A first look at interstitial fluid flow in the brain

July 3, 2018, American Institute of Physics
This MRI with contrast shows heterogenous interstitial fluid flow in glioblastoma. The tumor border is outlined in red. Credit: Kingsmore et al.

Interstitial fluid transports nutrients and removes waste between the organs and tissues in our body. In the brain, interstitial fluid is thought to be composed of circulating cerebrospinal fluid, cellular waste and blood plasma, and past research has shown a link between interstitial fluid flow and an increased invasion rate of glioblastoma, or brain tumor, cells. A team of biomedical researchers and electrical engineers from the University of Virginia and Virginia Tech recently developed a new method to measure and reconstruct interstitial fluid flow velocities in the brain.

This gives researchers a first look at interstitial flow dynamics in glioma models, and the can readily translate to clinical models already using contrast-enhanced magnetic resonance imaging (MRI). The team describes their method in a special issue focusing on the "Bioengineering of Cancer" in APL Bioengineering.

The team built on an existing dynamic contrast-enhanced MRI technique that's already frequently used in clinics to track tumor growth and movement. "We are excited about our technique because we could potentially translate it to patient data that already exists and look at interstitial fluid motion in those patients," said Jennifer Munson, a lead author on the paper.

Munson touted the team's rigorous validation approach in silico and in vitro. First, the team developed an in vitro model of interstitial fluid flow moving through extracellular space by placing fluid on top of a hydrogel and using MRI to measure how the fluid flowed from top to bottom. Then, they validated their computational model against their experimental measurements.

To further validate their technique, Daniel Abler and Russell Rockne, who are co-authors on the paper, created phantom fluid "flow field," in a computer and then reconstructed that flow using their new imaging methodology. Finally, the team implanted patient-derived glioma cells in mice and examined the mouse tumors using MRI to visualize a real flow field.

The team was surprised to find high variability in the flow's rate and magnitude. "There's been this classical idea that a tumor develops and there's this equivalent flow rate going out in all directions like a sphere," Munson said. "Our method and our visualization approach and modeling show that that's a large oversimplification and we have a very heterogenous system. Sometimes is going out, or in, or along the side."

One day, this technique could potentially help researchers predict how a might grow and, therefore, improve cancer treatments. More immediately, the team plans to use their established method "to understand the relationship between the fluid velocities and the growth of the tumors," Munson said.

Explore further: Noninvasive measurement enables use of IFP as potential biomarker for tumor aggressiveness

More information: Kathryn M. Kingsmore et al, MRI analysis to map interstitial flow in the brain tumor microenvironment, APL Bioengineering (2018). DOI: 10.1063/1.5023503

Related Stories

How the fluid between cells affects tumors

July 25, 2012

There are many factors that affect tumor invasion, the process where a tumor grows beyond the tissue where it first developed. While factors like genetics, tissue type and environmental exposure affect tumor metastasis and ...

New imaging process provides better picture of tumours

October 12, 2012

Cancer remains one of the leading causes of death in Europe and the world, and early detection and treatment remains vital in the fight. Researchers in Norway have validated a method of non-invasive imaging that they believe ...

Flow of cerebrospinal fluid regulates division

May 18, 2018

Stem cells in the brain can divide and mature into neurons participating in various brain functions, including memory. In a paper scientists have discovered that the flow of cerebrospinal fluid is a key signal for neural ...

Wireless sensor transmits tumor pressure

September 20, 2014

The interstitial pressure inside a tumor is often remarkably high compared to normal tissues and is thought to impede the delivery of chemotherapeutic agents as well as decrease the effectiveness of radiation therapy. While ...

Giraffes are living proof that cells' pressure matters

July 3, 2012

Physicists from the Curie Institute, France, explored the relative impact of the mechanical pressure induced by dividing cells in biological tissues. This approach complements traditional studies on genetic and biochemical ...

Recommended for you

Orangutan mothers found to engage in displaced reference

November 15, 2018

A pair of researchers with the University of St Andrews has observed orangutan mothers engaging in displaced reference after observation of a perceived threat. In their paper published in the journal Science Advances, Adriano ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

ForFreeMinds
1 / 5 (3) Jul 03, 2018
Since the interstitium was "discovered", this is a great area of research, especially regarding metastasis of cancer. We could save a lot of lives moving money going into climate change research into research of the interstitium.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.