Huijun Chen

Varying Correlation Between 18F-Fluorodeoxyglucose Positron Emission Tomography and Dynamic Contrast-Enhanced MRI in Carotid Atherosclerosis Implications for Plaque Inflammation

Background and Purpose— 18F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI have been proposed to quantitatively assess plaque inflammation by probing macrophages and neovessels, respectively. We examined their correlation to study the in vivo relationship between macrophage and neovessel activities in atherogenesis. Methods— Forty-one patients (34 men; aged 65±12 years) with a total of 68 carotid plaques (thickness ≥2 mm on ultrasound; 20 symptomatic) were assessed by both 18F-fluorodeoxyglucose positron emission tomography/computed tomography and dynamic contrast-enhanced MRI within 2 weeks, measured as target-to-background ratio and transfer constant (Ktrans), respectively. Results— Overall, the correlation between target-to-background ratio and Ktrans was weak and marginal (r=0.22; P=0.068). They were correlated in the symptomatic plaques (r=0.59; P=0.006) but not in the asymptomatic plaques (r=0.07; P=0.625; P=0.033 for difference in r). Neither target-to-background ratio nor Ktrans was significantly higher in the symptomatic plaques, but both showed an inverse relationship with time since last neurological event (r=−0.94 and −0.69 for target-to-background ratio and Ktrans, respectively). Conclusions— The correlation between 18F-fluorodeoxyglucose positron emission tomography and dynamic contrast-enhanced MRI measurements varied with clinical conditions, pointing to a complex interplay between macrophages and neovessels under different pathophysiological conditions. The moderate correlation shown only in symptomatic plaques indicates the presence of acute plaque inflammation with increased metabolic activity and cytokine production by inflammatory cells.

Longer duration of statin therapy is associated with decreased carotid plaque vascularity by magnetic resonance imaging.

OBJECTIVE Plaque neovasculature is a major route for lipoprotein and leukocyte ingress into plaques, and has been identified as a risk factor for carotid plaque disruption. Vp, a variable derived from pharmacokinetic modeling of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), correlates with plaque neovasculature density. Because lipid-lowering therapy has been associated with regression of neovasculature in animal models, we sought to determine clinical correlates of carotid plaque neovasculature (as assessed by Vp) in participants on statin therapy for established cardiovascular disease. METHODS 98 participants from an AIM-HIGH sub-study underwent DCE-MRI of their carotid arteries. Expert readers who were blinded to all clinical variables analyzed the MR images to measure carotid plaque Vp in all participants. Associations between Vp and duration of statin therapy and other clinical risk factors were analyzed. RESULTS Prior duration of statin treatment at enrollment ranged from <1 year (21%) 1-5 years (40%) and >5 years (39%). In univariate analyses, shorter duration of statin therapy (P = 0.01), the presence of metabolic syndrome (P = 0.02), and higher body mass index (P = 0.01) and lipoprotein(a) (P = 0.01) were all significantly associated with higher baseline Vp values. In multivariate analyses, significant associations remained between shorter duration of statin therapy (P = 0.004) and lipoprotein(a) (P = 0.04). CONCLUSIONS These are the first human, in vivo findings suggesting a relationship between duration of statin therapy and regression of carotid plaque neovasculature. Future longitudinal studies are warranted both to confirm this finding and to address whether changes in neovasculature may translate into change in risk for plaque disruption. CLINICALTRIALS. GOV IDENTIFIERS NCT00880178, NCT01178320 and NCT00120289.

Relationship between aneurysm wall enhancement and conventional risk factors in patients with unruptured intracranial aneurysms: A black-blood MRI study

Background and purpose Aneurysmal wall enhancement (AWE) has emerged as a new possible biomarker for depicting inflammation of the intracranial aneurysm (IA). However, the relationships of AWE with other risk factors are still unclear for unruptured IA. The purpose of this study was to investigate the association between AWE and other risk metrics. Methods Forty-eight patients with unruptured saccular IAs diagnosed by digital subtraction angiography were recruited to undergo magnetic resonance (MR) black-blood imaging. AWE was evaluated using the pre- and post-contrast black-blood MR images. Univariate and multivariate logistic regression analysis was performed to investigate the association of AWE with other risk factors, including size, maximal neck width, parent vessel diameter, location, multiplicity, daughter sacs and other clinical factors. The prevalence of AWE in each ISUIA grade was reported and compared by Wilcoxon rank sum test. Results In total, 61 aneurysms were detected in 48 patients. Aneurysm size was found to be an independent risk factor associated with AWE (OR 2.46 per mm increase, 95% CI 1.34–4.51; p = 0.004). Patient age was independently and inversely associated with AWE (OR 0.898 per year increase, 95% CI 0.812–0.994; p = 0.037). Higher prevalence of AWE was observed in larger aneurysms (12%, 71.4%, 100%, and 100% of ISUIA grade 1–4 IAs have AWE, respectively). Notably, 12% of small IAs (size <7 mm) exhibited AWE. The IAs with AWE had significant higher ISUIA grade than the IAs without (p < 0.001, Wilcoxon rank sum test). Conclusions The wall enhancement in contrast-enhanced black-blood MR images was independently associated with aneurysm size in unruptured IAs. However, some small unruptured aneurysms did exhibit wall enhancement, suggesting that AWE may provide additional aneurysm instability information to improve current size-based rupture risk evaluation metrics.

