Enlarged Perivascular Spaces Research Articles

MRI-visible enlarged perivascular spaces: imaging marker to predict cognitive impairment in older chronic insomnia patients.

Perivascular spaces (PVS), components of the glymphatic system in the brain, have been known to be important conduits for clearing metabolic waste, and this process mainly increases during sleep. Sleep disruption might result in PVS dysfunction and cognitive impairment. In this study, we aim to explore whether MRI-visible enlarged perivascular spaces (EPVS) could be imaging markers to predict cognitive impairment in chronic insomnia patients. We obtained data from 156 patients with chronic insomnia and 79 age-matched healthy individuals. Using T2-weighted MRI images, visible EPVS in various brain regions were measured and analyzed. The associations between EPVS numbers and cerebrospinal fluid (CSF) β-amyloid 42 (Aβ42), total tau (t-tau), and phosphorylated tau (p-tau) level in chronic insomnia patients were evaluated. Our results showed that MRI-visible EPVS in the frontal cortex, centrum semiovale, basal ganglia, and hippocampus of chronic insomnia patients with impaired cognition (ICG) significantly increased than that in normal cognition (NCG) patients. The increased MRI-visible EPVS in the frontal cortex, centrum semiovale, and basal ganglia were also associated with the increased CSF Aβ42, t-tau, and p-tau level in ICG patients. MRI-visible EPVS in the basal ganglia and centrum semiovale had high sensitivity and specificity in distinguishing ICG chronic insomnia patients from those with NCG. Our study indicated that MRI-visible EPVS in the basal ganglia and centrum semiovale might be valuable imaging markers to predict cognitive impairment in chronic insomnia patients. It will be meaningful to discern those cognitive decline patients in preclinical stage and take some measures to prevent disease progression. • Increased MRI-visible EPVS were associated with the increased CSF Aβ42, t-tau, and p-tau level in older chronic insomnia patients with impaired cognition.

Blood Neutrophil-to-Lymphocyte Ratio as a Predictor of Cerebral Small-Vessel Disease.

BackgroundIn recent studies, neutrophil-to-lymphocyte ratio (NLR) was reported to be a good predictor of acute ischemic stroke (AIS), but its role in cerebral small-vessel disease (CSVD) is still controversial. We aimed to explore the value of NLR to identify CSVD.Material/MethodsWe enrolled 466 CSVD patients and 413 controls. The total burden score of CSVD was calculated according to MRI results, and imaging subgroups were divided according to MRI. The 90-day outcome was evaluated using the modified Rankin scale (mRS). NIHSS score, mRS, clinical information, biochemical parameters, and NLR were recorded, and we analyzed the relationship between NLR and CSVD.ResultsNLR was a risk factor for CSVD (OR 1.58, 95%CI 1.015~1.322; P=0.029). NLR was positively correlated with CSVD (r=0.259; P=0.001). The AUC was 0.774, with a cut-off value of 1.89 (95% CI 0.742~0.806), P=0.000. NLR was significantly different among the different total burden score groups of CSVD (P=0.009). NLRs were significant different among enlarged perivascular space (EPVS) groups (P=0.017), periventricular white matter high signal (PWMHS) groups (P=0.028), and deep white matter high signal (DWMHS) groups (P=0.004), but no significant difference was found among cerebral microbleeds (CMBs) groups (P=0.118). NLR was correlated with short-term outcome of CSVD (P=0.000). The AUC was 0.732 (95% CI 0.684~0.779), with a cut-off value of 2.413 for predicting a poor CSVD prognosis.ConclusionsNLR has potential diagnostic value for CSVD, and it can predict the short-term outcome of CSVD. Therefore, NLR may be a useful biomarker to predict CSVD and its outcome.

Increased level of FAM19A5 is associated with cerebral small vessel disease and leads to a better outcome.

