Ferumoxytol‐enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion

Colbert, Caroline M; Le, Anna H; Shao, Jiaxin; Currier, Jesse W.; Ajijola, Olujimi A.; Hu, Peng; Nguyen, Kim‐Lien

doi:10.1002/nbm.4518

Cited by 8 publications

(6 citation statements)

References 45 publications

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“…Stress T1 mapping can detect changes in MBV, but unfortunately it is not sensitive to MBF, RPP, or PvO 2 , 26,73 suggesting that T2 is more sensitive to the underlying hemodynamic effects. Stress T1 also suffers from a narrow dynamic range that has plagued attempts to identify ischemic or infarcted myocardium; even in healthy remote myocardium, the rest‐stress percent change measured using T1 is 6% or less, 26,29,77–79 as compared with a more than 10% change detected using T2 29,50 . Additionally, while some studies report being able to differentiate ischemic or infarcted tissue from healthy myocardium using stress T1, they only do so successfully when the regions are previously demarcated by perfusion or late gadolinium imaging 77,79 ; differentiation by stress T1 alone, when blinded to the location of the ischemia, fails 77 .…”

Section: Discussionmentioning

confidence: 99%

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2

et al. 2021

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Stress imaging identifies ischemic myocardium by comparing hemodynamics during rest and hyperemic stress. Hyperemia affects multiple hemodynamic parameters in myocardium, including myocardial blood flow (MBF), myocardial blood volume (MBV), and venous blood oxygen levels (PvO2). Cardiac T2 is sensitive to these changes and therefore is a promising non‐contrast option for stress imaging; however, the impact of individual hemodynamic factors on T2 is poorly understood, making the connection from altered T2 to changes within the tissue difficult. To better understand this interplay, we performed T2 mapping and measured various hemodynamic factors independently in healthy pigs at multiple levels of hyperemic stress, induced by different doses of adenosine (0.14‐0.56 mg/kg/min). T1 mapping quantified changes in MBV. MBF was assessed with microspheres, and oxygen consumption was determined by the rate pressure product (RPP). Simulations were also run to better characterize individual contributions to T2. Myocardial T2, MBF, oxygen consumption, and MBV all changed to varying extents between each level of adenosine stress (T2 = 37.6‐41.8 ms; MBF = 0.48‐1.32 mL/min/g; RPP = 6507‐4001 bmp*mmHg; maximum percent change in MBV = 1.31%). Multivariable analyses revealed MBF as the dominant influence on T2 during hyperemia (significant β‐values >7). Myocardial oxygen consumption had almost no effect on T2 (β‐values <0.002); since PvO2 is influenced by both oxygen consumption and MBF, PvO2 changes detected by T2 during adenosine stress can be attributed to MBF. Simulations varying PvO2 and MBV confirmed that PvO2 had the strongest influence on T2, but MBV became important at high PvO2. Together, these data suggest a model where, during adenosine stress, myocardial T2 responds predominantly to changes in MBF, but at high hyperemia MBV is also influential. Thus, changes in adenosine stress T2 can now be interpreted in terms of the physiological changes that led to it, enabling T2 mapping to become a viable non‐contrast option to detect ischemic myocardial tissue.

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Section: Discussionmentioning

confidence: 99%

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2

et al. 2021

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“…This approach also eliminates quantification errors resulting from double contrast injections. Several groups have since adopted the blood-pool imaging approach and applied it to myocardial stress testing ( 12 , 13 ). Instead of Ablavar ® , however, whose production was discontinued in 2017 due to low sales, these papers used Feraheme ® (ferumoxytol), an iron-based compound currently still approved in the U.S. as an iron supplement and used off-label as a blood-pool MRI contrast agent.…”

Section: Imaging Microvascular Dysfunctionmentioning

confidence: 99%

Emerging MRI techniques for molecular and functional phenotyping of the diseased heart

Cheng

2022

Front. Cardiovasc. Med.

