MRI-visible Perivascular Spaces Research Articles

Markers of amyloid-β deposition and burden of enlarged perivascular spaces in patients with cognitive impairment and small vessel disease.

MRI-visible enlarged perivascular spaces (EPVS) are common in patients with cognitive impairment and possibly linked to Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). In a study of memory clinic patients (n = 450; mean age 66.5 ± 7.45, 45.8% female), we investigated CSF amyloid-β (Aβ)1-42 (AD biomarker) and strictly lobar microbleeds (CAA marker) in relation to centrum semiovale EPVS (CSO-EPVS). Age-controlled analyses showed that severe CSO-EPVS associated with Aβ status (odds ratio [OR] = 1.51, 95%CI = 1.02-2.24), but not strictly lobar microbleeds (OR = 1.39, 95%CI = 0.92-2.11), with no significant Aβ status and microbleeds interaction. This implies that in this setting, severe CSO-EPVS is not a specific indicator of CAA.

Linking human cerebral and ocular waste clearance: Insights from tear fluid and ultra-high field MRI

Impaired cerebral waste clearance (i.e., glymphatics) is evident in aging and neurodegenerative disorders, such as Alzheimer's disease, where an impaired waste clearance system could be related to the accumulation of pathological proteins (e.g., tau). One marker of impaired cerebral clearance is the abundance of enlarged perivascular spaces (PVS). Preclinical studies propose a similar clearance system in the eye, driven by intraocular pressure (IOP). This cross-sectional pilot study explores the link between ocular and the cerebral waste clearance by examining the association between MRI-visible PVS, tear total-tau, and IOP.Thirty cognitively healthy participants, all aged over 55 years, underwent 7 T MRI, with PVS visually rated in the centrum semiovale (CSO) and basal ganglia. Tear fluid was collected using paper Schirmer's strips and analyzed for total-tau using enzyme-linked immunosorbent assay. IOP was measured using non-contact tonometry. Partial Spearman's correlation coefficients of eye and brain markers were calculated, adjusted for age, sex, tear-wetting length, and hemispheric region of interest volume.Higher CSO PVS scores in the left and right hemisphere were associated with higher levels of tear total-tau. Higher CSO PVS scores in both hemispheres were related to lower ipsilateral IOP. The exploratory results suggest that higher tear total-tau and a reduced driving force of ocular waste clearance are connected to impaired cerebral waste clearance in cognitive healthy individuals. This study connects the potential ocular glymphatic system to cerebral waste clearance. Clarifying waste clearance biology and validating eye biomarkers for cerebral waste clearance could provide treatment targets and diagnostic opportunities for neurological diseases.

Lifetime history of head injury is associated with reduced perivascular space number in acute mild traumatic brain injury.

Traumatic brain injury impairs function of the glymphatic system, a perivascular network involved in waste clearance. Enlarged perivascular spaces visible on MRI are an emerging biomarker of glymphatic function. This study characterized enlarged perivascular spaces in acute head injury with 7 T MRI. Healthy controls (n = 8) and patients (n = 11) with mild traumatic brain injury underwent MRI within 7 days of injury and were evaluated for lifetime history of head injury, neurobehavioral symptoms and sleep disturbances. MRI-visible perivascular spaces were quantified and assessed according to published criteria. The number of enlarged perivascular spaces was significantly higher in traumatic brain injury patients than controls (P = 0.015). Among healthy controls, 6/8 scored 'none' or 'mild' on the perivascular space rating scale, while 10/11 patients scored 'moderate', 'frequent' or 'severe'. There was an inverse relationship between perivascular space number and number of lifetime head injuries. Patients with more prior head injuries exhibited fewer enlarged perivascular spaces (P = 0.014). These results indicate that mild head injury results in acute alterations in perivascular space number, and this effect is mediated by previous head injury history. Enlarged perivascular spaces may reflect a glymphatic response that is diminished after multiple head injuries, although this will require further study.

Macroscopic changes in aquaporin-4 underlie blast traumatic brain injury-related impairment in glymphatic function.

