Centrum Semiovale Research Articles

Cerebral Small Vessel Disease Is Associated with Motor, Cognitive, and Emotional Dysfunction in Multiple System Atrophy.

Cerebral small vessel disease (CSVD) has not been systematically studied in patients with multiple system atrophy (MSA). We sought to explore whether MSA patients suffer from a heavier CSVD burden relative to healthy individuals and whether CSVD has a relationship with motor, cognitive, and emotional dysfunction in patients with MSA. This study consecutively recruited 190 MSA patients and 190 matched healthy controls whose overall CSVD burden and single CSVD imaging markers (including white matter hyperintensity (WMH), microbleeds, lacunes, and enlarged perivascular spaces (EPVS)) were measured. Of the MSA patients, 118 completed multi-dimensional outcome assessments. Spearman's correlations and multivariable linear regressions were performed. We observed a greater burden of overall CSVD, WMH, and EPVS in MSA patients compared with controls, but not for microbleeds and lacunes. Motor dysfunction and cognitive impairment were significantly worse in subjects with severe CSVD than those with none-to-mild CSVD. In patients with MSA, the severity of CSVD burden was positively associated with motor impairments as measured by the Unified Multiple System Atrophy Rating Scale-II (β= 2.430, p = 0.039) and Scale for the Assessment and Rating of Ataxia (β= 1.882, p = 0.015). Of CSVD imaging markers, different associations with MSA outcomes were displayed. WMH was associated with motor, cognitive, and emotional deficits, while the EPVS in the centrum semiovale, basal ganglia, and hippocampus regions was correlated only with motor severity, anxiety, and cognition, respectively. Similar findings were noted in MSA-cerebellar and MSA-parkinsonian patients. Concomitant CSVD may be correlated with worse multi-dimensional dysfunction in patients with MSA.

Clinical Relevance of Enlarged Perivascular Spaces in Neurodegenerative Disease

Background: Enlarged perivascular space (ePVS) is recently reported to be associated with cerebral small vessel disease (SVD) and Alzheimer’s disease (AD). The topographical location of ePVS may relate to the underlying pathology; basal ganglia (BG)-ePVS has been associated with cerebral vascular diseases and centrum semi-ovale (CSO)-ePVS associated with cerebral amyloid angiopathy (CAA). However, the effects of ePVS on various neurological conditions remain still controversial. To investigate the clinical relevance of ePVS in neurodegenerative diseases, we tested relationships between ePVS and cognition, markers of SVD, vascular risk factors, or amyloid pathology.Methods: We retrospectively reviewed 292 patients (133 AD dementia, 106 mild cognitive impairment, 39 other neurodegenerative diseases, 14 subjective cognitive decline) who underwent both amyloid positron emission tomography and brain magnetic resonance imaging. Vascular risk factors and cognitive tests results were collected. The ePVS in the BG and CSO, SVD markers and the volume of white matter hyperintensities were measured.Results: There were no significant differences in the severity and distribution of ePVS among clinical syndromes. Both BG- and CSO-ePVS were not related to cognitive function. Patients with lacunes were more likely to have high-degree BG-ePVS. High degree CSO-ePVS had an odds ratio (OR) for amyloid positive of 2.351, while BG-ePVS was a negative predictor for amyloid pathology (OR, 0.336).Conclusions: Our findings support that ePVS has different underlying pathologies according to the cerebral topography. BG-ePVS would be attributed to hypertensive angiopathy considering the relation with SVD markers, whereas and CSO-ePVS would be attributed to CAA considering the association with amyloid pathology.

Association of Baseline Cerebrovascular Reactivity and Longitudinal Development of Enlarged Perivascular Spaces in the Basal Ganglia.

