# Imaging the molecular constituents of the brain vasculature and lymphatic connectome

> **NIH NIH U24** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2023 · $100,000

## Abstract

PIs: David Kleinfeld and Zhuhao Wu
 Project Summary
 Imaging the molecular constituents of the brain vasculature and lymphatic connectome
The intricate connectivity of the brain vasculature that extends into the skull and the meningeal lymphatic vessels
are vital in the systematic cerebral blood flow circulation, immunological responses, and waste product removal.
However, our understanding of these complex networks remains limited, largely because of the challenges in
imaging the complete three-dimensional structure of these structure at high resolution in heterogeneous
biological tissues.
Recent technical advances on two fronts, one in molecular characterization and labeling, and the other in tissue
clearing, led to the discovery of skull-meninge vascular connections. However, wavefront distortion through
imperfectly cleared skull and brain tissue severely deteriorate the resolution of imaging at depth. Here we
propose to advance sample preparation and imaging technologies that are compatible with labeling and that
mitigate the loss in resolution. Our optical methods involve non-linear imaging as well as the use of femtosecond
ablation with temporal focussing of bone and soft tissue. This will enable us to obtain diffraction-limited resolution
images at the skull/meningeal/brain transition zone.
This pilot project will establish a pipeline to image and reconstruct the entire vasculature system and lymphatic
system at cellular resolution in the mouse brain. This is a prelude to the long-term goal of imaging and
reconstructing similar atlases for all organs in the body.

## Key facts

- **NIH application ID:** 10834499
- **Project number:** 3U24EB028942-04S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** David Kleinfeld
- **Activity code:** U24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $100,000
- **Award type:** 3
- **Project period:** 2019-09-30 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834499

## Citation

> US National Institutes of Health, RePORTER application 10834499, Imaging the molecular constituents of the brain vasculature and lymphatic connectome (3U24EB028942-04S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10834499. Licensed CC0.

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