Functional tissue pulsatility imaging (fTPI) is a new ultrasonic technique being developed to map brain function by measuring changes in tissue pulsatility due to changes in blood flow with neuronal activation. The technique is based in principle on plethysmography, an older, non-ultrasound technology for measuring expansion of a whole limb or body part due to perfusion. Perfused tissue expands by a fraction of a percent early in each cardiac cycle when arterial inflow exceeds venous outflow and relaxes later in the cardiac cycle when venous drainage dominates. Tissue pulsatility imaging (TPI) uses tissue Doppler signal processing methods to measure this pulsatile "plethysmographic" signal from hundreds or thousands of sample volumes in an ultrasound image plane. A feasibility study was conducted to determine if TPI could be used to detect regional brain activation during a visual contrast-reversing checkerboard block paradigm study. During a study, ultrasound data were collected transcranially from the occipital lobe as a subject viewed alternating blocks of a reversing checkerboard (stimulus condition) and a static, gray screen (control condition). Multivariate Analysis of Variance (MANOVA) was used to identify sample volumes with significantly different pulsatility waveforms during the control and stimulus blocks. In 7 out 14 studies, consistent regions of activation were detected from tissue around the major vessels perfusing the visual cortex.