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Immobilization of iron oxide magnetic nanoparticles for enhancement of vessel wall magnetic resonance imaging--an ex vivo feasibility study.

ABSTRACT: Emerging data supports a role for negative wall remodeling in the failure of vascular interventions such as vein grafts, yet clinicians/researchers currently lack the ability to temporally/efficiently investigate adventitial surface topography/total vascular wall anatomy in vivo. We established a strategy of immobilizing commercially available iron oxide magnetic nanoparticles (Fe-NPs) onto the surface of human vein conduits to facilitate high-throughput total vascular wall demarcation with magnetic resonance (MR). Binding of activated Fe-NPs to amine groups on the surface of the veins induced a thin layer of negative contrast that differentiated the adventitia from surrounding saline signal in all MR images, enabling delineation of total wall anatomy; this was not possible in simultaneously imaged unlabeled control veins. Under the conditions of this ex vivo experiment, stable covalent binding of Fe-NPs can be achieved (dose-dependent) on human vein surface for MR detection, suggesting a potential strategy for enhancing the ability of MRI to investigate total wall adaptation and remodeling in vein graft failure.

SUBMITTER: Nguyen BT

PROVIDER: S-EPMC2923466 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Immobilization of iron oxide magnetic nanoparticles for enhancement of vessel wall magnetic resonance imaging--an ex vivo feasibility study.

Nguyen Binh Thai BT Vemula Praveen Kumar PK Mitsouras Dimitrios D Yu Peng P Tao Ming M Campagna Christina C Mulkern Robert V RV Rybicki Frank J FJ Karp Jeffrey M JM Ozaki C Keith CK

Bioconjugate chemistry 20100801 8

Emerging data supports a role for negative wall remodeling in the failure of vascular interventions such as vein grafts, yet clinicians/researchers currently lack the ability to temporally/efficiently investigate adventitial surface topography/total vascular wall anatomy in vivo. We established a strategy of immobilizing commercially available iron oxide magnetic nanoparticles (Fe-NPs) onto the surface of human vein conduits to facilitate high-throughput total vascular wall demarcation with magn ...[more]

PMID: 20608720

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Project description:Background and purposeIntracranial atherosclerotic disease is a common cause of stroke worldwide. Intracranial vessel wall magnetic resonance imaging may be able to identify imaging biomarkers of symptomatic plaque. We performed a meta-analysis to evaluate the strength of association of imaging features of symptomatic plaque leading to downstream ischemic events. Effects on the strength of association were also assessed accounting for possible sources of bias and variability related to study design and magnetic resonance parameters.MethodsPubMed, Scopus, Web of Science, EMBASE, and Cochrane databases were searched up to October 2019. Two independent reviewers extracted data on study design, vessel wall magnetic resonance imaging techniques, and imaging end points. Per-lesion odds ratios (OR) were calculated and pooled using a bivariate random-effects model. Subgroup analyses, sensitivity analysis, and evaluation of publication bias were also performed.ResultsTwenty-one articles met inclusion criteria (1750 lesions; 1542 subjects). Plaque enhancement (OR, 7.42 [95% CI, 3.35-16.43]), positive remodeling (OR, 5.60 [95% CI, 2.23-14.03]), T1 hyperintensity (OR, 2.05 [95% CI, 1.27-3.32]), and surface irregularity (OR, 4.50 [95% CI, 1.39-8.57]) were significantly associated with downstream ischemic events. T2 signal intensity was not significant (P=0.59). Plaque enhancement was significantly associated with downstream ischemic events in all subgroup analyses and showed stronger associations when measured in retrospectively designed studies (P=0.02), by a radiologist as a rater (P<0.001), and on lower vessel wall magnetic resonance imaging spatial resolution sequences (P=0.02).ConclusionsPlaque enhancement, positive remodeling, T1 hyperintensity, and surface irregularity emerged as strong imaging biomarkers of symptomatic plaque in patients with ischemic events. Plaque enhancement remained significant accounting for sources of bias and variability in both study design and instrument. Future studies evaluating plaque enhancement as a predictive marker for stroke recurrence with larger sample sizes would be valuable.

Project description:BACKGROUND AND PURPOSE:Our goal is to determine the added value of intracranial vessel wall magnetic resonance imaging (IVWI) in differentiating nonocclusive vasculopathies compared with luminal imaging alone. METHODS:We retrospectively reviewed images from patients with both luminal and IVWI to identify cases with clinically defined intracranial vasculopathies: atherosclerosis (intracranial atherosclerotic disease), reversible cerebral vasoconstriction syndrome, and inflammatory vasculopathy. Two neuroradiologists blinded to clinical data reviewed the luminal imaging of defined luminal stenoses/irregularities and evaluated the pattern of involvement to make a presumed diagnosis with diagnostic confidence. Six weeks later, the 2 raters rereviewed the luminal imaging in addition to IVWI for the pattern of wall involvement, presence and pattern of postcontrast enhancement, and presumed diagnosis and confidence. Analysis was performed on per-lesion and per-patient bases. RESULTS:Thirty intracranial atherosclerotic disease, 12 inflammatory vasculopathies, and 12 reversible cerebral vasoconstriction syndrome patients with 201 lesions (90 intracranial atherosclerotic disease, 64 reversible cerebral vasoconstriction syndrome, and 47 inflammatory vasculopathy lesions) were included. For both per-lesion and per-patient analyses, there was significant diagnostic accuracy improvement with luminal imaging+IVWI when compared with luminal imaging alone (per-lesion: 88.8% versus 36.1%; P<0.001 and per-patient: 96.3% versus 43.5%; P<0.001, respectively). There was substantial interrater diagnostic agreement for luminal imaging+IVWI (?=0.72) and only slight agreement for luminal imaging (?=0.04). Although there was a significant correlation for both luminal and IVWI pattern of wall involvement with diagnosis, there was a stronger correlation for IVWI finding of lesion eccentricity and intracranial atherosclerotic disease diagnosis than for luminal imaging (?=0.69 versus 0.18; P<0.001). CONCLUSIONS:IVWI can significantly improve the differentiation of nonocclusive intracranial vasculopathies when combined with traditional luminal imaging modalities.

