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Systemic Theophylline Augments the Blood Oxygen Level—Dependent Response to Forepaw Stimulation in Rats

Douglas W. Mortona, Kenneth R. Maravillaa, Joseph R. Menob and H. Richard Winnb

a Department of Radiology, University of Washington, Seattle
b Departments of Neurosurgery, University of Washington, Seattle
c Supported by the RSNA Research and Education Fund
d the University of Washington Royalty Research Foundation
e NIH grant NS21076



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FIG 1. Theophylline effect on the BOLD fMRI response to left forepaw electrical stimulation. Data are shown for a single section through the sensory cortex in a single animal at baseline (left) and 60 minutes after the administration of 0.1 mmol/kg systemic theophylline (right).

A, The number of activated voxels significantly increased 60 minutes after the administration of systemic theophylline. Arrows indicate the most significantly activated voxel, which had the same location on both images.

B, BOLD response for the voxel indicated in A. Bars to the right of each graph indicate the average signal intensity during forepaw stimulation (upper bars) and at rest (lower bars). The double-arrowhead vertical lines to the right of each graph indicate the BOLD response amplitude. The BOLD response amplitude significantly increased 60 minutes after systemic theophylline compared with the baseline. Horizontal bars above each graph indicate periods of forepaw electrical stimulation with a 4-second hemodynamic delay.



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FIG 2. Theophylline effect on the BOLD fMRI response to forepaw electrical stimulation. Results are the average for five test and four control animals. Five measurements were obtained in each animal: one before and four after the systemic injection of either 0.1 mmol/kg theophylline (n = 5) or an equivalent volume of normal saline (n = 4). The timing of each acquisition is relative to the systemic injection. The data for each animal were normalized to the preinjection value. * indicates a statistically significant difference compared with the baseline (P < .05).

A, The activated voxel count significantly increased 45 and 60 minutes after the administration of theophylline. It did not significantly change in the control group. The arrow indicates when theophylline or saline was administered, just after the first fMRI measurement.

B, The BOLD response amplitude significantly increased 45 and 60 minutes after the administration of theophylline, compared with baseline. It did not significantly change in the control group. The marker indicates when IP theophylline or saline was administered, just after the first fMRI measurement.