Transcranial displacement imaging in mice: an ex vivo parametric and an in vivo feasibility study

Focused ultrasound (FUS) enables a non-invasive, deep, and targeted modulation of neural activity. While various imaging techniques, in conjunction with FUS, have been employed to guide and monitor FUS neuromodulation, magnetic resonance acoustic radiation force imaging (MR-ARFI) serves as a gold-standard imaging technique for estimating microscopic displacement induced by FUS. Displacement imaging is analogous to MR-ARFI in that it provides an estimation of FUS-induced displacement, but it offers higher spatiotemporal resolution and sensitivity. Simultaneous displacement imaging with FUS, has been demonstrated in craniotomized mice, probing the causal hemodynamic response that spatially and quantitatively correlates with displacement. Despite the utility and need for displacement imaging in FUS applications, transcranial displacement imaging has, by comparison, been challenging. In this study, we developed and performed transcranial displacement imaging in mice under the ex vivo and in vivo experimental setups. In the ex vivo study, we imaged displacement at varying FUS pressures and frequencies, and demonstrated stronger skull aberration and attenuation in displacement (~ 32% at 1.68 MHz vs. ~ 42% at 4 MHz). Importantly, we showed a quadratic relationship between peak negative interframe displacement and peak positive pressures, which is in agreement with acoustic radiation force proportional to FUS intensity. In the in vivo study, we found focal displacement during relaxation with a peak negative interframe displacement of ~ 5 μm at 4.52 MPa and 1.68 MHz FUS. In addition, transcranial displacement imaging successfully differentiated focal displacement at multiple imaging planes with varying proximity to the FUS focus, demonstrating target-specificity of focal displacement induced by 1.68 MHz FUS. In both ex vivo and in vivo studies, we found that the peak negative interframe displacement during relaxation provides a robust and reliable estimate of acoustic radiation force. Our findings contribute to ongoing efforts in mechanistic monitoring of FUS neuromodulation and the translation of transcranial displacement imaging.