Very-long T2-weighted imaging of the non-lesional brain tissue in multiple sclerosis patients.

The purpose of this study is to demonstrate that T2-weighted imaging with very long echo time (TE > 300 ms) can provide relevant information in neurodegenerative/inflammatory disorder. Twenty patients affected by relapsing-remitting multiple sclerosis with stable disease course underwent 1.5 T 3D FLAIR, 3D T1-weighted, and a multi-echo sequence with 32 echoes (TE = 10-320 ms). Focal lesions (FL) were identified on FLAIR. T1-images were processed to segment deep gray matter (dGM), white matter (WM), FL sub-volumes with T1 hypo-intensity (T1FL), and dGM volumes (atrophy). Clinical-radiological parameters included Expanded Disability Status Scale (EDSS), disease duration, patient age, T1FL, and dGM atrophy. Correlation analysis was performed between the mean signal intensity (SI) computed on the non-lesional dGM and WM at different TE versus the clinical-radiological parameters. Multivariable linear regressions were fitted to the data to assess the association between the dependent variable EDSS and the independent variables obtained by T1FL lesion load and the mean SI of dGM and WM at the different TE. A clear trend is observed, with a systematic strengthening of the significance of the correlation at longer TE for all the relationships with the clinical-radiological parameters, becoming significant (p < 0.05) for EDSS, T1FL volumes, and dGM atrophy. Multivariable linear regressions show that at shorter TE, the SI of the T2-weighted sequences is not relevant for describing the EDSS variability while the T1FL volumes are relevant, and vice versa, at very-long TEs (around 300 ms); the SI of the T2-weighted sequences significantly (p < 0.05) describes the EDSS variability. By very long TE, the SI primarily originates from water with a T2 longer than 250 ms and/or free water, which may be arising from the perivascular space (PVS). Very-long T2-weighting might detect dilated PVS and represent an unexplored MR approach in neurofluid imaging of neurodegenerative/inflammatory diseases.

Impaired glymphatic function as a biomarker for subjective cognitive decline: An exploratory dual cohort study.

BACKGROUND: Subjective cognitive decline (SCD) has been recognized as a potential risk stage for progression to Alzheimer's disease (AD), while glymphatic dysfunction is considered an important characteristic of AD. We hypothesize that glymphatic dysfunction occurs during the SCD stage, aiming to discover potential biomarkers for SCD. METHODS: Participants from two independent studies, Sino Longitudinal Study on Cognitive Decline (SILCODE, n = 654) and the Alzheimer's Disease Neuroimaging Initiative (ADNI, n = 650), representing different ethnicities and disease stages, were included to assess glymphatic function using diffusion tensor image analysis along the perivascular space (DTI-ALPS). RESULTS: Abnormal glymphatic function occurs during the SCD stage, with the ALPS index demonstrating excellent classification performance for SCD and normal controls (area under the receiver operating characteristic curve [AUC]SILCODE = 0.816, AUCADNI = 0.797). Lower ALPS index indicates higher risk of cognitive progression, which is negatively correlated with Subjective Cognitive Decline Questionnaire 9 scores and amyloid positron emission tomography burden. DISSCUSION: Our study suggests the ALPS index has the potential to serve as a biomarker for SCD. HIGHLIGHTS: Glymphatic function characterized by the analysis along the perivascular space (ALPS) index becomes abnormal in subjective cognitive decline (SCD), the earliest symptomatic manifestation and preclinical stage of Alzheimer's disease (AD). The ALPS index demonstrates excellent classification performance for SCD and normal controls in the East Asian and Western cohorts. Participants with a lower ALPS index show a higher risk of clinical progression. The ALPS index is closely associated with serval cognitive scales and amyloid beta burden.

Glymphatic System Dysfunction in Congenital Sensorineural Hearing Loss: A DTI-ALPS Study.

