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Brain iron deposition after Ferumoxytol-enhanced MRI: A study of Porcine Brains.

ABSTRACT: Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered ferumoxytol nanoparticles are deposited in porcine brains. Methods: In an animal care and use committee-approved prospective case-control study, ten Göttingen minipigs received either intravenous ferumoxytol injections at a dose of 5 mg Fe/kg (n=4) or remained untreated (n=6). Nine to twelve months later, pigs were sacrificed and the brains of all pigs underwent ex vivo MRI at 7T with T2 and T2*-weighted sequences. MRI scans were evaluated by measuring R2* values (R2*=1000/T2*) of the bilateral caudate nucleus, lentiform nucleus, thalamus, dentate nucleus, and choroid plexus. Pig brains were sectioned and stained with Prussian blue and evaluated for iron deposition using a semiquantitative scoring system. Data of ferumoxytol exposed and unexposed groups were compared with an unpaired t-test and a Mann-Whitney U test. Results: T2 and T2* signal of the different brain regions was not visually different between ferumoxytol exposed and unexposed controls. There were no significant differences in R2* values of the different brain regions in the ferumoxytol exposed group compared to controls (p>0.05). Prussian blue stains of the same brain regions, scored according to a semiquantitative score, were not significantly different either between the ferumoxytol exposed group and unexposed controls (p>0.05). Conclusions: Our study shows that intravenous ferumoxytol doses of 5-10 mg Fe/kg do not lead to iron deposition in the brain of pigs. We suggest iron oxide nanoparticles as a promising alternative for gadolinium-enhanced MRI.

SUBMITTER: Theruvath AJ

PROVIDER: S-EPMC7332795 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Brain iron deposition after Ferumoxytol-enhanced MRI: A study of Porcine Brains.

Theruvath Ashok Joseph AJ Aghighi Maryam M Iv Michael M Nejadnik Hossein H Lavezo Jonathan J Pisani Laura Jean LJ Daldrup-Link Heike Elisabeth HE

Nanotheranostics 20200618 4

Recent evidence of gadolinium deposition in the brain has raised safety concerns. Iron oxide nanoparticles are re-emerging as promising alternative MR contrast agents, because the iron core can be metabolized. However, long-term follow up studies of the brain after intravenous iron oxide administration have not been reported thus far. In this study, we investigated, if intravenously administered ferumoxytol nanoparticles are deposited in porcine brains. <b>Methods:</b> In an animal care and use ...[more]

PMID: 32637297

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Project description:Purpose To investigate ferumoxytol-enhanced MRI as a noninvasive imaging biomarker of macrophages in adults with high-grade gliomas. Materials and Methods In this prospective study, adults with high-grade gliomas were enrolled between July 2015 and July 2017. Each participant was administered intravenous ferumoxytol (5 mg/kg) and underwent 3.0-T MRI 24 hours later. Two sites in each tumor were selected for intraoperative sampling on the basis of the degree of ferumoxytol-induced signal change. Susceptibility and the relaxation rates R2* (1/T2*) and R2 (1/T2) were obtained by region-of-interest analysis by using the respective postprocessed maps. Each sample was stained with Prussian blue, CD68, CD163, and glial fibrillary acidic protein. Pearson correlation and linear mixed models were performed to assess the relationship between imaging measurements and number of 400× magnification high-power fields with iron-containing macrophages. Results Ten adults (four male participants [mean age, 65 years ± 9 {standard deviation}; age range, 57-74 years] and six female participants [mean age, 53 years ± 12 years; age range, 32-65 years]; mean age of all participants, 58 years ± 12 [age range, 32-74 years]) with high-grade gliomas were included. Significant positive correlations were found between susceptibility, R2*, and R2' and the number of high-power fields with CD163-positive (r range, 0.64-0.71; P < .01) and CD68-positive (r range, 0.55-0.57; P value range, .01-.02) iron-containing macrophages. No significant correlation was found between R2 and CD163-positive (r = 0.33; P = .16) and CD68-positive (r = 0.24; P = .32) iron-containing macrophages. Similar significance results were obtained with linear mixed models. At histopathologic analysis, iron particles were found only in macrophages; none was found in glial fibrillary acidic protein-positive tumor cells. Conclusion MRI measurements of susceptibility, R2*, and R2' (R2* - R2) obtained after ferumoxytol administration correlate with iron-containing macrophage concentration, and this shows their potential as quantitative imaging markers of macrophages in malignant gliomas. © RSNA, 2018 Online supplemental material is available for this article.