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Recent advances in cardiac MRI (CMR) capabilities have truly transformed its potential for deep phenotyping of the diseased heart. Long known for its unparalleled soft tissue contrast and excellent depiction of three-dimensional (3D) structure, CMR now boasts a range of unique capabilities for probing disease at the tissue and molecular level. We can look beyond coronary vessel blockages and detect vessel disease not visible on a structural level. We can assess if early fibrotic tissue is being laid down in between viable cardiac muscle cells. We can measure deformation of the heart wall to determine early presentation of stiffening. We can even assess how cardiomyocytes are utilizing energy, where abnormalities are often precursors to overt structural and functional deficits. Finally, with artificial intelligence gaining traction due to the high computing power available today, deep learning has proven itself a viable contender with traditional acceleration techniques for real-time CMR. In this review, we will survey five key emerging MRI techniques that have the potential to transform the CMR clinic and permit early detection and intervention. The emerging areas are: (1) imaging microvascular dysfunction, (2) imaging fibrosis, (3) imaging strain, (4) imaging early metabolic changes, and (5) deep learning for acceleration. Through a concerted effort to develop and translate these areas into the CMR clinic, we are committing ourselves to actualizing early diagnostics for the most intractable heart disease phenotypes.

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“…Research in the field remains strong; for instance, Ferumoxytol offers possibilities for both T 1 - and T 2 -weighting modalities, and so it continues to be under evaluation as a versatile vascular contrast agent. , Suspensions of fully dispersed citrate-stabilized MNPs ( d core 4 nm) have also been considered for T 1 -weighted angiography. , MNPs of many types have been developed for stem cell tracking following uptake. − There are also many exciting recent examples of advanced multiresponsive magnetic iron oxide particles. For instance, smaller particles (in the 2–3 nm range, so the cores have no appreciable moment and are paramagnetic rather than superparamagnetic) are being developed for dual T 1 – T 2 contrast generation for evaluating vascular permeability in tumors .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

pH Dependence of MRI Contrast in Magnetic Nanoparticle Suspensions Demonstrates Inner-Sphere Relaxivity Contributions and Reveals the Mechanism of Dissolution

MacMahon

Brougham

2023

Langmuir

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Superparamagnetic iron oxide nanoparticles, MNPs, are under investigation as stimulus-responsive nanocarriers that can be tracked by magnetic resonance imaging. However, fundamental questions remain, including the effect of differing surface chemistries on MR image contrast efficacy (relaxivity), both initially and over time in the biological environment. The effects of pH and ligand type on the relaxivity of electrostatically and sterically stabilized spherical 8.8 nm superparamagnetic MNP suspensions are described. It is shown for the first time that across the pH ranges, within which the particles are fully dispersed, increasing acidity progressively reduces relaxivity for all ligand types. This effect is stronger for electrostatically (citrate or APTES) than for sterically stabilized (PEG5000) MNPs. NMR relaxation profiles (relaxivity as a function of 1H Larmor frequency) identified an inner-sphere effect, arising from the protonation of bare oxide or low-molecular-weight-bound species, as the cause. The suppression is not accounted for by the accepted model (SPM theory) and is contrary to previous reports of increased relaxivity at lower pH for paramagnetic iron oxide nanoparticles. We propose that the suppression arises from the orientation of water molecules, with the oxygen atom facing the surface increasingly preferred with increasing surface protonation. For APTES-stabilized MNPs, pendant amines and the silane layer confer exceptional chemical and colloidal stability at low pH. Dissolution of these particles at pH 1.8 was monitored over several months by combining in situ measurements of relaxation profiles with dynamic light scattering. It was shown that particles are magnetically intact for extended periods until they rapidly dissolve, once the silane layer is breached, in a process that is apparently second order in particle concentration. The findings are of interest for tracking MNP fate, for quantitation, and for retention of magnetic responsiveness in biological settings.

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Ferumoxytol‐enhanced magnetic resonance T1 reactivity for depiction of myocardial hypoperfusion

Cited by 8 publications

References 45 publications

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2

Myocardial blood flow is the dominant factor influencing cardiac magnetic resonance adenosine stress T2

Emerging MRI techniques for molecular and functional phenotyping of the diseased heart

pH Dependence of MRI Contrast in Magnetic Nanoparticle Suspensions Demonstrates Inner-Sphere Relaxivity Contributions and Reveals the Mechanism of Dissolution

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