Preprint Brain cerebral blood flow with MRI-visible enlarged perivascular space in adults, 2024, Yu et al.

[SNT Gatchaman]

Brain cerebral blood flow with MRI-visible enlarged perivascular space in adults
Chunyan Yu; Baijie Wang; Qiyuan Sun; Huiyan Huo; Lingyan Zhang; Du Hongyan

OBJECTIVES
To explore the correlation between enlarged perivascular spaces (EPVS) in the basal ganglia (BG-EPVS) and centrum semiovale (CSO-EPVS) and changes in adult brain cerebral blood flow (CBF).

METHODS
This cross-sectional single-center cohort study included individuals with varying degrees of EPVS, divided into the BG and CSO based on the established rating scale. Subsequently, the arterial spin labeling (ASL) sequence and its post-processing operation were utilized to obtain CBF values for different grades of BG-EPVS and CSO-EPVS. Logistic regression was conducted to identify risk factors associated with BG-EPVS and CSO-EPVS, and correlation analysis was employed to explore the associations between different grades of BG-EPVS and CSO-EPVS with CBF of the whole brain and specific regions of interest.

RESULTS
The regression analysis revealed that BG-EPVS was associated with age (odds ratio [OR]: 1.10, 95% confidence interval [CI]: 1.04-1.15), hypertension (4.91,1.55-15.6), and periventricular white matter hyperintensities (PVWMH) (4.34,1.46-12.95). Conversely, CSO-EPVS was linked to hypertension (4.40,1.43-13.57), drinking history (2.84,1.08-7.45), sleep duration (2.01,1.19-3.40), and PVWMH (12.20,3.83-38.85). Correlation analysis revealed a negative correlation between BG-EPVS and the CBF of the whole brain (r=-0.28, p=0.00) and most brain regions, except for the brain stem (r=-0.19, p=0.05). Conversely, CSO-EPVS was negatively correlated with CBF of temporal lobe white matter (r=-0.25, p=0.01); however, the significance was lost after FDR correction. CSO-EPVS was not correlated with CBF across various brain regions.

CONCLUSIONS
Brain CBF decreased with the increasing severity of BG-EPVS, suggesting that BG-EPVS could serve as an imaging marker for reflecting the changes in brain CBF and an effective indicator for early ischemic stroke.


Link | PDF (Preprint: MedRxiv) [Open Access]

 

[SNT Gatchaman]

Rapid highlights —

• EPVS are most commonly observed in the regions of the centrum semiovale and the basal ganglia

• Some studies have suggested that EPVS is one of the imaging manifestations of cerebral small vessel disease (CSVD)

• studies have suggested that EPVS may reflect the dysfunction of clearance of cerebrospinal fluid and metabolites around cerebral small vessels and microvascular dysfunction

• EPVS at different locations in the brain may have different pathological mechanisms

• EPVS in the basal ganglia (BG-EPVS) has been associated with cerebral atrophy in stroke

• rating scale: grade 0 = 0 EPVS, grade 1 = 1 –10 EPVS, grade 2 = 11–20 EPVS, grade 3 = 21–40 EPVS, and grade 4 => 40 EPVS

• DWMH were rated as follows: 0 = absence, 1 = punctate foci, 2 = beginning confluence of foci, and 3 = large confluent areas.

• Fazekas scale was used for white matter hyperintensities (WMH) in both periventricular (PVWMH) and deep white matter (DWMH). PVWMH was graded as follows: 0 = absence,1 = caps or pencil-thin lining, 2 = smooth halo, and 3 = irregular.

• 109 individuals, 55 men and 54 women; mean age of 47.1

• Our results revealed that as the severity of BG-EPVS increased, there was a decrease in CBF of the whole brain and almost all regions, which showed a negative correlation

• The BG-EPVS, rather than CSO EPVS, induced corresponding alterations in brain CBF. Therefore, BG-EPVS could be a potential imaging marker for monitoring CBF and an early imaging indicator for ischemic stroke.

• Evidence indicates that the PVS eliminates soluble waste from the brain. The pathologic mechanism of PVS is not yet fully understood, and current studies have highlighted the important role of aquaporin-4 (AQP4)-lined PVS, cerebrovascular pulsation, and metabolite clearance in normal central nervous system physiology.

• speculate that the primary pathogenesis may be associated with atherosclerotic disease

• Previous literature reported that BG-EPVS is an imaging biomarker associated with hypertensive arterial disease and arterial stiffness

• White matter exhibits lower cell density and greater susceptibility to stress than gray matter, which may contribute to the formation mechanism of CSO-EPVS

• A previous study demonstrated that age, hypertension, and WMH were the primary influencing factors of BG-EPVS

 

[SNT Gatchaman]

On the subject of why expanded perivascular spaces might be associated with reduced cerebral blood flow, the authors say —

Arterial stiffness is a characteristic feature of aging that may contribute to the EPVS development in the basal ganglia. This could be attributed to the impact of high pulse waves and restoration of damaged blood vessel walls, making the basal ganglia area more susceptible to damage than other regions. Furthermore, decreased elasticity and thickening of the vessel impair the contractile phenotype of smooth muscle cells, leading to reduced brain CBF. These could also cause alterations in the diameter and structure of small blood vessels, which in turn impairs fluid dynamics. All these structural changes ultimately lead to the expansion of the perivascular space, forming a pathological state.

Alterations in the relationship between EPVS and CBF may be ascribed to regulating the glial-vascular unit (GVU), which comprises glial cells (astrocytes and microglia) and perivascular cells (endothelial cells, pericytes, and perivascular macrophages). The neurovascular unit (NVU) is widely acknowledged for its utility in investigating intricate interactions among multicellular structures. […] The interplay between glial cells and perivascular cells within the PVS microenvironment promotes the effective execution of multiple functions, including CBF regulation, angiogenesis, blood-brain barrier (BBB) integrity maintenance, and neurotoxic waste clearance through the glymphatic system.

Consequently, the heightened severity of EPVS impairs overall GVU function, leading to more pronounced changes in the cerebral vasculature, specifically reduced CBF, which is somewhat consistent with our results. Our findings indicated that the alteration in CBF was specifically linked to BG-EPVS rather than CSO-EPVS, thus implying that the damage caused by CSO-EPVS may be entering a compensatory phase or not primarily affecting the function of vascular component units, thereby allowing GVU's regulation of CBF to remain unaffected. Nevertheless, further investigation is warranted.