Project description:BACKGROUND:One of the potentially important applications of three-dimensional (3D) intracranial vessel wall (IVW) cardiovascular magnetic resonance (CMR) is to monitor disease progression and regression via quantitative measurement of IVW morphology during medical management or drug development. However, a prerequisite for this application is to validate that IVW morphologic measurements based on the modality are reliable. In this study we performed comprehensive reliability analysis for the recently proposed whole-brain IVW CMR technique. METHODS:Thirty-four healthy subjects and 10 patients with known intracranial atherosclerotic disease underwent repeat whole-brain IVW CMR scans. In 19 of the 34 subjects, two-dimensional (2D) turbo spin-echo (TSE) scan was performed to serve as a reference for the assessment of vessel dimensions. Lumen and wall volume, normalized wall index, mean and maximum wall thickness were measured in both 3D and 2D IVW CMR images. Scan-rescan, intra-observer, and inter-observer reproducibility of 3D IVW CMR in the quantification of IVW or plaque dimensions were respectively assessed in volunteers and patients as well as for different healthy subjectsub-groups (i.e. < 50 and ≥ 50 years). The agreement in vessel wall and lumen measurements between the 3D technique and the 2D TSE method was also investigated. In addition, the sample size required for future longitudinal clinical studies was calculated. RESULTS:The intra-class correlation coefficient (ICC) and Bland-Altman plots indicated excellent reproducibility and inter-method agreement for all morphologic measurements (All ICCs > 0.75). In addition, all ICCs of patients were equal to or higher than that of healthy subjects except maximum wall thickness. In volunteers, all ICCs of the age group of ≥50 years were equal to or higher than that of the age group of < 50 years. Normalized wall index and mean and maximum wall thickness were significantly larger in the age group of ≥50 years. To detect 5% - 20% difference between placebo and treatment groups, normalized wall index requires the smallest sample size while lumen volume requires the highest sample size. CONCLUSIONS:Whole-brain 3D IVW CMR is a reliable imaging method for the quantification of intracranial vessel dimensions and could potentially be useful for monitoring plaque progression and regression.

Project description:BackgroundIron oxide nanoparticles (IONs) are a promising nanoplatform for contrast-enhanced MRI. Recently, magnetic particle imaging (MPI) was introduced as a new imaging modality, which is able to directly visualize magnetic particles and could serve as a more sensitive and quantitative alternative to MRI. However, MPI requires magnetic particles with specific magnetic properties for optimal use. Current commercially available iron oxide formulations perform suboptimal in MPI, which is triggering research into optimized synthesis strategies. Most synthesis procedures aim at size control of iron oxide nanoparticles rather than control over the magnetic properties. In this study, we report on the synthesis, characterization and application of a novel ION platform for sensitive MPI and MRI.Methods and resultsIONs were synthesized using a thermal-decomposition method and subsequently phase-transferred by encapsulation into lipidic micelles (ION-Micelles). Next, the material and magnetic properties of the ION-Micelles were analyzed. Most notably, vibrating sample magnetometry measurements showed that the effective magnetic core size of the IONs is 16 nm. In addition, magnetic particle spectrometry (MPS) measurements were performed. MPS is essentially zero-dimensional MPI and therefore allows to probe the potential of iron oxide formulations for MPI. ION-Micelles induced up to 200 times higher signal in MPS measurements than commercially available iron oxide formulations (Endorem, Resovist and Sinerem) and thus likely allow for significantly more sensitive MPI. In addition, the potential of the ION-Micelle platform for molecular MPI and MRI was showcased by MPS and MRI measurements of fibrin-binding peptide functionalized ION-Micelles (FibPep-ION-Micelles) bound to blood clots.ConclusionsThe presented data underlines the potential of the ION-Micelle nanoplatform for sensitive (molecular) MPI and warrants further investigation of the FibPep-ION-Micelle platform for in vivo, non-invasive imaging of fibrin in preclinical disease models of thrombus-related pathologies and atherosclerosis.

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Immobilization of iron oxide magnetic nanoparticles for enhancement of vessel wall magnetic resonance imaging--an ex vivo feasibility study.

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Immobilization of iron oxide magnetic nanoparticles for enhancement of vessel wall magnetic resonance imaging--an ex vivo feasibility study.

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