Gradient echo acquisition for superparamagnetic particles with positive contrast (GRASP): Sequence characterization in membrane and glass superparamagnetic iron oxide phantoms at 1.5T and 3T

Abstract

Iron oxides are used for cell trafficking and identification of macrophages in plaque using MRI. Due to the negative contrast, differentiation between signal loss caused by iron and native low signal in tissue may be problematic. It is, therefore, preferable to achieve positive contrast. The purpose of this study was to test the efficacy of a new MRI sequence GRASP (GRe Acquisition for Superparamagnetic Particles) to generate a positive signal in phantoms containing iron. Membrane phantoms were constructed containing Ferumoxide at 7 concentrations. Standard GRE sequences were modified with user controlled z-gradient rephasing (؎100%). CNR values were determined as a function of echo time (TE) and % rephasing at 1.5T and 3T. T 2 * values were determined using multiple double-echo GRE. The GRASP sequence generated positive signal enhancement in phantoms containing iron. For all rephasing values ≤30%, positive contrast was observed. The CNR generated at 1.5T was greater than the values at 3T for all concentrations tested. Correlation between CNR at 0% and 100% rephasing was observed at 1.5T(R ‫؍‬ 0.84). Additionally, correlation between field change across the volume and CNR was observed. Key words: iron oxide; gradient echo imaging; susceptibility; T 2 *; positive contrast MRI Super paramagnetic iron oxide particles (SPIOs) are currently used for organ specific MRI (i.e., liver imaging) (1) as well as stem cell labeling and trafficking (2,3). It has been shown that i.v. administered SPIOs are taken up by the mononuclear phagocytic system (MPS), resulting in hepatic, splenic, bone marrow, and nodal iron accumulation.This selective accumulation of iron particles in the MPS system has been successfully used for organ-specific MRI by exploiting their T 2 and T 2 * shortening effects (4 -7). Additionally, ultra-small iron oxide particles (USPIOs), with particle diameters less than 30 nm, have been used for a variety of indications. Since USPIOs are not immediately recognized by the hepatic and splenic MPS (8), the blood half-lives of UPSIOs are relatively long as compared to SPIOs. This, coupled with their inherent T 1 shortening properties, has allowed USPIOs to be used as MR angiography (MRA) blood pool agents (9). USPIOs have also been shown to extravasate through tight capillary pores, thereby enabling USPIO uptake in MPS cells throughout the body. It has been demonstrated that USPIO agents are capable of navigating through the interstitial endothelial pores of atherosclerotic plaque (10). The USPIOs are then taken up and compartmentalized within functional atherosclerotic plaque macrophages (11,12). The compartmentalization of the USPIOs within the plaque MPS allows for early detection of atherosclerotic changes by means of USPIO-associated T 2 and T 2 * shortening effects. Even though USPIOs are sometimes used for bright blood MRA (9), in plaques, the T 2 /T 2 * effects are always dominant due to the intracellular compartmentalization of the particles.SPIO and USPIO agents on MR images produce a negative contrast...

MRI study of atherosclerotic plaque progression using ultrasmall superparamagnetic iron oxide in Watanabe heritable hyperlipidemic rabbits

“…We are in the process of evaluating the usefulness of other sequences such as a more T 2 * weighted GRE sequence, T 2 weighted spin-echo axial images of highresolution MRI and positive-contrast techniques such as the GRASP sequence. 20,21 In conclusion, USPIO-enhanced MRI visualized the accumulation of macrophages in the early atherosclerotic plaques of WHHL rabbits. We consider it a promising technique for the detection of vulnerable plaques and for the assessment of the effects of therapy.…”

“…gradient echo acquisition of superparamagnetic particles (GRASP), have been studied. 20,21 Atherosclerosis can also be evaluated with invasive imaging techniques such as X-ray angiography and intravascular ultrasound. Because MRI is non-invasive and does not require ionizing radiation, USPIOs can be used in patients with renal dysfunction.…”

Molecular Imaging in Cardiovascular Diseases

“…Examples include the following methods: IRON (inversion-recovery with ON-resonant water suppression), GRASP (gradient acquisition for superparamagnetic particles) and SGM (susceptibility gradient mapping) ( • " Fig. 4) [43,59,60]. An alternative approach to detecting macrophages uses gadolinium-based micella which specifically bind with scavenger receptors expressed by activated macrophages and which exhibit high affinity for oxidized LDL.…”

Iron Oxide Nanoparticles Imaging Tracking by MR Advanced Techniques: Dual-Contrast Approaches

“…A similar gradient depashing technique termed gradient echo acquisition for superparamagnetic particles (GRASP), by dephasing of the background signal, has been used to detect positive-contrast from superparamagnetic particles based on the phenomena that the z-rephasing gradient is reduced so that dipolar fields generated by the cells are rephrased and positive signal can be observed (Mani, 2006a), also to image ferritin deposition in a rabbit model of carotid injury with relatively low concentrations of iron oxides at 1.5 T MR scanner (Mani, 2006b). The GRASP technique was used to successfully image low concentrations of ferumoxides (0.05 mM Fe corresponding to 2.8 μg Fe/mL) and ferritin (5 μg Fe/mL) in gel phantoms .…”