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Biomarkers of Neuroinflammation Proceedings of a Workshop (2018) / Chapter Skim
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5 Neuroimaging Biomarkers: Current Initiatives and Opportunities
Pages 37-44

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From page 37...
... is a putative biomarker for neuroinflammation, and second-generation PET ligands show an increase in TSPO binding that correlates with symptom severity in Alzheimer's disease (AD) , as well as in major depressive episodes (MDEs)
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From page 38...
... . • Molecular probes are being developed to enable magnetic resonance imaging of thrombin activity in neuroinflammatory disease (Akassoglou)
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From page 39...
... The National Institute of Mental Health team demonstrated that unmedicated MDE patients show increased TSPO density compared to healthy controls or patients treated with selective serotonin reuptake inhibitors (SSRIs) , suggesting that SSRI treatment itself may influence TSPO density.
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From page 40...
... Following primate studies that demonstrated dosedependent target occupancy, the team tested the ligand in an inflammatory rat model, where they showed that inducing neuroinflammation by injecting lipopolysaccharide locally into the striatum was associated with an increased uptake of 739, and that the antagonist blocked this effect, indicating that 739 may be useful to measure target engagement of P2X7R therapeutics and to image neuroinflammation. However, Szardenings noted that because P2X7R is evenly distributed throughout the brain, there is no reference region to allow calculation of occupancy and aid in image analysis.
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From page 41...
... These scans demonstrate the highly inflammatory nature of MS, the progressive enlargement of the ventricles suggesting ongoing atrophy over time, and neurodegeneration. However, in addition to the acute inflammation seen in these images, which is associated with the opening of the BBB, Absinta said that chronic inflammation occurs behind a partially intact BBB at the plaque level and within the leptomeninges.
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From page 42...
... She added that other chronic neuroinflammatory conditions show a similar pattern of blood‒meningeal barrier impairment due to meningeal inflammation using this technique, suggesting that it may be useful for patient selection and stratification in clinical trials of disease-modifying treatments for chronic inflammation. Correlating this imaging biomarker with cytokine profiles in the cerebrospinal fluid might also lead to a better understanding of what drives cortical demyelination in MS, she said.
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From page 43...
... mice and healthy controls injected with a fluorescently labeled thrombin probe demonstrate the potential to use this probe to detect early changes in clotting and fibrin deposition indicative of blood‒brain barrier leakage. SOURCE: Presentation by Akassoglou, March 21, 2017.
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Key Terms

  • chronic inflammation
  • fibrin deposition
  • pet ligands
  • imaging approaches
  • activated microglia

  • clinical trials
  • tspo density
  • tspo binding
  • chronic inactive
  • nuclear imaging

  • completely demyelinated
  • cognitive impairment
  • cell trafficking
  • neuroimaging biomarkers
  • leptomeningeal enhancement

  • resonance imaging
  • symptom severity
  • immune cell
  • meningeal inflammation
  • pet imaging

  • tspo pet
  • image chronic
  • image analysis
  • microglia activation
  • thrombin prob

  • bbb leakage
  • images using
  • inflammation associated
  • therapeutic compound
  • arachidonic acid


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