Label free, capillary-scale blood flow mapping in vivo reveals that low-intensity focused ultrasound evokes persistent dilation in cortical microvasculature
YuBing Y. Shen, Jyoti V. Jethe, Ashlan P. Reid, Jacob Hehir, Marcello Magri Amaral, Chao Ren, Senyue Hao, Chao Zhou, Jonathan A. N. Fisher
Communications Biology 2025 · 10.1038/s42003-024-07356-2
Abstract
Non-invasive, low intensity focused ultrasound is an emerging neuromodulation technique that offers the potential for precision, personalized therapy. An increasing body of research has identified mechanosensitive ion channels that can be modulated by FUS and support acute electrical activity in neurons. However, neuromodulatory effects that persist from hours to days have also been reported. The brain's ability to provide blood flow to electrically active regions involves a multitude of non-neuronal cell types and signaling pathways in the cerebral vasculature; an open question is whether persistent effects can be attributed, at least partly, to vascular mechanisms. Using an in vivo optical approach, we found that microvasculature, and not larger vessels, exhibit significant persistent dilation following sonication without the use of microbubbles. This finding reveals a heretofore unseen aspect of the effects of FUS in vivo and indicates that concurrent changes in neurovascular function may partially underly persistent neuromodulatory effects.
Abstract via europepmc.
Exposures
Exposure 1: FUS to forelimb somatosensory cortex
Target: primary somatosensory cortex — “the region overlying the forelimb’s representation on the primary somatosensory cortex”
Device: Sonic Concepts · Sonic Concepts, Inc. · customized H-205B ring transducer; TPO-106 transducer drive system ✓
| Waveform | pulsed | |
|---|---|---|
| Fundamental frequency (kHz) | 510 | ✓✓✓ |
| Pulse duration (ms) | 0.5 | ✓✓✓⚑ |
| Pulse repetition frequency (Hz) | 1,000 | ✓✓✓ |
| Duty cycle (%) | 50pulse duration × PRF gives 50% | ✓✓✓ |
| Sonication duration (s) | 20 | ✓✓✓ |
| Free-field pressure (kPa) | 124, 450swept | ✓✓✓ |
|---|---|---|
| Free-field Isppa (W/cm²) | 1, 10swept | ✓✓✓ |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
20 s of 510 kHz ultrasound as 0.5 ms pulses at 1 kHz (50% duty cycle), delivered twice with a 10-minute separation, at 1 W/cm2 or 10 W/cm2 Isppa in separate animals.
Flags from extraction
n_subjects— 28 animals total includes 3 shams and 5 for histology only (one of which was an unsonicated sham); 24 received sonication.exposures[0].unspecified_domain.pressure_kpa— Peak pressures of 0.124 and 0.45 MPa are given with beams characterised in a water tank, but the text does not say whether the Isppa and pressure values are free-field or in tissue; placed in unspecified_domain.exposures[0].unspecified_domain.isppa_w_cm2— Intensities 1 and 10 W/cm2 Isppa; a 1.2 W/cm2 and a 200 W/cm2 exposure were also used in a separate histology cohort.exposures[0].device.family— Custom H-205B ring transducer with a TPO-106 drive system; family set by transducer maker Sonic Concepts, not NeuroFUS.exposures[0].timing.pulse_duration_ms— Text calls the 20 s sonication a burst of 0.5 ms pulses at 1 kHz; stated pulse duration and duty cycle are consistent.