In a patient with good cardiac output, the initial plateau, upstroke and downstroke are all reached within 30 seconds. In this case, the upstroke only starts at about 30 seconds and as a result the VOF peak is not reached within the 50 second scan window. The VOF peak is important as it serves as a reference for normalization of the perfusion parameters and correction for volume averaging of arterial HU.

In patients with poor cardiac output, atrial fibrillation or severe vascular stenosis, the AIF will lag behind the true tissue density. Also, in these cases, the bolus forming the AIF is dispersed over multiple pathways proximal to the ROI (in CT perfusion, an assumption is that the ROI represents the only input to the tissue of interest). These factors lead to overestimated MTT (ie erroneous diagnosis of extensive ischemia or global hypoperfusion) and underestimated CBF.