Friday, January 25, 2019

In Vivo Magnetic Recording of Neuronal Activity

In Section 8.9 of Intermediate Physics for Medicine and Biology, Russ Hobbie and I discuss the detection of weak magnetic fields produced by the body.
The detection of weak fields from the body is a technological triumph. The field strength from lung particles is about 10-9 T [Tesla]; from the heart it is about 10-10 T; from the brain it is 10-12 T for spontaneous (α-wave) activity and 10-13 T for evoked responses. These signals must be compared to 10-4 T for the earth’s magnetic field. Noise due to spontaneous changes in the earth’s field can be as high as 10-7 T. Noise due to power lines, machinery, and the like can be 10-5–10-4 T.
This triumph was possible because of ultra-sensitive superconducting quantum interference device (SQUID) magnetometers. These magnetometers, however, operate at cryogenic temperatures and therefore must be used outside the body. For instance, to measure the magnetic field of the brain (the magnetoencephalogram), pickup coils must be at least several centimeters from the neurons producing the biomagnetic field because of the thickness of the scalp and skull. A great advantage of SQUIDs is they are completely noninvasive. Yet, when the magnetic field is measured far from the source reconstructing the current distribution is difficult.

Imagine what you could do with a really small magnetometer, say one you could put into the tip of a hypodermic needle. At the cost of being slightly invasive, such a device could measure the magnetic field inside the body right next to its source. The magnetic fields would be larger there and you could get exquisite spatial resolution.

Last September, Laure Caruso and her coworkers published an article about “In Vivo Magnetic Recording of Neuronal Activity” (Neuron, Volume 95, Pages 1283–1291, 2017).
Abstract: Neuronal activity generates ionic flows and thereby both magnetic fields and electric potential differences, i.e., voltages. Voltage measurements are widely used but suffer from isolating and smearing properties of tissue between source and sensor, are blind to ionic flow direction, and reflect the difference between two electrodes, complicating interpretation. Magnetic field measurements could overcome these limitations but have been essentially limited to magnetoencephalography (MEG), using centimeter-sized, helium-cooled extracranial sensors. Here, we report on in vivo magnetic recordings of neuronal activity from visual cortex of cats with magnetrodes , specially developed needle-shaped probes carrying micron-sized, non-cooled magnetic sensors based on spin electronics. Event-related magnetic fields inside the neuropil were on the order of several nanoteslas, informing MEG source models and efforts for magnetic field measurements through MRI. Though the signal-to-noise ratio is still inferior to electrophysiology, this proof of concept demonstrates the potential to exploit the fundamental advantages of magnetophysiology.
A Magnetrode. Adapted from Fig. 1a in Caruso et al. (2017) Neuron 95:1283–1291.
The measurements are made using giant magnetoresistance sensors: a magnetic-field dependent resistor. The size of the sensor was roughly 50 by 50 microns, and was etched to have the shape of a needle with a sharp tip. It can detect magnetic fields of a few nanoTesla (10-9 T). To test the system, Caruso and her colleagues measured evoked fields in a cat's visual cortex. Remarkably, they performed these experiments with no shielding whatsoever (SQUIDs often require bulky and expensive magnetic shields). When they recorded the magnetic field without averaging it was noisy, so most of their data is after 1000 averages. They removed 50 Hz power line contamination by filtering, and they could distinguish direct magnetic field coupling from capacitive coupling.

When I was in graduate school, John Wikswo and I measured the magnetic field of a single axon using a wire-wound toroidal core. We were able to measure 0.2 nT magnetic fields without averaging and with a signal-to-noise ratio over ten. However, our toroids had a size of a few millimeters, which is larger than Caruso et al.’s magnetrodes. Both methods are invasive, but John and I had to thread the nerve through the toroid, which I think is more invasive than poking the tissue with a needle-like probe.

A couple years ago in this blog, I discussed a way to measure small magnetic fields using optically probed nitrogen-vacancy quantum defects in diamond. That technique has a similar sensitivity as magnetrodes based on giant magnetoresistance, but the recording device is larger and requires an optical readout, which seems to me more complicated than just measuring resistance.

My favorite way to detect fields of the brain would be to use the biomagnetic field as the gradient in magnetic resonance imaging. This method would be completely noninvasive, could be superimposed directly on a traditional magnetic resonance image, and would measure the magnetic field in every pixel simultaneously. Unfortunately, such measurements are barely possible after much averaging even under the most favorable conditions.

Caruso et al. speculate about using implantable magnetrodes with no connecting wires.
Implanted recording probes play an important role in many neurotechnological scenarios. Untethered probes are particularly intriguing, as they avoid connection wires and corresponding limitations.
The recording of tiny biomagnetic fields seems to be undergoing a renaissance, as new detectors are developed. It is truly a technological triumph.

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