Purpose We investigated the effect of microcirculatory flow on oscillating gradient spin echo (OGSE) diffusion MRI at low b-values and developed a diffusion preparation method called diffusion encoding with dual-frequency orthogonal gradients (DEFOG) to suppress the effect. Methods Compared to conventional OGSE sequences, DEFOG adds a pulsed gradient that is orthogonal to the oscillating gradient and has a moderate diffusion weighting (e.g., 300 s/mm2). In vivo MRI data were acquired from adult mouse brains (n = 5) on an 11.7 Tesla scanner, with diffusion times from 23.2 to 0.83 ms and b-values from 50 to 700 s/mm2. Results Apparent diffusion coefficients (ADCs) measured using a conventional OGSE sequence at low b-values (< 200 mm2/s) were significantly higher than those measured at moderate b-values (> 300 mm2/s), potentially due to contributions from microcirculatory flow. In comparison, OGSE ADCs measured using the DEFOG method at low b-values were comparable to those measured at moderate b-values. The effect of microcirculatory flow on diffusion signals was diffusion time-dependent, and this dependency may reflect the capillary geometry and blood flow velocity in the mouse cortex. Conclusion Microcirculatory flow affects OGSE diffusion MRI measurements at low b-values, and this effect can be suppressed using the DEFOG method. Magn Reson Med 77:1583–1592, 2017.
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