This and other early (eg, refs 12-14) computational models of the BOLD phenomenon are currently understood to be largely accurate, albeit incomplete with respect to the mechanisms contributing to functional mapping signals. Some of these initially overlooked mechanisms (eg, inflow effects) form the basis of the successful use of lower

field strengths, such as 1.5 T, for the acquisition of functional images in human brain. Nevertheless, increased understanding of the origin of fMRI signals (see ref 15 and references therein) Inhibitors,research,lifescience,medical have also reconfirmed original expectations that there are major advantages in going to very high magnetic fields, and these have largely been experimentally verified by a plethora of studies

conducted with kinase inhibitor Pazopanib animal models (eg, refs 1, 16-18). For example, in Inhibitors,research,lifescience,medical fMRI, the contrast-to-noise ratio (CNR) of deoxyhemoglobin-based BOLD mapping signals increases linearly in high-resolution imaging for gradient echo (GE)-based techniques, the predominant approach employed in contemporary fMRI experiments. (Contrast in fMRI is defined as the magnitude of the signal change induced by a stimulus or a task. Contrast-to Inhibitors,research,lifescience,medical noise ratio CNR is the ratio of the contrast to the signal fluctuations in the fMRI time series). When image resolution is high, the latter is dominated by the “thermal” noise present in each image of the time series. At low resolution, CNR for GE fMRI increases less than linearly with field magnitude since the temporal fluctuations of signals become dominated by physiological processes (rather than thermal noise) and display a dependence on signal amplitude, hence magnetic field magnitude. For spin echo (SE) BOLD fMRI, which provides more accurate functional Inhibitors,research,lifescience,medical localization,1,16-17 albeit only at high magnetic

inhibitor expert fields and with smaller signal changes1,9,20 CNR can exhibit more than a linear dependence on magnetic field magnitude because of suprallnear gains in fractional signal change induced by neuronal activity19-20 and a linear Inhibitors,research,lifescience,medical elevation in intrinsic AV-951 image signal-to-noise ratio (SNR).21 The gains in fractional signal change, however, tend to level off at fields above -9 to 10 Tesla,15 leaving the SNR gains as the only potential source of CNR improvements. More importantly, however, higher magnetic fields provide significantly better spatial fidelity in the deoxyhemoglobin-based functional mapping signals (eg, refs 1,16,17). fMRI relies on secondary metabolic and vascular responses invoked by alterations in neuronal activity. Therefore, its accuracy can be degraded by limitations imposed by these secondary responses. However, in a critical experiment performed in the cat visual cortex, it was demonstrated that blood flow increase induced by functional activation is regulated at the level of orientation columns.