Mild traumatic brain injury (mTBI) has emerged as a potential risk factor for the development of neurodegenerative conditions such as Alzheimer's disease and chronic traumatic encephalopathy. Blast mTBI, caused by exposure to a pressure wave from an explosion, is predominantly experienced by military personnel and has increased in prevalence and severity in recent decades. Yet the underlying pathology of blast mTBI is largely unknown. We examined the expression and localization of AQP4 in human post-mortem frontal cortex and observed distinct laminar differences in AQP4 expression following blast exposure. We also observed similar laminar changes in AQP4 expression and localization and delayed impairment of glymphatic function that emerged 28 days following blast injury in a mouse model of repetitive blast mTBI. In a cohort of veterans with blast mTBI, we observed that blast exposure was associated with an increased burden of frontal cortical MRI-visible perivascular spaces, a putative neuroimaging marker of glymphatic perivascular dysfunction. These findings suggest that changes in AQP4 and delayed glymphatic impairment following blast injury may render the post-traumatic brain vulnerable to post-concussive symptoms and chronic neurodegeneration.

MRI-visible enlarged perivascular spaces in basal ganglia rather than centrum semiovale was associated with aneurysmal subarachnoid hemorrhage.

The subarachnoid space is continuous with the perivascular compartment in the central nervous system. However, whether the topography and severity of enlarged perivascular spaces (EPVS) correlates with spontaneous subarachnoid hemorrhage (SAH) remains unknown. Based on the underlying arteriopathy distributions, we hypothesized that EPVS in basal ganglia (BG-EPVS) are more closely associated with aneurysmal subarachnoid hemorrhage (aSAH) than other SAH without aneurysm. Magnetic resonance imaging (MRI) scans of 271 consecutive SAH survivors with and without aneurysm were analyzed for EPVS and other markers of imaging data. In the subgroup analysis, we compared the clinical characteristics and EPVS of SAH participants with and without pre-existing known risk factors (hypertension, diabetes, and smoking history) using multivariable logistic regression. Patients with aSAH (n = 195) had a higher severity of BG-EPVS and centrum semiovale EPVS (CSO-EPVS) than those without aneurysm (n = 76). Importantly, BG-EPVS predominance pattern (BG-EPVS>CSO-EPVS) only existed in aSAH survivors rather than other SAH without aneurysm. In the subgroup analysis, interestingly, we also found that a high degree of BG-EPVS showed an independent relationship with aSAH in patients without pre-existing risk factors (e.g., hypertension). In this cohort study, BG-EPVS predominance pattern was associated with aSAH patients compared with those without aneurysm. Moreover, BG-EPVS still showed a strong association with aSAH survivors without pre-existing vascular risk factors. Our present study suggested the BG-EPVS as a potential MRI-visible characteristic would shed light on the pathogenesis of glymphatic function at the skull base for aSAH.

Associations between MRI-visible perivascular spaces, brain atrophy, white matter hyperintensities, and speeded executive function, in neurodegenerative and cerebrovascular diseases.

Associations between MRI-visible perivascular spaces, brain atrophy, white matter hyperintensities, and speeded executive function, in neurodegenerative and cerebrovascular diseases.

Spatial Similarity of MRI-Visible Perivascular Spaces in Healthy Young Adult Twins.

This study aimed to determine whether genetic factors affect the location of dilated perivascular spaces (dPVS) by comparing healthy young twins and non-twin (NT) siblings. A total of 700 healthy young adult twins and NT siblings [138 monozygotic (MZ) twin pairs, 79 dizygotic (DZ) twin pairs, and 133 NT sibling pairs] were collected from the Human Connectome Project dataset. dPVS was automatically segmented and normalized to standard space. Then, spatial similarity indices [mean squared error (MSE), structural similarity (SSIM), and dice similarity (DS)] were calculated for dPVS in the basal ganglia (BGdPVS) and white matter (WMdPVS) between paired subjects before and after propensity score matching of dPVS volumes between groups. Within-pair correlations for the regional volumes of dVPS were also assessed using the intraclass correlation coefficient. The spatial similarity of dPVS was significantly higher in MZ twins [higher DS (median, 0.382 and 0.310) and SSIM (0.963 and 0.887) and lower MSE (0.005 and 0.005) for BGdPVS and WMdPVS, respectively] than in DZ twins [DS (0.121 and 0.119), SSIM (0.941 and 0.868), and MSE (0.010 and 0.011)] and NT siblings [DS (0.106 and 0.097), SSIM (0.924 and 0.848), and MSE (0.016 and 0.017)]. No significant difference was found between DZ twins and NT siblings. Similar results were found even after the subjects were matched according to dPVS volume. Regional dPVS volumes were also more correlated within pairs in MZ twins than in DZ twins and NT siblings. Our results suggest that genetic factors affect the location of dPVS.

