[Show abstract][Hide abstract] ABSTRACT: Multi-contrast vessel wall cardiovascular magnetic resonance (CMR) has demonstrated its capability for atherosclerotic plaque morphology measurement and component characterization in different vasculatures. However, limited coverage and partial volume effect with conventional two-dimensional (2D) techniques might cause lesion underestimation. The aim of this work is to evaluate the performance in a) blood suppression and b) vessel wall delineation of three-dimensional (3D) multi-contrast joint intra- and extracranial vessel wall imaging at 3T.
Three multi-contrast 3D black blood (BB) sequences with T1, T2 and heavy T1 weighting and a custom designed 36-channel neurovascular coil covering the entire intra- and extracranial vasculature have been used and investigated in this study. Two healthy subjects were recruited for sequence parameter optimization and twenty-five patients were consecutively scanned for image quality and blood suppression assessment. Qualitative image scores of vessel wall delineation as well as quantitative Signal-to-Noise Ratio (SNR) and Contrast-to-Noise Ratio (CNR) were evaluated at five typical locations ranging from common carotid arteries to middle cerebral arteries.
The 3D multi-contrast images acquired within 15mins allowed the vessel wall visualization with 0.8 mm isotropic spatial resolution covering intra- and extracranial segments. Quantitative wall and lumen SNR measurements for each sequence showed effective blood suppression at all selected locations (P < 0.0001). Although the wall-lumen CNR varied across measured locations, each sequence provided good or adequate image quality in both intra- and extracranial segments.
The proposed 3D multi-contrast vessel wall technique provides isotropic resolution and time efficient solution for joint intra- and extracranial vessel wall CMR.
Journal of Cardiovascular Magnetic Resonance 12/2015; 17(1):41. DOI:10.1186/s12968-015-0143-z · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Automatic in vivo segmentation of multicontrast (multisequence) carotid magnetic resonance for plaque composition has been proposed as a substitute for manual review to save time and reduce inter-reader variability in large-scale or multicenter studies. Using serial images from a prospective longitudinal study, we sought to compare a semi-automatic approach versus expert human reading in analyzing carotid atherosclerosis progression. Baseline and 6-month follow-up multicontrast carotid images from 59 asymptomatic subjects with 16-79 % carotid stenosis were reviewed by both trained radiologists with 2-4 years of specialized experience in carotid plaque characterization with MRI and a previously reported automatic atherosclerotic plaque segmentation algorithm, referred to as morphology-enhanced probabilistic plaque segmentation (MEPPS). Agreement on measurements from individual time points, as well as on compositional changes, was assessed using the intraclass correlation coefficient (ICC). There was good agreement between manual and MEPPS reviews on individual time points for calcification (CA) (area: ICC; 0.85-0.91; volume: ICC; 0.92-0.95) and lipid-rich necrotic core (LRNC) (area: ICC; 0.78-0.82; volume: ICC; 0.84-0.86). For compositional changes, agreement was good for CA volume change (ICC; 0.78) and moderate for LRNC volume change (ICC; 0.49). Factors associated with LRNC progression as detected by MEPPS review included intraplaque hemorrhage (positive association) and reduction in low-density lipoprotein cholesterol (negative association), which were consistent with previous findings from manual review. Automatic classifier for plaque composition produced results similar to expert manual review in a prospective serial MRI study of carotid atherosclerosis progression. Such automatic classification tools may be beneficial in large-scale multicenter studies by reducing image analysis time and avoiding bias between human reviewers.
The international journal of cardiovascular imaging 07/2015; DOI:10.1007/s10554-015-0704-0 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study sought to determine the multicenter reproducibility of magnetic resonance imaging (MRI) and the compatibility of different scanner platforms in assessing carotid plaque morphology and composition. A standardized multi-contrast MRI protocol was implemented at 16 imaging sites (GE: 8; Philips: 8). Sixty-eight subjects (61 ± 8 years; 52 males) were dispersedly recruited and scanned twice within 2 weeks on the same magnet. Images were reviewed centrally using a streamlined semiautomatic approach. Quantitative volumetric measurements on plaque morphology (lumen, wall, and outer wall) and plaque tissue composition [lipid-rich necrotic core (LRNC), calcification, and fibrous tissue] were obtained. Inter-scan reproducibility was summarized using the within-subject standard deviation, coefficient of variation (CV) and intraclass correlation coefficient (ICC). Good to excellent reproducibility was observed for both morphological (ICC range 0.98-0.99) and compositional (ICC range 0.88-0.96) measurements. Measurement precision was related to the size of structures (CV range 2.5-4.9 % for morphology, 36-44 % for LRNC and calcification). Comparable measurement variability was found between the two platforms on both plaque morphology and tissue composition. In conclusion, good to excellent inter-scan reproducibility of carotid MRI can be achieved in multicenter settings with comparable measurement precision between platforms, which may facilitate future multicenter endeavors that use serial MRI to monitor atherosclerotic plaque progression.
