MICROANATOMY AND PHYSIOLOGY:

Willem-et-al.,using electron-microscopy, found that arteries near anterior-perforated-substance and within globus-pallidus are surrounded by two leptomeningeal-layers, forming distinct periarterial-spaces. Conversely, cortical periarterial-spaces are bordered internally by adventitia and smooth-muscle cells, and externally by one leptomeningeal-layer. In basal-ganglia, PVS around veins appear continuous with subpial-space, and PVS in both humans and rodents communicate with basal-subarachnoid-space^[1-3]. The PVS function as conduits facilitating the exchange of extracellular-fluid within brain-tissue and CSF in the subarachnoid-space. 

Fig 1: FIGURE 1: Anatomy of perivascular spaces around basal and cortical perforating arterioles. Basal arterioles (left) enter the brain from subarachnoid-space and are invested in two leptomeningeal membranes, the inner membrane being closely applied to the arteriolar wall and the outer membrane being contiguous with the pia mater, meaning that the basal arteriolar perivascular spaces communicate directly with the subarachnoid space. Cortical arterioles (right), and all venules, have only one leptomeningeal membrane, closely applied to the vessel wall, and no outer layer; therefore, the cortical periarteriolar and perivenular spaces are thought to communicate with the subpial rather than the subarachnoid-space.

The brain contains 4 fluid-compartments: cerebrospinal-fluid(CSF),interstitial-fluid(ISF), intracellular-fluid, and blood-vasculature. Glymphatic-system facilitates CSF-ISF exchange, with CSF entering brain-tissue around paraarterial-spaces. Mediated by astrocytic Aquaporin-4(AQP4), ISF exits through paravenous-pathways, reaching circulation for clearance-via-cervical&nasal-lymph-nodes^[4-7]. 

Fig 2: FIGURE 2: SCHEMATIC REPRESENTATION OF GLYMPHATIC PATHWAY- inspired by Iliff JJ et al. Sci Transl Med 2012. CSF enters the brain along para-arterial routes, whereas ISF is cleared from the brain along paravenous routes. Convective bulk ISF flow between these influx and clearance routes is facilitated by AQP4-dependent astroglial water flux and drives the clearance of interstitial solutes and fluid from the brain parenchyma. From here, solutes and fluid may be dispersed into the subarachnoid CSF, enter the bloodstream across the postcapillary vasculature, or follow the walls of the draining veins to reach the cervical lymphatics.

The Glia-limitans, formed by astrocyte-processes, covers brain and spinal-cord surfaces externally and surrounds vessels internally; enabling unidirectional extracellular-fluid flow from brain-parenchyma along PVS into subarachnoid-space, driven by arterial-pulsation, compensating for absence of lymphatic-drainage in central-nervous-system^[8,9].

Fig 3: FIGURE 3: ILLUSTRATION OF GLYMPHATIC PATHWAY- The glymphatic system supports interstitial solute and fluid clearance from the brain.

IMAGING OF PERIVASCULAR-SPACES(PVS):

On-MRI, PVS exhibit signals-resembling-CSF, appearing bright on T2WI. Studies using 7-T MRI reveal that PVS align with arterioles^[11].Techniques to assess glymphatic-function include MRI-with Gadolinium-based-contrast-agents(GBCA) administered intravenously/intrathecally. It is hypothesized that GBCAs in CSF enter brain via glymphatic system. Intrathecal-GBCA offers direct CSF-access but poses safety risks like gadolinium-induced-encephalopathy^[10,12,13]. A novel-method called the DTI-ALPS index uses diffusion-tensor-imaging(DTI) to assess glymphatic-system-function in-vivo by measuring water-molecule-diffusivity along PVS. In relation to lateral-ventricle body, medullary-veins and PVS are oriented-perpendicularly, facilitating-evaluation-of-their-diffusivity^[14]. 

Fig 4: FIGURE 4: Types of PVS: Type I: Along the lenticulostriate arteries that enter the basal ganglia through the anterior perforated substance. Type II: Along the course of the perforating medullary arteries as they enter the cortical gray matter over the high convexities and extend into the white matter. Type III: Located in the midbrain and follow the path of the penetrating branches from the posterior cerebral artery Type IV: Subcortical white matter of the anterior superior temporal lobe; commonly related to a branch of the middle cerebral artery and a focal region of cortical absence or thinning. PVS typically have a cross-sectional diameter of less than 2 mm on MRI. When the diameter is between 3 and 15 mm, PVS are considered enlarged; those measuring 15 mm or more are defined as giant/tumefactive PVS.