This ultra-small probe promises to record neuron activity without invasive surgery 

An uncanny device called the MEV probe can travel to the deepest parts of your brain via the narrowest blood vessels that lead to them.
Rupendra Brahambhatt
MEV probe for neural recording across the blood vessel wall.
MEV probe for neural recording across the blood vessel wall.

Anqi Zhang, Stanford University

A team of researchers at Stanford University has developed a micro-endovascular (MEV) probe that can record deep brain activity without surgery. This novel brain-machine interface can be used to monitor and treat many neurological diseases minimally invasively.

The researchers successfully tested MEV in rats, where it could move forward smoothly in tiny (less than 100 micrometers in diameter) blood vessels of their brains and record single neuron activity without causing any damage.

Most recent work and commercial neural implants are more than 50 times larger than MEV and have only been introduced to large blood vessels more than 2 millimeters in diameter in large animals (e.g., sheep) or humans. 

“Since the probe can reach very tiny vessels with thin vessel walls (10-20 micrometers), it can record the neuron activity on the other side of the vessel wall with single-cell resolution,” Dr. Anqi Zhang, the first author of the study and a postdoc in Bioengineering and Chemical Engineering at Stanford University, told Interesting Engineering (IE).  

Recording single-neuron activity from deep brain regions was never achieved before with an endovascular probe like MEV and was previously only possible with surgical implantation directly into the brain tissue. However, such surgical procedures are risky as they involve invasive intracranial surgery that could lead to infections and brain damage. 

“Our study in rats breaks completely new ground in going to these very small vessels, which by extension could allow probing deep in the brain of humans, with high resolution but without invasive surgery,” said Dr. Charles M. Lieber, one of the study authors and an advisor to Dr. Zhang, added. 

How does the MEV probe work?

The MEV probe used in the current study is about 7 cm long (designed for rats). It has an ultra-flexible mesh-like device region at the tip, a stem in the middle, and an input/output (I/O) region at the tail. 

There are 16 platinum electrodes embedded in the mesh-like device region, and are delivered to the targeted blood vessel. The I/O region is left outside the skull and connected to the recording equipment.

For delivery, the MEV probe is first loaded into a flexible microcatheter connected to a syringe filled with saline solution; the microcatheter is then inserted through a blood vessel in the neck and advanced to the base of the brain. As the probe is much smaller than the microcatheter, saline flow in the microcatheter carries the probe much deeper into small sub-100-micrometer vessels. 

“We think it is useful for the readers to know that the procedure of catheter insertion into a blood vessel can be fairly routine in a hospital, and one of us (Charles Lieber) recently had catheters inserted through blood vessels through the neck and arm (to the heart) as part of cancer treatment with no ill effects,” said Dr. Zhang.

Before implantation, the highly-flexible mesh is rolled up radially inside the microcatheter. After injection, the ribbons with 16 electrodes relax and unroll so that the electrodes adhere against the inner vessel walls of the blood vessels, similar to vascular stent deployment.

According to the researchers, this is an essential design because it allows the electrodes to be closely attached to inner vessel walls, close to the neurons they are recording from, which improves the recording quality. 

Another benefit to the ultra-flexible design (besides the ability to be injected into really small blood vessels), and contrary to conventional devices and stents, is that it does not cause immune reactions inside the blood vessel that could cause clogging or change the blood flow.

MEV probe might help millions

According to the researchers, the MEV probe is a novel brain-machine interface (BMI) that can potentially diagnose and treat numerous brain disorders.

For instance, deep brain stimulation is routinely used in drug-resistant Parkinson’s disease patients, where electrodes are inserted into specified brain areas through open skull surgery to deliver electrical pulses to the region to restore normal movements.

The MEV probes might reach these areas without invasive brain surgery, deliver electrical pulses across the blood vessel walls, and achieve the same treatment effects without the invasiveness of the large deep-brain stimulators.

Although, in the current study, the probe doesn’t have a power source since Dr. Zhang and her team used it for passive neural recording. “In the future, we plan to do neural stimulation using these electrodes, which will need a power source to deliver electrical pulses to the electrodes. Such power sources are already in use in humans to power invasive deep-brain stimulators used to treat Parkinson’s disease,” said Dr. Lieber.

The researchers further claim that their MEV probe can also monitor epilepsy models and track the seizure foci (location in the brain from where a seizure originates), which could provide guidance for epilepsy surgery and help millions of epilepsy patients across the globe. 

Moreover, the probe could be utilized as an effective BMI to set up direct electrical connectivity between a patient’s brain and external electronic devices. Therefore, enabling people with paralysis and brain disorders to control prosthetics and other assistive devices much better. 

However, the current MEV design is suitable for use in rats. They suggest It will take some time before this technology is available for human use. In the near term, they will focus on improving the probe design and materials for better navigation. 

In the long term, they plan to use the improved designs to study the brain and diseases and achieve clinical translation to neurology and interventional radiology.

“While this is really exciting to us with the potential to impact in a positive way human conditions and diseases, it will take time to translate safely to clinical studies. In a small academic lab setting this could take 5 years or more, but more resources and individuals focused on the goal, for example in a small company, could definitely speed up the process,” Dr. Zhang told IE.

The study is published in the journal Science.

Study Abstract:

Implantable neuroelectronic interfaces have enabled advances in both fundamental research and treatment of neurological diseases, yet traditional intracranial depth electrodes require invasive surgery to place and can disrupt the neural networks during implantation. We developed an ultra-small and flexible endovascular neural probe that can be implanted into sub-100-micron scale blood vessels in the brains of rodents without damaging the brain or vasculature. In vivo electrophysiology recording of local field potentials and single-unit spikes have been selectively achieved in the cortex and the olfactory bulb. Histology analysis of the tissue interface showed minimal immune response and long-term stability. This platform technology can be readily extended as both research tools and medical devices for the detection and intervention of neurological diseases.

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