The International Journal of Cardiovascular Imaging 09/2014; 31(1). DOI:10.1007/s10554-014-0532-7 · 1.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Association between clinical factors and high-risk plaque features, such as, thin or ruptured cap, intraplaque hemorrhage, presence of lipid-rich necrotic core (LRNC), and increased LRNC volume as assessed by magnetic resonance imaging (MRI), was examined in patients with established vascular disease in the Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides (AIM-HIGH) trial. A total of 214 subjects underwent carotid MRI and had acceptable image quality for assessment of plaque burden, tissue contents, and MRI-modified American Heart Association lesion type by a core laboratory. We found that 77% of subjects had carotid plaques, 52% had lipid-containing plaques, and 11% had advanced American Heart Association type-VI lesions with possible surface defect, intraplaque hemorrhage, or mural thrombus. Type-VI lesions were associated with older age (odds ratio [OR] = 2.6 per 5 years increase, p <0.001). After adjusting for age, these lesions were associated with history of cerebrovascular disease (OR = 4.1, p = 0.01), higher levels of lipoprotein(a) (OR = 2.0 per 1 SD increase, p = 0.02), and larger percent wall volume (PWV [OR = 4.6 per 1 SD increase, p <0.001]) but, were negatively associated with metabolic syndrome (OR = 0.2, p = 0.02). Presence of LRNC was associated with the male gender (OR = 3.2, p = 0.02) and PWV (OR = 3.8 per 1 SD, p <0.001); however, it was negatively associated with diabetes (OR = 0.4, p = 0.02) and high-density lipoprotein cholesterol levels (OR = 0.7 per 1 SD, p = 0.02). Increased percent LRNC was associated with PWV (regression coefficient = 0.36, p <0.001) and negatively associated with ApoA1 levels (regression coefficient = -0.20, p = 0.03). In conclusion, older age, male gender, history of cerebrovascular disease, larger plaque burden, higher lipoprotein(a), and lower high-density lipoprotein cholesterol or ApoA1 level have statistically significant associations with high-risk plaque features. Metabolic syndrome and diabetes showed negative associations in this population.
The American Journal of Cardiology 08/2014; 114(9). DOI:10.1016/j.amjcard.2014.08.001 · 3.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
The aim of this study is to investigate the inter-scan reproducibility of kinetic parameters in atherosclerotic plaque using dynamic contrast-enhanced (DCE) cardiovascular magnetic resonance (CMR) in a multi-center setting at 3T.Methods
Carotid arteries of 51 subjects from 15 sites were scanned twice within two weeks on 3T scanners using a previously described DCE-CMR protocol. Imaging data with protocol compliance and sufficient image quality were analyzed to generate kinetic parameters of vessel wall, expressed as transfer constant (K trans ) and plasma volume (v p ). The inter-scan reproducibility was evaluated using intra-class correlation coefficient (ICC) and coefficient of variation (CV). Power analysis was carried out to provide sample size estimations for future prospective study.ResultsTen (19.6%) subjects were found to suffer from protocol violation, and another 6 (11.8%) had poor image quality (n¿=¿6) in at least one scan. In the 35 (68.6%) subjects with complete data, the ICCs of K trans and v p were 0.65 and 0.28, respectively. The CVs were 25% and 62%, respectively. The ICC and CV for v p improved to 0.73 and 28% in larger lesions with analyzed area larger than 25 mm2. Power analysis based on the measured CV showed that 50 subjects per arm are sufficient to detect a 20% difference in change of K trans over time between treatment arms with 80% power without consideration of the dropout rate.Conclusion
The result of this study indicates that quantitative measurement from DCE-CMR is feasible to detect changes with a relatively modest sample size in a prospective multi-center study despite the limitations. The relative high dropout rate suggested the critical needs for intensive operator training, optimized imaging protocol, and strict quality control in future studies.
