Brain positron emission tomography

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Brain positron emission tomography
PET scan of a normal brain
ICD-10-PCSC030

Brain positron emission tomography is a form of

radiolabeled chemical agents throughout the brain. PET measures emissions from radioactively labeled metabolically active chemicals that have been injected into the bloodstream. The emission data from brain PET are computer-processed to produce multi-dimensional images of the distribution of the chemicals throughout the brain.[1]
: 57 

Process

The

ligands used to map different aspects of neurotransmitter activity, with by far the most commonly used PET tracer being a labeled form of glucose, such as fluorodeoxyglucose (18F).[2]

Advantages and disadvantages

The greatest benefit of PET scanning is that different compounds can show

flow and oxygen, and glucose metabolism in the tissues of the working brain. These measurements reflect the amount of brain activity in the various regions of the brain and allow us to learn more about how the brain works. PET scans were superior to all other metabolic imaging methods in terms of resolution and speed of completion (as little as 30 seconds), when they first became available. The improved resolution permitted better study to be made as to the area of the brain activated by a particular task. The biggest drawback of PET scanning is that because the radioactivity decays rapidly, it is limited to monitoring short tasks.[1]
: 60 

Uses

Images obtained with PET (axial sections) that show the effects of chronic drug exposure on various proteins involved in dopamine (DA) neurotransmission and on brain function (as assessed by brain glucose metabolism). While some effects are common to many drugs of abuse,...others are more specific. These include the decrease...in brain monoamine oxidase B (...the enzyme involved in DA metabolism) in cigarette smokers. The rainbow scale was used to code the PET images; radiotracer concentration is displayed from higher to lower as red > yellow > green > blue.[3]

Before the use of

guided stereotactic surgery and radiosurgery for treatment of intracranial tumors, arteriovenous malformations and other surgically treatable conditions.[4]

PET scanning is also used for diagnosis of brain disease, most notably because brain tumors, strokes, and neurondegenerative diseases (such as Alzheimer's disease and Parkinson's disease) all cause great changes in brain metabolism, which in turn causes detectable changes in PET scans. PET is probably most useful in early cases of certain dementias (with classic examples being

Pick's disease
) where the early damage is too diffuse and makes too little difference in brain volume and gross structure to change CT and standard MRI images enough to be able to reliably differentiate it from the "normal" range of cortical atrophy which occurs with aging (in many but not all) persons, and which does not cause clinical dementia.

PET is also actively used for multiple sclerosis and other acquired demyelinating syndromes, but mainly for research into pathogenesis instead of diagnosis. They use specific radioligands for microglial activity. Currently is widely used the 18-kDa translocator protein (TSPO).[5] Also combined PET-CT are sometimes performed.[6]

Tracer Types

PET imaging with oxygen-15 indirectly measures blood flow to the brain. In this method, increased radioactivity signal indicates increased blood flow which is assumed to correlate with increased brain activity. Because of its 2-minute half-life, O-15 must be piped directly from a medical cyclotron for such uses, which is difficult.

PET imaging with 18F-FDG takes advantage of the fact that the brain is normally a rapid user of glucose. Standard 18F-FDG PET of the brain measures regional glucose use and can be used in neuropathological diagnosis.

The development of a number of novel probes for noninvasive, in vivo PET imaging of neuroaggregate in human brain has brought amyloid imaging to the doorstep of clinical use. The earliest amyloid imaging probes included 2-(1-{6-[(2-[18F]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile ([18F]FDDNP)

florbetapir that uses the longer-lasting radionuclide fluorine-18 to detect amyloid plaques using PET scans.[13]

Dedicated Brain PET Devices

NeuroLF - a dedicated brain PET system. Photo courtesy of Positrigo AG, Switzerland

In 2019 Catana et al.[14] published an overview article about the "Development of Dedicated Brain PET Imaging Devices: Recent Advances and Future Perspectives". Various companies worldwide are working on developing a dedicated brain PET system either for pure research and/or clinical routine use. One of these companies is Positrigo which is working on the NeuroLF system.

Challenges

Main article: Blood–brain barrier § Clinical significance

One main challenge for developing new PET tracers for neuroimaging is that these tracers must cross the blood-brain barrier. Commonly, small molecules which are fat soluble have been used as they can pass the blood-brain barrier through lipid mediated passive diffusion.

However, as pharmaceutics move towards large biomolecules for therapies, new research has also focused on using biomolecules, such as antibodies, for PET tracers. These new larger PET tracers have increased difficulty passing the BBB as they are too large to passively diffuse across. Therefore, recent research is investigating methods to carry biomolecules across the BBB using endogenous transport systems including carrier-mediated transporters such as glucose and amino acid carriers, receptor-mediated transcytosis for insulin or transferrin.[15]

References

  1. ^ a b Nilsson LG, Markowitsch HJ (1999). Cognitive Neuroscience of Memory. Seattle: Hogrefe & Huber Publishers. p. 57.
  2. OCLC 437345781.[page needed
    ]
  3. PMID 12750391
    .
  4. PMID 15235060
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  5. PMID 29632509
    .
  6. PMID 29215409
    .
  7. NAID 10025136171
    .
  8. PMID 10429709
    .
  9. S2CID 34075
    .
  10. PMID 11734604
    .
  11. PMID 11814781
    .
  12. S2CID 11057426
    .
  13. ^ Kolata, Gina (24 June 2010). "Promise Seen for Detection of Alzheimer's". The New York Times.
  14. PMID 31028166
    .
  15. PMID 31342134
    .
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