ObjectiveFAM19A5 plays an essential role in the development and acute or chronic inflammation of the central nervous system. The present study aimed to explore the association between FAM19A5 and cerebral small vessel disease (cSVD).MethodsA total of 344 recent small subcortical infarct (RSSI) patients and 265 healthy controls were included in this study. The difference in the FAM19A5 level between the two groups was compared and the correlation between FAM19A5 and cerebral infarction volume was analyzed. Also, the association between FAM19A5 and the total magnetic resonance imaging (MRI) burden with its imaging characteristics was explored. Moreover, the correspondence of FAM19A5 with the outcome was assessed via Δ National Institutes of Health Stroke Scale score (NIHSS) and the percentage of NIHSS improvement.ResultsFAM19A5 was highly expressed in the RSSI group (P = 0.023), showing a positive correlation with cerebral infarction volume (P < 0.01). It was positively correlated with total MRI cSVD burden (P < 0.001) and reflected the severity of white matter hyperintensity (WMH) (P < 0.01) and enlarged perivascular space (EPVS) (P < 0.01), but did not show any association with cerebral microbleed (CMB) and lacune. Moreover, FAM19A5 suggested a larger Δ NIHSS (P = 0.021) and NIHSS improvement percentage (P = 0.007).ConclusionSerum FAM19A5 was increased in RSSI and positively correlated with the infarct volume. It also reflects the total MRI burden of cSVD, of which the imaging characteristics are positively correlated with WMH and EPVS. In addition, higher FAM19A5 levels reflect better outcomes in RSSI patients.

Research progress in atrial fibrillation with cerebral small vessel disease.

Non-valvular atrial fibrillation is a common arrhythmia and a major risk factor for cardioembolic stroke. Small cerebral vascular disease is a syndrome of clinical, cognitive, imaging, and pathological manifestations caused by intracranial small vascular lesions. The imaging findings on cranial magnetic resonance usually shows recent subcortical small infarction, vascularised lacunae, white matter hypersignal, perivascular space enlargement, cerebral microhemorrhage, and brain atrophy. It is a major cause of neurological loss and cognitive function decline in the elderly. Current studies suggest that atrial fibrillation may increase the imaging load of cerebral small vessel disease through a series of mechanisms such as microembolization, hypoperfusion, inflammation, endothelial dysfunction, and lymphoid system dysfunction. The imaging of cerebral small vessel disease with atrial fibrillation has a potential relationship with cognitive function decline and is related to the occurrence and prognosis of stroke, even more has a potential role in suggesting the etiology and secondary prevention strategies of ischemic stroke.

Association between periodic limb movements during sleep and neuroimaging features of cerebral small vessel disease: A preliminary cross-sectional study.

Evidence on the relationship between periodic limb movements during sleep (PLMS) and cerebral small vessel disease is lacking. This study aimed to assess the association between the PLMS index and the neuroimaging features of cerebral small vessel disease on magnetic resonance imaging. Consecutive patients diagnosed with cerebral small vessel disease were enrolled. Data on the clinical characteristics, polysomnography, and brain magnetic resonance imaging were collected. The Accubrain software was used to calculate automatically the volume of white matter hyperintensities, the number of lacunar infarctions, and cerebral microbleeds. The severity of white matter hyperintensities, enlarged basal ganglia perivascular spaces, and the total cerebral small vessel disease scores were also rated visually using semiquantitative scales. The severity of PLMS was measured using the PLMS index, and the patients were divided into two groups using an established cut-off value of ≥15 per hour. Logistic regression was used to examine the association between PLMS and the neuroimaging features of cerebral small vessel disease. In total, 37 patients were included in the final analyses. The mean age was 66.49±11.31years, and 73.0% were males. The mean PLMS index was 19.30±10.18. In univariate analyses, it was found that patients with cerebral small vessel disease with a PLMS index ≥15had increased enlarged basal ganglia perivascular spaces (OR 6.136, 95%CI 1.101-34.214) and increased total cerebral small vessel disease scores (OR 6.0, 95%CI 1.253-28.742). Only the association between the PLMS index and the total cerebral small vessel disease burden score remained statistically significant after adjusting for age, sex, and the presence of moderate to severe obstructive sleep apnea syndrome. In conclusion, an elevated PLMS index is likely to be associated with a greater cerebral small vessel disease burden. PLMS might be a novel potential marker of cerebral small vessel disease.

CAIDE dementia risk score relates to severity and progression of cerebral small vessel disease in healthy midlife adults: the PREVENT-Dementia study

BackgroundMarkers of cerebrovascular disease are common in dementia, and may be present before dementia onset. However, their clinical relevance in midlife adults at risk of future dementia remains unclear. We...

