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AJNR - American Journal of Neuroradiology

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American Journal of Neuroradiology 23:588-593, April 2002
© 2002 American Society of Neuroradiology

BRAIN

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

Douglas W. Morton^a, Kenneth R. Maravilla^a, Joseph R. Meno^b and H. Richard Winn^b

^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

Address reprint requests to Douglas W. Morton, MD, PhD, Department of Radiology, RR-215, Box 357115, University of Washington, 1959 NE Pacific St, Seattle, WA 98195

Address reprint requests to Douglas W. Morton, MD, PhD, Department of Radiology, RR-215, Box 357115, University of Washington, 1959 NE Pacific St, Seattle, WA 98195.

BACKGROUND AND PURPOSE: Functional MR imaging with blood oxygen level—dependent (BOLD) contrast enhancement is believed to rely on changes in cerebral blood flow and deoxyhemoglobin level to estimate the location and degree of neural activation. We studied the relationship between neural activation and the observed BOLD response by using theophylline, an antagonist of the inhibitory neurotransmitter adenosine and a potent inhibitor of the vasodilatory response to neural activation.

METHODS: Using a rat model with electrical forepaw stimulation, we performed fMRI measurements before and after the systemic injection of either theophylline (0.1 mmol/kg) or an equivalent volume of saline. Changes in the BOLD response were quantified by determining the number of activated voxels and the amplitude of the BOLD response for each animal in the theophylline and saline groups.

RESULTS: The theophylline group had a significantly Tincreased BOLD response (70–150% increased activated voxel count and 60–65% increased BOLD response amplitude) at 45 and 60 minutes after systemic injection compared with baseline. The response of the saline-injected control group did not change significantly.

CONCLUSION: The administration of systemic theophylline significantly augmented the BOLD response due to either an elevation of resting deoxyhemoglobin levels or the neuroexcitatory effect of theophylline. This effect potentially could be used in human fMRI studies to increase the sensitivity of the BOLD response.

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