High-resolution fluorescence-guided transcranial ultrasound mapping in the live mouse brain
Hector Estrada, Justine Robin, Ali Özbek, Zhenyue Chen, Anne Marowsky, Quanyu Zhou, Daniel Beck, Beau le Roy, Michael Arand, Shy Shoham, Daniel Razansky
Science Advances 2021, 7 · 10.1126/sciadv.abi5464
Abstract
Understanding the physiological impact of transcranial ultrasound in rodent brains may offer an important preclinical model for human scale magnetic resonance–guided focused ultrasound methods. However, precision tools for high-resolution transcranial ultrasound targeting and real-time in vivo tracking of its effects at the mouse brain scale are currently lacking. We report a versatile bidirectional hybrid fluorescence-ultrasound (FLUS) system incorporating a 0.35-mm precision spherical-phased array ultrasound emission with a fiberscope-based wide-field fluorescence imaging. We show how the marriage between cortex-wide functional imaging and targeted ultrasound delivery can be used to transcranially map previously undocumented localized fluorescence events caused by reversible thermal processes and perform high-speed large-scale recording of neural activity induced by focused ultrasound. FLUS thus naturally harnesses the extensive toolbox of fluorescent tags and ultrasound’s localized bioeffects toward visualizing and causally perturbing a plethora of normal and pathophysiological processes in the living murine brain.
Abstract via europepmc.
Exposures
Exposure 1: Transcranial FUS to mouse cortex (sequences 1-3)
Target: cerebral cortex — “cortical locations (mouse cortex)”
Device: IGT / Imasonic · Imasonic ✓
| Waveform | continuous | |
|---|---|---|
| Fundamental frequency (kHz) | 3,000 | ✓✓✓ |
| Pulse duration (ms) | not applicable | |
| Pulse repetition frequency (Hz) | not applicable | |
| Duty cycle (%) | not applicable | |
| Sonication duration (s) | 0.1, 0.15, 0.3swept | ✓?⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | measurementmean or range across subjects | |
| In-situ pressure (kPa) | 3,000, 4,800swept | ✓✓✓⚑ |
| In-situ Isppa (W/cm²) | 284, 724swept | ✓✓✓ |
| In-situ Ispta (W/cm²) | not reported |
Continuous transcranial sonication delivered sequentially to cortical locations. Sequence 1: 150 ms, 3 MPa, delivered 250 times across 12 mice (0% CSD probability). Sequence 2: 100-300 ms, 3-3.9 MPa, delivered 23 times across 10 mice (8.7% CSD probability). Sequence 3: 150 ms, 4.8 MPa, delivered 5 times across 3 mice (100% CSD probability). Two mice received 150-ms pulses delivered sequentially every 11 s to two cortical locations 1 mm apart; 19 other mice received the sequences in Table 1 under isoflurane anesthesia.
Flags from extraction
exposures[0].timing.sonication_duration_s— Table 1 pairs pulse duration with pressure across three sequences (150ms/3MPa; 100-300ms/3-3.9MPa; 150ms/4.8MPa); flattening into lists loses this pairing and the CSD-probability association; consult Table 1 directly.exposures[0].in_situ.pressure_kpa— Pressure/intensity were measured with a hydrophone through an excised skull sample; treated here as in_situ though it is an ex vivo skull measurement rather than an in vivo measurement.n_sessions_per_subject— Not clearly stated how many separate sonication sessions each individual mouse received.direction_of_effect— This is a bioeffects/thermal characterization study rather than a neuromodulation study; excitatory/inhibitory classification does not map cleanly.