Journal of Cardiovascular Magnetic Resonance 08/2014; 16(1):51. DOI:10.1186/s12968-014-0051-7 · 4.56 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The main objective of cell therapy is regeneration of damaged tissues. To distinguish graft from host tissue by magnetic resonance imaging (MRI), a paramagnetic label must be introduced to cells prior to transplantation. The paramagnetic label can be either exogenous iron oxide nanoparticles or a genetic overexpression of ferritin, an endogenous iron storage protein. The purpose of this work was to compare efficacy of these 2 methods for MRI evaluation of engrafted cell survival in the infarcted mouse heart. Mouse skeletal myoblasts were labeled either by cocultivation with iron oxide particles or by engineering them to overexpress ferritin. Along with live cell transplantation, 2 other groups of mice were injected with dead-labeled cells. Both particle-labeled and ferritin-tagged grafts were detected as areas of MRI signal hypointensity in the left ventricle of the mouse heart using T2*-weighted sequences, although the signal attenuation decreased with ferritin tagging. Importantly, live cells could not be distinguished from dead cells when labeled with iron oxide particles, whereas the ferritin tagging was detected only in live grafts, thereby allowing identification of viable grafts using MRI. Thus, iron oxide particles can provide information about initial cell injection success but cannot assess graft viability. On the other hand, genetically based cell tagging, such as ferritin overexpression, despite having lower signal intensity in comparison with iron oxide particles, is able to identify live transplanted cells.
Journal of Cardiovascular Pharmacology and Therapeutics 03/2014; 19(4). DOI:10.1177/1074248414525999 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Growing interest in the in vivo characterization of plaque pathology has furthered the development of vessel wall imaging approaches beyond traditional techniques of luminal imaging. By leveraging histopathological information from carotid endarterectomy specimens, magnetic resonance imaging has been proven capable of providing qualitative and quantitative information on a number of morphological and pathological features of carotid atherosclerosis, including fibrous cap and necrotic core, intraplaque hemorrhage, plaque neovascularization, and inflammation. These technical advancements present new opportunities to expand the understanding of the pathophysiology of ischemic stroke and devise more efficient diagnostic and prognostic tools to address contemporary clinical problems in the management of carotid atherosclerosis. From a clinical perspective, this article introduces the various magnetic resonance techniques for carotid atherosclerosis imaging. The background and pathological basis of direct plaque imaging in carotid arteries are discussed, followed by available solutions and key technical considerations, as well as promising applications that have arisen from these techniques.
[Show abstract][Hide abstract] ABSTRACT: Molecular imaging of atherosclerotic biomarkers is critical for non-invasive detection and diagnosis of atherosclerotic plaques and therapeutic management. Fibrin and fibronectin accumulate at elevated levels in atherosclerotic plaques and are associated with atherogenesis and disease progression. Molecular imaging of these biomarkers has the potential to non-invasively characterize plaque burden. In this work, we investigated the effectiveness of a peptide-targeted macrocyclic Gd(III) chelate, CLT1-dL-(DOTA-Gd)4, specific to fibrin-fibronectin complexes for molecular MRI of atherosclerosis. Atherosclerotic plaques were induced in Apolipoprotein E-knockout (ApoE(-/-)) mice by feeding with high fat and cholesterol-enriched diet (HFD) for up to 30 weeks. MRI of the vessel wall in the arch aorta was performed at 10, 20 and 30 weeks after the onset of HFD. High spatial-resolution MRI was performed prior and up to 35 minutes after i.v. injection of CLT1-dL-(DOTA-Gd)4 or a nonspecific control agent at a dose of 0.1 mmol-Gd/kg. CLT1-dL-(DOTA-Gd)4 produced stronger enhancement in the atherosclerotic lesions of the aortic wall than the control at all time points in the mice. Cross sectional MR images of the aortic arch revealed progressive thickening of the atherosclerotic vessel wall in the mice on HFD for up to 30 weeks. This progression correlated well to histological staining, as well as fibrin and fibronectin immunochemical stained images. Molecular MRI with CLT1-dL-(DOTA-Gd)4 has a potential for detecting atherosclerosis and non-invasive monitoring of the progression of the plaques.
American Journal of Nuclear Medicine and Molecular Imaging 10/2013; 3(5):446-455. · 3.25 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To use magnetic resonance (MR) imaging to examine the short-term (6 months) natural history of the lipid-rich necrotic core (LRNC) in carotid artery plaques by examining the placebo group of a multicenter clinical trial.
