Abstract

Magnetic resonance imaging (MRI) is the only non-invasive, in vivo technique to detect perivascular spaces (PVS) in the brain. These spaces were first described on MR images as cerebrospinal fluid filled spaces that surround cerebral vessels in the brain parenchyma 1. The visible PVS are increasingly recognized as being of diagnostic value in diseases such as small vessel disease (SVD) and neurodegenerative diseases such as Alzheimer’s disease (AD) and cerebral amyloid angiopathy 2–4. Their number, size, shape and distribution on MRI of the brain, play a role in describing the possible underlying pathophysiology of several neurological diseases 5. Histological studies demonstrate that there are no perivascular spaces in the cortex, as the pia mater reflects on the arteries as they enter the cortex from the subarachnoid space 6. On the other hand in the white matter, basal ganglia and midbrain, there are two leptomeningeal sheets with a potential space in between them that enlarges in pathological conditions 7–9. Experimental studies demonstrate that intraparenchymal injections of soluble tracers results in their distribution along the basement membranes surrounding smooth muscle cells, the intramural periarterial drainage (IPAD) pathway, under the influence of the spontaneous contractions of smooth muscle cells 10,11. The pathway of entry of CSF into the parenchyma is along the perivascular compartment that contains the pial-glial basement membranes 10,12. Experimental studies using multiphoton microscopy suggest that CSF enters along the periarterial compartment and interstitial fluid drains out of the brain along the walls of veins, the so-called glymphatic pathway 13. It is difficult to reconcile the glymphatic pathway with the presence of amyloid in CAA within the IPAD pathways of arteries and not veins 14,15. The discrepancies are due to very different methodological approaches, as multiphoton microscopy is real time in vivo but low resolution, whereas histological studies are high resolution but offer static timepoints for examination. There is a huge opportunity for MRI to reconcile the fields, by using several timepoints of analyses after injection of contrast agents. Such approach has been used by injecting gadolinium-based contrast agents, both intravenously and intracisternally (in the lumbar spine), but our understanding of such observations is still partial and speculative as the studies focus on examination times of 30minutes or longer after the injection of tracers, potentially missing the fast process of IPAD 16,17.There is little doubt that PVS reflect important processes regarding the exchange and drainage of interstitial and cerebrospinal fluids. There is an urgent need to advance our knowledge regarding the anatomy, physiology, function and role of PVS in the human brain which will also allow for newer approaches for drug delivery 18. In vivo imaging of PVS still lacks the resolution of microscopic studies and efforts in this direction are necessary for a better comprehension of neurodegenerative and neurovascular diseases 19. The newly formed CLIC (Clearance of Interstitial and Cerebrospinal Fluids) group as part of the Vascular Professional Interest Area of the Alzheimer’s Association aims to address many of the challenges in the field, by utilizing human MRI alongside experimental studies.

Acknowledgements

No acknowledgement found.

References

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