Blood-Brain Barrier Disruption and Perivascular Spaces in Small Vessel Disease and Neurodegenerative Diseases: A Review on MRI Methods and Insights.

Perivascular spaces (PVS) and blood-brain barrier (BBB) disruption are two key features of cerebral small vessel disease (cSVD) and neurodegenerative diseases that have been linked to cognitive impairment and are involved in the cerebral waste clearance system. Magnetic resonance imaging (MRI) offers the possibility to study these pathophysiological processes noninvasively in vivo. This educational review provides an overview of the MRI techniques used to assess PVS functionality and BBB disruption. MRI-visible PVS can be scored on structural images by either (subjectively) counting or (automatically) delineating the PVS. We highlight emerging (diffusion) techniques to measure proxies of perivascular fluid and its movement, which may provide a more comprehensive understanding of the role of PVS in diseases. For the measurement of BBB disruption, we explain the most commonly used MRI technique, dynamic contrast-enhanced (DCE) MRI, as well as a more recently developed technique based on arterial spin labeling (ASL). DCE MRI and ASL are thought to measure complementary characteristics of the BBB. Furthermore, we describe clinical studies that have utilized these MRI techniques in cSVD and neurodegenerative diseases, particularly Alzheimer's disease (AD). These studies demonstrate the role of PVS and BBB dysfunction in these diseases and provide insight into the large overlap, but also into the differences between cSVD and AD. Overall, MRI techniques may provide valuable insights into the pathophysiological mechanisms underlying these diseases and have the potential to be used as markers for disease progression and treatment response. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Perivascular spaces mediate a relationship between diabetes and other cerebral small vessel disease markers in cerebrovascular and neurodegenerative diseases

Type 2 diabetes mellitus (T2DM) and hypertension are risk factors for cerebral small vessel disease (SVD); however, few studies have characterised their relationships with MRI-visible perivascular spaces (PVS). MRI was used to quantify deep (d) and periventricular (p) white matter hyperintensities (WMH), lacunes, PVS in the white matter (wmPVS) or basal ganglia (bgPVS), and diffusion metrics in white matter. Patients with T2DM had greater wmPVS volume and there were greater wmPVS volumes in patients with T2DM and hypertension together. Counterfactual moderated mediation models found indirect effects of T2DM on volumes of other SVD and diffusion markers that were mediated by wmPVS: pWMH, dWMH, periventricular lacunes, and deep lacunes, and progression of deep lacunes over 1 year, in patients with hypertension, but not in patients without hypertension. Studying the regulation of cortical perivascular fluid dynamics may reveal mechanisms that mediate the impact of T2DM on cerebral small vessels.

Enlarged perivascular spaces in patients with migraine: a case-control study based on 3T MRI.

To explore whether MRI-visible enlarged perivascular spaces (EPVS) are associated with migraine and may serve as a predictor of migraine. Then further explore its correlation with migraine chronification. A total of 231 participants (healthy control [HC] = 57, episodic migraine [EM] = 59, chronic migraine [CM] = 115) were included in this case-control study. A 3T MRI device and the validated visual rating scale were used to assess the grades of EPVS in centrum semiovale (CSO), midbrain (MB), and basal ganglia (BG). Comparisons between the two groups were made using the chi-square or Fisher's exact tests to initially determine whether high-grade EPVS were associated with migraine and migraine chronification. A multivariate logistic regression model was constructed to further investigate the role of high-grade EPVS in migraine. The prevalence of high-grade EPVS in CSO and MB were significantly higher in patients with migraine than in HCs (CSO: 64.94% vs. 42.11%, P = 0.002; MB: 55.75% vs. 29.82%, P = 0.001). Subgroup analysis showed no statistical difference between patients with EM and CM (CSO: 69.94% vs. 62.61%, P = 0.368; MB: 50.85% vs. 58.26%, P = 0.351). Individuals with high-grade EPVS in CSO (odds ratio [OR]: 2.324; 95% confidence interval [CI]: 1.136-4.754; P = 0.021) and MB (OR: 3.261; 95% CI: 1.534-6.935; P = 0.002) were more likely to suffer from migraine. This case-control study showed that high-grade EPVS in CSO and MB in clinical practice with the underlying mechanism of dysfunction of the glymphatic system could be a predictor of migraine, but no significant correlation had been found with migraine chronification.

