Introduction Recently, the benefits of image phase for the study of brain anatomy at high field (> 7 T) have been demonstrated [1]. In some brain regions, the improved contrast to noise ratio (over the magnitude images) between and within grey and white matter structures has provided the opportunity to study the laminar structure of the cortex. Several sources such as iron [1,2], myelin [3], deoxy-hemoglobin [4], and macromolecular concentration [5] have been suggested to contribute to the phase contrast. However, the relative contribution of these sources is not well understood. Recently, Marques et al. [6] used an oxygen challenge in rat to demonstrate a relatively small contribution of deoxy-hemoglobin. However, quantitative interpretation of this result was compromised by the limited contrast modulation introduced by this challenge and potential confounds such as associated blood volume changes. Therefore, the result did not fully eliminate deoxy-hemoglobin as a substantial contributor to gray/white matter phase contrast. Here, we administered iron oxide nanoparticles that induce a relatively large increase in vascular susceptibility to further confirm that deoxy-hemoglobin is not a major source for the gray/white matter contrast. Methods All scans were performed at a 7 Tesla (Bruker BioSpin) animal system with a 4 channel surface coil. The scan sequence for phase images was a 2D multi-echo GRE sequence with FOV = 2.56 x 2.56 cm, resolution = 67 x 67 x 500 μm, flip angle = 60o, TR = 1 sec, TE = 8 / 20 / 32 msec, 4 average, and total scan time = 27 min. After coil-combining, phase images were unwrapped and filtered by a 2D Gaussian high-pass filter (FWHM = 26 voxels) to remove large scale phase variations. The frequency images were calculated from a linear fit to the phase change over the three echoes. T2 * values were also calculated from the multi-echo magnitude data. Scans were performed on an isoflurane anesthetized rat before and after various intravascular administrations of an iron oxide nanoparticle solution (Molday ION, BioPAL). Cumulative doses of 0.5, 0.8, and 3 mg/kg (adjusted for half life) were used. Images were acquired 5 min. after each injection.
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