Synopsis
Both early and chronic inflammation are
therapeutic targets in brain trauma. New PET radioligands allow targeting of
several key components of the CNS inflammation. This talk will review the emerging
PET tracers for neuroinflammation, and consider them in the context of experimental
traumatic brain injury, temporal disease progression, and available MRI and MRS
approaches.
Content
Traumatic
brain injury (TBI) causes both immediate damage as well as launches a complex cascade
of events leading to the development secondary, slowly progressive injury, and –
on the other hand - to the tissue repair processes. Microbleeds, compromised
blood brain barrier (BBB), and the progressive atrophy of the primary lesion may
all evoke some type of inflammatory response - also chronically. The reactive
astrocytes form a glial scar around the necrotic lesion and local barrier
around the BBB leaks. However, if sustained, reactive astrogliosis and brain
inflammation may lead to co-morbidities and worse cognitive and functional
outcome. This talk will first describe the dynamics of TBI and associated brain
inflammation from the pre-clinical perspective (translational animal work).
Secondly, it will briefly list some of the MR methods used to detect brain
inflammation: indirect approaches targeting oedema, iron products, permeability
of BBB, or MR spectroscopic markers such as myoInositol. Thirdly, it will give an overview of the new
PET-radioligands that allow imaging of different inflammatory cells and
secreted proteins (inflammatory ‘messengers’). Particularly, the focus will be
on the mitochondrial 18kDa translocator protein (TSPO), which is highly expressed in reactive
astro- and microglia, and how TSPO has been used to image posttraumatic
neuroinflammation.
Target audience
Researchers and clinicians interested in
the multimodal imaging of the brain inflammation after experimental traumatic
brain injury. Anyone benefiting from the overview of the PET approaches on the different
components of the neuroinflammation.
Outcome/Objectives
To answer the following When, What and How:
1)
The progression of TBI over time
(months after the injury), i.e. When to scan?
2)
What is the inflammatory
response? What are the various types of cells and molecules involved and how are their
interactions with vasculature, i.e. What should/could we target?
3)
What kind of MRI and MRS
approaches do we have to target neuroinflammation, i.e. How to scan?
4)
PET-radioligands to target neuroinflammation,
i.e. How & What to scan by PET?
Acknowledgements
People at Kuopio Biomedical Imaging Unit,
and K. Jokivarsi and P. Poutiainen at SPECT/CT and PET laboratory.References
Virdee et al., 2012 Neurosci
Biobehav Rev. Applications of positron emission tomography in animal models of
neurological and neuropsychiatric disorders.
Wu et al., 2013 Theranostics. PET
Imaging of Inflammation Biomarkers.
Amhaoul et al., 2014
Neuroscience. Imaging brain inflammation in epilepsy.
Lee et al., 2010 Biochemistry. Peptide-based
probes for Targeted Molecular Imaging.
Chodobski et al., 2011 Transl
Stroke Res. Blood-brain barrier pathophysiology in traumatic brain injury.
Burda et al., 2016 Exp
Neurology. Astrocyte roles in traumatic brain injury.
http://missinglink.ucsf.edu/lm/immunology_module/