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

Spatial specificities of the calcium-dependent synaptic activity, hemodynam ic-based blood oxygenation level-dependent (BOLD) and cerebral blood flow ( CBF) fMRI were quantitatively compared in the same animals. Calcium-depende nt 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 stimu lation in alpha-chloralose anesthetized rat, water T-1 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 t he preferential intracellular Mn++ accumulation. Based on an in vitro calib ration, the estimated contralateral somatosensory cortex [Mn++] was similar to 100 mu M, 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 T-1 synaptic activity maps extend ed 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 mu m, s uggesting that hemodynamic-based fMRI techniques (at least at high field) c an be used to accurately map the spatial loci of synaptic activity. (C) 200 0 Wiley-Liss, Inc.