Non-invasive electrical stimulation as a novel therapeutic approach to brain tumors


In a first-of-its kind study, neurologists at Beth Israel Deaconess Medical Center (BIDMC) tested the use of non-invasive electrical stimulation as a novel therapeutic approach to brain tumors.

In an experiment published in Science Advances, the scientists – led by Emiliano Santarnecchi, Ph.D., principal investigator at the Berenson-Allen Center For Non-Invasive Brain Stimulation at BIDMC – demonstrated that applying low-intensity electrical stimulation to the brains of patients with tumors resulted in decreased blood flow within tumors while leaving the rest of the brain unchanged.

Although further study is needed, the findings suggest that a series of such treatments could modify tumor growth and progression.

“Many patients with brain tumors have limited therapeutic options, most of which come with severe side effects,” said Santarnecchi, who is also an Assistant Professor of Neurology at Harvard Medical School.

“Our study found that electrical stimulation resulted in a significant reduction of blood flow to the tumor, with no changes in the rest of the brain.

Given the safety profile of non-invasive brain stimulation, the ease of its application, its relatively low cost and the possibility of combining it with other drug-based therapies, our findings might lead to non-invasive therapeutic options for patients with brain tumors.”

Non-invasive brain stimulation – also known as transcranial electrical stimulation (tES) – is a 20- year old, FDA-approved technology that is used to treat a number of psychiatric conditions, including treatment-resistant depression.

Low-intensity electrical fields are delivered to the brain through the skull via electrodes placed on the scalp.

While many researchers continue to investigate the safe and relatively low cost treatment’s potential to treat psychiatric disorders and to enhance cognitive skills such as memory and concentration, this study represents the first time tES has been tested in patients with brain tumors.

Scientists at Harvard Medical School and University of Siena have developed and tested a novel therapeutic approach to modify brain activity in patients with brain tumors. Credit: Sprugnoli et al. Science Advances (2019). DOI: 10.1126/sciadv.aau9309

Santarnecchi and colleagues recruited 50 patients with brain tumors willing to participate. Given the delicate patient population, eight participants were able to complete the trial – six with glioblastoma, an aggressive tumor that originates in the brain, and two with metastatic tumors that originated in the lung.

The patients received transcranial stimulation while their brain blood flow was monitored using magnetic resonance imaging (MRI) technology.

Based on prior research showing a reduction of blood flow in bodily tumors exposed to electric stimulation, Santarnecchi and team predicted that tES would have a similar effect on the brain tumors.

However, the team was surprised to see significant reductions in blood flow to the tumors after a single tES session.

No changes in blood flow or activity in the rest of the brain were observed, and none of the patients reported any adverse effects.

“This technique still requires further testing to optimize frequency and duration of treatment and to fully personalize protocols for individual patients,” said Santarnecchi. “Future studies will investigate the impact of repeated tES sessions, evaluate the potential combination of tES with other cancer therapies and assess tES in other forms of brain tumors.”

There has been a persistent increase in the incidence of cardiovascular and circulatory diseases owing to the state of blood vessels and circulation characteristics [1].

Thus, blood flow velocity and vessel status are measurable markers that can be used to diagnose health status [2].

Nevertheless, measurement and prediction of circulatory features lack the required precision for clinical diagnosis and treatment.

Previous studies have evaluated the characteristics of the vasculature and blood flow [23]. S

pecifically, it is important to ascertain the heart rate, blood pressure, state of the blood vessels, and blood flow velocity to predict blood flow characteristics.

Therefore, among the diagnostic devices for vascular diseases, such as magnetic resonance imaging, ultrasonography, near-infrared imaging, and laser imaging [4], Doppler ultrasonography was used to detect moving reflectors.

Ultrasonography has the advantage of non-invasively measuring blood flow velocity in a quick and continuous manner based on the velocity of sound. Moreover, it enables examination of the state of the blood vessels from the vessel cross-section [5].

As the blood flows through the blood vessels, it maintains a constant shearing force with the endothelial cells in the vessel wall.

Thus, the interaction between the vessels and blood is determined by the state of the vasculature and blood flow characteristics [6]. Blood flow velocity is kept constant by a system of self-regulation, primarily controlled by the activity of the brain [7].

Therefore, the characteristics of blood flow and vascular transformation are organically interlinked with the circulatory system of the whole body.

In other words, blood flow is proportional to flow velocity and is inversely proportional to the cross-sectional area, which is affected by vascular contraction [8].

However, it is controversial whether an increase in blood flow velocity directly reflects a rise in blood flow [9].

Despite such controversy, blood flow velocity, as measured by vessel size, is a critical index used as an objective diagnostic criterion in functional tests in patients who are not using drugs that affect vascular resistance or in situations where the vascular resistance is not significantly altered [6].

Physiological changes caused by electrical stimulation include an increase in blood flow and an effect on the peripheral circulation [7].

The appropriate dose and duration of electrical stimulation can achieve various physiological responses [10].

Therefore, electrical stimulation affects the control of blood flow, and precise control of such electrical stimulation is essential to avoid tissue damage [5].

Interferential current (IFC) is one method of electrical stimulation used for pain management, and its clinical applications are diverse; low resistance of the skin and subcutaneous tissues allows focal application of electricity at certain points [10].

IFC uses a current in the mid-frequency range of 1-100 KHz; it is an amplitude-modulated alternative current produced by cross-interference of different currents within the body, thereby transmitting a burst frequency in the biological range into a continual flow of electric potential [11]

. In addition, evidence-based approaches of the objective circumstances are required for electrical stimulation conditions and levels [12].

The aim of this study is to quantitatively express blood flow characteristics and functional changes in the vasculature using Doppler ultrasonography.

Accordingly, the hypotheses established to examine the study aim are as follows:

1) blood flow velocity will differ per the amplitude and frequency of IFC and

2) vessel size will change depending on the amplitude and frequency of IFC.

More information: G. Sprugnoli et al. Reduction of intratumoral brain perfusion by noninvasive transcranial electrical stimulation, Science Advances (2019). DOI: 10.1126/sciadv.aau9309

Journal information: Science Advances
Provided by Beth Israel Deaconess Medical Center



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