PURPOSE: To study arterial spin labeling (ASL) MRI techniques and to investigate various problematic issues that still hinder the accurate and robust quantitative analysis of ASL data. MATERIALS AND METHODS: A pulsed-ASL (PASL) sequence was implemented on a 3-T imaging system and a protocol was developed for the measurement of perfusion based on fitting to a standard kinetic model. Both numerical simulations and multi-inversion time MRI data were analyzed. The effect of fitting a kinetic curve to a large region of interest (ROI) with a distribution of arterial transit times was compared to a pixel-by-pixel (PBP) method. RESULTS: It was found that a significant underestimation of perfusion of approximately 17+/-6% (P