion, DSA is not cost-effective in the routine diagnostic workup of most patients. DUS, with additional imaging in the form of CEMRA, is recommended, with a strategy of "CEMRA and selective DUS review" being shown to be the optimal imaging strategy.

Aged↗

In vivo detection of macrophages in human carotid atheroma: temporal dependence of ultrasmall superparamagnetic particles of iron oxide-enhanced MRI.

UNLABELLED: Background- It has been suggested that inflammatory cells within vulnerable plaques may be visualized by superparamagnetic iron oxide particle-enhanced MRI. The purpose of this study was to determine the time course for macrophage visualization with in vivo contrast-enhanced MRI using an ultrasmall superparamagnetic iron oxide (USPIO) agent in symptomatic human carotid disease. METHODS: Eight patients scheduled for carotid endarterectomy underwent multisequence MRI of the carotid bifurcation before and 24, 36, 48, and 72 hours after Sinerem (2.6 mg/kg) infusion. RESULTS: USPIO particles accumulated in macrophages in 7 of 8 patients given Sinerem. Areas of signal intensity reduction, corresponding to USPIO/macrophage-positive histological sections, were visualized in all 7 of these patients, optimally between 24 and 36 hours, decreasing after 48 hours, but still evident up to 96 hours after infusion. CONCLUSIONS: USPIO-enhanced MRI of carotid atheroma can be used to identify macrophages in vivo. The temporal change in the resultant signal intensity reduction on MRI suggests an optimal time window for the detection of macrophages on postinfusion imaging.

Aged↗

Evaluation of carotid stenosis with axial high-resolution black-blood MR imaging.

High-resolution axial black-blood MR imaging (BB MRI) has been shown to be able to characterise carotid plaque morphology. The aim of this study was to explore the accuracy of this technique in quantifying the severity of carotid stenosis. A prospective study of 54 patients with symptomatic carotid disease was conducted, comparing BB MRI to the gold standard, conventional digital subtraction X-ray angiography (DSA). The BB MRI sequence was a fast-spin echo acquisition (TE = 42 ms, ETL = 24, field of view = 100 x 100 mm, slice thickness = 3.0 mm) at 1.5 T using a custom-built phased-array coil. Linear measurements of luminal and outer carotid wall diameter were made directly from the axial BB MRI slices by three independent blinded readers and stenosis was calculated according to European Carotid Surgery Trial (ECST) criteria. There was good agreement between BB MRI and DSA (intraclass correlation = 0.83). Inter-observer agreement was good (average kappa = 0.77). BB MRI was accurate for detection of severe stenosis (> or = 80%) with sensitivity and specificity of 87 and 81%, respectively. Eight cases of "DSA-defined" moderate stenosis were overestimated as severe by BB MRI and this may be related to non-circular lumens. Axial imaging with BB MRI could potentially be used to provide useful information about severity of carotid stenosis.

Aged↗

MRI-derived measurements of fibrous-cap and lipid-core thickness: the potential for identifying vulnerable carotid plaques in vivo.

Vulnerable plaques have thin fibrous caps overlying large necrotic lipid cores. Recent studies have shown that high-resolution MR imaging can identify these components. We set out to determine whether in vivo high-resolution MRI could quantify this aspect of the vulnerable plaque. Forty consecutive patients scheduled for carotid endarterectomy underwent pre-operative in vivo multi-sequence MR imaging of the carotid artery. Individual plaque constituents were characterised on MR images. Fibrous-cap and lipid-core thickness was measured on MRI and histology images. Bland-Altman plots were generated to determine the level of agreement between the two methods. Multi-sequence MRI identified 133 corresponding MR and histology slices. Plaque calcification or haemorrhage was seen in 47 of these slices. MR and histology derived fibrous cap-lipid-core thickness ratios showed strong agreement with a mean difference between MR and histology ratios of 0.02 (+/- 0.04). The intra-class correlation coefficient between two readers for measurements was 0.87 (95% confidence interval, 0.73 and 0.93). Multi-sequence, high-resolution MR imaging accurately quantified the relative thickness of fibrous-cap and lipid-core components of carotid atheromatous plaques. This may prove to be a useful tool to characterise vulnerable plaques in vivo.

Aged↗

Contrast-enhanced MR angiography vs intra-arterial digital subtraction angiography for carotid imaging: activity-based cost analysis.

The aim of this study was to compare the costs of performing contrast-enhanced MR angiography (CE MRA) with intra-arterial digital subtraction angiography (DSA) for the evaluation of carotid atherosclerotic disease. Activity-based cost analysis was used to identify the costs of performing each procedure. The variable direct costs of performing CE MRA and DSA were determined in 20 patients by using detailed time and motion studies. All personnel directly involved in the cases were tracked to the nearest minute and all consumable items used were recorded. Moreover, procedure times were prospectively recorded for an additional 80 patients who underwent both DSA and CE MRA. The variable direct costs of bed usage in the angiography day-case unit, all direct fixed costs as well as indirect costs were assessed from hospital and departmental accounting records. Total costs for each procedure were calculated and compared using Wilcoxon signed-rank sum test. Mean aggregate costs were Euro 721 for DSA and Euro 306 for CE MRA, resulting in potential savings of Euro 415 per patient (p<0.0001). On average, a DSA procedure thus cost approximately 2.4 (95% confidence intervals: 2.2-2.6) times more than CE MRA to our medical institution. Sensitivity analyses confirmed the robustness of our conclusions across wide ranges of plausible values for various parameters. Assuming equal diagnostic performance, institutions may have substantial cost savings if CE MRA is used instead of DSA for carotid imaging.

Aged↗