Target audience

Radiologists, neuroscientists, and imaging scientists.

Outcome / Objectives

The attendees will learn about the consequences of inflammation on the central nervous system and will learn how to probe and quantify such consequences.

Main content that will be developed

Neuro-inflammation is a pathological hallmark of many brain disorders. Inflammation is the primary feature in inflammatory disorders (such as multiple sclerosis, neuromyelitis optica spectrum disorders, acute disseminated encephalomyelitis) or infectious disorders (encephalitis). Secondary inflammatory reactions can also be found after a wide range of brain insults such as stroke, brain trauma or even brain tumors.

Histologically a common feature of several inflammatory reaction subtypes is the modulation/alteration of the blood brain barrier (BBB). Many agents released during inflammation increase the permeability of the brain endothelium to serum proteins and water, leading to vasogenic edema. Such disruption of water homeostasis directly impacts the regulation of aquaporin 4 that is the main water channel in the brain and whose expression will have direct influence on the time course of the edematous component of inflammation. In the context of inflammation, pro-inflammatory cytokines and chemokines can also induce modifications of water homeostasis seen as intra-cellular edema. Diffusion MRI is the primary tools to quantify and monitor the edematous component of inflammation. Contrast agent such as gadolinium chelates also inform on the status of the BBB although with imperfect sensitivity and specificity. At the BBB level, inflammation is also characterize in several instances by infiltrations of immune cells from the blood stream (lymphocytes and macrophages) that can be tracked with imaging strategies such as iron oxide nanoparticles.

In terms of cellular consequences of neuro-inflammation, glial activation is an important hallmark. Especially, microglial cells that are the resident immune cells in the brain are rapidly activated which can also be the case for astrocytes. Several experimental data have demonstrated that over-activation of microglia could have deleterious effects on neurons through pruning of synapses and digestion of dendrites. Such modifications of tissue microstructure can be probed with diffusion tensor MRI with different b-values and different models to fit the data providing different specificities. Molecular imaging with PET tracers can also offer more specificities toward modifications of a given cell type.

It is also interesting to note that inflammation can be associated with an increase of some chemical components that can be seen with in vivo imaging. For instance, iron content can increase through the recruitment of iron-rich microglia and through the release of iron from damaged cells which can be quantified and monitored with specific MR methods such as R2* or QSM.

Conclusion

Neuro-inflammation induces several modifications in the CNS that are mainly linked to alterations of the BBB and activation of glial cells, all of them being more or less directly captured with in vivo imaging.

Acknowledgements

No acknowledgement found.

References

No reference found.