Homologous black‐bright‐blood and flexible interleaved imaging sequence (HOBBI) for dynamic contrast‐enhanced MRI of the vessel wall

To present a HOmologous Black‐Bright‐blood and flexible Interleaved imaging (HOBBI) sequence for dynamic contrast‐enhanced magnetic resonance imaging (MRI) of the vessel wall.

Atherosclerotic plaque inflammation quantification using dynamic contrast-enhanced (DCE) MRI

Inflammation plays an important role in atherosclerosis. Given the increasing interest in using in-vivo imaging methods to study the physiology and treatment effects in atherosclerosis, noninvasive intraplaque inflammation quantitative method is needed. Dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) has been proposed and validated to quantitatively characterize atherosclerotic plaque inflammation. Recent studies have optimized the imaging protocol, pharmacokinetic modeling techniques. All of these technical advances further promoted DCE-MRI to clinical investigations in plaque risk assessment and therapeutic response monitor. Although larger clinical studies are still needed, DCE-MRI has been proven to be a promising tool to reveal more about intraplaque inflammation by in vivo quantitative inflammation imaging.

Hepatic function imaging using dynamic Gd-EOB-DTPA enhanced MRI and pharmacokinetic modeling

To determine whether pharmacokinetic modeling parameters with different output assumptions of dynamic contrast–enhanced MRI (DCE‐MRI) using Gd‐EOB‐DTPA correlate with serum‐based liver function tests, and compare the goodness of fit of the different output assumptions.

Characterization of Craniocervical Artery Dissection by Simultaneous MR Noncontrast Angiography and Intraplaque Hemorrhage Imaging at 3T

BACKGROUND AND PURPOSE: Craniocervical artery dissection is the most common cause of ischemic stroke identified in young adults. For the diagnosis of craniocervical artery dissection, multisequence MR imaging is recommended but is time-consuming. Recently, investigators proposed a simultaneous noncontrast angiography and intraplaque hemorrhage imaging technique allowing simultaneous noncontrast MRA and vessel wall imaging in a single scan. This study sought to investigate the feasibility of 3D simultaneous noncontrast angiography and intraplaque hemorrhage MR imaging in the characterization of craniocervical artery dissection. MATERIALS AND METHODS: Twenty-four symptomatic patients (mean age, 45.0 ± 16.1 years; 21 men) with suspected craniocervical artery dissection were recruited. The 3D simultaneous noncontrast angiography and intraplaque hemorrhage 3D TOF MRA and black-blood imaging sequences were performed on a 3T MR imaging scanner. The agreement between simultaneous noncontrast angiography and intraplaque hemorrhage imaging and multisequence MR imaging in evaluating arterial dissection was determined. RESULTS: Dissection was found to involve 1 artery in 22 patients and 2 arteries in 2 patients. The intramural hematoma and luminal occlusion were detected in 19 (79.2%) and 11 (45.8%) patients, respectively. In measuring stenosis, the Cohen κ value between 3D TOF MRA and simultaneous noncontrast angiography and intraplaque hemorrhage imaging was 0.82 (P < .001). All intramural hematomas on multisequence imaging were successfully identified by simultaneous noncontrast angiography and intraplaque hemorrhage imaging. CONCLUSIONS: 3D simultaneous noncontrast angiography and intraplaque hemorrhage imaging showed excellent agreement with multisequence MR imaging in evaluating luminal stenosis and intramural hematoma in patients with craniocervical artery dissection. The simultaneous noncontrast angiography and intraplaque hemorrhage imaging saved nearly 50% of scanning time compared with multisequence MR imaging. Our findings suggest that 3D simultaneous noncontrast angiography and intraplaque hemorrhage imaging might be an alternative, time-efficient diagnostic tool for craniocervical artery dissection.

