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Biomedical subjects

Jonathan H Gillard

Publications and source records attributed to Jonathan H Gillard.

26 records · Page 2Linked to original sources

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.

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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.

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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.

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Imaging the ischaemic penumbra.

PURPOSE OF REVIEW: Imaging the penumbra is essential, not only to identify patients who might benefit from thrombolysis, but also to further understanding of the ischaemic process, thereby potentially revealing new opportunities for therapeutic intervention. Here we review recent imaging studies of the acute stroke process. RECENT FINDINGS: Perfusion-computed tomography and computed tomography angiography enable assessment of the haemodynamic status and site of occlusion, leading to their promising use in guiding thrombolysis. The magnetic resonance concept of the diffusion-perfusion 'mismatch' being representative of penumbra appears to be an oversimplification. The mapping of simple variables such as time-to-peak might not directly reveal true penumbral perfusion levels. Also, lesions seen with diffusion-weighted imaging may be reversible as a result of early reperfusion. This reversal with subsequent normalization may represent selective neuronal damage. Late secondary injury, as indicated by the reappearance of the diffusion-weighted imaging lesion, has recently been documented; the mechanisms are unknown but form potential targets for future therapies. Despite these caveats, diffusion-weighted imaging-perfusion-weighted imaging remains the most useful approach to map the pathophysiology of stroke in the clinical setting. Acute/subacute flumazenil positron emission tomography studies are being used as markers of neuronal integrity to help shed further light on infarction thresholds, and potentially document selective neuronal loss. F-labelled fluoromisonidazole positron emission tomography imaging of brain hypoxia documents the temporal and spatial progression of the penumbra. SUMMARY: The goal of understanding the complex process that is acute ischaemia in stroke, and subsequently the development of therapeutic strategies, continues to be advanced by imaging the penumbra in novel ways.

Brain Ischemia↗

Does the acute diffusion-weighted imaging lesion represent penumbra as well as core? A combined quantitative PET/MRI voxel-based study.

In acute ischemic stroke, the diffusion-weighted imaging (DWI) lesion is widely held to represent the core of irreversible damage and is therefore crucial in selecting patients for thrombolysis. However, recent research suggests it may also represent penumbra. An illustrative patient was imaged 7 hours after stroke onset with back-to-back 3T diffusion tensor imaging and quantitative positron emission tomography, which showed a DWI lesion and misery perfusion, respectively. Using previously validated voxel-based probabilistic CBF, CMRO2, and Oxygen Extraction Fraction (OEF) thresholds, the authors show that the DWI lesion contained not only core but also substantial proportions of penumbra. Also, severe apparent diffusion coefficient reductions were present within the potentially salvageable penumbra as well as in the core. These findings have potential implications regarding treatment decisions.

Brain Ischemia↗

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.

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Increased anisotropy in acute stroke: a possible explanation.

BACKGROUND AND PURPOSE: The increase in fractional anisotropy (FA) in acute stroke has yet to be explained. Using an engineering methodology known as pq diagrams, we sought to explain the increase in FA by describing changes in the total magnitude of the diffusion tensor (L) as well as the isotropic (p) and anisotropic (q) components. METHODS: Diffusion tensor imaging was performed in 10 patients with stroke <27 hours old. The diffusion tensor was decomposed into the p and q components and plotted to describe the diffusion trajectories. FA was also calculated and compared. RESULTS: There was significant and consistent reduction in p, q, and L (p: mean, -50.0%; range, -36.6% to -64.5%; q: mean, -50.8%; range, -30.8% to -72.8%; L: mean, -50.3%; range, -37.0% to -65.1%). There were inconsistent changes in FA (mean, -0.5%; range, -44.9% to +45.0%). Five patients had elevated FA due to proportionately higher loss of L than q. CONCLUSIONS: Changes in FA only occur when there is a change in the ratio of q/L. Acute elevation of FA occurred in the context of a larger reduction in L than q. The elevation in FA occurs in the context of a reduction in the anisotropic tensor and therefore is a consequence of ratio-metric measurement. This appears to clarify the reported increase in FA in terms of alterations in the shape of the apparent diffusion tensor. pq diagrams appear to offer improved resolution of acute diffusion changes in ischemia.

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