# From Optogenetic Functional MRI to Mechanogenetic Functional Ultrasound

> **NIH NIH DP1** · STANFORD UNIVERSITY · 2020 · $1,103,900

## Abstract

Project Summary / Abstract:
Many neuroscience studies have shown that specific cell types within a brain network have unique
contributions to behavioral output and that even a single neuron makes connections to large portions of the
brain. Therefore, in order to truly get at the problem of uncovering brain function we need measurements with
cellular specificity across the whole brain during behavior. As such, due to technological limitations, our current
understanding of global brain circuit mechanisms is extremely limited. My recent development of optogenetic
functional magnetic resonance imaging (ofMRI) technology provides a partial solution. However, challenges
still remain: how do you non-invasively deliver cell type specific neuromodulation? How do you image the
whole brain function in freely moving subjects? In this Pioneer Award proposal, I propose a novel approach
that enables non-invasive, cell type specific, whole mammalian brain imaging in freely moving subjects. In
particular, we propose to develop a non-invasive cell type specific stimulation in mammalian brain termed
“Mechanogenetics” and a functional ultrasound (fUS) imaging technology that can image whole brain function
in awake-behaving animals. Mechanogenetics will utilize mechanosensitive ion channels expressed in
selective cell types enabling neuromodulation using mechanical deflection from ultrasound probes delivered
non-invasively instead of using optical probes that need to be surgically implanted. For imaging, miniaturized
functional ultrasound technologies with high-resolution, 3D real-time imaging capability that can be mountable
on the subject's head will be developed. The resulting “Mechanogenetic functional ultrasound (MfUS)”
technology will enable non-invasive flexible modulation of neuronal populations while the impact of such
modulation can be monitored in freely moving animals across the whole brain with high spatiotemporal
resolution. Instead of measuring large-scale neuronal activity associated with binary behavioral readout or
complex behaviors related to single neuronal populations, my goal is to establish a new paradigm for
understanding brain function, where cell type specific whole brain function during behavior can be monitored
continuously. With such data, combined with computational modeling, whole brain algorithms of behavioral
control can be constructed. Furthermore, the Mechanogenetics technology can bring cell type specific
neuromodulation closer to human translation. Functional ultrasound technology development will also enable
human brain function monitoring in non-laboratory settings. This will ultimately enable brain circuits to be
engineered the way electrical engineers engineer electronic circuits allowing direct treatment of neurological
disease including Alzheimer's disease and related dementias or directly manage pain addressing the opioid
crisis.

## Key facts

- **NIH application ID:** 10022345
- **Project number:** 5DP1NS116783-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Jin Hyung Lee
- **Activity code:** DP1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,103,900
- **Award type:** 5
- **Project period:** 2019-09-30 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10022345

## Citation

> US National Institutes of Health, RePORTER application 10022345, From Optogenetic Functional MRI to Mechanogenetic Functional Ultrasound (5DP1NS116783-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10022345. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*