Noninvasive neuroimaging provides evidence for deterioration of the glymphatic system in Parkinson's disease relative to essential tremor

IntroductionGrowing evidence has demonstrated dysfunction of the glymphatic system in α-synucleinopathy and related diseases. In this study, we aimed to use diffusion tensor image analysis along the perivascular space (DTI-ALPS) and MRI-visible enlarged perivascular spaces (EPVS) to evaluate glymphatic system function quantitatively and qualitatively and its relationship to clinical scores of disease severity in Parkinson's disease (PD) and essential tremor (ET). MethodsOverall, 124 patients with PD, 74 with ET, and 106 healthy controls (HC) were enrolled. Two trained neurologists performed quantitative calculations of ALPS on DTI and visual ratings of EPVS on T2-weighted images in the centrum semiovale (CSO), basal ganglia (BG), midbrain, and cerebellum. ResultsThe ALPS index was lower in patients with PD than in patients with ET (p < 0.001) and HC (p < 0.001). Similarly, patients with PD showed a more severe EPVS burden in the CSO, BG, and midbrain compared to ET and HC. Moreover, the ALPS index was negatively correlated with disease severity in the PD subgroups; however, it did not differ within the ET subgroup. No differences in ALPS or EPVS were observed between the ET and HC groups. ConclusionIn conclusion, DTI-ALPS and EPVS both provide neuroimaging evidence of glymphatic system dysfunction in PD, which further supports that PD is an α-synucleinopathy disease, while ET is a cerebellar dysfunction-related disease.

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.

Deep white matter hyperintensity is spatially correlated to MRI-visible perivascular spaces in cerebral small vessel disease on 7 Tesla MRI

BackgroundThe association between perivascular space (PVS) and white matter hyperintensity (WMH) has been unclear. Normal-appearing white matter (NAWM) around WMH is also found correlated with the development of focal WMH....

Aging, prevalence and risk factors of MRI-visible enlarged perivascular spaces.

Background and purpose: Cerebral small vessel disease (CSVD) increases with age and is associated with stroke and cognitive decline. Enlarged Perivascular Spaces (ePVS) is an emerging marker of CSVD, but its prevalence over the life span remain unclear. We characterized the age and sex-specific prevalence of ePVS and relation to age-specific risk factors, in a large community-based sample.Methods: We included 3,710 Framingham Heart Study participants with available brain MRI (average age 61.4±14.6, 46% men). ePVS burden was rated in the centrum semiovale (CSO) and basal ganglia (BG) regions. Individual vascular risk factors were related to ePVS burden in the CSO, BG, and mixed CSO-BG regions using multivariable adjusted ordinal logistic regression analysis.Results: Severe ePVS prevalence increased with age in men and women, and paralleled increase in vascular risk factors, and prevention treatment use. Older age, hypertension (and resulting higher treatment use), higher systolic and diastolic blood pressure, and smoking were associated with higher burden of ePVS in the CSO, BG and mixed regions.Conclusions: Our observations reinforce the hypothesis that ePVS may be a marker of aging-driven brain vascular pathologies, and its association with vascular risk factors support their role as CSVD imaging biomarker.

MRI-Visible Perivascular Spaces Associated With Cognitive Impairment in Military Veterans With Traumatic Brain Injury Mediated by CSF P-Tau.