Materials and methods:
Study procedures and consent forms were approved by the institutional review board for this HIPAA-compliant study. Written informed consent was obtained for all enrolled subjects. Subjects in the placebo group of a multicenter clinical trial who showed LRNC at screening MR imaging had a follow-up MR imaging examination after 6 months. Lumen and wall volumes and LRNC volume and percentage were measured on images from both examinations by readers who were blinded to the time sequence. Plaque progression was calculated as annualized change in common coverage by using the carotid artery bifurcation as a landmark. Associations of clinical and imaging variables with LRNC progression were examined by using linear regression analysis.
Fifty-nine of 73 (81%) subjects completed the study, with a mean interval ± standard deviation of 6.9 months ± 1.0. The mean progression rates per year ± standard deviation of LRNC volume and percentage were -5.2 mm(3) ± 34.3 (P = .249) and -1.74% ± 6.27% (P = .038), respectively. Of the clinical and imaging variables examined, presence of intraplaque hemorrhage (IPH) was significantly associated with LRNC progression (P = .001). Plaques with IPH had increased LRNC volume per year (62.9 mm(3) ± 46.2 vs -8.8 mm(3) ± 29.9, P < .001) and percentage per year (3.67% ± 1.85% vs -2.03% ± 6.30%, P = .126) compared with those without IPH. Spearman correlation analysis showed that change in LRNC positively correlated with change in wall volume (ρ = 0.60, P < .001), but not with change in lumen volume (ρ = -0.17, P = .201).
Serial MR imaging of the carotid artery allowed observation of changes in LRNC over a short follow-up period and demonstrated the complexity of plaque progression patterns related to tissue composition. LRNC progression may be influenced not only by clinical characteristics, but also and to a large extent by plaque characteristics such as IPH.
[Show abstract][Hide abstract] ABSTRACT: Aim:
To assess whether the three-dimensional (3D) black-blood motion-sensitized driven equilibrium (MSDE) prepared rapid gradient-echo sequence (3D MERGE) magnetic resonance imaging (MRI) sequence is sensitive enough to detect differences in atherosclerotic plaque size and morphology occurring in the adductor canal and the proximal bifurcation segment.
Materials and methods:
Fifty pairs of adductor canal and bifurcation segments from 25 patients with intermittent claudication were examined using 3D MERGE. The two-dimensional (2D) transverse section showing the largest plaque burden in each segment was chosen for comparison. Wall and lumen boundaries were segmented from each 2D section and quantified using six metrics: wall area (WA), lumen area (LA), normalized wall index (NWI), maximum wall thickness (MaxWT), minimum wall thickness (MinWT), and eccentricity.
The mean LA in the adductor region was significantly lower than that in the bifurcation segment (p < 0.0001). Mean NWI, MaxWT, and eccentricity in the adductor region were significantly higher than those at bifurcation (p < 0.0001, p < 0.0021, and p < 0.0045, respectively). Mean WA and MinWT of the two segments did not show a statistically significant difference. WA in both regions was positively correlated with eccentricity (p < 0.0049 and p < 0.0049, respectively). LA was negatively correlated with eccentricity (p < 0.0017), and NWI was positively correlated with eccentricity only in the adductor region (p < 0.0004).
The results suggest that compensatory enlargement was limited in the adductor canal when compared to the proximal bifurcation segment. 3D MERGE, as a fast and non-invasive sequence, may assist the evaluation of femoral atherosclerosis by assessing the size and morphology of plaques, knowledge of which can guide clinical treatment.
[Show abstract][Hide abstract] ABSTRACT: Manifestations of atherosclerotic plaque in different arterial beds range from perfusion deficits to overt ischemia such as stroke and myocardial infarction. Atherosclerotic plaque composition is associated with its propensity to rupture and cause vascular events. Magnetic resonance (MR) imaging of atherosclerotic plaque using clinical 1.5 T scanners can detect plaque composition. Plaque MR imaging at higher field strengths offers both opportunities and challenges to improving the high spatial resolution and contrast required for this type of imaging. This article summarizes the technological requirements required for high-field plaque MR imaging and its application in detecting plaque components.
Neuroimaging Clinics of North America 05/2012; 22(2):271-84, xi. DOI:10.1016/j.nic.2012.02.011 · 1.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To evaluate the performance of automatic segmentation of atherosclerotic plaque components using solely multicontrast 3D gradient echo (GRE) magnetic resonance imaging (MRI).
