Imaging glymphatic response to glioblastoma

Authors

Jasleen Kaur, Henry Ford HealthFollow
Guangliang Ding, Henry Ford HealthFollow
Li Zhang, Henry Ford HealthFollow
Yong Lu, Henry Ford HealthFollow
Hao Luo, Henry Ford HealthFollow
Lian Li, Henry Ford HealthFollow
Edward Boyd, Henry Ford HealthFollow
Qingjiang Li, Henry Ford HealthFollow
Min Wei, Henry Ford HealthFollow
Zhenggang Zhang, Henry Ford HealthFollow
Michael Chopp, Henry Ford HealthFollow
Quan Jiang, Henry Ford HealthFollow

Recommended Citation

Kaur J, Ding G, Zhang L, Lu Y, Luo H, Li L, Boyd E, Li Q, Wei M, Zhang Z, Chopp M, and Jiang Q. Imaging glymphatic response to glioblastoma. Cancer Imaging 2023; 23(1):107.

Document Type

Article

Publication Date

10-30-2023

Publication Title

Cancer Imaging

Abstract

BACKGROUND: The glymphatic system actively exchanges cerebrospinal fluid (CSF) and interstitial fluid (ISF) to eliminate toxic interstitial waste solutes from the brain parenchyma. Impairment of the glymphatic system has been linked to several neurological conditions. Glioblastoma, also known as Glioblastoma multiforme (GBM) is a highly aggressive form of malignant brain cancer within the glioma category. However, the impact of GBM on the functioning of the glymphatic system has not been investigated. Using dynamic contrast-enhanced magnetic resonance imaging (CE-MRI) and advanced kinetic modeling, we examined the changes in the glymphatic system in rats with GBM.

METHODS: Dynamic 3D contrast-enhanced T1-weighted imaging (T1WI) with intra-cisterna magna (ICM) infusion of paramagnetic Gd-DTPA contrast agent was used for MRI glymphatic measurements in both GBM-induced and control rats. Glymphatic flow in the whole brain and the olfactory bulb was analyzed using model-derived parameters of arrival time, infusion rate, clearance rate, and residual that describe the dynamics of CSF tracer over time.

RESULTS: 3D dynamic T1WI data identified reduced glymphatic influx and clearance, indicating an impaired glymphatic system due to GBM. Kinetic modeling and quantitative analyses consistently indicated significantly reduced infusion rate, clearance rate, and increased residual of CSF tracer in GBM rats compared to control rats, suggesting restricted glymphatic flow in the brain with GBM. In addition, our results identified compromised perineural pathway along the optic nerves in GBM rats.

CONCLUSIONS: Our study demonstrates the presence of GBM-impaired glymphatic response in the rat brain and impaired perineural pathway along the optic nerves. Reduced glymphatic waste clearance may lead to the accumulation of toxic waste solutes and pro-inflammatory signaling molecules which may affect the progression of the GBM.

Medical Subject Headings

Rats; Animals; Glioblastoma; Brain; Glymphatic System; Magnetic Resonance Imaging; Contrast Media

PubMed ID

37904254

Volume

23

Issue

1

First Page

107

Last Page

107