BACKGROUND: The neural mechanisms underlying congenital sensorineural hearing loss (CSNHL) remain elusive. OBJECTIVE: This study evaluated the function of the glymphatic system in children with CSNHL compared to normal-hearing children using the DTI-ALPS approach, which utilizes diffusion tensor imaging along the perivascular space. METHODS: Twenty-six children with CSNHL and 30 age- and sex-matched healthy controls (HCs) with normal hearing thresholds were recruited. The DTIALPS index was calculated for each group. We analyzed the discrepancies in the DTI-ALPS index between patients with CSNHL and healthy controls. Additionally, Spearman's correlation analysis was performed to investigate the relationship between the DTI-ALPS index and age in children with CSNHL. RESULTS: Significant differences in the DTI-ALPS index were observed between the two groups. Compared with HCs, the DTI-ALPS index in CSNHL patients was significantly lower (1.49388±0.11441 vs. 1.61402±0.15430, p=0.002). In addition, diffusivity along the z-axis in the association fiber (Dzzassoc) index was significantly higher in the CSNHL group than in the HC group (0.00041±0.00006 vs. 0.00036±0.00004, p=0.003). Furthermore, we discovered a noteworthy downward correlation between the DTI-ALPS index and age in children with CSNHL (rho = -0.544, p=0.005). CONCLUSION: In this present study, glymphatic system activity in CSNHL children was investigated for the first time using the DTI-ALPS index. A significant decrease in glymphatic system function was detected in CSNHL children, which correlated well with age. The DTI-ALPS index could serve as a valuable biomarker for tracking disease progression and treatment in CSNHL and unraveling the neural mechanisms of early hearing deprivation in children with CSNHL.

Glymphatic function and its influencing factors in different glucose metabolism states.

BACKGROUND: Dysfunction of the glymphatic system in the brain in different stages of altered glucose metabolism and its influencing factors are not well characterized. AIM: To investigate the function of the glymphatic system and its clinical correlates in patients with different glucose metabolism states, the present study employed diffusion tensor imaging along the perivascular space (DTI-ALPS) index. METHODS: Sample size was calculated using the pwr package in R software. This cross-sectional study enrolled 22 patients with normal glucose metabolism (NGM), 20 patients with prediabetes, and 22 patients with type 2 diabetes mellitus (T2DM). A 3.0T magnetic resonance imaging was used to evaluate the function of the glymphatic system. The mini-mental state examination (MMSE) was used to assess general cognitive function. The DTI-ALPS index of bilateral basal ganglia and the mean DTI-ALPS index was calculated. Further, the correlation between DTI-ALPS and clinical features was assessed. RESULTS: The left-side, right-side, and mean DTI-ALPS index in the T2DM group were significantly lower than that in the NGM group. The right-side DTI-ALPS and mean DTI-ALPS index in the T2DM group were significantly lower than those in the prediabetes group. DTI-ALPS index lateralization was not observed. The MMSE score in the T2DM group was significantly lower than that in the NGM and prediabetes group. After controlling for sex, the left-side DTI-ALPS and mean DTI-ALPS index in the prediabetes group were positively correlated with 2-hour postprandial blood glucose level; the left-side DTI-ALPS index was negatively correlated with total cholesterol and low-density lipoprotein level. The right-side DTI-ALPS and mean DTI-ALPS index were negatively correlated with the glycosylated hemoglobin level and waist-to-hip ratio in the prediabetes group. The left-side, right-side, and mean DTI-ALPS index in the T2DM group were positively correlated with height. The left-side and mean DTI-ALPS index in the T2DM group were negatively correlated with high-density lipoprotein levels. CONCLUSION: Cerebral glymphatic system dysfunction may mainly occur in the T2DM stage. Various clinical variables were found to affect the DTI-ALPS index in different glucose metabolism states. This study enhances our understanding of the pathophysiology of diabetic brain damage and provides some potential biological evidence for its early diagnosis.

Noninvasive evaluation of the glymphatic system in diffuse gliomas using diffusion tensor image analysis along the perivascular space.

