Lineage and geometry of MRI‐visible perivenous and periarterial spaces in white matter confirmed on immunohistochemical microscopy

Abstract

AbstractBackgroundMRI‐visible perivascular spaces (mrPVS) in the brain, typically found in white matter and assumed to be pathologically enlarged though historically considered a benign finding, have been more recently associated with normal aging as well as with various disease states, including traumatic brain injury, sleep apnea, Alzheimer’s Disease (AD), Parkinson’s Disease, and cerebral amyloid angiopathy. One putative cause for their pathological enlargement has been damage to the parenchyma surrounding the PVS, bounded by the astrocytic endfoot, caused by an increase in vascular pressure or pulsatility. Arteries are more pulsatile than veins, and thus it is expected that mrPVS, presumed to be enlarged, will be predominately around arteries. This pre and post mortem MRI + immunohistochemistry (IHC) study sought to clarify the lineage and spatial distribution of PVS visible at the resolution of MRI in aged individuals who were cognitively normal (C), mildly cognitively impaired (MCI), had clinical signs of dementia and mixed AD and vascular disease at pathology (AD/VD), and had pathology‐confirmed AD only (AD).MethodDetailed imaging and IHC acquisition, as well as MRI and IHC processing and registration methods, can be found at [https://pubmed.ncbi.nlm.nih.gov/36343095/ and https://pubmed.ncbi.nlm.nih.gov/36054513/]. Each MRI was inspected for PVS by an experienced rater (JH) and trichrome and smooth muscle actin (SMA) IHC of the corresponding vessels were judged to be arteries or veins based on SMA positivity and morphology (DLS).Result35 mrPVS over 19 subjects’ post mortem MRIs were unequivocally identified on trichrome and SMA. Of these, 23 surrounded arteries (SMA+, Fig. 1), and 12 surrounded veins (faint/thin/uneven SMA, Fig. 2). Mean distance (range) to the cortical ribbon from mrPVS surrounding arteries and veins were 2.8mm[0‐8mm] and 5.4mm[2‐14mm], respectively.ConclusionPVS large enough to be visible on MRI are more frequently arterial if nearer the cortical ribbon; mrPVS nearer the ventricle are more likely to be collecting veins. As collecting veins nearer the ventricles and arterioles in cortex tend to have higher pulse pressures, this finding is congruent with the hypothesis that PVS may enlarge as a result of higher vascular pressures common in older age and cerebrovascular disease.