As brain tumours grow, they must do one of two things: push against the brain or use finger-like extensions to invade and destroy surrounding tissue.

Previous research found tumours that push — or put mechanical force on the brain — cause more neurological dysfunction than tumours that destroy tissue.

But what else can these different tactics of tumour growth tell us?

Now, the same team of researchers from the University of Notre Dame, Harvard Medical School/Massachusetts General Hospital, and Boston University has developed a technique for measuring a brain tumour’s mechanical force and a new model to estimate how much brain tissue a patient has lost.

Published in Clinical Cancer Research, the study explains how these measurements may help inform patient care and be adopted into surgeons’ daily workflow.

“During brain tumour removal surgery, neurosurgeons take a slice of the tumour, put it on a slide and send it to a pathologist in real-time to confirm what type of tumour it is. Tumours that originally arise in the brain, like glioblastoma, are prescribed different treatments than tumours that metastasise to the brain from other organs like lung or breast, so these differences inform post-surgical care,” said Meenal Datta, assistant professor of aerospace and mechanical engineering at Notre Dame and co-lead author of the study.

“By adding a two-minute step to a surgeon’s procedure, we were able to distinguish between a glioblastoma tumour versus a metastatic tumour based on mechanical force alone.”

Datta and collaborators collected data from 30 patients’ preoperative MRIs and their craniotomies, which include exposing the brain and using Brainlab neuronavigation technology.

This technology provides surgeons with real-time, 3D visualisation during brain surgeries and is considered commonly available for neurological procedures.

Neurosurgeons can use this technique to measure the bulge caused by brain swelling from the tumour’s mechanical forces before the tumour is resected.

Then this patient data was used to determine whether brain tissue was displaced by a tumour’s mechanical force or replaced by a tumour.

The researchers found that when there is more mechanical force on the brain (displacement), the swelling will be more substantial.

But when a tumour invades and destroys surrounding tissue (replacement), the swelling will be less significant.

The researchers created computational models based on a point system of measurements and biomechanical modelling that can be employed by doctors to measure a patient’s brain bulge, to determine the mechanical force that was being exerted by the tumour, and to determine the amount of brain tissue lost in each patient.

Funded by the National Institutes of Health, National Science Foundation and various cancer research foundations, this study is among the first to show how mechanics can distinguish between tumour types.

“Knowing the mechanical force of a tumour can be useful to a clinician because it could inform patient strategies to alleviate symptoms. Sometimes patients receive steroids to reduce brain swelling, or antipsychotic agents to counter neurological effects of tumours,” said Datta, an affiliate of Notre Dame’s Harper Cancer Research Institute.

Datta recently showed that even affordable and widely used blood pressure medications can counter these effects.

“We’re hoping this measurement becomes even more relevant and that it can help predict outcomes of chemotherapy and immunotherapy.”

To get a better idea of what else mechanical force could indicate, the research team used animal modelling of three different brain tumours: breast cancer metastasis to the brain, glioblastoma and childhood ependymoma.

In the breast cancer metastasis tumour, researchers used a form of chemotherapy that is known to work in reducing metastasis brain tumour size.

While waiting for the tumour to respond to the chemotherapy, the team found that a reduction in mechanical force changed before the tumour size was shown to change in imaging.

“In this model, we showed that mechanical force is a more sensitive readout of chemotherapy response than tumour size,” Datta said.

“Mechanics are sort of disease-agnostic in that they can matter regardless of what tumour you are looking at.”

Datta hopes that doctors employ the patient models from the study to continue to grow the field’s understanding of how mechanical force can improve patient care management.

Source: University of Notre Dame