OBJECTIVE: The aim of this study was to noninvasively explore the glymphatic system (GS) in glioma and its association with glioma characteristics and prognosis by using diffusion tensor image analysis along the perivascular space (ALPS). METHODS: In the period from April 2015 to November 2021, all patients with pathologically confirmed unihemispheric glioma who had not undergone surgery, chemotherapy, radiotherapy, or stereotactic biopsy; who did not have severe brain deformation; who had undergone preoperative conventional and advanced whole-brain diffusion-weighted imaging; and whose data were available and uncompromised were included in this study. Age- and sex-matched healthy controls (HCs) who had undergone diffusion-weighted imaging were also included. The ALPS index was calculated based on diffusivity maps, allowing noninvasive analysis of the GS. The contralateral ALPS index was measured in all glioma patients, and the ipsilateral ALPS index was measured in glioma patients without severe deformation of the ipsilateral hemisphere. The ALPS index was compared between glioma patients and HCs according to tumor grade, IDH genotype, tumor and edema volume, and tumor location. The association between the bilateral ALPS index of gliomas and tumor characteristics was further analyzed. Survival analysis was conducted using Kaplan-Meier survival curves with the log-rank test and univariable and multivariable Cox regressions. RESULTS: Ninety-one patients with unihemispheric glioma (33 female, mean age 46 ± 13 years) and 59 age- and sex-matched HCs were included in this study. The ipsilateral ALPS index decreased in the glioma group versus the HC group, regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.048), whereas the contralateral ALPS index decreased in gliomas with a high grade, IDH wildtype, larger edema volume, different tumor volumes and locations (p ≤ 0.009). The ipsilateral versus contralateral ALPS index was lower regardless of tumor grade, IDH genotype, tumor and edema volume, or tumor location (p ≤ 0.044). Univariable linear regression revealed age (ß = -0.004, p = 0.026), tumor grade (ß = -0.114, p = 0.011), and IDH genotype (ß = 0.120, p = 0.008) were associated with the ipsilateral ALPS index in glioma. Age (ß = -0.005, p < 0.001), tumor grade (ß = -0.144, p < 0.001), IDH genotype (ß = 0.154, p < 0.001), tumor volume (ß = -0.002, p = 0.001), and peritumoral edema volume (ß = -0.002, p < 0.001) were correlated with the contralateral ALPS index in glioma. Multivariable linear regression revealed that tumor grade (ß = -0.125, p = 0.005) was independently associated with the ipsilateral ALPS index. Age (ß = -0.003, p = 0.022), IDH status (ß = 0.132, p = 0.001), and tumor volume (ß = -0.002, p < 0.001) were independently associated with the contralateral ALPS index. Kaplan-Meier analysis showed different survival times between low and high contralateral ALPS groups (log-rank = 10.574, p = 0.001). Univariable Cox regression analysis demonstrated that the lower contralateral ALPS index was related to a shorter survival time (HR 0.095, p = 0.005). Multivariable Cox regression analysis revealed IDH status as the only independent factor for survival (HR 0.138, p < 0.001). CONCLUSIONS: GS function was impaired in glioma and correlated with tumor characteristics, and worse contralateral GS function was associated with a shorter survival time.

Navigating Central Oxytocin Transport: Known Realms and Uncharted Territories.

Complex mechanisms govern the transport and action of oxytocin (Oxt), a neuropeptide and hormone that mediates diverse physiologic processes. While Oxt exerts site-specific and rapid effects in the brain via axonal and somatodendritic release, volume transmission via CSF and the neurovascular interface can act as an additional mechanism to distribute Oxt signals across distant brain regions on a slower timescale. This review focuses on modes of Oxt transport and action in the CNS, with particular emphasis on the roles of perivascular spaces, the blood-brain barrier (BBB), and circumventricular organs in coordinating the triadic interaction among circulating blood, CSF, and parenchyma. Perivascular spaces, critical conduits for CSF flow, play a pivotal role in Oxt diffusion and distribution within the CNS and reciprocally undergo Oxt-mediated structural and functional reconstruction. While the BBB modulates the movement of Oxt between systemic and cerebral circulation in a majority of brain regions, circumventricular organs without a functional BBB can allow for diffusion, monitoring, and feedback regulation of bloodborne peripheral signals such as Oxt. Recognition of these additional transport mechanisms provides enhanced insight into the systemic propagation and regulation of Oxt activity.

