Functional MRI of calcium-dependent synaptic activity: Cross correlation with CBF and BOLD measurements

Spatial specificities of the calcium-dependent synaptic activity, hemodynamic-based blood oxygenation level-dependent (BOLD) and cerebral blood flow (CBF) fMRI were quantitatively compared in the same animals. Calcium- dependent synaptic activity was imaged by exploiting the manganese ion (Mn⁺⁺) as a calcium analog and an MRI contrast agent at 9.4 T. Following forepaw stimulation in α-chloralose anesthetized rat, water T₁ of the contralateral forepaw somatosensory cortex (SI) was focally and markedly reduced from 1.99 ± 0.03 sec to 1.30 ± 0.18 sec (mean ± SD, N = 7), resulting from the preferential intracellular Mn⁺⁺ accumulation. Based on an in vitro calibration, the estimated contralateral somatosensory cortex [Mn⁺⁺] was ~100μM, which was 2-5-fold higher than the neighboring tissue and the ipsilateral SI. Regions with the highest calcium activities were localized around cortical layer IV. Stimulus-induced BOLD and CBF changes were 3.4 ± 1.6% and 98 ± 33%, respectively. The T₁ synaptic activity maps extended along the cortex, whereas the hemodynamic-based activation maps extended radially along the vessels. Spatial overlaps among the synaptic activity, BOLD, and CBF activation maps showed excellent co-registrations. The center-of-mass offsets between any two activation maps were less than 200 μm, suggesting that hemodynamic-based fMRI techniques (at least at high field) can be used to accurately map the spatial loci of synaptic activity. (C) 2000 Wiley-Lies, Inc.