Number Of Perivascular Spaces Research Articles

Strategic Lacunes Associated With Mild Cognitive Impairment in Rural Chinese Older Adults: A Population-Based Study.

Lacunes are associated with cognitive impairment. We sought to identify strategic lacune locations associated with mild cognitive impairment (MCI) and subtypes of MCI among older adults, and further to examine the role of white matter hyperintensities and perivascular spaces in the association. This population-based cross-sectional study included 1230 dementia-free participants in the brain magnetic resonance imaging substudy (2018-2020) in MIND-China (Multimodal Interventions to Delay Dementia and Disability in Rural China). Lacunes were visually identified in frontal lobe, parieto-occipital lobe, temporal lobe, insula, basal ganglia, thalamus, cerebellum, and brainstem. MCI, amnestic MCI (aMCI), and nonamnestic MCI (naMCI) were defined following the Petersen's criteria. Data were analyzed using logistic regression models. Of the 1230 participants (age, ≥60 years; mean age, 69.40; SD, 4.30 years; 58.5% women), lacunes were detected in 357 people and MCI was defined in 286 individuals, including 243 with aMCI and 43 with naMCI. Lacunes in the supratentorial area, internal capsula, putamen/pallidum, and insula was significantly associated with increased odds ratio of MCI (multivariable-adjusted odds ratio ranged 1.40-3.21; P<0.05) and aMCI (multivariable-adjusted odds ratio ranged 1.46-3.36; P<0.05), whereas lacunes in the infratentorial area and brainstem were significantly associated with naMCI (multivariable-adjusted odds ratio ranged 2.68-3.46; P<0.01). Furthermore, the associations of lacunes in insula and internal capsula with MCI and aMCI, as well as the associations of lacunes in infratentorial area and brainstem with naMCI were present independent of white matter hyperintensities volume and perivascular spaces number. Lacunes in the internal capsula, putamen/pallidum, insula, and brainstem may represent the strategic lacunes that are independently associated with MCI, aMCI, or naMCI in Chinese older adults. URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800017758.

Impaired damping of cerebral blood flow velocity pulsatility is associated with the number of perivascular spaces as measured with 7T MRI

Arterial walls stiffen with age, cardiovascular risk factors, and various vascular diseases, which may lead to less damping of the arterial blood flow pulse, subsequent microvascular damage, and enlarged perivascular spaces (PVS). However, the exact interplay between these processes is unclear. This study aimed to investigate the relation between blood flow velocity pulsatility in the small lenticulostriate arteries and their supplying middle cerebral artery and the respective damping factor (DF), with the number of MRI-visible PVS in elderly subjects. Blood flow velocity waveforms were obtained in 45 subjects (median age [range]: 64 [48–81] years, 47% male) using 7T MRI. PVS were scored in the basal ganglia (BG) and centrum semiovale (CSO). Spearman correlation analyses were used to determine associations of the blood flow pulsatility and the DF, with PVS score, adjusted for age and sex. We found a significant association between a lower DF and a higher number of PVS in the BG (rs = −0.352, P = 0.021), but not in the CSO. This finding supports the supposed pathophysiological mechanism in which excessive kinetic energy deposition leads to damage of small perforating arteries and contributes to the enlargement of PVS at the level of the BG, but possible other pathways might also be of influence.

Association of Type 2 Diabetes Mellitus With Perivascular Spaces and Cerebral Amyloid Angiopathy in Alzheimer's Disease: Insights From MRI Imaging.

According to the amyloid cascade hypothesis, fibrillary amyloid-beta load in the brain causes Alzheimer's disease (AD) with toxic effects. Recently, perivascular spaces (PVSs), fluid-filled cavities around small penetrating arterioles and venules in the brain, and the glymphatic system relationship with type 2 diabetes mellitus (DM2) and AD has been an important research topic from a physiopathological point of view. There are two types of PVSs that are associated with sporadic atherosclerosis and cerebral amyloid angiopathy. In this study, we evaluated the relationship between the number and localization of enlarged PVSs in AD. A total of 254 patients with AD and 125 healthy controls were included in this study All the patients were evaluated with neurological and cognitive examinations and magnetic resonance imaging (MRI). PVSs on MRI were graded by recording their number and location. The study was a retrospective study. In our study, the number of white matter convexity-central semiovale localized PVSs was higher in patients than in the control group. In addition, the number of PVSs in this localization score was higher in patients with DM2. Cerebral PVS counts were higher in patients with AD than in the control group. These results suggest the important role of cerebral amyloid angiopathy, one of the vascular risk factors, and the glymphatic system in the pathogenesis of AD. In addition, the results of our study suggest that the evaluation of PVSs levels, especially at the (centrum semiovale), using imaging studies in AD is a potential diagnostic option.