Longitudinal assessment of glymphatic changes following mild traumatic brain injury: Insights from perivascular space burden and DTI-ALPS imaging.

Introduction: Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. Methods: In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Results: Our key findings include: (1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. (2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. (3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information. Conclusion: ePVS burden and ALPS index offers distinct values in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.

A Predictive Model of the Progression to Alzheimer's Disease in Patients with Mild Cognitive Impairment Based on the MRI Enlarged Perivascular Spaces.

Background: Mild cognitive impairment (MCI) is a heterogeneous condition that can precede various forms of dementia, including Alzheimer's disease (AD). Identifying MCI subjects who are at high risk of progressing to AD is of major clinical relevance. Enlarged perivascular spaces (EPVS) on MRI are linked to cognitive decline, but their predictive value for MCI to AD progression is unclear. Objective: This study aims to assess the predictive value of EPVS for MCI to AD progression and develop a predictive model combining EPVS grading with clinical and laboratory data to estimate conversion risk. Methods: We analyzed 358 patients with MCI from the ADNI database, consisting of 177 MCI-AD converters and 181 non-converters. The data collected included demographic information, imaging data (including perivascular spaces grade), clinical assessments, and laboratory test results. Variable selection was conducted using the Least Absolute Shrinkage and Selection Operator (LASSO) method, followed by logistic regression to develop predictive model. Results: In the univariate logistic regression analysis, both moderate (OR = 5.54, 95% CI [3.04-10.18]) and severe (OR = 25.04, 95% CI [10.07-62.23]) enlargements of the centrum semiovale perivascular space (CSO-PVS) were found to be strong predictors of disease progression. LASSO analyses yielded 12 variables, refined to six in the final model: APOE4 genotype, ADAS11 score, CSO-PVS grade, and volumes of entorhinal, fusiform, and midtemporal regions, with an AUC of 0.956 in the training and 0.912 in the validation cohort. Conclusions: Our predictive model, emphasizing EPVS assessment, provides clinicians with a practical tool for early detection and management of AD risk in MCI patients.

Astrocyte regulation of extracellular space parameters across the sleep-wake cycle.

Multiple subfields of neuroscience research are beginning to incorporate astrocytes into current frameworks of understanding overall brain physiology, neuronal circuitry, and disease etiology that underlie sleep and sleep-related disorders. Astrocytes have emerged as a dynamic regulator of neuronal activity through control of extracellular space (ECS) volume and composition, both of which can vary dramatically during different levels of sleep and arousal. Astrocytes are also an attractive target of sleep research due to their prominent role in the glymphatic system, a method by which toxic metabolites generated during wakefulness are cleared away. In this review we assess the literature surrounding glial influences on fluctuations in ECS volume and composition across the sleep-wake cycle. We also examine mechanisms of astrocyte volume regulation in glymphatic solute clearance and their role in sleep and wake states. Overall, findings highlight the importance of astrocytes in sleep and sleep research.

Is cerebral small vessel disease a central nervous system interstitial fluidopathy?

A typical anatomical congregate and functionally distinct multicellular cerebrovascular dynamic confer diverse blood-brain barrier (BBB) and microstructural permeabilities to conserve the health of brain parenchymal and its microenvironment. This equanimity presupposes the glymphatic system that governs the flow and clearance of metabolic waste and interstitial fluids (ISF) through venous circulation. Following the introduction of glymphatic system concept, various studies have been carried out on cerebrospinal fluid (CSF) and ISF dynamics. These studies reported that the onset of multiple diseases can be attributed to impairment in the glymphatic system, which is newly referred as central nervous system (CNS) interstitial fluidopathy. One such condition includes cerebral small vessel disease (CSVD) with poorly understood pathomechanisms. CSVD is an umbrella term to describe a chronic progressive disorder affecting the brain microvasculature (or microcirculation) involving small penetrating vessels that supply cerebral white and deep gray matter. This review article proposes CSVD as a form of "CNS interstitial fluidopathy". Linking CNS interstitial fluidopathy with CSVD will open a better insight pertaining to the perivascular space fluid dynamics in CSVD pathophysiology. This may lead to the development of treatment and therapeutic strategies to ameliorate the pathology and adverse effect of CSVD.

