# Multimodal probes for multiscale calcium imaging

> **NIH NIH R21** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2021 · $231,825

## Abstract

A major goal of the BRAIN Initiative is to promote the development of neural activity measurement tools that
bridge between spatial scales, so that the processing roles of individual neurons and microcircuits can be related
to broader regional or brain-wide dynamics. Here we propose to create novel chemical probes of neuronal cal-
cium signaling that will enable cross-modal comparison of readouts obtained at multiple scales, using both inva-
sive and noninvasive imaging methods. Using these multifunctional probes, investigators will be able to record
wide-field neural activity dynamics at varying depths and spatiotemporal resolutions from well-defined molecular
sources that permit precise interpretation, without the potential for artifacts associated with parallel application
of disparate probe modalities. This will be particularly valuable for validation and use of the probes in noninvasive
imaging modalities, for which probe technologies are still relatively rudimentary and untested, and relating wide-
field signals to micron-resolution optical results could be especially informative. The new probes we will create
are derived from a cell-permeable aromatic chelator called texaphryin (Tex). Complexes of Tex variants with
different metal ions function as potent fluorophores, photoacoustic reporters, and T1-weighted contrast agents
for magnetic resonance imaging (MRI). We recently discovered that combining paramagnetic Tex complexes
with calcium-responsive moieties such as 1,2-bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (BAPTA)
results in strong calcium-dependent contrast changes, thus providing a promising basis for synthesis of sensors
suitable for simultaneous or parallel measurement by MRI, optical, and photoacoustic readouts. In this project,
we will synthesize and optimize the multimodal sensors, evaluate their optical and magnetic imaging capabilities,
and begin in vivo validation studies that directly exploit the unique advantages these novel probes offer. These
experiments will establish a first-of-its-kind molecular platform with potentially powerful capability for multimodal
analysis of neural activity dynamics across spatial and temporal scales in a variety of species and behavioral
contexts.

## Key facts

- **NIH application ID:** 10154098
- **Project number:** 1R21EY032369-01
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Alan Jasanoff
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,825
- **Award type:** 1
- **Project period:** 2021-05-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10154098

## Citation

> US National Institutes of Health, RePORTER application 10154098, Multimodal probes for multiscale calcium imaging (1R21EY032369-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10154098. Licensed CC0.

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