Associations of MRI-visible perivascular spaces with longitudinal cognitive decline across the Alzheimer’s disease spectrum

ObjectiveTo investigate the characteristics and associations of MRI-visible perivascular spaces (PVS) with clinical progression and longitudinal cognitive decline across the Alzheimer’s disease spectrum.MethodsWe included 1429 participants (641 [44.86%] female) from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. PVS number and grade in the centrum semiovale (CSO-PVS), basal ganglia (BG-PVS), and hippocampus (HP-PVS) were compared among the control (CN), mild cognitive impairment (MCI), and Alzheimer’s disease (AD) groups. PVS were tested as predictors of diagnostic progression (i.e., CN to MCI/AD or MCI to AD) and longitudinal changes in the 13-item Alzheimer’s Disease Assessment Scale-cognitive subscale (ADAS-Cog 13), Mini-Mental State Examination (MMSE), memory (ADNI-MEM), and executive function (ADNI-EF) using multiple linear regression, linear mixed-effects, and Cox proportional hazards modeling.ResultsCompared with CN subjects, MCI and AD subjects had more CSO-PVS, both in number (p < 0.001) and grade (p < 0.001). However, there was no significant difference in BG-PVS and HP-PVS across the AD spectrum (p > 0.05). Individuals with moderate and frequent/severe CSO-PVS had a higher diagnostic conversion risk than individuals with no/mild CSO-PVS (log-rank p < 0.001 for all) in the combined CN and MCI group. Further Cox regression analyses revealed that moderate and frequent/severe CSO-PVS were associated with a higher risk of diagnostic conversion (HR = 2.007, 95% CI = 1.382–2.914, p < 0.001; HR = 2.676, 95% CI = 1.830–3.911, p < 0.001, respectively). A higher CSO-PVS number was associated with baseline cognitive performance and longitudinal cognitive decline in all cognitive tests (p < 0.05 for all).ConclusionsCSO-PVS were more common in MCI and AD and were associated with cognitive decline across the AD spectrum.

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.

Cerebral Small Vessel Disease Associated With Atrial Fibrillation Among Older Adults: A Population-Based Study.

Cerebral small vessel disease, as a potential mechanism underlying the association between atrial fibrillation (AF) and dementia, remains poorly investigated. In this cohort study, we sought to examine the association between AF and cerebral small vessel disease markers among older adults. Data on 336 participants (age ≥60 years, mean 70.2 years; 60.2% women) free of dementia, disability, and cerebral infarcts were derived from the population-based Swedish National Study on Aging and Care in Kungsholmen. Structural brain magnetic resonance imaging examinations were performed at baseline (2001–2004) and follow-ups (2004–2007 and 2007–2010). Magnetic resonance imaging markers of cerebral small vessel disease included perivascular spaces, lacunes, and volumes of white matter hyperintensities, lateral ventricles, and total brain tissue. AF was assessed at baseline and follow-ups through clinical examinations, electrocardiogram, and medical records. Data were analyzed using linear mixed-effects models. At baseline, 18 persons (5.4%) were identified to have prevalent AF and 17 (5.6%) developed incident AF over the 6-year follow-up. After multivariable adjustment, AF was significantly associated with a faster annual increase in white matter hyperintensities volume (β coefficient=0.45 [95% CI, 0.04–0.86]) and lateral ventricular volume (0.58 [0.13–1.02]). There was no significant association of AF with annual changes in perivascular spaces number (β coefficient=0.53 [95% CI, −0.27 to 1.34]) or lacune number (−0.01 [−0.07 to 0.05]). Independent of cerebral infarcts, AF is associated with accelerated progression of white matter lesions and ventricular enlargement among older adults.

