Combined ¹⁸ F-FDG PET-CT and DCE-MRI to Assess Inflammation and Microvascularization in Atherosclerotic Plaques

Abstract

S troke is the fourth leading cause of death in the UnitedStates and a leading cause of long-term disability. Atherosclerosis is underlying in the majority of clinical cardiovascular events, such as stroke. 1 Inflammation is an important feature of plaque progression and vulnerability.2,3 It can be quantified noninvasively with 18 fluorine-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography/computed tomography (PET-CT) with excellent reproducibility. [4][5][6] Neovascularization is another important feature of vulnerable atherosclerotic plaques. Dynamic contrast-enhanced MRI (DCE-MRI) enables quantitative assessment of neovascularization in carotid atherosclerotic plaques.7-9 K trans is a parameter that reflects microvascular flow, permeability, and surface area. The aim of the present study was to investigate the relation between inflammation and neovascularization as assessed with PET-CT and DCE-MRI, respectively. In a secondary analysis, we investigated the relation between these parameters and plaque morphology itself as determined with MRI. In addition, the relation between clinical characteristics, K trans and 18 F-FDG uptake were evaluated.Background and Purpose-Hallmarks of vulnerable atherosclerotic plaques are inflammation that can be assessed with 18 fluorine-fluorodeoxyglucose positron emission tomography/computed tomography, and increased neovascularization that can be evaluated by dynamic contrast-enhanced-MRI. It remains unclear whether these parameters are correlated or represent independent imaging parameters. This study determines whether there is a correlation between inflammation and neovascularization in atherosclerotic carotid plaques. Methods-A total of 58 patients with transient ischemic attack or minor stroke in the carotid territory and ipsilateral carotid artery stenosis of 30% to 69% were included. All patients underwent positron emission tomography/ computed tomography and dynamic contrast-enhanced-MRI of the carotid plaque. 18 Fluorine-fluorodeoxyglucose standard uptake values with target/background ratio were determined. Neovascularization was quantified by the mean (leakage) volume transfer constant K trans . Spearman rank correlation coefficients between target/background ratio and K trans were calculated. Results-Images

Increased Microvascularization and Vessel Permeability Associate With Active Inflammation in Human Atheromata

“…13 In contrast, Trujman et al recently reported a positive and significant weak correlation (r s 0.30, P = 0.035) between FDG TBR and mean K trans in 49 patients with carotid stenosis of 30-69% and transient ischemic attack or minor stroke. 14 Furthermore, in 17 patients with suspected supra-aortic arteritis, Cyran et al showed a positive significant strong correlation between mean FDG TBR and DCE-MRI extraction fraction. 26 The discrepancy in correlations may relate to the magnitude of plaque inflammatory activity at the time of noninvasive imaging.…”

“…Molecular and pharmacokinetic imaging techniques, such as 2-Deoxy-2-[ 18 F]fluoroglucose (FDG) positron emission tomography/computed tomography (PET/CT) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allow measurement of metabolic activity 8-10 and neovascularization, 11, 12 respectively. While studies have shown the feasibility of imaging plaques with FDG-PET and DCE-MRI, 13, 14 and some have attempted limited correlation between histological staining and PET 15, 16 or MRI, 12 inconsistent results have emerged, perhaps underscoring that the mere presence of macrophages or microvessels may not reflect the prevailing inflammatory activity. Indeed, mononuclear phagocytes exhibit considerable functional diversity, such that simply enumerating these cells discloses little about their state of inflammatory activation.…”

Can Dynamic Contrast-Enhanced MRI (DCE-MRI) and Diffusion-Weighted MRI (DW-MRI) Evaluate Inflammation Disease

“…25 Meanwhile, some studies have investigated the relation between inflammation and angiogenesis using DCE-MRI. 26,27 …”

Head-to-Head Comparison of Inflammation and Neovascularization in Human Carotid Plaques

“…Some authors have found a weak correlation between the 2 processes, 20 which is contradicted by others. 21 We could find no correlation between either of these major determinants of plaque vulnerability, highlighting the practical challenges in defining imaging strategies with which to assess plaque vulnerability.…”

“…23,24 In previous studies to image vulnerable plaques, multimodality imaging has been investigated. In particular, the combined assessment of inflammation by 18 F-FDG PET-CT and neovascularization by dynamic contrast-enhanced magnetic resonance imaging has been evaluated in patients with carotid plaques, 20,25,26 with divergent results reported (inverse, weak, or a moderate correlation between inflammation and neovascularization). However, systematic histological validation was either lacking in those studies or limited to a comparatively small number of patients.…”