The Triglyceride Glucose Index Is a Risk Factor for Enlarged Perivascular Space

The triglyceride glucose (TyG) index is considered a simple surrogate marker for insulin resistance and has been associated with cerebrovascular diseases. However, limited information is available regarding its association with the subclinical cerebral small vessel disease (CSVD). Here, we investigated the association of TyG index with the burden and distribution of enlarged perivascular space (EPVS) in the non-diabetic population. The data of 531 non-diabetic patients from 2017 to 2020 were assessed. Participants were grouped according to the burden of EPVS. TyG index was calculated using the log scale of fasting triglycerides (mg/dl) × fasting glucose (mg/dl)/2. The association of TyG index with EPVS burden and distribution was evaluated. In the multivariable logistic regression analysis, the TyG index was associated with moderate to severe EPVS [odds ratio (OR): 2.077; 95% CI = 1.268–3.403]. The TyG index was significantly associated with an increased risk of moderate to severe EPVS in subgroups of age <65 years, male, diastolic blood pressure (DBP) <90 mmHg, low-density lipoprotein cholesterol (LDL-C) ≥2.85 mmol/L, serum homocysteine <10 μmol/L, and estimated glomerular filtration rate (eGFR) <90 ml/min/1.73 m2, as well as those without smoking. Further analysis of EPVS distribution, the TyG index was found to be associated with moderate to severe EPVS in the centrum semiovale (CSO), not in the basal ganglia (BG). Conclusively, the TyG index was independently and positively associated with moderate to severe CSO EPVS. TyG index may serve as an independent risk factor for CSVD in clinical practice.

Lesion Volume in Relapsing Multiple Sclerosis is Associated with Perivascular Space Enlargement at the Level of the Basal Ganglia.

Perivascular spaces surround the blood vessels of the brain and are involved in neuroimmune functions and clearance of metabolites via the glymphatic system of the brain. Enlarged perivascular spaces could be a marker of dysfunction in these processes and, therefore, are highly relevant to monitoring disease activity in MS. This study aimed to compare the number of enlarged perivascular spaces in people with relapsing MS with MR imaging markers of inflammation and brain atrophy. Fifty-nine patients (18 with clinically isolated syndrome, 22 with early and 19 with late relapsing-remitting MS) were scanned longitudinally (mean follow-up duration = 19.6 [SD, 0.5] months) using T2-weighted, T1-weighted, and FLAIR MR imaging. Two expert raters identified and counted enlarged perivascular spaces on T2-weighted MR images from 3 ROIs (the centrum semiovale, basal ganglia, and midbrain). Baseline and change with time in the number of enlarged perivascular spaces were correlated with demographics and lesion and brain volumes. Late relapsing-remitting MS had a greater average number of enlarged perivascular spaces at baseline at the level of the basal ganglia (72.3) compared with early relapsing-remitting MS (60.5) and clinically isolated syndrome (54.7) (F = 3.4, P = .042), and this finding correlated with lesion volume (R = 0.44, P = .0004) but not brain atrophy (R = -0.16). Enlarged perivascular spaces increased in number with time in all regions, and the rate of increase did not differ among clinical groups. Enlarged perivascular spaces at the level of the basal ganglia are associated with greater neuroinflammatory burden, and the rate of enlargement appears constant in patients with relapsing-remitting disease phenotypes.

Perivascular space is associated with brain atrophy in patients with multiple sclerosis.

Perivascular space (PVS) is associated with neurodegenerative and neuroimmune diseases. Multiple sclerosis (MS) is traditionally a neuroimmune disease. However, studies show neurodegeneration also plays a vital role in MS. At present, most studies conclude severer PVS in MS is an imaging marker of neuroinflammation, while a 7T MRI study suggests that PVS in MS is associated with neurodegeneration. In this study, 82 MS patients (n=82) and 32 healthy controls (n=32) were enrolled. The following indexes were measured: the number, size and distribution of PVS, the PVS score, corpus callosum index (CCI), corpus callosum area (CCA), the ratio of the corpus callosum to the cranium (CCR), aligned third ventricle width (a3VW), and unaligned third ventricle width (u3VW). The PVS score (4 vs. 3, P=0.041), PVSs number (103.280±45.107 vs. 87.625±30.139, P=0.035), and enlarged perivascular spaces (EPVSs) number (9 vs. 1, P<0.001) of MS patients were significantly higher than in the healthy controls. PVSs number (23.5 vs. 13) and EPVSs number (1 vs. 0) in the basal ganglia (BG), and EPVSs number (3 vs. 0) in centrum semiovale (CSO) of MS patients were significantly higher than in the healthy controls, P<0.001. In MS patients, PVS was correlated with age and hypertension but not to the extended disability status scale (EDSS) score and other clinical data. In MS patients, PVS score was correlated with CCA (rs=0.272; P=0.013) and the CCR (rs=0.219; P=0.048), and PVSs number was correlated with CCA (rs=0.255; P=0.021), the correlation disappeared after adjusting hypertension and age. In MS patients in remission, PVSs number was correlated with CCA (rs=0.487; P=0.019), CCR (rs=0.479; P=0.021), and PVS score was correlated with CCA (rs=0.453; P=0.03). After adjustment of hypertension and age, the total number of PVSs was correlated with CCA (rs=0.419; P=0.049). The PVS load in MS patients was heavier than healthy people, especially in BG and CSO. PVS was not correlated with EDSS in MS patients. The PVS of MS patients was associated with CCA and CCR, and PVSs number was independently related with CCA in MS patients in remission.

