For the patient data, with administered contrast agent, the mean post-contrast signal enhancement is equivalent to about 4 signal units in gray matter,

1 in white matter, 3 in CSF and 64 in blood, with changes over the imaging period following the first post-contrast time point being around −1.3 in gray matter, −0.5 in white matter, 2.2 in CSF and −15 in blood. These small signal differences will be influenced by discretization errors, as the signal is sampled as integer values. However, as the contrast Staurosporine purchase agent uptake curves are obtained by averaging data from many voxels, these effects are expected to largely cancel out. Simulations performed based on the data obtained in this study indicate that the discretization error for white matter would be less than 0.01% for data averaged from 1000 voxels, far fewer than that used to generate the curves in Fig. 1. Nevertheless, if the NVP-BEZ235 solubility dmso ultimate aim is to compare data on a voxel-by-voxel basis, then discretization errors need to be reduced, possibly by improving scanner electronics

or the procedure used for setting the receiver gain. The theoretical analysis demonstrated that to cause a greater signal enhancement for a given contrast agent concentration, either T10 or r1 must be increased. The 9.15% increase observed in deep gray matter Etave between high- and low Fazekas-rated patients would require the baseline T10 to be increased by 86 ms in the high Fazekas-rated

group compared to the low Fazekas-rated group. While this is greater than the 35-ms increase observed, it is within experimental error. Similarly, the observed differences between high- and low Fazekas-rated groups in cortical gray matter, white matter, CSF and blood Etave of 4.29%, 15.02%, −23.68% and 12.81% would require T10 to differ by 43, 81, −1092 and 180 ms, respectively. The observed mean T10 differences in each of these tissues are 7, 62, −37 and −140 ms, which, while being consistently lower in magnitude than that required to cause the observed enhancement differences, are generally within experimental error of the simulated values due to the large error associated with these measurements. Similarly, if a difference in r1 between high- and low Fazekas-rated patients were to be responsible for the Carbachol differences in Etave, then r1 would need to be altered from its assumed value of 4.3 s−1 mM−1 by 0.43, 0.20, 0.94, −0.93 and 1.04 s−1 mM−1 in each of deep gray matter, cortical gray matter, white matter, CSF and blood, respectively. These changes are equivalent to 9.6%, 4.4%, 20.9%, −20.7% and 23.1% deviations from the assumed r1 in each of the respective tissues. These simulated data suggest that the signal enhancement differences seen in this study of 0.003 in cortical gray and white matter, 0.006 in deep gray matter and 0.