Automated diffusion-weighted image analysis along the perivascular space index reveals glymphatic dysfunction in association with brain parenchymal lesions.

Brain glymphatic dysfunction is critical in neurodegenerative processes. While animal studies have provided substantial insights, understandings in humans remains limited. Recent attention has focused on the non-invasive evaluation of brain glymphatic function. However, its association with brain parenchymal lesions in large-scale population remains under-investigated. In this cross-sectional analysis of 1030 participants (57.14 ± 9.34 years, 37.18% males) from the Shunyi cohort, we developed an automated pipeline to calculate diffusion-weighted image analysis along the perivascular space (ALPS), with a lower ALPS value indicating worse glymphatic function. The automated ALPS showed high consistency with the manual calculation of this index (ICC = 0.81, 95% CI: 0.662-0.898). We found that those with older age and male sex had lower automated ALPS values (ß = -0.051, SE = 0.004, p < .001, per 10 years, and ß = -0.036, SE = 0.008, p < .001, respectively). White matter hyperintensity (ß = -2.458, SE = 0.175, p < .001) and presence of lacunes (OR = 0.004, 95% CI < 0.002-0.016, p < .001) were significantly correlated with decreased ALPS. The brain parenchymal and hippocampal fractions were significantly associated with decreased ALPS (ß = 0.067, SE = 0.007, p < .001 and ß = 0.040, SE = 0.014, p = .006, respectively) independent of white matter hyperintensity. Our research implies that the automated ALPS index is potentially a valuable imaging marker for the glymphatic system, deepening our understanding of glymphatic dysfunction.

Perivascular spaces around arteries exceed perivenous spaces in the mouse brain.

The perivascular space (PVS) surrounds cerebral blood vessels and plays an important role in clearing waste products from the brain. Their anatomy and function have been described for arteries, but PVS around veins remain poorly characterized. Using in vivo 2-photon imaging in mice, we determined the size of the PVS around arteries and veins, and their connection with the subarachnoid space. After infusion of 70 kD FITC-dextran into the cerebrospinal fluid via the cisterna magna, labeled PVS were evident around arteries, but veins showed less frequent labeling of the PVS. The size of the PVS correlated with blood vessel size for both pial arteries and veins, but not for penetrating vessels. The PVS around pial arteries and veins was separated from the subarachnoid space by a thin meningeal layer, which did not form a barrier for the tracer. In vivo, FITC-dextran signal was observed adjacent to the vessel wall, but minimally within the wall itself. Post-mortem, there was a significant shift in the tracer's location within the arterial wall, extending into the smooth muscle layer. Taken together, these findings suggest that the PVS around veins has a limited role in the exchange of solutes between CSF and brain parenchyma.

Abnormally glymphatic system functional in patients with migraine: a diffusion kurtosis imaging study.

BACKGROUND: The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine. METHODS: The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables. RESULTS: There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables. CONCLUSIONS: DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function.

Atypical Presentation of Idiopathic Intracranial Hypertension: A Case Series and Literature Review.

