# Development of a high throughput system for molecular imaging of different cell types in mouse brain tissues

> **NIH NIH RF1** · PURDUE UNIVERSITY · 2021 · $1,511,433

## Abstract

Development of a high throughput system for molecular imaging of different cell types in mouse brain
tissues
Mass spectrometry imaging (MSI) is a powerful tool for developing detailed molecular maps of biological
tissues with high specificity and sensitivity. This label-free technique enables simultaneous imaging of
multiple classes of molecules including lipids, metabolites, and proteins thereby advancing the
understanding of tissue organization and function. In this project, we will advance brain cell census
research by developing an innovative platform for the acquisition of a comprehensive spatially-resolved
cell-specific atlas of lipids, metabolites, and proteins in mouse brain tissue. The platform will combine MSI
with immunofluorescence imaging to place the detailed molecular maps into the spatial cellular context
within the brain tissue, which will facilitate image registration to the common coordinate system.
Furthermore, we will develop deep learning and data mining approaches to enable automated assignment
of molecular signatures to different cell types and efficient data sharing and comparison with other
techniques. This research will address the existing bottlenecks in the experimental throughout and
molecular coverage of the current MSI technologies along with the limitations of data analysis tools.
Furthermore, our approach will compensate for signal suppression during ionization also called ‘matrix
effects’, which is particularly severe in imaging of brain tissue. Such matrix effects common to all the MSI
modalities including commercial MALDI MSI instruments interfere with the accurate measurement of the
spatial localization of molecules. To overcome these challenges, we will advance the capabilities of
nanospray desorption electrospray ionization (nano-DESI) - an ambient ionization technique, which
efficiently compensates for matrix effects and thereby enables accurate and sensitive imaging of chemical
gradients for hundreds of metabolites and lipids in biological tissue sections. Nano-DESI MSI does not require
sample pretreatment, has a sub-femtomole sensitivity, and high spatial resolution. The new nano-DESI MSI
system will provide a 5-fold increase in the experimental throughput and improve the spatial resolution of
protein imaging in whole tissue sections from ~80 µm to ~10 µm. Coupling nano-DESI MSI with a high-
resolution ion mobility mass spectrometer will substantially enhance molecular coverage. Meanwhile, co-
registration of MSI with immunofluorescence data will be used to generate comprehensive 3D molecular
maps of the mouse brain tissue. Collectively, these efforts will establish a robust imaging platform, which will
transform our ability to generate detailed molecular maps of different cell types in brain tissues.

## Key facts

- **NIH application ID:** 10369883
- **Project number:** 1RF1MH128866-01
- **Recipient organization:** PURDUE UNIVERSITY
- **Principal Investigator:** GAURAV CHOPRA
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,511,433
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-09-14

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369883

## Citation

> US National Institutes of Health, RePORTER application 10369883, Development of a high throughput system for molecular imaging of different cell types in mouse brain tissues (1RF1MH128866-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10369883. Licensed CC0.

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