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Purpose  Filter exchange imaging (FEXI) is sensitive to the rate of diffusional water exchange, which depends, eg, on the cell membrane permeability. The aim was to optimize and analyze the ability of FEXI to infer differences in the apparent exchange rate (AXR) in the brain between two populations.    Methods  A FEXI protocol was optimized for minimal measurement variance in the AXR. The AXR variance was investigated by test‐retest acquisitions in six brain regions in 18 healthy volunteers. Preoperative FEXI data and postoperative microphotos were obtained in six meningiomas and five astrocytomas.    Results  Protocol optimization reduced the coefficient of variation of AXR by approximately 40%. Test‐retest AXR values were heterogeneous across normal brain regions, from 0.3 ± 0.2 s −1  in the corpus callosum to 1.8 ± 0.3 s −1  in the frontal white matter. According to analysis of statistical power, in all brain regions except one, group differences of 0.3–0.5 s −1  in the AXR can be inferred using 5 to 10 subjects per group. An AXR difference of this magnitude was observed between meningiomas (0.6 ± 0.1 s −1 ) and astrocytomas (1.0 ± 0.3 s −1 ).    Conclusions  With the optimized protocol, FEXI has the ability to infer relevant differences in the AXR between two populations for small group sizes. Magn Reson Med 77:1104–1114, 2017. © 2016 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

Optimal experimental design for filter exchange imaging: Apparent exchange rate measurements in the healthy brain and in intracranial tumors