Idiopathic intracranial hypertension (IIH) is a condition in which intracranial pressure (ICP) increases without an apparent cause. Typically, patients present with headaches, dizziness, pulsatile tinnitus, visual disturbances, blurred vision, diplopia, photophobia, visual field defects, and papilledema on fundoscopy. The association between IIH, spontaneous cerebrospinal fluid (CSF) rhinorrhea, and arachnoid cysts has been discussed in the literature; however, there is no clear explanation for this association. We aimed to present a series of four patients with a confirmed diagnosis of IIH with atypical presentations, discuss the management of each case, and provide an explanation for this association to alert clinicians to the atypical presentation of IIH and facilitate early diagnosis and proper treatment of this condition by CSF diversion. This was a retrospective case series of all patients who were diagnosed with IIH and showed improvement after ventriculoperitoneal shunt insertion after failure of at least one operative intervention resulting from primary radiological and clinical findings in 2001 to 2022. Data on demographics, clinical presentation, radiological findings, surgical management, and diagnostic criteria for IIH were recorded. We identified four patients with a confirmed diagnosis of IIH who presented with atypical presentations as follows: intracranial arachnoid cyst, cervical spine arachnoid cyst, giant Virchow perivascular space, and spontaneous CSF (CSF) rhinorrhea. All patients responded to CSF diversion after failure of surgical treatment targeting the primary pathology. IIH should be suspected after the failure of primary surgical treatment in cases of spontaneous CSF rhinorrhea, spinal and cranial arachnoid cysts, and symptomatic ventriculoperitoneal shunt. Treatment in such situations should be directed toward IIH with CSF diversion.

Quantifying dilated perivascular spaces in children with sickle cell disease.

Sickle cell disease (SCD)-related neurological effects are particularly devastating. Dilated perivascular spaces (dPVS) are a well-described component of cerebral small vessel disease in older adults without SCD. However, the burden and association of dPVS with neurological complications in children with SCD have not been described. In this study, we used the international consensus criteria to quantify dPVS in the centrum semiovale and basal ganglia in T2-weighted magnetic resonance images (MRI) of children with SCD who were randomized as part of the Silent Cerebral Infarct Transfusion (SIT) trial. We examined the relationship between global and/or regional dPVS burden and presence or area of silent cerebral infarctions, hematological measures, demographic variables, and full-scale intelligence quotient (FSIQ) scores. The study included 156 SIT trial participants who had pre-randomization and study exit MRI. Their median age was 9.6 (5-15) years, 39% were female, and 94 (60%) participants had a high dPVS burden. Participants randomized to the blood transfusion arm and who had a high dPVS burden at baseline had a moderate decline in dPVS score over 36 months compared to no change in the observation group. On multivariable logistic regression, intelligence quotient was not associated with dPVS burden. Children with SCD included in the SIT trial have a high burden of dPVS compared to children without SCD. However, dPVS do not appear to have the same pathophysiology of silent cerebral infarcts. Further study is needed to determine both their etiology and clinical relevance.

The time-course augmentation of perivascular space enlargement in the basal ganglia among a community-dwelling elder population.

PURPOSE: We examined whether time-course augmentation of perivascular space enlargement in the basal ganglia (BG-PVS) reflected cerebral small vessel disease (CSVD) severity by considering white matter hyperintensity lesion (WMHL) as an indicator for CSVD. MATERIALS AND METHODS: This study population included 416 older participants from a community-based cohort. They participated in magnetic resonance imaging (MRI) studies more than once during the study period. The grades for BG-PVS and WMHL were evaluated by visual rating scales; BG-PVS time-course augmentation in 4-9 years was also evaluated. At baseline, the participants were asked about their smoking and drinking history, and medical history. They also underwent a blood examination and their office blood pressure (BP) examination. In addition, 24-h ambulatory BP monitoring was also performed within the study period. RESULTS: Of the 416 participants, 48 participants (11.5%) had BG-PVS time-course augmentation. The participants with BG-PVS augmentation had significantly lower LDL levels, hyper-nighttime BP, and lower nighttime BP fall in univariate analysis (p = 0.03, p = 0.03, p = 0.003, respectively). In multivariate analysis, lower nighttime BP fall and male sex showed significance (p = 0.02, 0.03, respectively). Additionally, BG-PVS time-course augmentation was significantly associated with subsequent WMHL severity in univariate analysis (p < 0.001), which remained significant in multivariate analysis adjusted by imaging and demographic factors (p = 0.03). In multivariate analysis, additionally adjusted by the clinical factors, the significance disappeared (p = 0.07). CONCLUSION: This study revealed that the lower nighttime BP fall in ambulatory blood pressure monitoring was a factor significantly associated with BG-PVS augmentation. Moreover, the BG-PVS time-course augmentation would be a notable finding that was associated with the subsequent WMHL.

