Elsevier

Magnetic Resonance Imaging

Volume 30, Issue 7, September 2012, Pages 1017-1021
Magnetic Resonance Imaging

Original contribution
Ex vivo study of carotid endarterectomy specimens: quantitative relaxation times within atherosclerotic plaque tissues

https://doi.org/10.1016/j.mri.2012.02.018Get rights and content

Abstract

Purpose

Previous studies reporting relaxation times within atherosclerotic plaque have typically used dedicated small-bore high-field systems and small sample sizes. This study reports quantitative T1, T2 and T2 relaxation times within plaque tissue at 1.5 T using spatially co-matched histology to determine tissue constituents.

Methods

Ten carotid endarterectomy specimens were removed from patients with advanced atherosclerosis. Imaging was performed on a 1.5-T whole-body scanner using a custom built 10-mm diameter receive-only solenoid coil. A protocol was defined to allow subsequent computation of T1, T2 and T2 relaxation times using multi-flip angle spoiled gradient echo, multi-echo fast spin echo and multi-echo gradient echo sequences, respectively. The specimens were subsequently processed for histology and individually sectioned into 2-mm blocks to allow subsequent co-registration. Each imaging sequence was imported into in-house software and displayed alongside the digitized histology sections. Regions of interest were defined to demarcate fibrous cap, connective tissue and lipid/necrotic core at matched slice-locations. Relaxation times were calculated using Levenberg-Marquardt's least squares curve fitting algorithm. A linear-mixed effect model was applied to account for multiple measurements from the same patient and establish if there was a statistically significant difference between the plaque tissue constituents.

Results

T2 and T2 relaxation times were statistically different between all plaque tissues (P=.026 and P=.002 respectively) [T2: lipid/necrotic core was lower 47±13.7 ms than connective tissue (67±22.5 ms) and fibrous cap (60±13.2 ms); T2: fibrous cap was higher (48±15.5ms) than connective tissue (19±10.6 ms) and lipid/necrotic core (24±8.2 ms)]. T1 relaxation times were not significantly different (P=.287) [T1: Fibrous cap: 933±271.9 ms; connective tissue (1002±272.9 ms) and lipid/necrotic core (1044±304.0 ms)]. We were unable to demarcate hemorrhage and calcium following histology processing.

Conclusions

This study demonstrates that there is a significant difference between qT2 and qT2 in plaque tissues types. Derivation of quantitative relaxation times shows promise for determining plaque tissue constituents.

Introduction

Atherosclerosis is a major contributor to morbidity and mortality with the associated cardio- and cerebrovascular ischemia ranking as leading causes of death [1], [2]. Carotid atherosclerosis is a major contributor to ischaemic stroke [3]. The ability to determine to what extent an individual patient will benefit from a particular therapy, such as carotid endarterectomy or pharmacotherapy, is of paramount importance in addressing the disease. To date, clinicians predominantly rely upon the degree of luminal stenosis, as determined by ultrasound or angiography, to guide treatment decisions [4], [5], [6]. Despite these guidelines, uncertainty exists concerning the relevance of stenosis in dictating therapy [7], [8], and current evidence suggests that factors such as plaque inflammation, fibrous cap thickness, and presence of lipid-rich necrotic core play a role in developing ischaemic symptoms [9]. Within the research domain a large number of studies have exploited the inherent soft tissue contrast provided by magnetic resonance imaging (MRI) to identify plaque composition and improve risk stratification [10], [11].

A multitude of studies have applied quantitative MRI (qMRI) to characterize the normal range of healthy tissues and quantify change in tissues due to pathophysiology [12]. qT2 values have previously been reported on carotid endarterectomy specimens using both small bore ultra high-field (9.4T) systems (13–16) and clinical (1.5 T) systems (13,17–19). One such study reported the effect of temperature and formaldehyde fixation on T2 relaxation times [13]. A separate study compared in vivo and ex vivo T2 relaxation times and reported similar distributions; shortening of T2 relaxation times within lipid core was also reported [14].

High resolution ex vivo studies which report relaxation times at field strengths utilized within clinical examinations have the potential to enable future studies to optimize the relative contrast between tissues. Determining ideal sequences to assess the presence of lipid components is particularly important as the presence of a lipid core is known to increase the chances of subsequent stroke [15], [16], [17]. The ability to detect and measure fibrous cap is similarly important as fibrous cap thickness has been prospectively identified as a risk factor for cerebrovascular events [17].

This study aims to image carotid endarterectomy specimens from patients with advanced atherosclerotic disease on a clinical 1.5-T system in combination with a custom-built receive-only solenoid coil for micro-imaging. By segmenting plaque components on the basis of histological classification, the specific T1, T2 and T2 relaxation times for each plaque component are computed. This study aims to investigate if the differences in relaxation times between plaque components are statistically significant.

Section snippets

Experiment

Nine patients scheduled for carotid endarterectomy were recruited and gave informed written consent prior to surgery. The study design was approved by the local research ethics committee. One patient had bilateral disease and both plaques were removed (giving us a total sample size of n = 10). The patients had the following demographics [7/9 male, age: 72±6.9 years, luminal stenosis: 78.3±13.5%, 8/9 hypertensive, 7/9 hyperlipidemic, 1/9 diabetic]. Stenoses were measured using previous clinical

Results

The total number of demarcated ROIs, for quantitative T1, T2 and T2, respectively, were as follows (fibrous cap: n=16, 10 and 7; connective tissue: n=29, 22 and 8; lipid/necrotic core: n=17, 13 and 8). The total numbers varied and was dependent on the number of matching slice locations with spatially matched histology, acceptability of curve fitting and variations in spatial resolution between pulse sequences.

Our study observed no significant difference in T1 relaxation between plaque tissues (

Discussion

Identification of atherosclerotic plaque components with greater risk of thromboembolic activity is paramount in establishing the clinical utility of carotid MRI. A recent review speculates that carotid MRI is poised for multi-centre trial evaluation to assess if the technique can prospectively improve patient outcome [18]. Existing limitations, which have confined the technique within the research domain, include the necessity to have a dedicated in vivo coil, total length of scan time and the

Acknowledgments

This study was supported by a National Institute of Health Research, Cambridge Biomedical Research Centre grant.

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