Link between Mild Traumatic Brain Injury, Poor Sleep, and Magnetic Resonance Imaging: Visible Perivascular Spaces in Veterans.

Impaired clearance of perivascular waste in the brain may play a critical role in morbidity after mild traumatic brain injury (mTBI). We aimed to determine the effect of mTBI on the burden of magnetic resonance imaging (MRI)-visible perivascular spaces (PVSs) in a cohort of U.S. military veterans and whether sleep modulates this effect. We also investigated the correlation between PVS burden and severity of persistent post-concussive symptoms. Fifty-six Iraq/Afghanistan veterans received 3 Tesla MRI as part of a prospective cohort study on military blast mTBI. White matter PVS burden (i.e., number and volume) was calculated using an established automated segmentation algorithm. Multi-variate regression was used to establish the association between mTBIs sustained in the military and PVS burden. Covariates included age, blood pressure, number of impact mTBIs outside the military, and blast exposures. Correlation coefficients were calculated between PVS burden and severity of persistent post-concussive symptoms. There was a significant positive relationship between the number of mTBIs sustained in the military and both PVS number and volume (p = 0.04). A significant interaction was found between mTBI and poor sleep on PVS volume (p = 0.04). A correlation was found between PVS number and volume, as well as severity of postconcussive symptoms (p = 0.03). Further analysis revealed a moderate correlation between PVS number and volume, as well as balance problems (p < 0.001). In Iraq/Afghanistan veterans, mTBI is associated with an increase in PVS burden. Further, an interaction exists between mTBI and poor sleep on PVS burden. Increased PVS burden, which may indicate waste clearance dysfunction, is associated with persistent post-concussive symptom severity.

Quantitative measurements of enlarged perivascular spaces in the brain are associated with retinal microvascular parameters in older community-dwelling subjects.

Perivascular Spaces (PVS) become increasingly visible with advancing age on brain MRI, yet their relationship to morphological changes in the underlying microvessels remains poorly understood. Retinal and cerebral microvessels share morphological and physiological properties. We compared computationally-derived PVS morphologies with retinal vessel morphologies in older people. We analysed data from community-dwelling individuals who underwent multimodal brain MRI and retinal fundus camera imaging at mean age 72.55 years (SD=0.71). We assessed centrum semiovale PVS computationally to determine PVS total volume and count, and mean per-subject individual PVS length, width and size. We analysed retinal images using the VAMPIRE software suite, obtaining the Central Retinal Artery and Vein Equivalents (CRVE and CRAE), Arteriole-to-Venule ratio (AVR), and fractal dimension (FD) of both eyes. We investigated associations using general linear models, adjusted for age, gender, and major vascular risk factors. In 381 subjects with all measures, increasing total PVS volume and count were associated with decreased CRAE in the left eye (volume β=-0.170, count β=-0.184, p<0.001). No associations of PVS with CRVE were found. The PVS total volume, individual width and size increased with decreasing FD of the arterioles (a) and venules (v) of the left eye (total volume: FDa β=-0.137, FDv β=-0.139, p<0.01; width: FDa β=-0.144, FDv β=-0.158, p<0.01; size: FDa β=-0.157, FDv β=-0.162, p<0.01). Increase in PVS number and size visible on MRI reflect arteriolar narrowing and lower retinal arteriole and venule branching complexity, both markers of impaired microvascular health. Computationally-derived PVS metrics may be an early indicator of failing vascular health and should be tested in longitudinal studies.