Increasing evidence suggests that enlarged perivascular spaces (ePVS) are associated with cognitive dysfunction in aging. However, the pathogenesis of ePVS remains unknown. Here, we tested the possibility that baseline cerebrovascular dysfunction, as measured by a magnetic resonance imaging measure of cerebrovascular reactivity, contributes to the later development of ePVS. Fifty cognitively unimpaired, older adults (31 women; age range, 60-84 years) underwent magnetic resonance imaging scanning at baseline and follow-up separated by ≈2.5 years. ePVS were counted in the basal ganglia, centrum semiovale, midbrain, and hippocampus. Cerebrovascular reactivity, an index of the vasodilatory capacity of cerebral small vessels, was assessed using carbon dioxide inhalation while acquiring blood oxygen level-dependent magnetic resonance images. Low baseline cerebrovascular reactivity values in the basal ganglia were associated with increased follow-up ePVS counts in the basal ganglia after controlling for age, sex, and baseline ePVS values (estimate [SE]=-3.18 [0.96]; P=0.002; [95% CI, -5.11 to -1.24]). This effect remained significant after accounting for self-reported risk factors of cerebral small vessel disease (estimate [SE]=-3.10 [1.00]; P=0.003; [CI, -5.11 to -1.09]) and neuroimaging markers of cerebral small vessel disease (estimate [SE]=-2.72 [0.99]; P=0.009; [CI, -4.71 to -0.73]). Our results demonstrate that low baseline cerebrovascular reactivity is a risk factor for later development of ePVS.

Acute psychosis as the presenting manifestation of lupus: case reports

Introduction: Systemic lupus erythematosus (SLE) is an autoimmune disorder that affects multiple organs with a wide range of clinical manifestations. Neuropsychiatric manifestation (NPSLE) is present among 28–40% of the SLE patients. Psychosis is rarely the only initial symptom of lupus, as neuropsychiatric lupus is often associated with systemic activity. We present two cases of young ladies presenting with acute psychosis as the predominant symptom and further diagnosed with SLE disease. Case reports: Case 1 A 20-year-old female, unmarried, presented to the Psychology Department with acute behavioral abnormality associated with staring, insomnia and, aggressive behavior, hearing voices for the last 3 days. No other psychiatric or neurological symptoms; she was taking 20 mg oral prednisolone prescribed according to a history of fatigue, low-grade fever, loss of appetite, pain in almost all joints, and myalgia for the last 1 month. There was no sign of focal neurological deficit or meningeal irritation. Examination of other systems did not find any clinical abnormality except for the presence of photosensitivity. A psychiatric consultation was ordered. Laboratory tests: white blood cells 3200 cell/mm3 (range=4000–11 000) with normal differentiation, hemoglobin 9.2 mg/dl (range=12.5–16), platelet 90 000/dl (range=150 000–400 000), C-reactive protein (CRP) 65 mg/l (n≤6), and erythrocyte sedimentation rate (ESR) 100 mm/h(range=0–20). anti-nuclear antibody (ANA) profile which was positive in 1:320 dilution, homogenous type, along with anti-ds-DNA positive (+), decreased C3 and C4. The diagnosis of SLE was done according to the European League Against Rheumatism/American College of Rheumatology Classification Criteria (EULAR/ACR Criteria). Case2 A 37-year-old married female with 3 children presented to the Psychology Department with disorientation, staring, hearing voices, seeing images of people who want to hurt her, refusing to respond to people, and insomnia for the last 10 days. She had complained of fatigue and low-grade fever for last month. A psychiatric consultation was ordered, and the patient was managed with an injection of haloperidol 5 mg BD. Laboratory tests: white blood cells 7300 cells/mm3 (range=4000–11 000) with normal differentiation, hemoglobin 8.7 mg/dl (range=12.5–16), platelet 90 000/dl (range=150 000–400 000), reticulocyte:1.4, CRP 7 mg/l (n≤6), and ESR 50mm/h (range=0–20). The ANA profile was positive in 1:320 dilution, homogenous type, along with the anti-ds-DNA negative (−), decreased C3, and normal C4. Brain magnetic resonance imaging (MRI) showed a high white matter signal around the lateral ventricles and in the semi-oval centers. Mild dilation of the lateral ventricles and slight elevation of the left insular and medial temporal lobe signal. Conclusion: Our case reports showed that organic disorders should be considered while evaluating acute psychosis, especially autoimmune disorders. The presence of laboratory features like anemia, elevated ESR, and elevated CRP should be taken with utmost importance.

Cerebral Microstructural and Microvascular Changes in Non-Neuropsychiatric Systemic Lupus Erythematosus: A Study Using Diffusion Kurtosis Imaging and 3D Pseudo-Continuous Arterial Spin Labeling.