Multimodal neuroimaging exploration of the mechanisms of sleep quality deterioration after SARS-CoV-2 Omicron infection.

BACKGROUND: To evaluate the neurological alterations induced by Omicron infection, to compare brain changes in chronic insomnia with those in exacerbated chronic insomnia in Omicron patients, and to examine individuals without insomnia alongside those with new-onset insomnia. METHODS: In this study, a total of 135 participants were recruited between January 11 and May 4, 2023, including 26 patients with chronic insomnia without exacerbation, 24 patients with chronic insomnia with exacerbation, 40 patients with no sleep disorder, and 30 patients with new-onset insomnia after infection with Omicron (a total of 120 participants with different sleep statuses after infection), as well as 15 healthy controls who were never infected with Omicron. Neuropsychiatric data, clinical symptoms, and multimodal magnetic resonance imaging data were collected. The gray matter thickness and T1, T2, proton density, and perivascular space values were analyzed. Associations between changes in multimodal magnetic resonance imaging findings and neuropsychiatric data were evaluated with correlation analyses. RESULTS: Compared with healthy controls, gray matter thickness changes were similar in the patients who have and do not have a history of chronic insomnia groups after infection, including an increase in cortical thickness near the parietal lobe and a reduction in cortical thickness in the frontal, occipital, and medial brain regions. Analyses showed a reduced gray matter thickness in patients with chronic insomnia compared with those with an aggravation of chronic insomnia post-Omicron infection, and a reduction was found in the right medial orbitofrontal region (mean [SD], 2.38 [0.17] vs. 2.67 [0.29] mm; P < 0.001). In the subgroups of Omicron patients experiencing sleep deterioration, patients with a history of chronic insomnia whose insomnia symptoms worsened after infection displayed heightened medial orbitofrontal cortical thickness and increased proton density values in various brain regions. Conversely, patients with good sleep quality who experienced a new onset of insomnia after infection exhibited reduced cortical thickness in pericalcarine regions and decreased proton density values. In new-onset insomnia patients post-Omicron infection, the thickness in the right pericalcarine was negatively correlated with the Self-rating Anxiety Scale (r = - 0.538, P = 0.002, PFDR = 0.004) and Self-rating Depression Scale (r = - 0.406, P = 0.026, PFDR = 0.026) scores. CONCLUSIONS: These findings help us understand the pathophysiological mechanisms involved when Omicron invades the nervous system and induces various forms of insomnia after infection. In the future, we will continue to pay attention to the dynamic changes in the brain related to insomnia caused by Omicron infection.

DTI-ALPS index decreased in patients with Type 2 Diabetes Mellitus.

Backgrounds: Type 2 Diabetes Mellitus (T2DM) has become a significant global public health issue, characterized by a rising prevalence and associated deficits across multiple organ systems. Our study aims to utilize the DTI-ALPS technique to assess the change of ALPS index in T2DM patients, and to explore whether such changes are correlated with cognition level and diffusion parameters. Methods: The study involved 41 patients with T2DM (mean age, 60.49 ± 8.88 years) and 27 healthy controls (mean age, 58.00 ± 7.63 years). All subjects underwent MRI examination, cognitive assessment, and laboratory tests. Tract-based spatial statistics (TBSS) was used to evaluate white matter changes. GLM was performed to check the DTI-ALPS index difference between T2DM and HC groups. Spearman correlation analysis and partial correlation analysis were used to analyze the correlation between the DTI-ALPS index and diffusion properties & cognitive scores. Results: The results show that the ALPS index was lower in T2DM patients. MoCA score was significantly correlated with the ALPS index. Patients with T2DM had a significant increase in both mean diffusivity (MD) and radial diffusivity (RD) and decrease in fractional anisotropy (FA) compared to the HC group. Conclusion: The results suggest that the ALPS index is decreased in T2DM patients and associates with cognitive level.