Subclinical hypothyroidism is associated with basal ganglia enlarged perivascular spaces and overall cerebral small vessel disease load.

The association between subclinical hypothyroidism (SCH) and cerebral small vessel disease (CSVD) in the stroke-free population is currently unclear. A total of 354 individuals without a history of stroke were enrolled in this study. Demographic data, medical history, vascular risk factors, carotid arteriosclerosis, and the results of laboratory tests were collated. SCH is defined as an elevation in thyroid-stimulating hormone levels, but with normal free thyroxine levels. Magnetic resonance imaging (MRI) was used to assess 4 markers of CSVD, including white matter hyperintensities (WMHs), lacunes, deep microbleeds, and enlarged perivascular spaces (EPVSs). The overall CSVD load was then ranked using an ordinal scale ranging from 0 to 4. Brain atrophy was measured semi-quantitatively on MRI. A binary logistic regression model was used to explore the association of SCH with each CSVD marker after adjusting for confounding factors. The ordinal regression model was used to explore the association of SCH with CSVD burden and brain atrophy after adjusting for confounding factors. The mean age of the participants (66.9% males) was 69.4±12.8 years. SCH was observed in 44 (12.4%) participants. MRI findings revealed 13% of cases with lacunes, 6.2% with microbleeds, 50.3% with confluent WMH, and 49.2% with extensive basal ganglia EPVS. Assessment of total CSVD burden showed that 29.1% scored 1, 30.5% scored 2, 6.5% scored 3, and 2.3% scored ≥3. SCH was associated with extensive basal ganglia EPVS [odds ratio (OR) =2.175; 95% confidence interval (CI): 1.075 to 4.401] and total CSVD load (OR =1.879; 95% CI: 1.028 to 3.438). SCH was not associated with advanced brain atrophy. SCH is associated with the advanced total burden of CSVD and basal ganglia EPVS in the stroke-free population.

Abstract 118: Cerebral Venous Reflux And Dilated Basal Ganglia Perivascular Space In Hypertensive Small Vessel Disease

Background: Cerebral venous flow alterations have been considered as a contributor in white matter ischemia and cognitive impairment, but their role in small vessel disease has never been investigated. Method: 297 patients with spontaneous hypertensive intracerebral hemorrhage who underwent brain MRI were included. Presence of cerebral venous reflux (CVR) was defined as abnormal signal intensity in the dural venous sinus (cavernous, inferior petrosal, sigmoid or transverse sinus) or internal jugular vein using MR angiography (Figure). Dilated basal ganglia (BG) perivascular spaces (PVS) was defined as the number of PVS &gt;20 or any PVS with size &gt; 3mm in short axis (L-PVS). The association between CVR and dilated BG-PVS were evaluated in univariate and multivariable models. Stroke recurrence was also analyzed in cox regression model. Results: Compared to patients without CVR, patients with CVR (n=37, 12,5%) had similar demographics, but showed a trend toward more severe SVD markers including microbleeds, white matter hyperintensities and lacunes. In addition, presence of CVR is significantly associated with dilated BG-PVS (BG-PVS &gt; 20, 62.2% vs. 34.6%, P = 0.002; L-PVS, 48.6% vs. 18.8%, P &lt; 0.001). In multivariable model, the presence of CVR remained independently associated with dilated BG-PVS (odds ratio 4.03 [1.68-9.68], p=0.002) after adjustment for age and other SVD markers. In cox model, CVR predicts higher risk of stroke recurrence independent of conventional SVD markers (odds ratio 2.32 [1.00-5.34], P = 0.049). Conclusion: We demonstrated a close relationship between CVR and dilated BG PVS, suggesting the potential role of venous drainage dysfunction in the formation of enlargement of PVS in hypertensive SVD.