The purpose of this study was to observe cerebral microstructure and microcirculation features, as well as changes in white matter (WM) and gray matter (GM) among patients with non-neuropsychiatric systemic lupus erythematosus (non-NPSLE). We compared 36 female patients with non-NPSLE and 20 age- and gender-matched healthy controls (HCs) who underwent 3.0T MRI imaging with diffusion kurtosis imaging (DKI) and 3D pseudo-continuous Arterial Spin Labeling (pCASL). Mean kurtosis (MK), mean kurtosis tensor (MKT), and cerebral blood flow (CBF) values were obtained from 25 brain regions, including WM and GM. We analyzed the correlation between imaging indicators and clinical data. When compared with HCs, patients with non-NPSLE had reduced MK and MKT values in regional WM, deep GM, and the left frontal lobe cortical GM, and increased CBF in the right parietal lobe WM and right semioval center (SOC). The MK and MKT values were weakly correlated with CBF in some regions, including WM and GM. Complement 3 (C3) and Complement 4 (C4) showed a weak positive correlation with MK and MKT in some regions, including WM and deep GM, while platelet (PLT) was positively correlated with MKT in the left frontal lobe WM; dsDNA antibody was correlated negatively with MK in the right occipital lobe WM; and erythrocyte sedimentation rate (ESR) was correlated negatively with CBF in the left SOC. Our findings revealed the presence of brain microstructural and microvascular abnormalities in non-NPSLE patients, indicating microstructural damage in the cortical GM, which was less commonly reported. We found DKI and pCASL useful in detecting early brain lesions, and MK was a more sensitive and beneficial indicator.

Abstract 017: Rapid Progression Of Microhemorrhage In A Patient With An Atypical CADASIL Variant

Introduction CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is a rare inherited disorder in which thickening occurs in the walls of small and medium‐sized blood vessels, which results in decreased cerebral blood delivery. CADASIL is most often established as a diagnosis with identification of a heterozygous pathogenic variant of the NOTCH3 gene by way of molecular genetic testing. In this abstract we identify an atypical presentation of CADASIL with a heterozygous pathologic variant of the HTRA1 gene. This case is unusual in its late onset, as the disease typically presents in the third to fourth decade of life. Additionally, the prevalence of microbleeds in CADASIL typically correlates with patient age. Methods Electronic charts of a patient with recurrent strokes and positive genetic testing were reviewed. Results A 63‐year‐old right‐handed African American male with hypertension, hyperlipidemia, diabetes mellitus, and a history of cerebrovascular disease and cervical myelopathy initially presenting in 2020 lower extremity weakness and progressive apraxia of speech. He had a documented history of transient‐ischemic attack and was noted to have undergone progressive cognitive decline. His presentation raised concern for etiology such as vasculitis or multiple sclerosis and prompted a genetic workup, which was obtained on outpatient follow‐up. The patient presented several more times emergently with similar symptoms that included the reoccurrence and progression of his spastic lower extremity weakness as well as the development of a pseudo‐bulbar affect. Initial MRI brain demonstrated areas of DWI hyperintensity scattered throughout the bilateral hemispheres without ADC correlation. Post‐contrast T2 sequencing demonstrated hyperintensities in the callosal splenium and left centrum semiovale. Genetic testing consisting of Hereditary Cerebral Small Vessel Disease and Hereditary Spastic Paraplegia panels through Invitae were obtained. The first panel evaluates 10 genes for variants which are associated with hereditary forms of cerebral small vessel disease, encompassing those conditions in which small arteries, arterioles, venules, and capillaries of the brain are compromised. The Hereditary Cerebral Small Vessel Disease genetic panel resulted in the positive identification of a likely‐pathogenic variant of the HTRA1 gene, which is associated with CADASIL 2. The Hereditary Spastic Paraplegia genetic panel was unremarkable, as were CSF studies obtained for evaluation of a demyelinating or inflammatory cause. Repeat MRI obtained twice more over the patient’s repeated presentations and demonstrated a large interval increase in areas of low‐signal gradient echo over the course of approximately three months, which represented an evolution in the number of microhemorrhages beyond what would be expected in such a short period of time. Conclusion Scientific literature describes the prevalence of microhemorrhages in CADASIL to be somewhere between 38‐75%. However, there have been few studies which detail such a rapid progression of microhemorrhages in this patient population as well as such a late progression of the disease. Our case demonstrates a unique presentation of CADASIL and provides a remarkable example of rapid, late‐in‐life disease presentation. Further research is needed to elucidate and characterize disease leading to early diagnosis and management.

