Operating room technology


grids currently used to map brains for resection are spaced 1cm apart, meaning neurosurgeons need to work from an approximate and linear extrapolation of the boundaries between the multifarious wonders and mysteries of their patients’ minds. Although the established practice is to leave wide resection margins – approximately 9mm for language and 5mm for motor function – to minimise the risk of damage, cortical columns in the brain exist on a very different scale from today’s ECoG grids, meaning brain surgeons have to play a sort of dot-to-dot with a knife and the irregular, pulsating tissue inside another human’s skull. None of this is to denigrate the work of neurosurgeons; their job is idiomatic for a reason. But surely no one would complain if it could be made a little easier. Lee and Dayeh have ways to help with that.


As accurate as possible Much as they always have been, today’s ECoG devices are made of millimetre-scale electrodes pressed into a layer of biocompatible silicone approximately 1mm thick and then hand-soldered to electrical wires. The difficulty of that process prevents contacts being spaced any less than 1cm apart, meaning grids in clinical use are limited to between four and 64 electrodes. Although larger 16x16cm grids of 256 contacts also exist, their size and expense mean they are only used for research purposes. Not that they would be much more help for a surgery, however big one of these grids gets, its resolution will still be equivalent to a pixel per square centimetre. That might make it sound too accurate. Tissue is not shaped like computer monitors or TV screens. Thin as a 1mm layer of silicone might seem in those contexts, it is still too thick to fully conform to a human brain, which further complicates things by refusing to stay still. To address those issues, Dayeh and his team used microfabrication techniques to integrate platinum nanorods into a transparent, biocompatible layer of parylene C. The material choices make all the difference. Parylene C is soft and pliable enough to conform and move with the surface of the brain without obscuring it. “Therefore, you can record with very high fidelity and isolate the activity in local brain regions because the electrical contact is always in intimate contact with the surface of the brain,” Dayeh explains. Moreover, by fabricating platinum nanorods into the parylene C, the team was able to shrink its ECoG contacts down from the millimetre to the micron scale without introducing extra noise to their readings. “What we wanted to do is make sure we maintained a high capacitance and a facile ability of the electrode to participate in redox reactions,” explains Dayeh. “To do that, you would


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want to use a highly catalytic material like platinum, but you also need to increase its surface area, so that it’s capacitance is large.” The planar forms used for current ECoG contacts can’t help with that, but structures formed of nanorods are three dimensional. All those nanoscale edges also work to intensify electrical fields, enabling more efficient electrochemical interactions between the brain and the sensor.


“That was the key ingredient for scaling,” Dayeh notes. “Once we accomplished that and validated it with a lower number of channels, we came up with a way to put many of these contacts on grids that are suitable for covering a large brain area.” In fact, the UC San Diego team’s grids, which have been validated in both human and animal models, incorporate 1,024 or 2,048 1mm-spaced ECoG electrodes across a layer just 7μ thick. It is a 100 times increase in resolution. “We provide a resolution that’s exactly one millimetre spacing, so that you can have basically a resection margin of half a millimetre,” Dayeh explains. “Now you can look at the curvilinear boundary of the tumour, and only resect the tumour and preserve function.”


The precision of PING


Not every neurosurgery needs to be a resection. Advances in using different types of thermal ablation to tackle drug-resistant epilepsy – and even, in some cases, to remove tumours – have made neurosurgery far more accessible and palatable for patients. Kevin Lee would happily speak on the excellences of each different approach, but he is part of a team that has developed a new low-intensity focused ultrasound technique that solves a problem none have yet addressed. He calls it precise intracerebral non- invasive guided surgery, or (in a reference to The Hunt for Red October) PING.


Even the most precise resections and thermal ablations (including high-frequency focused ultrasound) cause collateral damage. It is only the neurons that are responsible for seizures, but all the currently available techniques for removing them also impact nearby blood vessels and axons of passage. “A very common feature of temporal lobe epilepsy surgery is that the more tissue you take out, the better outcome you get,” explains Lee. “The problem is that the temporal lobe, and this holds for the rest of the brain as well, has other axons that are passing to and from it – from areas that are important for other things that you don’t want to damage.


PING is a technique for preventing this sort of damage. Whereas high-frequency focused ultrasound ablates its targets with heat, its low- frequency counterpart just warms them enough


53


100x 93%


Increase in


resolution achieved by UCSD’s next- generation ECoG grids.


Percentage reduction of average seizure frequency in rat models treated with PING.


Experimental Neurology, Volume 343, 113761.


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