ObjectiveTo investigate the association of MRI-visible perivascular spaces (PVS) with cognitive impairment in military veterans with traumatic brain injury (TBI), and whether cerebrospinal fluid (CSF) p-tau and Aβ mediate this effect.Materials and MethodsWe included 55 Vietnam War veterans with a history of TBI and 52 non-TBI Vietnam War veterans from the Department of Defense Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. All the subjects had brain MRI, CSF p-tau, Aβ, and neuropsychological examinations. MRI-visible PVS number and grade were rated on MRI in the centrum semiovale (CSO-PVS) and basal ganglia (BG-PVS). Multiple linear regression was performed to assess the association between MRI-visible PVS and cognitive impairment and the interaction effect of TBI. Additionally, mediation effect of CSF biomarkers on the relationship between MRI-visible PVS and cognitive impairment was explored in TBI group.ResultsCompared with military control, TBI group had higher CSO-PVS number (p = 0.001), CSF p-tau (p = 0.022) and poorer performance in verbal memory (p = 0.022). High CSO-PVS number was associated with poor verbal memory in TBI group (β = -0.039, 95% CI −0.062, −0.016), but not in military control group (β = 0.019, 95% CI −0.004, 0.043) (p-interaction = 0.003). Further mediation analysis revealed that CSF p-tau had a significant indirect effect (β = −0.009, 95% CI: −0.022 −0.001, p = 0.001) and mediated 18.75% effect for the relationship between CSO-PVS and verbal memory in TBI group.ConclusionMRI-visible CSO-PVS was more common in Vietnam War veterans with a history of TBI and was associated with poor verbal memory, mediated partially by CSF p-tau.

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.

MRI-visible perivascular spaces in basal ganglia but not centrum semiovale or hippocampus were related to deep medullary veins changes

Our purpose is to assess the role of deep medullary veins (DMVs) in pathogenesis of MRI-visible perivascular spaces (PVS) in patients with cerebral small vessel disease (cSVD). Consecutive patients recruited in the CIRCLE study (ClinicalTrials.gov ID: NCT03542734) were included. Susceptibility Weighted Imaging-Phase images were used to evaluate DMVs based on a brain region-based visual score. T2 weighted images were used to evaluate PVS based on the five-point score, and PVS in basal ganglia (BG-PVS), centrum semiovale (CSO-PVS) and hippocampus (H-PVS) were evaluated separately. 270 patients were included. The severity of BG-PVS, CSO-PVS and H-PVS was positively related to the increment of age (all p < 0.05). The severity of BG-PVS and H-PVS was positively related to DMVs score (both p < 0.05). Patients with more severe BG-PVS had higher Fazekas scores in both periventricle and deep white matter (both p < 0.001) and higher frequency of hypertension (p = 0.008). Patients with more severe H-PVS had higher frequency of diabetes (p < 0.001). Besides, high DMVs score was an independent risk factor for more severe BG-PVS (β = 0.204, p = 0.001). Our results suggested that DMVs disruption might be involved in the pathogenesis of BG-PVS.

MRI-Visible Perivascular Spaces in the Centrum Semiovale Are Associated with Brain Amyloid Deposition in Patients with Alzheimer Disease-Related Cognitive Impairment.

The association of perivascular spaces in the centrum semiovale with amyloid accumulation among patients with Alzheimer disease-related cognitive impairment is unknown. We evaluated this association in patients with Alzheimer disease-related cognitive impairment and β-amyloid deposition, assessed with [18F] florbetaben PET/CT. MR imaging and [18F] florbetaben PET/CT images of 144 patients with Alzheimer disease-related cognitive impairment were retrospectively evaluated. MR imaging-visible perivascular spaces were rated on a 4-point visual scale: a score of ≥3 or <3 indicated a high or low degree of MR imaging-visible perivascular spaces, respectively. Amyloid deposition was evaluated using the brain β-amyloid plaque load scoring system. Compared with patients negative for β-amyloid, those positive for it were older and more likely to have lower cognitive function, a diagnosis of Alzheimer disease, white matter hyperintensity, the Apolipoprotein E ε4 allele, and a high degree of MR imaging-visible perivascular spaces in the centrum semiovale. Multivariable analysis, adjusted for age and Apolipoprotein E status, revealed that a high degree of MR imaging-visible perivascular spaces in the centrum semiovale was independently associated with β-amyloid positivity (odds ratio, 2.307; 95% CI, 1.036-5.136; P = .041). A high degree of MR imaging-visible perivascular spaces in the centrum semiovale independently predicted β-amyloid positivity in patients with Alzheimer disease-related cognitive impairment. Thus, MR imaging-visible perivascular spaces in the centrum semiovale are associated with amyloid pathology of the brain and could be an indirect imaging marker of amyloid burden in patients with Alzheimer disease-related cognitive impairment.