MRI Visible Perivascular Spaces and the Risk of Incident Mild Cognitive Impairment in a Community Sample.

Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the community-based Framingham Heart Study (FHS). FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included. PVS were rated according to severity in the basal ganglia and centrum semiovale (CSO) using established criteria. Cox regression analyses were used to relate PVS to incident MCI adjusted for demographic and cardiovascular variables. The mean age of the sample (1,314 participants) at MRI was 68 years (SD, 9; 54% women). There were 263 cases of incident MCI over a median 7.4 years follow-up (max, 19.8 years). MCI risk increased with higher PVS severity in the CSO. Relative to persons with the lowest severity rating, persons with the highest severity rating in the CSO had a higher risk of incident MCI (hazard ratio [HR] = 2.55; 95% confidence interval [CI], 1.48-4.37; p = 0.0007). In secondary analysis, this association seemed stronger in women. Risk of incident MCI was nominally higher for participants with the highest severity grade of PVS in the basal ganglia, though not statistically significant relative to the lowest grade (HR = 2.19; 95% CI, 0.78-6.14; p = 0.14). PVS burden in the CSO may be a risk marker for early cognitive impairment.

SLASER and PRESS perform similarly at revealing metabolite-age correlations at 3 T.

To compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate at 3 T. MRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale and posterior cingulate cortex (PCC). Acquisition parameters included TR/TE = 2000/30 ms, 96 transients, and 2048 datapoints sampled at 2 kHz. Spectra were analyzed using Osprey. SNR, FWHM linewidth of total creatine, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement. SNR and linewidth were significantly higher (p < 0.01) for sLASER than PRESS in PCC. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. PRESS-sLASER measurements were significantly correlated (p < 0.05) for most metabolites. Metabolite-age relationships were consistently identified using both methods. Similar coefficients of variation were observed for most metabolites. The study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in centrum semiovale and PCC data acquired at 3 T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in homogeneous brain regions at clinical field strength.

Apparent diffusion coefficient values can predict neuromotor outcome in term neonates with hypoxic-ischaemic encephalopathy.

To determine the apparent diffusion coefficient (ADC) in brain structures during the first 2 weeks of life and its relation with neurological outcome for hypoxic-ischaemic encephalopathy (HIE) in term neonates. We retrospectively evaluated 56 term-born neonates. The ADC values were measured for 11 brain regions. The clinical outcomes at least 2 years of age were defined as normal outcome, mild disability and severe disability. The area under curves (AUCs) by ROC analysis were performed to predict the neurodevelopmental outcomes. The clinical outcomes were compared between favourable outcome and adverse outcome and also between normal outcome and unfavourable outcome. Thirty-four patients were judged as normal outcome, 10 as mild disability and 12 as severe disability. When the clinical outcomes were compared between favourable outcome and adverse outcome, the AUC on the 1st week was highest value at the thalamus. When the clinical outcomes were compared between normal outcome and unfavourable outcome, the AUC on the 1st week was highest at the thalamus. The ADC values in the thalamus in the 1st week can predict the neurological outcome. The ADC values in centrum semiovale on the 2nd week can be used to predict neurodevelopmental outcomes.