A total of 15 patients with a history of recent transient ischemic attacks or stroke underwent carotid vessel wall imaging bilaterally with a combination of 2D turbo spin echo (TSE) sequences and 3D GRE sequences. The TSE sequences included T1-weighted, T2-weighted, and contrast-enhanced T1-weighted scans. The 3D GRE sequences included time-of-flight (TOF), magnetization-prepared rapid gradient echo (MP-RAGE), and motion-sensitized driven equilibrium prepared rapid gradient echo (MERGE) scans. From these images, the previously developed morphology-enhanced probabilistic plaque segmentation (MEPPS) algorithm was retrained based solely on the 3D GRE sequences to segment necrotic core (NC), calcification (CA), and loose matrix (LM). Segmentation performance was assessed using a leave-one-out cross-validation approach via comparing the new 3D-MEPPS algorithm to the original MEPPS algorithm that was based on the traditional multicontrast protocol including 2D TSE and TOF sequences.
Twenty arteries of 15 subjects were found to exhibit significant plaques within the coverage of all imaging sequences. For these arteries, between new and original MEPPS algorithms, the areas per slice exhibited correlation coefficients of 0.86 for NC, 0.99 for CA, and 0.80 for LM; no significant area bias was observed.
The combination of 3D imaging sequences (TOF, MP-RAGE, and MERGE) can provide sufficient contrast to distinguish NC, CA, and LM. Automatic segmentation using 3D sequences and traditional multicontrast protocol produced highly similar results.
Journal of Magnetic Resonance Imaging 04/2012; 35(4):812-9. DOI:10.1002/jmri.22886 · 3.21 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vessel wall imaging techniques have been introduced to assess the burden of peripheral arterial disease (PAD) in terms of vessel wall thickness, area or volume. Recent advances in a 3D black-blood MRI sequence known as the 3D motion-sensitized driven equilibrium (MSDE) prepared rapid gradient echo sequence (3D MERGE) have allowed the acquisition of vessel wall images with up to 50 cm coverage, facilitating noninvasive and detailed assessment of PAD. This work introduces an algorithm that combines 2D slice-based segmentation and 3D user editing to allow for efficient plaque burden analysis of the femoral artery images acquired using 3D MERGE.
The 2D slice-based segmentation approach is based on propagating segmentation results of contiguous 2D slices. The 3D image volume was then reformatted using the curved planar reformation (CPR) technique. User editing of the segmented contours was performed on the CPR views taken at different angles. The method was evaluated on six femoral artery images. Vessel wall thickness and area obtained before and after editing on the CPR views were assessed by comparison with manual segmentation. Difference between semiautomatically and manually segmented contours were compared with the difference of the corresponding measurements between two repeated manual segmentations.
The root-mean-square (RMS) errors of the mean wall thickness (t(mean)) and the wall area (WA) of the edited contours were 0.35 mm and 7.1 mm(2), respectively, which are close to the RMS difference between two repeated manual segmentations (RMSE: 0.33 mm in t(mean), 6.6 mm(2) in WA). The time required for the entire semiautomated segmentation process was only 1%-2% of the time required for manual segmentation.
The difference between the boundaries generated by the proposed algorithm and the manually segmented boundary is close to the difference between repeated manual segmentations. The proposed method provides accurate plaque burden measurements, while considerably reducing the analysis time compared to manual review.
Medical Physics 10/2011; 38(10):5370-84. DOI:10.1118/1.3633899 · 2.64 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Black-blood MRI is a promising tool for carotid atherosclerotic plaque burden assessment and compositional analysis. However, current sequences are limited by large slice thickness. Accuracy of measurement can be improved by moving to isotropic imaging but can be challenging for patient compliance due to long scan times. We present a fast isotropic high spatial resolution (0.7×0.7×0.7 mm3) three-dimensional black-blood sequence (3D-MERGE) covering the entire cervical carotid arteries within 2 min thus ensuring patient compliance and diagnostic image quality. The sequence is optimized for vessel wall imaging of the carotid bifurcation based on its signal properties. The optimized sequence is validated on patients with significant carotid plaque. Quantitative plaque morphology measurements and signal-to-noise ratio measures show that 3D-MERGE provides good blood suppression and comparable plaque burden measurements to existing MRI protocols. 3D-MERGE is a promising new tool for fast and accurate plaque burden assessment in patients with atherosclerotic plaque.
Magnetic Resonance in Medicine 03/2011; 65(3):627-37. DOI:10.1002/mrm.22642 · 3.57 Impact Factor