# Magnetic Resonance Imaging Reveals Meningeal Lymphatic Impairment in Lung Adenocarcinoma Brain Metastasis Progression

## TL;DR

This study shows that lung cancer spreading to the brain disrupts meningeal lymphatic vessels, impairing immune surveillance and disease management.

## Contribution

The study introduces non-invasive MRI biomarkers to analyze meningeal lymphatic structure and function in brain metastasis.

## Key findings

- Meningeal lymphatic vessels near the superior sagittal sinus are disrupted in lung adenocarcinoma brain metastasis.
- Impaired meningeal lymphatic drainage correlates with disease progression in clinical cases.
- mLV ablation in mice reduces intrathecal chemotherapy efficacy, highlighting their functional importance.

## Abstract

Meningeal lymphatic vessels (mLVs) contribute to brain immune surveillance; however, their structural and functional alterations in brain metastasis remain incompletely defined. Here, we optimized a magnetic resonance imaging protocol to quantitatively analyze mLV structure and drainage function. Using murine lung adenocarcinoma brain metastasis models and clinical imaging data, we reveal significant mLV disruption surrounding the superior sagittal sinus (SSS), which results in impaired drainage to deep cervical lymph nodes (dCLNs). Among ten cervical lymph‐node levels assessed clinically, level IIA lymph nodes most accurately reflect mLV drainage efficiency. Functionally, mLV ablation compromised intrathecal chemotherapy efficacy in mice, while clinically, greater mLV structural and functional impairment correlates with disease progression in lung adenocarcinoma brain metastasis. Collectively, our findings demonstrate that lung adenocarcinoma brain metastases disrupt SSS‐adjacent mLVs (mLVs‐SSS), which potentially facilitates metastatic progression through compromised immune surveillance.

This study demonstrates meningeal lymphatic impairment associated with lung adenocarcinoma brain metastasis progression in both human patients and mouse models, establishes clinically applicable non‐invasive imaging biomarkers for quantitative analyzing mLV structure and function, and reveals mLVs as robust prognostic indicators and promising potential therapeutic targets for effective brain metastasis management.