Early Brain Volume Changes After Stroke: Subgroup Analysis From the AXIS-2 Trial.

Background and PurposeThe evolution of total brain volume early after stroke is not well understood. We investigated the associations between age and imaging features and brain volume change in the first month after stroke.MethodsWe retrospectively studied patients with acute ischemic stroke enrolled in the AXIS-2 trial. Total brain volume change from hyperacute MRI data to the first month after stroke was assessed using unified segmentation in SPM12. We hypothesized that age, ischemic brain lesion size, and white matter (WM) changes were associated with larger brain volume change. Enlarged perivascular spaces (EPVSs) and white matter hyperintensities (WMHs) were rated visually and the presence of lacunes was assessed.ResultsWe enrolled 173 patients with a mean age of 67 ± 11 years, 44% were women. There was a median 6 ml decrease in volume (25th percentile −1 ml to 75th percentile 21 ml) over time, equivalent to a median 0.5% (interquartile range [IQR], −0.07%−1.4%), decrease in brain volume. Age was associated with larger brain volume loss (per 10 years of age, 5 ml 95% CI 2–8 ml). Baseline diffusion weighted imaging (DWI) lesion volume was not associated with greater volume loss per 10 ml of lesion volume, change by 0 ml (95% CI −0.1 to 0.1 ml). Increasing Fazekas scores of deep WMH were associated with greater tissue loss (5 ml, 95% CI 1–10 ml).ConclusionsTotal brain volume changes in a heterogenous fashion after stroke. Volume loss occurs over 1 month after stroke and is associated with age and deep WM disease. We did not find evidence that more severe strokes lead to increased early tissue loss.

Serum Cortisol Is Associated With Cerebral Small Vessel Disease-Related Brain Changes and Cognitive Impairment.

ObjectiveTo evaluate the relationship between serum cortisol, cerebral small vessel disease (CSVD) neuroimaging markers, and cognitive performance.MethodsWe recruited patients over 50 years old who attended our hospital for physical examination between November 2020 and July 2021. All participants were subject to brain magnetic resonance imaging (MRI), serum cortisol examination, and the Montreal cognitive function assessment (MoCA). On brain MRI, we scored the presence of each marker of CSVD, including white matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs), and enlarged perivascular spaces (EPVS). One point was awarded for the presence of each marker, producing a score between 0 and 4.ResultsIn total, 158 participants were included in this study with a mean age of 60.5 (56.0–66.3) years; 55.1% were male. In the multivariable analyses, serum cortisol level was an independent predictor of WMH severity, the presence of lacunes/CMBs, moderate-severe EPVS and total CSVD burden after adjusting for confounding factors. Serum cortisol level had positive associations with periventricular/deep Fazekas score, burdens of lacunes/CMBs, moderate-severe EPVS, and total CSVD burden in dose-dependent manner, and was an independent predictor of cognitive impairment. Furthermore, the results of the receiver operating characteristic (ROC) curve analysis revealed an area under curve (AUC) of 0.745 with 64.1% sensitivity and 82.5% specificity, and an AUC of 0.705 with 52.1% sensitivity and 85.5 specificity of cortisol in detecting patients with high CSVD burden and MCI, respectively.ConclusionsSerum cortisol level is independently associated with each CSVD MRI markers, total CSVD burden and cognitive impairment. These findings provide clues for pathological mechanisms and suggest serum cortisol as a promising biomarker associated with CSVD.

Automated grading of enlarged perivascular spaces in clinical imaging data of an acute stroke cohort using an interpretable, 3D deep learning framework

Enlarged perivascular spaces (EPVS), specifically in stroke patients, has been shown to strongly correlate with other measures of small vessel disease and cognitive impairment at 1 year follow-up. Typical grading of EPVS is often challenging and time consuming and is usually based on a subjective visual rating scale. The purpose of the current study was to develop an interpretable, 3D neural network for grading enlarged perivascular spaces (EPVS) severity at the level of the basal ganglia using clinical-grade imaging in a heterogenous acute stroke cohort, in the context of total cerebral small vessel disease (CSVD) burden. T2-weighted images from a retrospective cohort of 262 acute stroke patients, collected in 2015 from 5 regional medical centers, were used for analyses. Patients were given a label of 0 for none-to-mild EPVS (< 10) and 1 for moderate-to-severe EPVS (≥ 10). A three-dimensional residual network of 152 layers (3D-ResNet-152) was created to predict EPVS severity and 3D gradient class activation mapping (3DGradCAM) was used for visual interpretation of results. Our model achieved an accuracy 0.897 and area-under-the-curve of 0.879 on a hold-out test set of 15% of the total cohort (n = 39). 3DGradCAM showed areas of focus that were in physiologically valid locations, including other prevalent areas for EPVS. These maps also suggested that distribution of class activation values is indicative of the confidence in the model’s decision. Potential clinical implications of our results include: (1) support for feasibility of automated of EPVS scoring using clinical-grade neuroimaging data, potentially alleviating rater subjectivity and improving confidence of visual rating scales, and (2) demonstration that explainable models are critical for clinical translation.

