Dosage Determination of Ultrasmall Particles of Iron Oxide for the Delineation of Microvasculature in the Wistar Rat Brain

Abstract

Purpose-This investigation sought to optimize ultrasmall particles of iron oxide (USPIO) contrast agent dosage for visualizing cerebral microvasculature on an 8.0-Tesla ultra high field magnetic resonance imaging system. Materials and Methods-USPIO contrast agent was intravenously administered to 3 groups of 4 rats at 1, 2, and 3 mg Fe/kg. Each animal was scanned before and after injection of USPIO using a high resolution T2*-weighted gradient recalled echo sequence with an in-plane resolution of 78 µm. The signal-to-noise ratio (SNR) and the number of microvessels visualized within the cortex and basal ganglia were calculated and compared before and after the administration of USPIO.Results-As the USPIO dose increased, microvascular conspicuity increased, and SNR decreased. A dosage of 2 mg Fe/kg improved microvascular visualization in both cortex and basal ganglion regions relative to 1 mg Fe/kg without significantly sacrificing SNR as was the case at 3 mg Fe/kg. Conclusion-Two mg Fe/kg USPIO is an optimal dose when imaging normal rat cerebral microvasculature using GRE T2*-weighted MR imaging at a field strength of 8 T. KeywordsUSPIO; magnetic resonance imaging; brain; microvasculature Ultrasmall particles of iron oxide (USPIOs) are magnetic resonance (MR) contrast agents, which are cleared by the polymorphonuclear system. Because of their unique clearance characteristics, the plasma half-life of USPIOs is prolonged and has been categorized as a blood-pool MR contrast agent for magnetic resonance angiography (MRA). [1][2][3][4][5] In these studies, USPIO produced a strong T1 effect to visualize the vessels at conventional 1.5-Tesla (T) magnetic field strength. In addition, USPIO also has a strong T2* effect, which can be detected by T2*-sensitive sequences, such as gradient recalled echo (GRE). [6][7][8] In the central nervous system, the distinct macrophage-microglia is quiescent in the presence of an intact blood-brain barrier. Under physiological conditions, USPIO only circulates in cerebral blood vessels rather than penetrating the blood-brain barrier. 7 This leads to a concentration gradient between cerebral vessels and surrounding brain parenchyma, which provides an opportunity to visualize cerebral microvasculature on steady state T2* GRE sequences. Ultra high field (UHF) MR systems provide significantly higher signal to noise ratio (SNR) and more pronounced susceptibility effect relative to lower field systems. 9-12 These 2 advantages of UHF MRI combined with the use of USPIO intravascular contrast agents make it possible to obtain high-resolution negative-enhanced images of the normal rodent brain microvasculature.The purpose of the present study was to determine the optimal dosage of USPIO in normal Wistar rat brain using an 8-T MRI system. This dosage can then be applied toward the in vivo visualization of microvascularity in rodent brain pathologies such as stroke and glioma. Ultimately, it can serve as a reference for establishing dosages for imaging microvascularity in human pathology. M...

High Resolution Ultra High Field Magnetic Resonance Imaging of Glioma Microvascularity and Hypoxia Using Ultra-Small Particles of Iron Oxide

“…As previously reported, microvascularity within high grade gliomas can be visualized directly on HR GRE UHF MRI 5,6,9,25. In the present study we have demonstrated that the use of USPIO as a blood pool agent enhanced the visualization of microvessels in the F98 glioma using HR GRE UHF MRI.…”

“…A second set of GRE images were acquired approximately 30 to 60 seconds after infusion of USPIO (2 mg Fe/kg) (SHU 555 C, Supravist, Bayer Healthcare AG, Berlin) administration. The USPIO dose previously had been optimized for the imaging parameters used in this study 9. The SHU 555 C solution was diluted with 0.9% sodium chloride to 0.1 mmol/mL at room temperature before injection.…”

Quantitative Evaluation of Microvascular Density after Stroke in Rats using MRI

“…Very little leakage of contrast agent should not significantly affect MVD measurements in the recovery region or normal tissue where MVD is relatively large, but will lead to large errors in the ischemic core where MVD is very small. A higher dose of contrast agent will decrease the signal-to-noise ratio, resulting in some loss of vessel and tissue detail, and most likely this would reduce image quality even further (Laghi et al , 2004; Yang et al , 2005). Other factors affecting measurement of low MVD in the ischemic core may involve the relatively low signal-to-noise ratio of Δ R 2 and $\Delta R_2^{\ast }$ (3.8%; Laghi et al , 2004; Yang et al , 2005).…”

MRI Using Ferumoxytol Improves the Visualization of Central Nervous System Vascular Malformations

“…9,18 The most important limitation of this study is that two different ferumoxytol doses were applied. In 14 out of our 19 participants ferumoxytol was injected at a constant dose of 510 mg (approximately 7 mg/kg in case of a 70-kg patient), while in five patients it was given at a dose of 4 mg/kg.…”

“…8 Iron oxide nanoparticles increase the visibility of both normal and tumor microvessels in the brain on T 2 *-weighted scans. 9,10 On the other hand, for the evaluation of intracellularly trapped USPIOs in patients with central nervous system (CNS) malignancies, the 24-hour T 1 -weighted spin echo (SE) and T 2 -weighted images were found to be the most helpful. 11 …”