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Experimental data up to 7.0 T show that the blood oxygenation level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) increases with higher magnetic field strength. Although several studies at 11.7 T report higher BOLD signal compared with studies at 7.0 T, no direct comparison at these two field strengths has been performed under the exact same conditions. It therefore remains unclear whether the expected increase of BOLD effect with field strength will still continue to hold for fields Ͼ7.0 T. To examine this issue, we compared the BOLD activation signal at 7.0 and 11.7 T with the two common sequences, spin-echo (SE) and gradient-echo (GE) echo planar imaging (EPI). We chose the physiologically well controlled rat model of electrical forepaw stimulation under medetomidine sedation. While a linear to superlinear increase in activation with field strengths up to 7.0 T was reported in the literature, we observed no significant activation difference between 7.0 and 11.7 T with either SE or GE. Discussing the results in light of the four-component model of the BOLD signal, we showed that at high field only two extravascular contributions remain relevant, while both intravascular components vanish. Constancy of the BOLD effect is discussed due to motional narrowing, i.e., susceptibility gradients become so strong that phase variance of diffusing spins decreases and therefore the BOLD signal also decreases. This finding will be of high significance for the planning of future human and animal fMRI studies at high fields and their quantitative analysis.

Intravenous administration of iron oxide nanoparticles after experimental stroke has been shown to produce focal signal intensity changes in the ischemic boundary on MRI images. These changes have been attributed to the influx of iron-laden blood-borne macrophages, although it has been suggested that this effect might not always be completely specific to inflammatory cells. The aim of the present study was to investigate this phenomenon in a subacute time frame that is more relevant to the peripheral inflammatory response. Imaging experiments (T(2) -, T(2)*- and T(1) -weighted sequences) were acquired in Wistar rats 6 days after transient middle cerebral artery occlusion (MCAO). Animals were intravenously infused with different doses of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles (300, 600 or 1000 µmol Fe/kg), or saline and gadolinium, and imaged again 24 h later. Tissue was immediately processed for immunohistochemistry with the macrophage marker ED-1, in combination with Prussian blue for iron. Ischemic tissue exhibited a large increase in T(2) values, and overall contrast enhancement was apparent in the brain and surrounding muscle. In contrast with previous reports, there were no regions of focal signal intensity changes in the ischemic territory in any of the images, although a region of interest analysis revealed a trend towards iron accumulation in the ischemic hemisphere, particularly in the cortex of T(2)* images. However, histological examination revealed that, despite extensive ED-1-positive macrophage accumulation in the entire ischemic territory, none of these cells were Prussian blue positive, except in the meninges of one animal that received a high dose of USPIO nanoparticles. These results imply that the observed trend is a result of the presence of contrast agent in the blood, or meninges, and not iron-containing inflammatory cells.