There’s a lot of great medicines out there that don’t work for the brain. That’s primarily because they aren’t membrane-soluble and therefore can’t penetrate the blood brain barrier (BBB) that surrounds its vasculature. For things like cancer or infection, the only way in is to tap into the spine for a one-shot charge, or put in a more permanent indwelling tube that in-and-of itself can lead to further infection. Furthermore, any drug delivered by these extraordinary means can only penetrate as deep as the cerebro-spinal fluid can percolate. Fortunately, there may now be better ways to do it.

Researchers at the Université de Montréal, Canada were able to bypass the BBB by delivering iron-oxide magnetic nanoparticles to a precise region of a mouse brain, and then heating them up with a remote RF field. To prove all this, they injected a blue dye into the blood, and then looked to see if it showed up on the business side of the BBB. To give some measure of confidence that the heating was not damaging the brain, they analyzed sliced-and-diced samples of brain for the presence of a protein known as CD68. This molecule, while certainly not the only telltale indicator of inflammation, is manufactured and/or released after many kinds of injury.

If and when this treatment becomes available to us, we are probably looking at something like a 30-minute bask in the radiative field of a scaled down MRI machine to get a two-hour window for an open BBB. A potential inconvenience would be that you might have to stop taking any other medicines you might be on that you wouldn’t necessarily want getting into your brain. An optimist, however, might note that such treatment would open up hundreds of freely available remedies to try that just might have interesting or otherwise useful cerebral effects.

We are not advocating this kind of wanton exploration in any way, but simply feel obliged to mention it for completeness. Come to think of it, something like theobromine, which is a close analog of caffeine commonly found in tea, is just the type of molecule that we might be talking about here.

This research was lead by Sylvain Martel and was published in the Journal of Controlled Release. Although it is obviously more of a niche publication than ExtremeTech, there is actually a fair bit more to this whole picture, technology-wise, then at first may appear. Sylvain previously demonstrated that it is possible not only to remotely steer magnetically-active catheters into specific fine branches of blood vessels in the liver, but that it is also possible to guide drug-laden nanoparticles with magnetic fields once they are released in the blood or tissue.

For the studies here, the researchers deposited nanoparticles into the middle cerebral artery of a mouse. This is the big one for us humans, the one where you can loose speech, mobility, and aspects vision all at a stroke. The ability not just to guide agents to specific blood vessels, but to keep them there, and then thermally activate them all with the same basic instrument, is fairly exciting stuff. If you follow biomedical tech, you may know that RF heating is not the only game in town when it comes to breaching the BBB. Ultrasound, combined with microbubbles coated with sodium hexaflouride (the gas that gives you that deep voice when inhaled), has been used to more-or-less blast chemotherapy drugs into the brain.

The concern in all this is that no one really knows how much energy in any form the brain can take, let alone the best way to measure and quantify that energy. The study just mentioned, for example, delivered an acoustic power of 3W and a peak negative pressure = 0.6 MPa. According to the FDA, who regulates these matters, you’re good to go as long as you keep the action to within 720 mW/cm2 of power. For RF power, on the other hand, it is the FCC who steps in and sets the bar several orders of magnitude below that level at around 1-10 mW/cm2. Sylvain’s group seems to think their method is much safer. However, the question of how much thermal power and energy tissue can take still needs to be properly explored.

Perhaps more critical than just raw heat, is what is the maximum temperature that is attained anywhere. Proteins can irreversibly denature or unfold, and neurons can spontaneously fire extra spikes, or fail to fire them altogether above certain temperatures. These issues are also important to define, because there are many related optical technologies waiting in the wings — namely various optogenetic methods to activate neurons, drugs, and even genes with lasers that may deposit energy in the thermal range.

We recently took stock of the current state of the art in using light- or RF- active nanoparticles for the intriguing prospect of pinpoint remote deep brain stimulation. Combined with new technology that might image down to resolutions approaching 10 um, and focus RF fields to specific neural structures, remote control of the interior of the brain using both the RF and magnetic fields of a hot-rodded MRI machine is rapidly coming a possibility.