# Multiphoton In Vivo Microscopy (Core 2)

> **NIH NIH P01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $45,825

## Abstract

Discovering the basic molecular and cellular mechanisms of post-traumatic epileptogenesis in a
biophysically realistic model of traumatic brain injury will require having longitudinal, high-resolution
access to the gyrencephalic, large animal brain. Fluorescence microscopy enhances such capabilities,
enabling multimodal data collection through the use of genetically targeted and ion-selective
fluorophores. In the tool development Phase I of this project, we developed an instrument and
supporting technologies that afford us the unique ability to perform such measurements. These
technologies include a custom two-photon microscope with a gantry design that can accommodate
imaging in vivo, with subcellular resolution, brains of animals weighing >80kg. Microscopic in vivo
imaging in animals of this size (to our knowledge, the largest by a factor of 2-4x) required substantial
development and optimization of motion artifact mitigation tools, including heartbeat-triggered, high
speed image stack acquisition; flexible, penetrable, transparent sub-dural windows; and post-hoc image
registration algorithms. Finally, the microscope can perform digital fluorescence lifetime imaging,
enabling quantification of extracellular chloride using novel single-wavelength dyes. The Microscopy
Core will implement the imaging tools developed in Phase I, as well as optimize for calcium imaging and
long-term repeated access. As these tools require substantial cost and technical expertise, the
Microscopy Core represents a cost-effective consolidation and consistent implementation for the
proposed program.

## Key facts

- **NIH application ID:** 10896225
- **Project number:** 5P01NS127769-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Kyle Patrick Lillis
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $45,825
- **Award type:** 5
- **Project period:** 2023-08-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10896225

## Citation

> US National Institutes of Health, RePORTER application 10896225, Multiphoton In Vivo Microscopy (Core 2) (5P01NS127769-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10896225. Licensed CC0.

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