Development and validation of a rating scale for perivascular spaces on 3T MRI

Background and purposeTo develop and validate a novel perivascular space rating scale, based on single axial slices in the basal ganglia and the centrum semiovale on T1-weighted and FLAIR images obtained on a 3T MRI scanner. Methods414 community dwelling older adults age 70–90 were assessed. The number of perivascular spaces in the slices 2 mm (basal ganglia) and 37 mm (centrum semiovale) above the anterior commissure were counted. The construct validity of the scale was tested by examining associations with age, sex, vascular risk factors and neuroimaging markers of small vessel disease; white matter hyperintensities, lacunes and cerebral microbleeds. Associations with cross sectional global and domain specific cognition were also examined. ResultsThe rating scale had excellent inter-rater reliability (intraclass correlation coefficient in basal ganglia 0.82 and centrum semiovale 0.96), good intra-rater reliability (ICC in basal ganglia 0.72 and centrum semiovale 0.87) and reasonable concurrent validity with an existing perivascular spaces scale (Spearman rho = 0.49, p < .001). There was a median of four basal ganglia and zero centrum semiovale perivascular spaces. Basal ganglia perivascular spaces were more common in men and associated with the other neuroimaging markers. Perivascular spaces in either location were not independently associated with global or domain specific cognitive impairment. ConclusionThe new rating scale is easy to use, quick, has good psychometric properties and performs better than existing scales in a community dwelling older cohort. Further studies are needed to validate the scale in more diverse cohorts with greater cerebrovascular burden.

Association Between Subclinical Brain Infarcts and Functional Decline Trajectories.

To test associations between subclinical brain infarcts (SBIs) and functional decline independently of intervening clinical vascular events and other vascular risk factors. Longitudinal follow-up for a mean 7.3 years. Generalized estimating equation models were used to test associations between SBIs, number of perivascular spaces (PVSs), baseline Barthel Index (BI), and change in BI, adjusting for sociodemographic, vascular, and cognitive risk factors and for stroke and myocardial infarction occurring during follow-up. Population-based prospective cohort study. Stroke-free individuals from the racially and ethnically diverse Northern Manhattan Study (N=1,290). Annual functional assessments using the BI (range 0-100). Mean age was 70.6 ± 9.0, 40% of participants were male, 66% were Hispanic, 193 (16%) had SBIs, and 508 (42%) had large PVSs. SBIs were not associated with baseline BI. In a fully adjusted model, there was a change in BI of -0.85 points per year (95% confidence interval (CI)=-1.01 to -0.69); those with SBI had an additional change in BI 0f -0.88 points (95% CI=-1.43 to -0.32). There were no associations between PVS and baseline BI or change in BI. In a large population-based study, we found a strong and independent association between "subclinical" markers of cerebrovascular injury and important clinical, person-centered functional trajectories. Future research could clarify the evolution of such subclinical markers over time and test strategies to prevent their progression and minimize related disability. J Am Geriatr Soc 66:2144-2150, 2018.

Multi-channel multi-scale fully convolutional network for 3D perivascular spaces segmentation in 7T MR images.

Accurate segmentation of perivascular spaces (PVSs) is an important step for quantitative study of PVS morphology. However, since PVSs are the thin tubular structures with relatively low contrast and also the number of PVSs is often large, it is challenging and time-consuming for manual delineation of PVSs. Although several automatic/semi-automatic methods, especially the traditional learning-based approaches, have been proposed for segmentation of 3D PVSs, their performance often depends on the hand-crafted image features, as well as sophisticated preprocessing operations prior to segmentation (e.g., specially defined regions-of-interest (ROIs)). In this paper, a novel fully convolutional neural network (FCN) with no requirement of any specified hand-crafted features and ROIs is proposed for efficient segmentation of PVSs. Particularly, the original T2-weighted 7T magnetic resonance (MR) images are first filtered via a non-local Haar-transform-based line singularity representation method to enhance the thin tubular structures. Both the original and enhanced MR images are used as multi-channel inputs to complementarily provide detailed image information and enhanced tubular structural information for the localization of PVSs. Multi-scale features are then automatically learned to characterize the spatial associations between PVSs and adjacent brain tissues. Finally, the produced PVS probability maps are recursively loaded into the network as an additional channel of inputs to provide the auxiliary contextual information for further refining the segmentation results. The proposed multi-channel multi-scale FCN has been evaluated on the 7T brain MR images scanned from 20 subjects. The experimental results show its superior performance compared with several state-of-the-art methods.

