PET Imaging: The Real Positronic Brain?

In Isaac Asimov’s 1950 short story collection I, Robot, intelligent robots with positronic brains exist alongside humans. Unlike conventional computer hardware, the word positronic implies that electrical current is carried in the wires of these robots’ brains by  positrons, the antimatter counterpart of the familiar electron. Though the advantage of antimatter here is anyone’s guess, the stories of I, Robot may have introduced the positron to the public.  And as bizarre as Asimov’s fantasy sounds, neuroimaging has given the term “positronic brain” yet another meaning.

Positron Emission Tomography, or PET, is a technique for imaging metabolic activity in the body using collisions between positrons and electrons that emit telltale radiation. Because PET allows doctors and researchers to infer the energy bill of different parts of the body, it can be used to investigate which parts of the brain are involved in a cognitive task, or which tissues in the body contain glucose-hungry cancer cells.

How does PET work?

Molecules needed for metabolism, such as glucose, are stealthily modified to include a special fluorine atom that emits positrons through radioactive decay, the process by which one  chemical element changes to another. When injected into the blood, such radiotracers can be used to measure blood flow in the brain and other tissue. Positrons emitted by the radiotracer are antimatter, particles with the same mass but opposite charge of more familiar particles like electrons. When an antiparticle and a particle meet, they annihilate each other. Yet because mass and energy are really the same thing (remember Einstein’s E = mc²?) and can be neither created nor destroyed, the mass of the particles is conserved as the energy of two gamma ray photons. Photons, of course, are particles of light or electromagnetic radiation. And gamma rays, being the most energetic of all photons, give a powerful signature through emission, easily readable by a machine.

How is PET used?

PET both saves the lives of cancer patients and shows us the inner workings of the brain. And it really is as strange as it sounds, like something straight from the pages of an Asimov’s novel. A radioactive substance is injected into your blood, giving off antimatter which collides with matter in your body to give off tremendously powerful gamma rays picked up by a detector. Eureka! In fact, the radioiostopes used in PET imaging decay so quickly that they must be “cooked up” on the spot, generated by collisions inside of a medical cyclotron that waits on standby.

Because of its ability to visualize brain activity, PET imaging, like other neuroimaging technologies, has often captured the public’s attention as if it were harnessing some mysterious power to see into the soul. Alternatively, given its ability to reduce psychology to biology, some may regard PET as a scientific exorcist obliterating the very notion of a soul. One need only read Tom Wolfe’s 1997 essay Sorry, But Your Soul Just Died to understand the latter perspective through Wolfe’s breathless awe of PET imaging.

Caveats of PET imaging?

And yet, we must be very careful to remember what PET is actually measuring. Unlike technologies such electroencephalography (EEG) and magnetoencephalography (MEG), PET does not directly measure brain activity. In fact, it measures regional blood flow. The more energy a tissue uses, the more blood presumably flows to it. As PET measures the flow of blood, the technology itself has changed with the flow of time. Invented in the 1960s and constantly refined in the years since, PET brain imaging arguably met its match in the 1990s with the advent of functional magnetic resonance imaging, or fMRI. Like PET, fMRI measures brain activity by observing which parts of the brain are using energy. But unlike PET, fMRI does not expose a person to potentially harmful radiation. In fact, it requires nothing to be injected into the body and, moreover, sheds the expenses of the medical cyclotron needed on standby for PET. Finally, fMRI goes a step beyond measuring blood flow by actually measuring the brain’s use of oxygen. Nonetheless, both technologies fall a step short of directly measuring brain activity in the truest sense of the word.

Has fMRI rendered PET obsolete?

No. With increasing creativity, neuroscientists have found ways to attach radioisotopes to increasingly complex molecules beyond glucose. These range from florbetapir — a chemical that binds to the insidous amyloid molecules thought to cause Alzheimer’s disease — to L-DOPA — the chemical precursor of the neurotransmitter dopamine. Radioactive “reporter probe” molecules that localize to cells expressing a specific gene have also been developed. The results are variants of PET imaging that can show the location of amyloid deposits, dopamine receptors, and gene expression in the brain. Moreover, PET imaging can be synergistically combined with MR imaging using special scanners that potentially reveal more information than either method alone.

That a substance as esoteric as antimatter has immediate relevance to neuroscience and medicine forces us to question the boundaries between traditional disciplines in science. Though Asimov’s positronic brain may sound absurd, PET imaging is the real deal. In Knowing Neurons’  interview with CERN’s Andre David, the physicist laments the fact that antimatter wears such an exotic moniker. Pick up an object as mundane as a banana, and you will be holding a positron emitter. Yes, bananas occasionally give off antimatter by virtue of containing the radioisotope potassium-40. And medical uses of antimatter may not be limited to PET imaging. CERN’s Antimatter Cell Experiment (ACE) has investigated whether antiprotons may be useful for fighting tumors. Though much work remains to be done, one thing remains clear: cooperation between different disciplines can result in magnificent achievements.  Asimov, who published in fields as varied as physics, history, religion, Shakespearean literature, chemistry, and mathematics, would surely agree.

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Written by Joel Frohlich

Illustrated by Jooyeun Lee

Translated by Dalí Jiménez

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References:

Antoch, G., & Bockisch, A. (2009). Combined PET/MRI: a new dimension in whole-body oncology imaging?. European journal of nuclear medicine and molecular imaging, 36(1), 113-120.

Elsinga, P. H., Hatano, K., & Ishiwata, K. (2006). PET tracers for imaging of the dopaminergic system. Current medicinal chemistry, 13(18), 2139-2153.

James, O. G., Doraiswamy, P. M., & Borges-Neto, S. (2015). PET imaging of tau pathology in Alzheimer’s disease and tauopathies. Frontiers in neurology, 6, 38.

Okamura, N., Harada, R., Furumoto, S., Arai, H., Yanai, K., & Kudo, Y. (2014). Tau PET imaging in Alzheimer’s disease. Current neurology and neuroscience reports, 14(11), 1-7.

Wolfe, T. (1996). Sorry, but your soul just died. Forbes ASAP, 210-219.

Yaghoubi, S. S., Campbell, D. O., Radu, C. G., & Czernin, J. (2012). Positron emission tomography reporter genes and reporter probes: gene and cell therapy applications. Theranostics, 2(4).