Evaluation of basilar artery atherosclerotic plaque distribution by 3D MR vessel wall imaging

Basilar artery (BA) atherosclerosis is an important cause of perforator stroke in the brainstem due to plaque involvement of the perforator ostia in BA dorsal or lateral walls. Therefore, to acquire information on plaque distribution is important to better understand and prevent the perforator stroke. This study aimed to comprehensively evaluate BA plaque distribution with 3D magnetic resonance imaging (MRI) vessel wall imaging.

Carotid Intraplaque Hemorrhage Imaging with Quantitative Vessel Wall T1 Mapping: Technical Development and Initial Experience

Purpose To develop a three-dimensional (3D) high-spatial-resolution time-efficient sequence for use in quantitative vessel wall T1 mapping. Materials and Methods A previously described sequence, simultaneous noncontrast angiography and intraplaque hemorrhage (SNAP) imaging, was extended by introducing 3D golden angle radial k-space sampling (GOAL-SNAP). Sliding window reconstruction was adopted to reconstruct images at different inversion delay times (different T1 contrasts) for voxelwise T1 fitting. Phantom studies were performed to test the accuracy of T1 mapping with GOAL-SNAP against a two-dimensional inversion recovery (IR) spin-echo (SE) sequence. In vivo studies were performed in six healthy volunteers (mean age, 27.8 years ± 3.0 [standard deviation]; age range, 24-32 years; five male) and five patients with atherosclerosis (mean age, 66.4 years ± 5.5; range, 60-73 years; five male) to compare T1 measurements between vessel wall sections (five per artery) with and without intraplaque hemorrhage (IPH). Statistical analyses included Pearson correlation coefficient, Bland-Altman analysis, and Wilcoxon rank-sum test with data permutation by subject. Results Phantom T1 measurements with GOAL-SNAP and IR SE sequences showed excellent correlation (R2 = 0.99), with a mean bias of -25.8 msec ± 43.6 and a mean percentage error of 4.3% ± 2.5. Minimum T1 was significantly different between sections with IPH and those without it (mean, 371 msec ± 93 vs 944 msec ± 120; P = .01). Estimated T1 of normal vessel wall and muscle were 1195 msec ± 136 and 1117 msec ± 153, respectively. Conclusion High-spatial-resolution (0.8 mm isotropic) time-efficient (5 minutes) vessel wall T1 mapping is achieved by using the GOAL-SNAP sequence. This sequence may yield more quantitative reproducible biomarkers with which to characterize IPH and monitor its progression.

Atherosclerotic plaque features and distribution in bilateral carotid arteries of asymptomatic elderly population: A 3D multicontrast MR vessel wall imaging study

PURPOSE This study sought to investigate the characteristics of morphology, compositions and distribution of carotid atherosclerotic plaques in asymptomatic elderly population using three dimensional (3D) multicontrast magnetic resonance vessel wall imaging. MATERIALS AND METHODS 146 asymptomatic elderly subjects (≥60years) were recruited and underwent 3D multicontrast MR vessel wall imaging for bilateral carotid arteries on a 3.0T MR scanner. The presence of carotid atherosclerotic plaque was determined and the stenosis was measured. The characteristics of plaque morphology and compositions were evaluated and compared among distal internal carotid artery (D-ICA), proximal-ICA (P-ICA), carotid bulb (CB), distal common carotid artery (D-CCA) and proximal-CCA (P-CCA). RESULTS Of all recruited 140 subjects (72.1±5.7years, 63 males), 87 (62.1%) had carotid plaques, 17 (12.1%) had high-risk plaques and 51 (36.4%) had multiple plaques. Of all 280 carotid arteries, only 16 (5.7%) had luminal stenosis (21.1%±11.4%). Among carotid arteries without luminal stenosis, the prevalence of plaque and high-risk plaques was 43.2% and 8.3%, respectively. Carotid plaques were mostly found in CB segment (33.9%), followed by P-ICA (13.6%), P-CCA (11.1%), D-CCA (4.6%) and D-ICA (3.6%). Age was independently associated with presence of multiple carotid plaques (odds ratio, 1.835; 95% confidence interval, 1.196-2.815; P=0.005). CONCLUSION Carotid artery atherosclerotic plaques are prevalent and a substantial number of high-risk plaques can be found in the asymptomatic elderly subjects. Longitudinal studies are warranted to investigate the risk of having ischemic stroke for asymptomatic elderly individuals with carotid artery high risk plaques.