With the advent of new, long intravenous half-life gadolinium-based contrast agents, such as MS-325 (EPIX Medical Systems, Cambridge, Mass), we hypothesized that it would be possible to perform functional imaging by using T1-weighted pulse sequences with a gadolinium-based agent. MION is an ideal agent for this purpose because of its very long plasma half-life. The increased MION, with its high magnetic susceptibility, causes proton dephasing, decreasing signal intensity in active portions of the brain on T2*-weighted imaging sequences. As arterioles and capillaries dilate in response to neural activity, cerebral blood volume increases in these active regions, increasing the amount of MION in active portions of brain. Mandeville et al 6 have shown that a long intravenous half-life contrast agent, monocrystalline iron oxide nanoparticles (MION) can be used for functional imaging based on changes in regional cerebral blood volume that occur in response to neural activity. In addition, the BOLD signal intensity depends on a complex interaction between many processes, including cerebral blood flow, vascular permeability, and rate of oxygen consumption. BOLD fMRI pulse sequences are typically heavily T2*-weighted, which results in areas of significant signal intensity loss as a result of susceptibility differences at air-tissue interfaces, such as near the mastoid air cells and paranasal sinuses. The most widely used fMRI technique, blood oxygen level–dependent (BOLD) fMRI, relies on changes in the magnetic susceptibility reflecting altered oxygen levels in response to increased neural activity. This could reduce the susceptibility artifacts associated with fMRI.įunctional MR imaging (fMRI) techniques have gained widespread application in neuroscience research and clinical medicine. Using a boxcar stimulation pattern with a standard correlation analysis, the locations of the most significantly activated voxels (ie, highest Z score) in the MS-325 and BOLD fMRI measurements were not significantly different.ĬONCLUSIONS: MS-325 fMRI has the advantage of using a T1-weighted sequence, rather than the highly T2*-weighted sequences used in other common fMRI techniques. RESULTS: We found that a dose of 0.1 mmol/kg MS-325 produced adequate signal intensity changes in rat sensory cortex to demonstrate activations. MS-325 was then intravenously administered and a MS-325 fMRI measurement was performed by using a 3D gradient-echo sequence. Standard blood oxygen level–dependent (BOLD) fMRI measurement was initially performed. METHODS: All fMRI measurements used a rat model of sensory cortex activation with forepaw electrical stimulation under α-chloralose anesthesia. PURPOSE: We describe a technique for functional MR imaging (fMRI) with high spatial and temporal resolution using a long intravascular half-life gadolinium-based contrast agent, MS-325.
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