Spotlight on the January 18 Issue

#### Notable in Neurology This Week This issue features an article that explores the risk of cognitive deterioration in children after epilepsy surgery; another investigates how sun and ultraviolet radiation exposure contribute to risk of pediatric-onset multiple sclerosis. A featured Review examines the physiologic and clinical implications of enlarged perivascular spaces in the aging brain. ### Epilepsy-Related Mortality in Children and Young Adults in Denmark: A Nationwide Cohort Study ![Graphic][1]</img> This population-based, retrospective study examined the primary cause of death in people with and … [1]: /embed/inline-graphic-1.gif

Asymmetric distribution of enlarged perivascular spaces in centrum semiovale may be associated with epilepsy after acute ischemic stroke.

ObjectiveTo investigate the factors influencing enlarged perivascular space (EPVS) characteristics at the onset of acute ischemic stroke (AIS), and whether the PVS characteristics can predict later post‐stroke epilepsy (PSE).MethodsA total of 312 patients with AIS were identified, of whom 58/312 (18.6%) developed PSE. Twenty healthy participants were included as the control group. The number of PVS in the basal ganglia (BG), centrum semiovale (CS), and midbrain (MB) was manually calculated on T2‐weighted MRI. The scores and asymmetry index (AI) of EPVS in each region were compared among the enrolled participants. Other potential risk factors for PSE were also analyzed, including NIHSS at admission and stroke etiologies.ResultsThe EPVS scores were significantly higher in the bilateral BG and CS of AIS patients compared to those of the control group (both p < 0.01). No statistical differences in EPVS scores in BG, CS, and MB were obtained between the PSE group and the nonepilepsy AIS group (all p > 0.01). However, markedly different AI scores in CS were found between the PSE group and the nonepilepsy AIS group (p = 0.004). Multivariable analysis showed that high asymmetry index of EPVS (AI≥0.2) in CS was an independent predictor for PSE (OR = 3.7, 95% confidence interval 1.5–9.1, p = 0.004).ConclusionsAsymmetric distribution of EPVS in CS may be an independent risk factor and a novel imaging biomarker for the development of PSE. Further studies to understand the mechanisms of this association and confirmation with larger patient populations are warranted.

An Enlarged Perivascular Space: Clinical Relevance and the Role of Imaging in Aging and Neurologic Disorders

혈관주위공간(perivascular space; 이하 PVS)는 뇌 실질을 관통하는 세동맥 둘러싸고 있는 공간으로, 최근에는 별아교세포의 종족(astrocyte endfoot)에 의해 가장 바깥쪽이 경계지워지는, 체액, 세포, 결합조직으로 구성된 혈관벽내, 혈관벽 주위의 구획을 모두 아우르는 개념으로 이해하고 있다. 정상적으로는 현미경적 해부학 구조물이지만 이 구조물이 늘어나게 되면 MRI T1 혹은 T2 이미지에서 확인할 수 있게 된다. PVS의 명확한 실체나 임상적인 의의에 대해서는 아직 분명치 않은 부분이 많이 있지만 PVS의 확장(enlarged PVS; 이하 EPVS)은 다양한 퇴행성 뇌질환 뿐만 아니라 뇌출혈 및 외상성 뇌손상, 당뇨성 신질환 같은 다양한 질병과의 연관성이 있다는 연구 결과들이 발표되고 있다. 이번 종설에서는 PVS와 EPVS가 가지는 임상적 의의와 병태 생리에 대한 최근 문헌을 고찰하고, MRI를 이용한 정성적 평가 및 최적화에 대해 논의해 보고자 한다.

Long-term hemodialysis may affect enlarged perivascular spaces in maintenance hemodialysis patients: evidence from a pilot MRI study.

