# Image-based Systems Biology of Vascular Co-option in Brain Tumors

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2024 · $427,988

## Abstract

ABSTRACT:
Recent clinical and preclinical evidence has shown that gliomas can initially grow, invade, evade antiangiogenic therapies
and eventually recur by hijacking or “co-opting” the brain’s preexisting blood vessels. Vascular co-option is a
nonangiogenic glioma growth mechanism in which, co-opting tumor cells cause astrocytes to lose intimate contact with
blood vessels, i.e. cause gliovascular uncoupling (GVU), and alter cerebral hemodynamics. Additionally, in aggressive high-
grade gliomas (e.g. glioblastoma or GBM), vessel co-option facilitates the migration and invasion of cancer cells into
healthy brain tissue. Yet, the evolution of vessel co-option over the glioma’s life-time, resultant GVU and hemodynamic
changes remain poorly understood due to a lack of microvascular-resolution lifecycle and multimodality/multiscale
imaging approaches. Moreover, co-optive glioma growth is radiologically undetectable due to an absence of contrast
enhancement and the lack of specificity of conventional MRI (e.g. T2/FLAIR) approaches. Therefore, our goal is to use an
image-based systems biology approach to elucidate the hemodynamics of co-optive glioma over its lifecycle and
develop an fMRI biomarker of co-option induced GVU. Guided by compelling preliminary data, we will pursue three
Specific Aims: (1) Characterize vessel co-option in a patient-derived glioma xenograft (PDX) over its lifecycle with
multiscale imaging; (2) Develop an image-based model of brain-wide hemodynamic changes induced by vessel co-option
in glioma; and (3) Determine if rs-fMRI can detect vessel co-option induced GVU in a patient-derived glioma xenograft.
Under Aim1, we propose a paradigm-shifting approach that employs a miniscope for microvessel resolution (~5 µm)
multicontrast in vivo imaging of co-option induced hemodynamic changes over the lifecycle of a patient-derived glioma
xenograft. We will complement these microvascular-scale measurements with multimodality/multiscale whole-brain data
from ex vivo CT/MRI/light sheet microscopy (LSM) in the same animal to corelate structural/functional/cellular changes
in the vascular microenvironment (VME). Under Aim2, we employ these data in a model of co-option induced
hemodynamic dysregulation to simulate brain-wide changes that could be exploited as fMRI biomarkers of co-optive
glioma. Under Aim3, we will determine if resting-state fMRI (rs-fMRI) can detect GVU in a co-optive PDX and differentiate
it from non-co-optive glioma growth. Our approach is innovative because it blends cutting-edge advances in miniaturized
microscopy, multiscale/multimodality imaging and image-based systems biology. The proposed research is significant
because these studies will establish: (i) freely downloadable, co-registered multiscale data for cancer systems biology
investigators; (ii) a hemodynamic model for co-optive glioma; (iii) a novel biomarker of glioma co-option with the potential
to transform patient management and stimulate the development of th...

## Key facts

- **NIH application ID:** 10833666
- **Project number:** 5R01CA196701-07
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Arvind P Pathak
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $427,988
- **Award type:** 5
- **Project period:** 2023-04-27 → 2028-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10833666

## Citation

> US National Institutes of Health, RePORTER application 10833666, Image-based Systems Biology of Vascular Co-option in Brain Tumors (5R01CA196701-07). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10833666. Licensed CC0.

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