Dataset Information

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.

ABSTRACT:

Background

Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems.

Methods

Twenty volunteers were recruited: 10 imaged each at 1.5 T and 3 T. T2* and late gadolinium enhanced (LGE) MRI was conducted at baseline with further T2* imaging conducted approximately 24 h after USPIO infusion (ferumoxytol, 4 mg/kg). Regions of interest were selected in the myocardium and compared to other tissues.

Results

Following administration, USPIO was detected by changes in R2* from baseline (1/T2*) at 24 h in myocardium, skeletal muscle, kidney, liver, spleen and blood at 1.5 T, and myocardium, kidney, liver, spleen, blood and bone at 3 T (p < 0.05 for all). Myocardial changes in R2* due to USPIO were 26.5 ± 7.3 s-1 at 1.5 T, and 37.2 ± 9.6 s-1 at 3 T (p < 0.0001 for both). Tissues showing greatest ferumoxytol enhancement were the reticuloendothelial system: the liver, spleen and bone marrow (216.3 ± 32.6 s-1, 336.3 ± 60.3 s-1, 69.9 ± 79.9 s-1; p < 0.0001, p < 0.0001, p = ns respectively at 1.5 T, and 275.6 ± 69.9 s-1, 463.9 ± 136.7 s-1, 417.9 ± 370.3 s-1; p < 0.0001, p < 0.0001, p < 0.01 respectively at 3 T).

Conclusion

Ferumoxytol-enhanced MRI is feasible at both 1.5 T and 3 T. Careful data selection and dose administration, along with refinements to echo-time acquisition, post-processing and analysis techniques are essential to ensure reliable and robust quantification of tissue enhancement.

Trial registration

ClinicalTrials.gov Identifier - NCT02319278 . Registered 03.12.2014.

SUBMITTER: Stirrat CG

PROVIDER: S-EPMC4964058 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Publications

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.

Stirrat Colin G CG Alam Shirjel R SR MacGillivray Thomas J TJ Gray Calum D CD Forsythe Rachael R Dweck Marc R MR Payne John R JR Prasad Sanjay K SK Petrie Mark C MC Gardner Roy S RS Mirsadraee Saeed S Henriksen Peter A PA Newby David E DE Semple Scott I K SI

Journal of cardiovascular magnetic resonance : official journal of the Society for Cardiovascular Magnetic Resonance 20160727 1

<h4>Background</h4>Ultrasmall superparamagnetic particles of iron oxide (USPIO)-enhanced magnetic resonance imaging (MRI) can detect tissue-resident macrophage activity and identify cellular inflammation. Clinical studies using this technique are now emerging. We aimed to report a range of normal R2* values at 1.5 and 3 T in the myocardium and other tissues following ferumoxytol administration, outline the methodology used and suggest solutions to commonly encountered analysis problems.<h4>Metho ...[more]

PMID: 27465647

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Project description:BackgroundBright-blood and black-blood cardiovascular magnetic resonance (CMR) techniques are frequently employed together during a clinical exam because of their complementary features. While valuable, existing black-blood CMR approaches are flow dependent and prone to failure. We aim to assess the effectiveness and reliability of ferumoxytol enhanced (FE) Half-Fourier Single-shot Turbo Spin-echo (HASTE) imaging without magnetization preparation pulses to yield uniform intra-luminal blood signal suppression by comparing FE-HASTE with pre-ferumoxytol HASTE imaging.MethodsThis study was IRB-approved and HIPAA compliant. Consecutive patients who were referred for FE-CMR between June 2013 and February 2017 were enrolled. Qualitative image scores reflecting the degree and reliability of blood signal suppression were based on a 3-point Likert scale, with 3 reflecting perfect suppression. For quantitative evaluation, homogeneity indices (defined as standard deviation of the left atrial signal intensity) and signal-to-noise ratios (SNR) for vascular lumens and cardiac chambers were measured.ResultsOf the 340 unique patients who underwent FE-CMR, HASTE was performed in 257. Ninety-three patients had both pre-ferumoxytol HASTE and FE-HASTE, and were included in this analysis. Qualitative image scores reflecting the degree and reliability of blood signal suppression were significantly higher for FE-HASTE images (2.9 [IQR 2.8-3.0] vs 1.8 [IQR 1.6-2.1], p < 0.001). Inter-reader agreement was moderate (k = 0.50, 95% CI 0.45-0.55). Blood signal suppression was more complete on FE-HASTE images than on pre-ferumoxytol HASTE, as indicated by lower mean homogeneity indices (24.5 [IQR 18.0-32.8] vs 108.0 [IQR 65.0-170.4], p < 0.001) and lower blood pool SNR for all regions (5.6 [IQR 3.2-10.0] vs 21.5 [IQR 12.5-39.4], p < 0.001).ConclusionFE-HASTE black-blood imaging offers an effective, reliable, and simple approach for flow independent blood signal suppression. The technique holds promise as a fast and routine complement to bright-blood cardiovascular imaging with ferumoxytol.