Increased perivascular space volume in white matter and basal ganglia is associated with cognition in Parkinson’s Disease

Perivascular spaces (PVS), fluid-filled compartments surrounding brain vasculature, are an essential component of the glymphatic system responsible for transport of waste and nutrients. Glymphatic system impairment may underlie cognitive deficits in Parkinson’s disease (PD). Studies have focused on the role of basal ganglia PVS with cognition in PD, but the role of white matter PVS is unknown. This study examined the relationship of white matter and basal ganglia PVS with domain-specific and global cognition in individuals with PD. Fifty individuals with PD underwent 3T T1w magnetic resonance imaging (MRI) to determine PVS volume fraction, defined as PVS volume normalized to total regional volume, within (i) centrum semiovale, (ii) prefrontal white matter (medial orbitofrontal, rostral middle frontal, superior frontal), and (iii) basal ganglia. A neuropsychological battery included assessment of global cognitive function (Montreal Cognitive Assessment, and global cognitive composite score), and cognitive-specific domains (executive function, memory, visuospatial function, attention, and language). Higher white matter rostral middle frontal PVS was associated with lower scores in both global cognitive and visuospatial function. In the basal ganglia higher PVS was associated with lower scores for memory with a trend towards lower global cognitive composite score. While previous reports have shown that greater amount of PVS in the basal ganglia is associated with decline in global cognition in PD, our findings suggest that increased white matter PVS volume may also underlie changes in cognition.

The dependence of cerebral interstitial fluid on diffusion-sensitizing directions: A multi-b-value diffusion MRI study in a memory clinic sample

Three-component intravoxel incoherent motion (3C-IVIM) imaging with spectral analysis provides a proxy for interstitial fluid (ISF) (e.g., in perivascular spaces (PVS), granting a potential marker for altered cerebral clearance. When 3C-IVIM images are acquired with three orthogonal diffusion-sensitizing directions, these are often averaged into the Trace image. This may result in loss of valuable direction-specific information, particularly in PVS-rich regions (basal ganglia (BG) and centrum semiovale (CSO)).This study assessed the dependence of individual diffusion-sensitizing directions to the ISF fraction in PVS-rich regions. Additionally, we explored the value of diffusion direction-specific information on ISF characteristics in distinguishing thirty-one patients with cognitive impairment (CI) (Alzheimer's disease (n = 15) or Mild Cognitive Impairment (n = 16)) from thirty cognitively healthy elderly controls (CON). Multi-b-value diffusion-weighted images were acquired in three orthogonal directions (L-R (left-right), A-P (anterior-posterior) and S-I (superior-inferior)) at 3 T. Voxel-based spectral analysis using non-negative least squares was conducted to independently analyze the L-R, A-P, S-I, and Trace images. 3C-IVIM measures were first compared between diffusion-sensitizing directions and the Trace within the BG using repeated measures ANOVA. Subsequently, the 3C-IVIM measures were compared per direction between the CI and CSO group in the BG and CSO with multivariable linear regression.Our results show that the ISF fraction significantly differs between all diffusion-sensitizing directions and Trace in the BG, with the highest ISF fraction detected using S-I. Solely using S-I, a higher ISF fraction was identified in CI compared to CON in the BG (p = .020) and CSO (p = .046).Thereby, this study found that the measured ISF fraction depends on the acquired diffusion-sensitizing direction, where S-I is most sensitive to detect ISF and differences between CI and CON. The Trace approach is not always sensitive enough to ISF characteristics. Solely acquiring S-I may offer an alternative to reduce scanning time.

Higher critical closing pressure is independently associated with enlarged basal ganglia perivascular spaces.

This study aimed to explore the association between cerebral hemodynamic parameters focused on the critical closing pressure (CCP) and enlarged perivascular spaces (EPVS). Cerebral blood velocity in the middle cerebral artery (MCAv) and non-invasive continuous blood pressure (NIBP) were measured using a transcranial Doppler (TCD) and Finometer, followed by the calculation of cerebral hemodynamic parameters including CCP, resistance area product (RAP), pulsatility index (PI), and pulse pressure (PP). EPVS were graded separately in the basal ganglia (BG) and centrum semiovale (CSO), using a visual semiquantitative ordinal scale. Patients with EPVS >10 were classified into the severe BG-EPVS group and severe CSO-EPVS group, and the remainder into the mild BG-EPVS group and the mild CSO-EPVS group. Spearman's correlation and binary logistic regression analysis were performed to analyze the relationship between hemodynamic parameters and BG-EPVS and CSO-EPVS, respectively. Overall, 107 patients were enrolled. The severe BG-EPVS group had higher CCP, mean arterial blood pressure (MABP), systolic blood pressure (SBP), and diastolic blood pressure (DBP) than that in the mild BG-EPVS group (p < 0.05). There was no statistical difference in hemodynamic parameters between the severe CSO-EPVS group and the mild CSO-EPVS group. Spearman's correlation analysis showed that CCP was positively associated with BG-EPVS (rho = 0.331, p < 0.001) and CSO-EPVS (rho = 0.154, p = 0.044). The binary logistic regression analysis showed that CCP was independently associated with severe BG-EPVS (p < 0.05) and not with CSO-EPVS (p > 0.05) after adjusting for confounders. CCP representing cerebrovascular tension was independently associated with BG-EPVS.