Glymphatic function from diffusion-tensor MRI to predict conversion from mild cognitive impairment to dementia in Parkinson's disease.

BACKGROUND: Although brain glymphatic dysfunction is a contributing factor to the cognitive deficits in Parkinson's disease (PD), its role in the longitudinal progression of cognitive dysfunction remains unknown. OBJECTIVE: To investigate the glymphatic function in PD with mild cognitive impairment (MCI) that progresses to dementia (PDD) and to determine its predictive value in identifying individuals at high risk for developing dementia. METHODS: We included 64 patients with PD meeting criteria for MCI and categorized them as either progressed to PDD (converters) (n = 29) or did not progress to PDD (nonconverters) (n = 35), depending on whether they developed dementia during follow-up. Meanwhile, 35 age- and gender-matched healthy controls (HC) were included. Bilateral diffusion-tensor imaging analysis along the perivascular space (DTI-ALPS) indices and enlarged perivascular spaces (EPVS) volume fraction in bilateral centrum semiovale, basal ganglia (BG), and midbrain were compared among the three groups. Correlations among the DTI-ALPS index and EPVS, as well as cognitive performance were analyzed. Additionally, we investigated the mediation effect of EPVS on DTI-ALPS and cognitive function. RESULTS: PDD converters had lower cognitive composites scores in the executive domains than did nonconverters (P < 0.001). Besides, PDD converters had a significantly lower DTI-ALPS index in the left hemisphere (P < 0.001) and a larger volume fraction of BG-PVS (P = 0.03) compared to HC and PDD nonconverters. Lower DTI-ALPS index and increased BG-PVS volume fraction were associated with worse performance in the global cognitive performance and executive function. However, there was no significant mediating effect. Receiver operating characteristic analysis revealed that the DTI-ALPS could effectively identify PDD converters with an area under the curve (AUC) of 0.850. CONCLUSION: The reduction of glymphatic activity, measured by the DTI-ALPS, could potentially be used as a non-invasive indicator in forecasting high risk of dementia conversion before the onset of dementia in PD patients.

Longitudinal Assessment of Glymphatic Changes Following Mild Traumatic Brain Injury: Insights from PVS burden and DTI-ALPS Imaging.

Traumatic brain injury (TBI) even in the mild form may result in long-lasting post-concussion symptoms. TBI is also a known risk to late-life neurodegeneration. Recent studies suggest that dysfunction in the glymphatic system, responsible for clearing protein waste from the brain, may play a pivotal role in the development of dementia following TBI. Given the diverse nature of TBI, longitudinal investigations are essential to comprehending the dynamic changes in the glymphatic system and its implications for recovery. In this prospective study, we evaluated two promising glymphatic imaging markers, namely the enlarged perivascular space (ePVS) burden and Diffusion Tensor Imaging-based ALPS index, in 44 patients with mTBI at two early post-injury time points: approximately 14 days (14Day) and 6-12 months (6-12Mon) post-injury, while also examining their associations with post-concussion symptoms. Additionally, 37 controls, comprising both orthopedic patients and healthy individuals, were included for comparative analysis. Our key findings include: 1) White matter ePVS burden (WM-ePVS) and ALPS index exhibit significant correlations with age. 2) Elevated WM-ePVS burden in acute mTBI (14Day) is significantly linked to a higher number of post-concussion symptoms, particularly memory problems. 3) The increase in the ALPS index from acute (14Day) to the chronic (6-12Mon) phases in mTBI patients correlates with improvement in sleep measures. Furthermore, incorporating WM-ePVS burden and the ALPS index from acute phase enhances the prediction of chronic memory problems beyond socio-demographic and basic clinical information, highlighting their distinct roles in assessing glymphatic structure and activity. Early evaluation of glymphatic function could be crucial for understanding TBI recovery and developing targeted interventions to improve patient outcomes.