To develop a generalized signal model for dual-module velocity-selective arterial spin labeling (dm-VSASL) that can integrate arbitrary saturation and inversion profiles. A recently developed mathematical framework for single-module VSASL is extended to address the increased complexity of dm-VSASL and to model the use of realistic velocity-selective profiles in the label-control and vascular crushing modules. Expressions for magnetization difference, arterial delivery functions, labeling efficiency, and cerebral blood flow (CBF) estimation error are presented. Sources of error are examined and timing requirements to minimize quantification errors are derived. For ideal velocity-selective profiles, the predicted signals match those of prior work. With realistic profiles, a CBF-dependent estimation error can occur when velocity-selective inversion (VSI) is used for the labeling modules and velocity-selective saturation (VSS) is used for the vascular crushing module. The error reflects a mismatch between the leading and trailing edges of the delivery function for the second bolus and can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal saturation cutoff velocity. In the presence of and inhomogeneities, the labeling efficiency of dual-module VSI is more attenuated than that of dual-module VSS. The proposed signal model will enable researchers to more accurately assess and compare the performance of realistic dm-VSASL implementations and improve the quantification of dm-VSASL CBF measures.
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