An ultrasound-scanning <i>in vivo</i> light source.
Authors: Jiang S, Malinao MG, Yang F, Zeng Y, Hou SS, Wu X, Rommelfanger NJ, Chaunsali L, Ding J, Chen X, Zhou Q, Sontheimer H, Hong G
Biological systems operate across distributed regions with fast, localized dynamics, yet existing biointerfaces fail short in providing both high spatiotemporal precision and the ability to dynamically target any region without disturbing surrounding tissue. Here, we present an <i>in vivo</i> deep-tissue light source based on focused ultrasound (FUS) scanning of mechanoluminescent nanotransducers (MLNTs) circulating through the vasculature. We demonstrate the programmability of this approach in tissue-mimicking phantoms and the endogenous circulatory system of animals, where tunable spatial resolution and dynamic light patterning can be achieved. We validate the functionality of the ultrasound-scanning light source in opsin-expressing neurons through electrophysiological recordings and immunostaining. We showcase dynamic three-dimensional brain targeting and temporally resolved behavioral control in freely moving animals via the ultrasound-scanning <i>in vivo</i> light source. This non-invasive deep-tissue light source offers a versatile strategy for body-wide optical interfacing.
Introduction
Purpose
Transcranial ultrasound stimulation
Study Objective
Develop and validate a non-invasive, programmable deep-tissue light source that uses focused ultrasound to activate circulating mechanoluminescent nanotransducers for spatiotemporally precise optical control in vivo.
Animal model / Human subject
Mouse (Mus musculus); strains: C57BL/6J (Jackson Lab 000664), Thy1-ChR2-YFP (Jackson Lab 007612), D1-cre (Drd1 tm1(cre)Rpa), A2a-cre (MMRRC 036158); age: adult 6–9 weeks; sex: male and female (both sexes used)
Disease model
Healthy
Targeted brain region(s)
Dentate gyrus
Target coordinates
Fiber probe (motor cortex): AP +1.0 mm, ML -1.5 mm, DV -1.0 mm (relative to bregma); Ground (cerebellum): AP -6.0 mm, ML -2.0 mm, DV -2.0 mm (relative to bregma); Stimulation targets — M1: AP +1.0 mm, ML -1.5 mm, DV -1.0 mm; S1: AP -2.0 mm, ML -1.5 mm, DV -1.0 mm; V1: AP -3.5 mm, ML -2.0 mm, DV -1.0 mm; dDG (dorsal dentate gyrus): AP -2.0 mm, ML -1.0 mm, DV -2.0 mm; vDG (ventral dentate gyrus): AP -3.0 mm, ML -2.5 mm, DV -2.5 mm (all relative to bregma)
Cargo name and characteristics
Mechanoluminescent nanotransducers (MLNTs)
Route of administration
Retro-orbital injection
Outcomes and Safety
Summary of Outcomes
Focused ultrasound activated circulating mechanoluminescent nanotransducers to generate localized light, producing region-specific neuronal activation, c-Fos expression, and behavioral modulation in freely moving mice.
Safety-related matter
No significant neuronal loss, astrocyte activation, or microglial activation detected at 1 or 4 weeks post treatment. Brain temp increase duration stimulation was less than 0.2 C and no major toxicity or tissue damage observed.
Brain Region
Ultrasound Parameters
Ultrasound instrument
1.5 MHz ring transducer (Image Guided Therapy, Pessas, France)
FUS Frequency
1.5 MHz
FUS Pressure
1 Mpa
FUS Mode
pulsed
Pulse duration
200 ms (for 1 Hz, 20% duty cycle); 20 ms (for 10 Hz, 20% duty cycle)
Duration of a single FUS session
3 minutes
Focal Characteristics
Focal depth: None; Focal length: None; Aperture size: None
Treatment frequency
Single
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