# Toward functional molecular neuroimaging using vasoactive probes in human subjects

> **NIH NIH U01** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2024 · $527,497

## Abstract

We propose to develop a probe technology for monitoring human brain function with molecular precision;
in conjunction with magnetic resonance imaging (MRI) or other imaging modalities, the probes will provide a
combination of sensitivity and resolution that could permit unprecedented noninvasive studies of dynamic neu-
rophysiological processes in people. Our strategy is based on a fundamentally new type of chemical imaging
probe designed to produce neuroimaging readouts by purposefully manipulating endogenous hemodynamic
contrast in the brain—repurposing the blood oxygen level dependent (BOLD) effect that underlies conventional
functional MRI (fMRI). This new “vasoprobe” concept offers three key advantages: First, by providing time-de-
pendent sensitivity to dilute molecular species such as neurotransmitters, the probes can enable well-defined
neurobiological phenomena to be mapped dynamically across the entire brain, dramatically surpassing existing
nonspecific fMRI approaches. Second, because of the endogenous contrast source they influence, the probes
are detectable on a variety of spatiotemporal scales by noninvasive imaging modalities complementary to fMRI,
such as diffuse optical or ultrasound-based methods. Third, by circumventing limitations of established optical,
magnetic, and radioactive probe designs, vasoprobes combine exquisite sensitivity approaching that of positron
emission tomography (PET) with the resolution and versatility of MRI. In this project, we will build on our recent
proof-of-concept work with vasoprobes to establish noninvasive brain-wide delivery strategies and to develop
robust neurochemical sensors that function in primates. The technology we establish will address multiple goals
in basic and applied neuroscience, and we expect it to yield molecular probes that will be appropriate for clinical
evaluation in human subjects by the end of the project period.
 In Aim 1, we will create vasoprobe variants that can be delivered to the brain via intravenous injection and
spontaneous permeation through the blood-brain barrier (BBB). We will form conjugates of vasoprobe-based
sensors with “brain shuttle” antibodies that have previously been shown to enable brain import via receptor-
mediated transcytosis. Demonstration of brain-permeable vasoprobes will establish a clinically viable path for
facile, noninvasive applications of vasoprobes throughout the brain. In Aim 2, we will optimize vasoprobes to
sense the key neurotransmitters dopamine and glutamate; we will then apply them on a brain-wide scale for
molecular-level fMRI in rodent brains. These experiments, in conjunction with outcome of Aim 1, will set the
stage for applications of neurotransmitter-sensitive vasoprobes and related sensors in primate brains. Accord-
ingly, in Aim 3, we will adapt neurotransmitter-sensitive vasoprobe technology for functional molecular neuroim-
aging in marmosets, a tractable primate species with which we have previous experience. Success...

## Key facts

- **NIH application ID:** 10906791
- **Project number:** 5U01EB031641-04
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Alan Jasanoff
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $527,497
- **Award type:** 5
- **Project period:** 2021-09-09 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10906791

## Citation

> US National Institutes of Health, RePORTER application 10906791, Toward functional molecular neuroimaging using vasoactive probes in human subjects (5U01EB031641-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10906791. Licensed CC0.

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