Hemodialysis (HD) causes various nervous system abnormalities. Alterations in white matter (WM) microstructure after long-term HD have been reported in a few previous studies; however, no studies have been performed to investigate enlarged perivascular spaces (PVS) in WM regions. We measured cerebral blood flow (CBF) and white matter volume (WMV) in HD patients to assess enlarged PVS severity in the WM across the whole brain and suggest possible explanations for this. Fifty-one HD patients and 51 age-, sex-, and education-matched healthy controls (HCs) were recruited. The number of enlarged PVS in the centrum semiovale (CS), cerebral watershed (CW), and basal ganglia (BG) regions were assessed by T2-weighted MRI. CBF was estimated by arterial spin labeling (ASL), which is a non-invasive perfusion imaging technique. WMV was assessed by the computational anatomy toolbox (CAT12), which is a statistical analysis package. Differences in descriptive variables (two-tailed t-tests, χ2 tests, Mann-Whitney U tests, and Friedman M tests), an intra-class correlation between radiologists, the relationship between enlarged PVS number and HD duration, normalized CBF and WMV (multiple regression), and group differences in CBF and WMV {voxel-wise t-tests with age and sex as covariates [cluster size >50 voxels, false discovery rate (FDR) corrected, P<0.05]} were assessed. HD patients displayed a more significant number of CS-PVS and CW-PVS in WM regions compared with the HCs, but there was no significant difference in the number of BG-PVS. The number of CS-PVS and CW-PVS were positively associated with HD duration. The number of CW-PVS was positively associated with CBF changes and WMV alteration in HD patients. Meanwhile, significant differences in the blood pressure (BP) readings pre-HD, intra-HD, and post-HD were observed in HD patients. Compared with the HCs, the HD patients showed higher CBF in the CS, CW, and BG regions (P<0.05). Hence, decreased WMV in the CS, CW, and BG regions were shown in the HD patients compared with the HCs (P<0.05). Enlarged CS-PVS and CW-PVS on MRI might be a feature of long-term HD patients. Enlarged CW-PVS number is associated with higher CBF in the CW region and lower WMV in the CW region in HD patients.

Perivascular space dilation is associated with vascular amyloid-β accumulation in the overlying cortex.

Perivascular spaces (PVS) are compartments surrounding cerebral blood vessels that become visible on MRI when enlarged. Enlarged PVS (EPVS) are commonly seen in patients with cerebral small vessel disease (CSVD) and have been suggested to reflect dysfunctional perivascular clearance of soluble waste products from the brain. In this study, we investigated histopathological correlates of EPVS and how they relate to vascular amyloid-β (Aβ) in cerebral amyloid angiopathy (CAA), a form of CSVD that commonly co-exists with Alzheimer's disease (AD) pathology. We used ex vivo MRI, semi-automatic segmentation and validated deep-learning-based models to quantify EPVS and associated histopathological abnormalities. Severity of MRI-visible PVS during life was significantly associated with severity of MRI-visible PVS on ex vivo MRI in formalin fixed intact hemispheres and corresponded with PVS enlargement on histopathology in the same areas. EPVS were located mainly around the white matter portion of perforating cortical arterioles and their burden was associated with CAA severity in the overlying cortex. Furthermore, we observed markedly reduced smooth muscle cells and increased vascular Aβ accumulation, extending into the WM, in individually affected vessels with an EPVS. Overall, these findings are consistent with the notion that EPVS reflect impaired outward flow along arterioles and have implications for our understanding of perivascular clearance mechanisms, which play an important role in the pathophysiology of CAA and AD.

Teaching NeuroImage: Traumatic Dissection of Lenticulostriate Arteries Within an Enlarged Perivascular Space

A 33-year-old woman was admitted with right side hemiplegia after head trauma. Brain MRI revealed an acute ischemic stroke in the left lenticulostriate territory and a parenchymal hematoma (Figure 1). The hematoma occurred within an enlarged perivascular space (PVS), which had been incidentally discovered 10 years earlier.1,2 It was suspected that a traumatic dissection of lenticulostriate arteries within the PVS was responsible for both ischemic and hemorrhagic events (Figure 1). Healing of the hematoma and disappearance of the PVS and the lenticulostriate arteries were observed 2 months later (Figure 2). Excessive mobility of lenticulostriate arteries within an enlarged PVS may explain the mechanism of traumatic dissection in this case.