Magnetic resonance imaging findings of the posterior fossa in 47 patients with mucopolysaccharidoses: A cross-sectional analysis.

BackgroundMucopolysaccharidoses (MPS) is a group of hereditary multisystemic lysosomal disorders. Most neuroimaging studies in MPS have focused on the supratentorial compartment and craniocervical junction abnormalities, and data regarding posterior fossa findings are scarce in the literature. Thus, our purpose is to describe posterior fossa findings on magnetic resonance imaging (MRI) of MPS patients.MethodsWe reviewed routine MRI scans of MPS patients being followed up at our institution (types I, II, III, IV, and VI), focusing on posterior fossa structures.ResultsForty‐seven MPS patients were included. MRI‐visible perivascular spaces were commonly found in the midbrain and adjacent to the dentate nuclei (85% and 55% of patients, respectively). White‐matter lesion was not identified in most cases. Its most frequent localizations were in the pons and cerebellum (34% and 30% of patients, respectively). Enlargement of cerebrospinal fluid (CSF) spaces in the posterior fossa was present in 55% of individuals and was more frequent in neuronopathic patients (73% vs 40%; P = .02). Cerebellar volume was classified as normal, apparent macrocerebellum, atrophic, and hypoplastic in 38%, 38%, 21%, and 3% of patients, respectively. A depression of the posterior fossa floor in the midline sagittal plane was found in 22 patients (47%), which was statistical significantly associated with enlargement of CSF spaces (P = .02) and with apparent macrocerebellum (P = .03).ConclusionThe present study compiled the main posterior fossa findings in MPS patients. Classically described in the supratentorial compartment, MRI‐visible perivascular spaces, white matter lesions, and enlarged perivascular spaces were also found in the posterior fossa. However, atrophy, which commonly affects cerebral hemispheres, was not the most frequent cerebellar morphology found in our study. Moreover, potential findings for future research were described.

Abstract P342: Histopathological Correlates of MRI-Visible Perivascular Spaces in Cerebral Amyloid Angiopathy

Perivascular spaces (PVS) are fluid-filled spaces surrounding cerebral blood vessels. MRI-visible, supposedly enlarged, PVS in the centrum semiovale (CSO) have been associated with cerebral amyloid angiopathy (CAA). PVS enlargement may be due to perivascular clearance impairments, potentially caused by increased amyloid-β (Aβ) accumulation in the walls of vessels in the overlying cortex. We test this hypothesis, using MRI-guided histopathological examination of PVS in CAA autopsy cases. The cohort included 19 CAA (74.1±8.2y, 7F) and 5 non-CAA control cases (88.0±4.9y, 3F). Formalin-fixed hemispheres were scanned on a 3T MRI scanner, including a 500μm T2-weighted sequence. PVS enlargement was assessed in the CSO on in vivo and ex vivo MRI. In addition, local score of PVS enlargement was assessed in four pre-defined juxtacortical areas (Fig.A), using a semiquantitative score and on the corresponding histological sections (Fig.B). Severity of leptomeningeal and cortical CAA were assessed on adjacent Aβ-stained sections, using a semiquantitative scale.PVS enlargement was more severe in CAA cases compared to controls, both on in vivo and ex vivo MRI (p&lt;0.05). PVS enlargement on ex vivo MRI positively correlated with the severity of PVS enlargement on the corresponding histopathological samples (Fig.C). Within CAA cases, the degree of PVS enlargement on ex vivo MRI was positively associated with leptomeningeal CAA severity (n=52 samples, ρ=0.35, p=0.011), but not cortical CAA severity (n=52 samples, ρ=0.10, p=0.472). These preliminary findings confirm that the degree of MRI-visible PVS in juxtacortical brain areas reflects enlargement on histopathology. Moreover, they suggest that PVS enlargement in cases with CAA corresponds to increased CAA severity in the overlying leptomeningeal vessels, possibly as a result of impaired perivascular clearance. Future directions include characterization of individual blood vessels associated with PVS enlargement.