Evaluation of microcirculation in asymptomatic cerebral infarction with multi-parameter imaging of spectral CT

ObjectiveTo investigate the role of spectral CT multiparametric imaging in the evaluation of cerebral microcirculatory perfusion. MethodsThe imaging data of 145 patients with asymptomatic cerebral infarction confirmed by MR were retrospectively analyzed, and all cases underwent head CTA and cranial CT perfusion imaging (CTP) on double-layer detector spectral CT. Single energy level images (MonoE45 keV), iodine density maps, and effective atomic number maps were reconstructed based on spectral CTA data, and CT values, iodine density values, and effective atomic number values were measured in the infarcted area, healthy control area, centrum semiovale and posterior limb of the internal capsule, respectively; perfusion values, such as cerebral blood volume (CBV) values, cerebral blood flow (CBF) values, time to peak (TTP) values, and mean passage time, were measured in the above-mentioned areas on CTP images. (TTP) values, and mean time to passage (MTT) values. CT values, iodine density values, effective atomic number values, and perfused CBV, CBF, TTP, and MTT values were compared between the infarcted area and the healthy side, the center of the hemianopia, and the posterior limb of the internal capsule. The role of spectral CT parameters and perfusion parameters in the evaluation of asymptomatic cerebral infarction was analyzed. ResultsCT values, iodine density values, and effective atomic number values were statistically different between the infarcted area and the healthy side; CT values, iodine density values, and effective atomic number values were not statistically different between the infarcted side and the healthy side of the hemispheric centrum and the posterior limb of the internal capsule; CBV and CBF were statistically different between the infarcted side and the healthy side, and MTT and TTP were not statistically different. There were statistically significant differences in TTP between the infarcted area and the healthy side of the hemiaxial center, and no statistically significant differences in CBV, CBF, and MTT. There were no statistical differences in CBV, CBF, TTP, and MTT in the inner capsule area. ROC curve analysis of spectral CT-related parameters and CT perfusion parameters for the diagnosis of asymptomatic cerebral infarction: area under the curve of MonoE 45Kv 0.71, area under the curve of iodine density values 0.76, area under the curve of effective atomic number values 0.74; area under the curve of CBV value 0.64, area under the curve of CBF value 0.61, area under the curve of MTT value 0.50, The area under the TTP curve was 0.52. The area under the ROC curve of the multivariate logistic regression model based on spectral parameters is 0.76, which is higher than that of the logistic regression model with perfusion parameters (P < 0.05). ConclusionSpectral CT can better demonstrate small intracranial ischemic lesions, and iodine density values have a better evaluation of microcirculation in asymptomatic cerebral infarcts.

Enlarged Perivascular Spaces in Relation to Cumulative Blood Pressure Exposure and Cognitive Impairment.

Hypertension and enlarged perivascular spaces (EPVS) are thought to be associated with cognitive impairment. However, the correlations among hypertension, EPVS, and cognitive impairment have not been studied yet. We aimed to investigate the relationships between cumulative blood pressure (cBP) exposure with EPVS and cognitive impairment and whether EPVS may mediate the relationship between cBP and cognitive impairment. A total of 1507 subjects from the Kailuan prospective cohort study were enrolled. cBP was calculated from 2006 to 2022. The effects of cBP, EPVS scores, and cognitive impairment were evaluated using a logistic regression model. The relationships among cBP, EPVS score, and cognitive impairment were analyzed using a mediation model. An increase in cBP was positively correlated with an increase in EPVS score. For every SD increase in cBP, the odds ratios (95% CI) of increased EPVS score of the centrum semiovale were 1.67 (1.43-1.95), 1.63 (1.4-1.9), and 1.35 (1.17-1.56), respectively; the odds ratios (95% CI) of increased EPVS score of the basal ganglia were 1.83 (1.56-2.15), 2.01 (1.7-2.36), and 1.31 (1.13-1.52), respectively; and the odds ratios (95% CI) of developing cognitive impairment were 1.28 (1.06-1.53), 1.13 (0.95-1.34), and 1.28 (1.07-1.5), respectively. Basal ganglia-EPVS score accounted for 10.46% to 18.32% of the mediating effects on the relationships of cBP/SD with cognitive impairment. High cBP exposure was an independent risk factor for EPVS, and basal ganglia-EPVS score mediated the effects of cBP on cognitive impairment. URL: https://www. gov; Unique identifier: ChiCTR-TNRC-11001489.

