Tiny, ultra-flexible neural probes without cranial surgery open up new potentials for in vivo brain research

Researchers from Stanford University and Harvard Medical School have developed tiny, ultra-flexible mesh neural probes that can be implanted into blood vessels smaller than 100 micrometers in the brains of rodents.

In their article, “Ultraflexible Endovascular Probes for brain recording by vasculature at the micrometric scale”, published in Science, the researchers demonstrate the potential of their device by measuring field potentials and unit spikes in the cortex and olfactory bulb of a rat without open-skull surgery and without damaging the brain or vasculature. A Perspective article in the same journal issue discusses the work done by the team.

The unique feature of this technology is the use of ultra-flexible endovascular probes that can be precisely introduced into tiny blood vessels without the need for invasive surgery. Probes can access brain regions which are difficult to achieve safely with other methods, achieving selective implantation in different branches of the brain by adjusting the mechanical properties of the probe.

Inspired by minimally invasive catheter-based injection procedures, researchers designed ultra-flexible polymer-based micro-endovascular (MEV) probes that can be loaded and injected from flexible microcatheters.

A saline flow through the microcatheter allows the probe to then be transported into a deeper vasculature. The microcatheter is then retracted, leaving the MEV probes in place. Traditional intracranial depth electrodes for neuroelectronic interfaces require invasive surgery and can damage neural networks upon implantation.

In histological tests, the probes demonstrated long-term stability with minimal immune response. The probes could not deform or penetrate the walls of the vessel, causing no damage to the blood-brain barrierand did not significantly reduce blood flow or cause neurological deficits.

In vivo electrophysiological recording has been successfully performed in the cortex and olfactory bulb of anesthetized rats. The probes demonstrated selective branch implantation and function, revealing different gating properties in neurological disease models. Single unit activity recording was performed, demonstrating single cell resolution through vessel walls.

Cerebral vasculature ranges from large superficial cortical vessels to microvasculature and capillary beds in the cortex. In the rat brain, about 5% of the vessels have a diameter greater than 100 μm, which the MEV probes in the study could target.

Targeting of smaller diameter vessels could be achieved by further reducing the size bending stiffness of the probes. Currently available endovascular probes for humans and sheep were only able to target the largest vessel over 2.4 mm in diameter.

The study authors conclude that “…the technology of the platform could be extended to the detection and treatment of numerous neurological diseases as a research tool and could serve as the basis for the clinical translation of minimally invasive neuroelectronic interfaces”.

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