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.
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