Pharmacological MRI with Continuous ASL in Conscious Rats: Characterizing the Relationship Between CBF Response to CNS Compounds & Plasma Concentration Levels

Alexandre Coimbra¹, Denise Welsh¹, Diane Posavec¹, Amy Vanko¹, Richard Baumgartner², Christopher Regan³, Andrew Danziger³, Matthew Baran³, Kristina Groover³, Jacquelynn Cook¹, Joseph Lynch³, Jason Uslaner³, Donald Williams¹

Pharmacological functional MRI techniques have been used to assess drug effects in the central nervous system, however little has been done to characterize the relationship between the phMRI pharmacodynamic (PD) response and plasma concentration (pharmacokinetics, PK) of the compound being evaluated. This study aimed at exploring PK/PD relationships of phMRI response to two CNS acting compounds in conscious rats, donepezil and lorazepam using arterial spin labeling (ASL) measurements of CBF. Overall, these results provide insight into CBF PK/PD relationships and suggest potential use of conscious rat ASL as a platform providing translational biomarkers for CNS compound dose selection.