1. High-field continuous arterial spin labeling with long labeling duration: Reduced confounds from blood transit time and postlabeling delay In quantitative perfusion imaging using arterial spin labeling, variable blood transit times and postlabeling delays are two confounding factors that may compromise the accuracy of perfusion quantifications. In this study, theoretical analyses and experimental data at 9.4 T demonstrate that increasing labeling duration not only enhances the contrast of the arterial spin labeling signal but also minimizes the effect of variable postlabeling delays in multislice arterial spin labeling acquisitions. With a labeling duration of 6.4 sec, arterial spin labeling signal acquired in multislice mode (11 slices) is very similar to that acquired in single-slice mode. Previous studies have shown that inserting a delay between the spin labeling pulse and the image acquisition pulse could reduce confounds resulting from variable blood transit times at the expense of arterial spin labeling sensitivity. Our simulations suggest that enhancing the contrast of arterial spin labeling signal offers the opportunity for extending the postlabeling delay to a longer duration, minimizing systematic errors associated with a wide range of blood transit times, which could have significant implications for applying arterial spin labeling techniques to perfusion imaging of pathological conditions in animal models. (Magn Reson Med, 2010, in press) 2. Temporary disruption of the rat blood-brain barrier with a monoclonal antibody: a novel method for dynamic manganese-enhanced MRI Manganese (Mn(2+)) has limited permeability through the blood-brain barrier (BBB). Opening the BBB such that a sufficient amount of Mn(2+) enters the extracellular space is a critical step for dynamic manganese-enhanced magnetic resonance imaging (ME-MRI) experiments. The traditional BBB opening method uses intracarotid hyperosmolar stress which results in suboptimal BBB opening, and practically is limited to nonsurvival experiments due to substantial surgical trauma. In the present ME-MRI study, we investigate the feasibility of opening the BBB with an antibody that targets the endothelial barrier antigen (EBA) specifically expressed by rat endothelial cells. Results demonstrate that intravenous infusion of the anti-EBA agent SMI-71 leads to BBB disruption of the whole brain as detected by ME-MRI and confirmed by Evans blue dye staining. Physiologically, injection of SMI-71 leads to a hypertensive response followed by a sustained hypotensive response in animals anesthetized with urethane alone. Incorporating isoflurane partially mitigated both pressor responses. In general, BBB disruption via intravenous infusion of SMI-71 is straightforward and obviates technical difficulties associated with intracarotid hyperosmolar stress, opening new possibilities for in vivo neuroimaging with ME-MRI. The data also suggest that ME-MRI may be used as an imaging method to assess BBB integrity complementary to the Evans blue dye method, a classical but highly invasive technique, permitting longitudinal assessment of the integrity of the BBB on the same animal. (NeuroImage 50:7-14, 2010) 3. Isolated turtle brain model to study mechanisms of functional MRI signals Isolated turtle brain/eye preparation has recently been used as a bloodless animal model for detecting the magnetic resonance imaging (MRI) signal changes produced by visually evoked neuronal currents. The present work aims to determine whether checkerboard-patterned or full field flash (blank) stimulation should be used in order to achieve stronger neuronal responses in turtle brain/eye preparation. The knowledge gained in this study is essential for optimizing the visual stimulation methods in functional neuroimaging studies using turtle brain/eye preparation. In this study, visually evoked local field potentials (LFPs) were measured and compared in turtle visual cortex and optic tectum elicited by checkerboard and full field flash stimuli with three different inter-stimulus intervals (ISIs=5, 10, and 16s). It was found that the behavior of neuronal adaptation in the cortical and tectal LFP signals for checkerboard stimulation was comparable to flash stimulation. In addition, there was no significant difference in the LFP peak amplitudes (ISI=16s) between these two stimuli. These results indicate that the intensity of neuronal responses to checkerboard is comparable to flash stimulation. These two stimulation methods should be equivalent in functional neuroimaging studies using turtle brain/eye preparation. (J Neurosci Methods, 187:26-32, 2010) 4. Morphological changes of rhesus monkey brain induced by early life stress using deformation-based morphometry (DBM) with unbiased group registration DBM is an automatic computational method to detect voxel-wise anatomical differences between populations by examining deformation fields generated from registering their images. It has been used for detecting brain structural changes during development, aging and in various neuropathological states. We used DBM with an unbiased group-wise image registration method, which provides more accurate results, to analyze the morphological changes due to early life stress. The DBM analysis confirms our previous findings of enlarged dorsomedial prefrontal, dorsal anterior cingulated and vermis volumes. It also suggests that early life stress induces morphological abnormalities of the cortico-striato-pallidal system. 5. Magnetic resonance spectroscopy (MRS) techniques to measure neurochemicals We are developing spectral editing MRS techniques that utilizes different spin properties such as chemical bond, chemical shift frequency and etc, to eliminate the the strong resonances overlapping with coupled metabolites such as GABA and NAAG. The difference spectroscopy MEGA-PRESS has been applied on the Bruker 9.4 T animal scanner and has successfully detected the GABA signal in vivo. Several localization methods have been used to suppress the chemical shift displacement under high-field magnet in order to improve signal intensity of small voxel studies. We are also developing full spectrum detection methods such as the SPECIAL sequence to observe the concentrations of more than 10 metabolites simultaneously. Different profiles of pulse shape have been explored to improve the performance of STEAM and SPECIAL. The macromolecular elimination method is also under development to improve the fitting accuracy. Simulation tools such as GAVA have been applied to generate fitting basis set. Fitting softwares such as LCModel have been used to examine the improvement on the quantification of the new method.
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