The BOLD signal consists of an intravascular (IV) and an extravascular (EV) component from both small and large vessels. Their relative contributions are dependent on field strength, imaging technique, and echo time. The IV and EV contributions were investigated in the human visual cortex at 4 and 7 T using spin-echo and gradient-echo BOLD fMRI with and without suppression of blood effects. Spin-echo acquisition suppresses EV BOLD from large veins and reflects predominantly blood T 2 changes and EV BOLD signal from small blood vessels. At a short echo time (32 ms), diffusion gradient-based suppression of blood signals resulted in a 75% and 20% decrease in spin-echo BOLD changes at 4 T and 7 T, respectively. However, at echo times (55-65 ms) approximating tissue T 2 typically used for optimal BOLD contrast, these gradients had much smaller effects at both fields, consistent with the decreasing blood T 2 with increasing field strength. Gradient-echo BOLD percent changes, with relatively long echo times at both fields, were virtually unaffected by gradients that attenuated the blood contribution because the EV BOLD surrounding both large and small vessels dominated. These results suggest that spin-echo BOLD fMRI at 4 and 7 T, with TE approximating tissue T 2 , significantly reduces nonspecific mapping signals from large vessels and significantly accentuates microvasculature contributions.

The Hahn spin-echo (HSE)-based BOLD effect at high magnetic fields is expected to provide functional images that originate exclusively from the microvasculature. The blood contribution that dominates HSE BOLD contrast at low magnetic fields (e.g., 1.5 T), and degrades specificity, is highly attenuated at high fields because the apparent T 2 of venous blood in an HSE experiment decreases quadratically with increasing magnetic field. In contrast, the HSE BOLD contrast is believed to arise from the microvasculature and increase supralinearly with the magnetic field strength. In this work we report the results of detailed and quantitative evaluations of HSE BOLD signal changes for functional imaging in the human visual cortex at 4 and 7 T. This study used high spatial resolution, afforded by the increased signal-to-noise ratio (SNR) of higher field strengths and surface coils, to avoid partial volume effects (PVEs), and demonstrated increased contrast-to-noise ratio (CNR) and spatial specificity at the higher field strengths. The HSE BOLD signal changes induced by visual stimulation were predominantly linearly dependent on the echo time (TE). They increased in magnitude almost quadratically in going from 4 to 7 T when the blood contribution was suppressed using Stejskal-Tanner gradients that suppress signals from the blood due to its inhomogeneous flow and higher diffusion constant relative to tissue. The HSE signal changes at 7 T were modeled accurately using a vascular volume of 1.5%, in agreement with the capillary volume of gray matter. Furthermore, high-resolution acquisitions indicate that CNR increased with voxel sizes < 1 mm 3 due to diminishing white matter or cerebrospinal fluidspace vs. gray matter PVEs. It was concluded that the high-field HSE functional MRI (fMRI) signals originated largely from the capillaries, and that the magnitude of the signal changes associated with brain function reached sufficiently high levels at 7 T to make it a useful approach for mapping on the millimeter to submillimeter spatial scale. Functional parcellation in the brain is known to exist at a much finer spatial scale than the several-millimeter voxel dimensions currently used in functional imaging studies. However, initiatives aimed at functional mapping on such a scale are confronted with questions about the specificity (i.e., the accuracy of the maps relative to the actual boundaries of altered neuronal activity) and the magnitude of the imaging signals. Currently, most functional MRI (fMRI) studies in humans employ T * 2 -weighted, gradient-echo (GRE) BOLD fMRI because it provides the highest contrastto-noise ratio (CNR) and is the easiest to implement. T * 2 -weighted BOLD signals at low fields were shown to be dominated by contributions from large draining veins (1-6) that can be distant from the activated site, with no evidence of a capillary contribution (3). Even at 4 T (7) and 4.7 T (8), large vein contributions are prominent. At higher magnetic fields, such as 7 T, the contribution of large vessels to GRE BOLD d...

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 ␣-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 the preferential intracellular Mn ؉؉ accumulation. Based on an in vitro calibration, the estimated contralateral somatosensory cortex [Mn ؉؉ ] was ϳ100M, 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 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 m, suggesting that hemodynamic-based fMRI techniques (at least at high field) can be used to accurately map the spatial loci of synaptic activity. Magn Reson Med 43:383-392, 2000.