Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction

Stirrat, Colin; Alam, Shirjel; MacGillivray, Tom; Gray, Calum; Dweck, Marc R; Raftis, Jennifer; Jenkins, William; Wallace, William; Pessotto, Renzo; Lim, Ki-Dong; Mirsadraee, Saeed; Henriksen, Peter; Semple, Scott; Newby, David E.

doi:10.1136/heartjnl-2016-311018

Cited by 46 publications

(48 citation statements)

References 21 publications

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“…Inflammation appears to peak at 2-3 days and dissipate by week 2, as suggested by a second study of 31 patients undergoing serial ferumoxytol-enhanced MRI. 58 The presence of macrophages engulfing SPIONs in the infarct zone was confirmed by histology. Additional studies that include histological confirmation and outcome correlation (e.g., changes in left ventricular function, development of heart failure, death) are needed to determine whether in vivo monitoring of inflammation and its modulation will be clinically valuable.…”

Section: Introductionmentioning

confidence: 87%

Molecular Imaging of Inflammation in Ischemic Heart Disease

Bakerman

Wardak

Nguyen

2018

Curr Cardiovasc Imaging Rep

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Purpose of Review Ischemic heart disease is caused by atherosclerosis, the build-up of plaque in the coronary arteries, which can lead to the development of heart attacks and heart muscle damage. Despite the advent of medical and surgical therapy to prevent and treat atherosclerosis and its adverse clinical effects, ischemic heart disease remains a leading cause of morbidity and mortality. Recent studies have suggested that the immune system may play a greater role in the development of plaque rupture and adverse left ventricular remodeling after myocardial infarction. Understanding the molecular processes by which inflammation contributes to the pathophysiology of ischemic heart disease is, therefore, worthwhile. This review focuses on new molecular imaging techniques to visualize immune cells to study their contribution to ischemic heart disease. Recent Findings A common technique applied to imaging inflammation in ischemic heart disease is targeting the up-regulation and trafficking of immune cells, which may contribute to the adverse consequences associated with atherosclerosis. In the past five years, advances in cell labeling for imaging with PET and MRI, including radioisotopes and nanoparticles, have confirmed that inflammatory cells can be visualized in vivo and in greater abundance in unstable cardiovascular disease and in areas of ischemic damage. The major criticisms of these studies to date include their small sample size, lack of histological correlation, limited association with long-term outcomes, and bias toward macrophage imaging. Summary While much progress has been made in imaging inflammation in ischemic heart disease over the past five years, additional studies in larger cohorts with histological validation and outcome correlation are needed. Nevertheless, imaging inflammation using PET or MRI has the potential to become an important adjunct tool to improve the diagnosis, risk stratification, and therapeutic monitoring of patients with ischemic heart disease.

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Section: Introductionmentioning

confidence: 87%

Molecular Imaging of Inflammation in Ischemic Heart Disease

Bakerman

Wardak

Nguyen

2018

Curr Cardiovasc Imaging Rep

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“…Thus, high SNR may need to be achieved to provide accurate R2* and B0 field estimations at high ferumoxytol concentrations, especially in macrophages of the reticuloendothelial system (eg, liver, spleen, bone marrow) where iron deposition can remain high after ferumoxytol injection . In macrophages outside the reticuloendothelial system in inflammation response, however, moderate iron concentrations have been observed that can be detectable with current CSE‐MRI techniques . Thus, the dynamic range of the iron concentration at macrophage homing sites of inflammation at the maternal–fetal interface is expected to be moderate, although the exact range is still unknown (and is under current investigation in our ongoing projects).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of a motion‐robust 2D chemical shift‐encoded technique for R2* and field map quantification in ferumoxytol‐enhanced MRI of the placenta in pregnant rhesus macaques

Zhu

Reeder

Johnson

et al. 2019

Magnetic Resonance Imaging

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Background 3D chemical shift‐encoded (CSE)‐MRI techniques enable assessment of ferumoxytol concentration but are unreliable in the presence of motion. Purpose To evaluate a motion‐robust 2D‐sequential CSE‐MRI for R2* and B0 mapping in ferumoxytol‐enhanced MRI of the placenta. Study Type Prospective. Animal Model Pregnant rhesus macaques. Field Strength/Sequence 3.0T/CSE‐MRI. Assessment 2D‐sequential CSE‐MRI was compared with 3D respiratory‐gated CSE‐MRI in placental imaging of 11 anesthetized animals at multiple timepoints before and after ferumoxytol administration, and in ferumoxytol phantoms (0 μg/mL–440 μg/mL). Motion artifacts of CSE‐MRI in 10 pregnant women without ferumoxytol administration were assessed retrospectively by three blinded readers (4‐point Likert scale). The repeatability of CSE‐MRI in seven pregnant women was also prospectively studied. Statistical Tests Placental R2* and boundary B0 field measurements (ΔB0) were compared between 2D‐sequential and 3D respiratory‐gated CSE‐MRI using linear regression and Bland–Altman analysis. Results In phantoms, a slope of 0.94 (r2 = 0.99, concordance correlation coefficient ρ = 0.99), and bias of –4.8 s‐1 (limit of agreement [LOA], –41.4 s‐1, +31.8 s‐1) in R2*, and a slope of 1.07 (r2 = 1.00, ρ = 0.99) and bias of 11.4 Hz (LOA –12.0 Hz, +34.8 Hz) in ΔB0 were obtained in 2D CSE‐MRI compared with 3D CSE‐MRI for reference R2* ≤390 s‐1. In animals, a slope of 0.92 (r2 = 0.97, ρ = 0.98) and bias of –2.2 s‐1 (LOA –55.6 s‐1, +51.3 s‐1) in R2*, and a slope of 1.05 (r2 = 0.95, ρ = 0.97) and bias of 0.4 Hz (LOA –9.0 Hz, +9.7 Hz) in ΔB0 were obtained. In humans, motion‐impaired R2* maps in 3D CSE‐MRI (Reader 1: 1.8 ± 0.6, Reader 2: 1.3 ± 0.7, Reader 3: 1.9 ± 0.6), while 2D CSE‐MRI was motion‐free (Reader 1: 2.9 ± 0.3, Reader 2: 3.0 ± 0, Reader 3: 3.0 ± 0). A mean difference of 0.66 s‐1 and coefficient of repeatability of 9.48 s‐1 for placental R2* were observed in the repeated 2D CSE‐MRI. Data Conclusion 2D‐sequential CSE‐MRI provides accurate R2* and B0 measurements in ferumoxytol‐enhanced placental MRI of animals in the presence of respiratory motion, and motion‐robustness in human placental imaging. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2020;51:580–592.

