We recently presented a new two-coil approach to continuous arterial spin labeling (CASL), (dubbed Turbo-CASL) (1), that significantly enhances the temporal resolution of ASL measurements while the SNR of the measurement is maintained. An additional benefit of the technique is that its sensitivity to transit time changes can be leveraged to increase the sensitivity to brain responses. In brief, Turbo-CASL consists of a continuous labeling experiment in which the control image is collected immediately after the tagging pulse, but before the tag reaches the plane of interest. The tagged image is collected when the tissue concentration of the label reaches its maximum. With Turbo-CASL one can collect samples at a much faster rate compared to standard CASL techniques, and still allow for a long labeling time. In our previous publication (1) we showed that the Turbo-CASL method also had an advantage in terms of SNR per unit of time, even though the amount of accumulated tag is not allowed to reach its steady-state maximum. The method is very sensitive to transit time changes. This makes quantification of perfusion more difficult, but it can also serve to exaggerate the perfusion increases that occur during activation and hence improve detection power, as shown in our previous work. In this follow-up paper we address the quantification issues that arise as a result of these transit time changes.Quantification of blood flow from ASL measurements is a difficult problem that requires the measurement of many parameters. A number of models have been presented to quantify perfusion, for a number of ASL acquisition schemes. These models are largely based on the first-order kinetics of the wash-in and wash-out of the inversion label into the tissue, taking into account its T 1 decay and exchange properties. The current models aim to quantify the microvascular perfusion, and consequently the larger arterial signal is routinely suppressed by the use of crusher gradients or postinversion delays. These delays have the added benefit of desensitizing the signal to the arterial transit time (ATT) (2-4). These models were developed for the cases of steady-state flow and transit time (5-10). Under such circumstances, the uptake of the arterial tag can be modeled as a linear system.However, in addition to the flow increase, neuronal activation is also accompanied by a reduction in the ATT of approximately 10 -20%, as observed by Gonzalez-At et al. (10) and Yang et al. (11). In the case of Turbo-CASL, we have calculated (1,12) that the signal can potentially change approximately 15% by a transit time change alone using the existing models.As a result, the ASL signal observed in our Turbo-CASL approach has nonlinear characteristics that are not easily explained by existing models, and likely distort the underlying flow response. In this study we extended the general framework of the kinetics of the arterial label to the case in which flow and transit times change dynamically in a given paradigm. We then developed and implemented a method...