Correlation of glymphatic system abnormalities with Parkinson's disease progression: a clinical study based on non-invasive fMRI.

The glymphatic system is reportedly involved in Parkinson's disease (PD). Based on previous studies, we aimed to confirm the correlation between the glymphatic system and PD progression by combining two imaging parameters, diffusion tensor image analysis along the perivascular space (DTI-ALPS), and enlarged perivascular spaces (EPVS). Fifty-one PD patients and fifty healthy control (HC) were included. Based on the Hoehn-Yahr scale, the PD group was divided into early-stage and medium-to late-stage. All PD patients were scored using the Unified PD Rating Scale (UPDRS). We assessed the DTI-ALPS indices in the bilateral hemispheres and EPVS numbers in bilateral centrum semiovale (CSO), basal ganglia (BG), and midbrain. The DTI-ALPS indices were significantly lower bilaterally in PD patients than in the HC group, and EPVS numbers in any of the bilateral CSO, BG, and midbrain were significantly higher, especially for the medium- to late-stage group and the BG region. In PD patients, the DTI-ALPS index was significantly negatively correlated with age, while the BG-EPVS numbers were significantly positively correlated with age. Furthermore, the DTI-ALPS index was negatively correlated with UPDRS II and III scores, while the BG-EPVS numbers were positively correlated with UPDRS II and III scores. Similarly, the correlation was more pronounced in the medium- to late-stage group. The DTI-ALPS index and EPVS numbers (especially in the BG region) are closely related to age and PD progression and can serve as non-invasive assessments for glymphatic dysfunction and its interventions in clinical studies.

Association of MRI Visible Perivascular Spaces and Neurofilament Light Chain: The Framingham Heart Study.

Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification. To relate PVS burden according to brain topography and plasma NfL. Framingham Heart Study (FHS) participants with brain MRI and NfL measurements were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) using validated methods and categorized based on counts. A mixed region variable representing high burden PVS in either BG or CSO was assessed. Multivariable linear regression analyses were used to relate PVS burden to log-transformed NfL levels in models adjusted for age, sex, FHS cohort, time between MRI and clinic exam, and image view (model 1), vascular risk factors (model 2), and white matter hyperintensity volume, covert brain infarcts, and cerebral microbleeds (model 3). Among 1,457 participants (68.1±8.5 years, 45% males), NfL levels increased with higher PVS burden. Multivariable analysis showed an association of high PVS burden strictly in BG with NfL (β= 0.117, 95% CI 0.014-0.221; p = 0.027), but attenuated in model 3. The associations were mainly in participants≥65 years (β= 0.122, 95% CI 0.015-0.229, p = 0.026), women (β= 0.156, 95% CI 0.024-0.288, p = 0.021), and APOE ɛ4 non-carriers (β= 0.140, 95% CI 0.017-0.263, p = 0.026). The association of strictly BG high PVS burden with NfL suggests a role for PVS as markers of neuroaxonal injury, but our results are hypothesis generating and require further replication.