Project description:PurposeTo assess the feasibility of ferumoxytol-enhanced anesthesia-free cardiac MRI in neonates and young infants for complex congenital heart disease (CHD).Materials and methodsWith Institutional Review Board approval, 21 consecutive neonates and young infants (1 day to 11 weeks old; median age of 3 days) who underwent a rapid two-sequence (MR angiography [MRA] and four-dimensional [4D] flow) MRI protocol with intravenous ferumoxytol without sedation (n = 17) or light sedation (n = 4) at 3 Tesla (T) (except one case at 1.5T) between June 2014 and February 2016 were retrospectively identified. Medical records were reviewed for indication, any complications, if further diagnostic imaging was performed after MRI, and surgical findings. Two radiologists scored the images in two sessions on a 5-point scale for overall image quality and delineation of various anatomical structures. Confidence interval of proportions for likelihood of requiring additional diagnostic imaging after MRI was determined. For the possibility of reducing the protocol to a single rapid sequence, Wilcoxon-rank sum test was used to assess whether 4D flow and MRA significantly differed in anatomical delineation.ResultsOne of 21 patients (4.8%, 80% confidence interval 0-11%) required additional imaging, a computed tomography angiography to assess lung parenchyma and peripheral pulmonary arteries. Only 1 of 13 patients (7.7%) with operative confirmation had a minor discrepancy between radiology and operative reports (80% confidence interval 0-17%). 4D flow was significantly superior to MRA (P < 0.05) for the evaluation of systemic arteries, valves, ventricular trabeculae, and overall quality. Using Cohen's kappa coefficient, there was good interobserver agreement for the evaluation of systemic arteries by 4D flow (κ = 0.782), and systemic veins and pulmonary arteries by MRA (κ > 0.6). Overall 4D flow measurements (mean κ = 0.64-0.74) had better internal agreement compared with MRA (mean κ = 0.30-0.64).ConclusionFerumoxytol-enhanced cardiac MRI, without anesthesia, is feasible for the evaluation of complex CHD in neonates and young infants, with a low likelihood of need for additional diagnostic studies. The decreased risk by avoiding anesthesia must be balanced against the potential for adverse reactions with ferumoxytol.Level of evidence2 J. MAGN. RESON. IMAGING 2017;45:1407-1418.

Project description:Mapping the vascular organization of the brain is of great importance across various domains of basic neuroimaging research, diagnostic radiology, and neurology. However, the intricate task of precisely mapping vasculature across brain regions and cortical layers presents formidable challenges, resulting in a limited understanding of neurometabolic factors influencing the brain's microvasculature. Addressing this gap, our study investigates whole-brain vascular volume using ferumoxytol-weighted laminar-resolution multi-echo gradient-echo imaging in macaque monkeys. We validate the results with published data for vascular densities and compare them with cytoarchitecture, neuron and synaptic densities. The ferumoxytol-induced change in transverse relaxation rate (ΔR2*), an indirect proxy measure of cerebral blood volume (CBV), was mapped onto twelve equivolumetric laminar cortical surfaces. Our findings reveal that CBV varies 3-fold across the brain, with the highest vascular volume observed in the inferior colliculus and lowest in the corpus callosum. In the cerebral cortex, CBV is notably high in early primary sensory areas and low in association areas responsible for higher cognitive functions. Classification of CBV into distinct groups unveils extensive replication of translaminar vascular network motifs, suggesting distinct computational energy supply requirements in areas with varying cytoarchitecture types. Regionally, baseline R2* and CBV exhibit positive correlations with neuron density and negative correlations with receptor densities. Adjusting image resolution based on the critical sampling frequency of penetrating cortical vessels, allows us to delineate approximately 30% of the arterial-venous vessels. Collectively, these results mark significant methodological and conceptual advancements, contributing to the refinement of cerebrovascular MRI. Furthermore, our study establishes a linkage between neurometabolic factors and the vascular network architecture in the primate brain.

Dataset Information

Brain iron deposition after Ferumoxytol-enhanced MRI: A study of Porcine Brains.

Publications

Brain iron deposition after Ferumoxytol-enhanced MRI: A study of Porcine Brains.

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