Project description:Fractional myocardial blood volume (fMBV) estimated using ferumoxytol-enhanced magnetic resonance imaging (MRI) (FE-MRI) has the potential to capture a hemodynamic response to myocardial hypoperfusion during contrast steady state without reliance on gadolinium chelates. Ferumoxytol has a long intravascular half-life and its use for steady-state MRI is off-label. The aim of this prospective study was to optimize and evaluate a two-compartment model for estimation of fMBV based on FE-MRI. Nine healthy swine and one swine with artificially induced single-vessel coronary stenosis underwent MRI on a 3.0 T clinical magnet. Myocardial longitudinal spin-lattice relaxation rate (R1) was measured using the 5(3)3(3)3 modified Look-Locker inversion recovery (MOLLI) sequence before and at contrast steady state following seven ferumoxytol infusions (0.125-4.0 mg/kg). fMBV and water exchange were estimated using a two-compartment model. Model-fitted fMBV was compared to simple fast-exchange fMBV approximation and percent change in pre- and postferumoxytol R1. Dose undersampling schemes were investigated to reduce acquisition duration. Variation in fMBV was assessed using one-way analysis of variance. Fast-exchange fMBV and ferumoxytol dose undersampling were evaluated using Bland-Altman analysis. Healthy normal swine showed a mean mid-ventricular fMBV of 7.2 ± 1.4% and water exchange rate of 11.3 ± 5.1 s-1 . There was intersubject variation in fMBV (p < 0.05) without segmental variation (p = 0.387). fMBV derived from eight-dose and four-dose sampling schemes had no significant bias (mean difference = 0.07, p = 0.541, limits of agreement -1.04% [-1.45, -0.62%] to 1.18% [0.77, 1.59%]). Pixel-wise fMBV in one swine model with coronary artery stenosis showed elevated fMBV in ischemic segments (apical anterior: 11.90 ± 4.00%, apical septum: 16.10 ± 5.71%) relative to remote segments (apical inferior: 9.59 ± 3.35%, apical lateral: 9.38 ± 2.35%). A two-compartment model based on FE-MRI using the MOLLI sequence may enable estimation of fMBV in studies of ischemic heart disease. LEVEL OF EVIDENCE: 2. TECHNICAL EFFICACY STAGE: 2.

Project description:Myocardial T1 reactivity, defined as the relative change in T1 between rest and vasodilator-induced stress, has been proposed as a magnetic resonance imaging (MRI) biomarker of tissue perfusion. We hypothesize that the superparamagnetic iron-oxide nanoparticle, ferumoxytol, sensitizes T1 to changes in the intramyocardial vascular compartment and improves the sensitivity and specificity of T1 reactivity as an imaging biomarker of tissue perfusion. We aim to assess the diagnostic performance of ferumoxytol-enhanced (FE) myocardial T1 reactivity in swine models of myocardial hypoperfusion. We induced acute myocardial hypoperfusion in 13 swine via percutaneous, transcatheter deployment of a 3D printed intracoronary stenosis implant into the left anterior descending coronary artery. We performed native and FE adenosine stress testing using 5(3)3(3)3 MOLLI and SASHA T1 mapping sequences with bSSFP readout on a clinical 3.0 T magnet. MOLLI T1 maps were fitted using both the conventional MOLLI and the Instantaneous Signal Loss (InSiL) T1-fitting algorithms. Regardless of the MOLLI or SASHA pulse sequence or T1-fitting algorithm, ferumoxytol contrast increased the dynamic range of T1 reactivity in both the remote and ischemic myocardial regions. Relative to remote myocardium, native and FE T1 reactivity were blunted in ischemic myocardium (p < 0.05) with InSiL-MOLLI, MOLLI and SASHA. An InSiL-MOLLI-derived FE T1 reactivity threshold of -4.65% had 73.3% sensitivity and 96.2% specificity for prediction of regional wall motion abnormalities (AUC 0.915, 95% CI 0.786-0.979), whereas a SASHA-derived FE T1 reactivity threshold of -5.25% had 75.0% sensitivity and 95.2% specificity (AUC 0.905, 95% CI 0.751-0.979). Ferumoxytol significantly increased the dynamic range of T1 reactivity as a measure of myocardial hypoperfusion in vasodilator stress T1 mapping studies. FE T1 reactivity maps can be used to quantitatively distinguish ischemic and remote myocardium with high specificity in swine models of acute myocardial hypoperfusion.

Dataset Information

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.

Background

Methods

Results

Conclusion

Trial registration

Publications

Ferumoxytol-enhanced magnetic resonance imaging methodology and normal values at 1.5 and 3T.

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