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“…11 Moreover, it has been shown that USPIO accumulation can describe the cellular myocardial inflammatory response following acute myocardial infarction. [17][18][19] Indeed, we have described the early time course of macrophage-mediated inflammation that occurs in the first 2 weeks following an acute myocardial infarction. 18 For this reason, USPIO-enhanced MRI can be used to temporally track tissue inflammation and describe the natural history of disease progression.…”

Section: Chapter 1 Introductionmentioning

confidence: 99%

Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study

et al. 2018

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Background Abdominal aortic aneurysm (AAA) rupture is a common cause of sudden death. Pre-emptive elective surgical repair can prevent aneurysm rupture and be life-saving. Ultrasmall superparamagnetic particles of iron oxide (USPIO) detect cellular inflammation using magnetic resonance imaging (MRI) in patients with AAAs. For this reason, USPIO-enhanced MRI represents a promising new technique that could improve risk prediction and better guide surgical intervention. Objectives To assess whether or not USPIO-enhanced MRI can predict aneurysm growth rates and clinical outcomes in patients with AAAs. Design A prospective multicentre open-label observational cohort study. Setting Three secondary and tertiary care hospitals in Scotland. Participants Patients (n = 342) aged > 40 years with a maximum anteroposterior AAA diameter of ≥ 40 mm confirmed by abdominal ultrasonography, and under ultrasonographic surveillance as part of routine clinical care. Interventions USPIO-enhanced MRI of AAA. Main outcome measures The primary end point was the composite of aneurysm rupture or repair. Secondary outcomes included rate of aneurysm growth, all-cause mortality and aneurysm-related mortality. Results Participants (85% male, aged 73.1 ± 7.2 years) had a baseline aneurysm diameter of 49.6 ± 7.7 mm, and USPIO enhancement was identified in 146 participants (42.7%), absent in 191 participants (55.8%) and indeterminate in 5 participants (1.5%). During follow-up (1005 ± 280 days), there were 17 AAA ruptures (5.0%), 126 AAA repairs (36.8%) and 48 deaths (14.0%). Compared with those without uptake, patients with USPIO enhancement have increased rates of aneurysm expansion (3.1 ± 2.5 vs. 2.5 ± 2.4 mm/year; p = 0.0424), although this was not independent of current smoking habits (p = 0.1993). The primary end point (aneurysm rupture or repair) occurred more frequently in participants with USPIO enhancement [69/146 (47.3%) vs. 68/191 (35.6%), difference 11.7%, 95% confidence interval 1.1% to 22.2%; p = 0.0308]: this was similar for each component of rupture (6.8% vs. 3.7%; p = 0.1857) or repair (41.8% vs. 32.5%; p = 0.0782). USPIO enhancement was associated with reduced event-free survival for aneurysm rupture or repair (p = 0.0275). Baseline AAA diameter (p < 0.0001) and current smoking habits (p = 0.0446) also predicted the primary outcome, and the addition of USPIO enhancement to the multivariate model did not improve event prediction (c-statistic 0.7935 to 0.7936). Conclusions USPIO-enhanced MRI is a novel approach to the identification of aortic wall cellular inflammation in patients with AAAs, and predicts the rate of aneurysm growth and clinical outcome. USPIO-enhanced MRI does not provide independent prediction of aneurysm expansion or clinical outcomes in a model incorporating known clinical risk factors. Larger trials are now needed to explore the prediction of emergent aneurysm events to establish the added benefit of USPIO-enhanced MRI. Comparative outcome studies should determine whether or not using other imaging biomarkers that track alternative disease processes have better predictive capability than USPIO-enhanced MRI. Trial registration Current Controlled Trials ISRCTN76413758. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

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Ferumoxytol-enhanced magnetic resonance imaging assessing inflammation after myocardial infarction

Cited by 46 publications

References 21 publications

Molecular Imaging of Inflammation in Ischemic Heart Disease

Molecular Imaging of Inflammation in Ischemic Heart Disease

Evaluation of a motion‐robust 2D chemical shift‐encoded technique for R2* and field map quantification in ferumoxytol‐enhanced MRI of the placenta in pregnant rhesus macaques

Magnetic resonance imaging using ultrasmall superparamagnetic particles of iron oxide for abdominal aortic aneurysm: a risk prediction study

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