O3.02 * RADIATION-INDUCED LEUKOENCEPHALOPATHY IS A DEFINITE TYPE OF SMALL VESSEL DISEASE - NEUROPSYCHOLOGICAL AND MRI DESCRIPTION IN 40 PATIENTS

BACKGROUND: Currently, the most common and serious delayed complication of cerebral RT is radiation-induced leukoencephalopathy (RIL), roughly defined, in absence of strictly consensual criteria, by cognitive dysfunctions associated with diffuse FLAIR MRI white matter hyperintensity (HI). The objective of our study is to clearly define the RIL criteria. METHODS: Patients, addressed to our center between June 2010 and June 2012, with medical history of focal or whole brain RT who developed a persistent cognitive complain at least six months after the end of the brain RT, and presenting brain MRI FLAIR abnormalities were eligible. There was a clinical evaluation by a neurologist and a neuropsychological assessment (Edinburgh scale for lateralization, educational level, Mattis dementia rating scale (DRS) and Folsteins'MMSE, Grober and Buschke memory evaluation, forward and backward digit span, phonemic and semantic verbal fluencies, DO80). All patients were scanned by a standardized MRI protocol. White matter FLAIR lesions were evaluated with a 1 to 14 points score according to a modified Scheltens rating scale. Brain atrophy was visually assessed. Consensually defined signs of small vessels diseases (CSVD) were assessed for each patient. RESULT: Fourty patients were enrolled in our study (mostly stage 3 gliomas (27.5%)). The mean fraction dose was 2 Gy (range 1,5-3) and a mean total dose of 49 Gy (range 30-60). Most patient had gait difficulties, urinary trouble and cognitive complain. Memory difficulties were reported by 77% of patients. Neuropsychological assessment showed global and severe cognitive decline. Mattis DRS was abnormal in 75% of the patients. Forward and backward digit span were pathological in 80% patients. On brain MRI, an extensive FLAIR HI with anterior predominance was shown in 68,5% patients. Brain atrophy was present in 87% cases. T2*-weighted- MRI showed hypointensities like “black dots” probably corresponding to microbleeds or radiation induced cavernomas in 52,6% patients. We found no recent small cortical infarct. We found no correlation between FLAIR HI extension, brain atrophy, microbleeds numbers or location, perivascular spaces number, lacunes of presumed vascular origin and the cognitive compound score. We found no correlation between the delay from RT and one of the MRI lesions described above. The patients displayed a loss of executive functions responsible of severe cognitive disability and dementia as previously described in patients with CSVD. Our study give strong clinical and MRI arguments to consider that the RIL is a delayed progressive CSVD, with characteristic evolution and distribution pattern namely implicating distal brain superficial perforating arterioles that serve dorsolateral loops of white matter in the corona radiata and sparing basal ganglia perforating arterioles that spring from the cerebral medial artery.

Visualization of Perivascular Spaces and Perforating Arteries With 7 T Magnetic Resonance Imaging

The objectives of this study were to explore the possibilities of 7 T brain magnetic resonance imaging to visualize perivascular spaces (PVS) and to depict their related blood vessels. Five subjects aged 19 to 27 years and 5 subjects aged 51 to 72 years were scanned. High-resolution 3-dimensional T1-, T2-, as well as T2*-weighted sequences and time-of-flight angiography were used for the visualization of PVS, veins, and perforating arteries. Three extra subjects were scanned with a 2-dimensional time-of-flight sequence tailored to visualize small arteries and veins in the semioval center. The anatomy of PVS and their spatial relation with blood vessels were examined. The number and size of PVS in the semioval center were compared between the 2 groups. In the basal ganglia, PVS were connected to the basal cisterns. Prominent dilations were observed in these PVS around the lower end of the putamen. From here, they ran upward and frequently showed caliber changes along their track. In the semioval center, smoothly shaped PVS started a few millimeters below the cortex, converged and tapered toward the ventricles, and ended 1 to 2 cm before the ventricle wall. Perivascular spaces correlated spatially with lenticulostriate arteries and with perforating arteries in the semioval center, but not with veins. The mean (SD) number of PVS was larger in the older subjects (55 [14]) than in the younger subjects (22 [11]), (P = 0.004). No difference in PVS diameter was observed. Seven-tesla magnetic resonance imaging offers detailed 3-dimensional visualization of PVS, their morphological features, and their related perforating arteries. This may offer new opportunities to study the role of PVS in ageing and cerebral small vessel disease.