Effects of sleep on brain perivascular space in a cognitively healthy population

The magnetic resonance imaging (MRI) visible perivascular space (PVS) reportedly clears amyloid-β and metabolic waste during sleep. Previous studies reported an association between sleep and the PVS in small vessel disease, traumatic brain injury, and Alzheimer's disease. However, this relationship in a healthy cohort is still unclear. Here, we used the Human Connectome Project Aging dataset to analyze the relationship between sleep and the PVS in cognitively healthy adults across the aging continuum. We measured sleep parameters using the self-reported Pittsburgh Sleep Quality Index questionnaire. We found that older adults who had better sleep quality and sleep efficiency presented with a larger PVS volume fraction in the basal ganglia (BG). However, sleep measures were not associated with PVS volume fraction in the centrum semiovale (CSO). In addition, we found that body mass index (BMI) influenced the BG-PVS across middle-aged and older participants. In the entire cognitively healthy cohort, the effect of sleep quality on PVS volume fraction was mediated by BMI. However, BMI did not influence this effect in the older cohort. Furthermore, there are significant differences in PVS volume fraction across racial/ethnic cohorts. In summary, the effect of sleep on the PVS volume alteration was different in the middle-aged adults and older adults.

Myelin oligodendrocyte glycoprotein antibody‐associated disease presenting with dystonia

AbstractMyelin oligodendrocyte glycoprotein antibody‐associated disease (MOGAD) commonly presents as optic neuritis or transverse myelitis. We report an atypical clinical presentation for MOGAD in a 28‐year‐old female experiencing right‐arm dystonic episodes. MRI scans demonstrated multifocal periventricular and subcortical lesions, including in the left centrum semiovale and corona radiata. Despite the atypical presentation, her clinical, serological, and radiographic features favor a MOGAD diagnosis. This report emphasizes the heterogeneity of MOGAD phenotypes and the need to consider MOGAD, even in a non‐typical presentation.

Relation of MRI-Visible Perivascular Spaces and Other MRI Markers of Cerebral Small Vessel Disease.

Perivascular spaces (PVS) visible on brain MRI signal cerebral small vessel disease (CSVD). The coexistence of PVS with other CSVD manifestations likely increases the risk of adverse neurological outcomes. We related PVS to other CSVD manifestations and brain volumes that are markers of vascular brain injury and neurodegeneration. Framingham Heart Study (FHS) participants with CSVD ratings on brain MRI were included. PVS were rated in the basal ganglia (BG) and centrum semiovale (CSO) into grades I-IV and a category reflecting high burden in single or mixed CSO-BG regions. We related PVS to covert brain infarcts (CBI), white matter hyperintensities (WMH), cerebral microbleeds (CMB), total brain, hippocampal, and cortical gray matter volumes using adjusted multivariable regression analyses. In 2454 participants (mean age 54 ± 12 years), we observed that higher PVS burden in both BG and CSO was related to CMB in lobar and deep brain regions and increased WMH. Greater CSO PVS burden was associated with decreased total cortical gray volumes. PVS are associated with ischemic markers of CSVD and neurodegeneration markers. Further studies should elucidate the causality between PVS and other CSVD manifestations.

An interactive triangle-based ODF glyph rendering for high angular resolution diffusion imaging

Diffusion magnetic resonance imaging quantifies the diffusion of water molecules. It is unique in showing white matter fiber structures and connectivity in-vivo, relying on the fact that the water molecules’ displacements are more significant along with the fiber orientation than in other directions due to biological barriers. High angular resolution diffusion imaging (HARDI) acquisition enables the differentiation of multiple fiber signals passing through a voxel. Advanced methods for processing diffusion data were developed to synthesize the HARDI data of each voxel into an orientation distribution function (ODF) that relates each direction sample to its probability of water diffusion. Visualizing ODFs through glyphs helps gain insight into the local structure of the brain white matter. Because of the high dimensionality of the data, interactive glyph exploration remains a challenge for a volume containing millions of voxels. This work presents a 3D triangle-based multi-resolution rendering scheme for the ODF glyph. We explored data properties and GPU features to make the triangle-based rendering interactive. Linear performance relative to some fixed-resolution rendered glyphs was assessed using NVIDIA® Nsight Visual StudioTM. A control volume, available in the Retest dataset of the WU-Minn Human Connectome Project, was used to assess the effectiveness of interactive 3D visualization over a multiplanar and curvilinear reformatted volume of ODF glyphs in voxels with multiple fibers, namely the triple crossing at the centrum semiovale, the fanning at the corona radiata, and the crossing of the cingulum and corpus callosum fiber bundles.