Figure - available from: Frontiers in Neuroscience
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Quantification of perivascular spaces (PVS). PVS burden as shown on a T1-weighted MRI in a patient with bvFTD. (Left) Manual segmentation of PVS highlighted in red. (Right) Automated segmentation of PVS using the Multimodal Autoidentification of Perivascular Spaces (MAPS) algorithm highlighted in green.
Source publication
Background
Behavioural Variant Frontotemporal Dementia (bvFTD) is a rapidly progressing neurodegenerative proteinopathy. Perivascular spaces (PVS) form a part of the brain’s glymphatic clearance system. When enlarged due to poor glymphatic clearance of toxic proteins, PVS become larger and more conspicuous on MRI. Therefore, enlarged PVS may be a u...
Citations
... Two studies found no direct or significant association between general cognition (general cognitive ability, Montreal Cognitive Assessment score) and PVS burden ). Valdés Hernandez et al. (2019 reported PVS burden as predictive of reduced fluid intelligence in Huntington's disease patients but not in family members without overt disease, while Soitgu et al., (2023) did not find association between PVS burden and IQ in autistic children In mild cognitive impaired (MCI) and dementia, all studies reported different measures of PVS being more relevant in MCI (Seperhband et al., 2021;Bown et al., 2023) and frontotemporal dementia (Moses et al., 2022) groups than in controls. Jokinen et al (2020) reported PVS volume to be a significant predictor of processing speed, decline in processing speed, decline in memory, and of total vascular dementia assessment (VADAS-cog) score. ...
... Huntington's disease Li et al., 2023), CADASIL (Karvelas et al., 2023), TBI (Hicks et al., 2023), MCI (Seperhband et al., 2021;Bown et al., 2023;Kamagata et al., 2023), frontotemporal dementia (Moses et al., 2022), and AD (Kamagata et al., 2023). One study involving elderly patients aged 65-84 enrolled in the LADIS study (Pantoni et al., 2005), also reported a positive association between PVS burden and cognition. ...
Research into magnetic resonance imaging (MRI)- visible perivascular spaces (PVS) has recently increased, as results from studies in different diseases and populations are cementing their association with sleep, disease phenotypes, and overall health indicators. With the establishment of worldwide consortia and the availability of large databases, computational methods that allow to automatically process all this wealth of information are becoming increasingly relevant. Several computational approaches have been proposed to assess PVS from MRI, and efforts have been made to summarise and appraise the most widely applied ones. We systematically reviewed and meta-analysed all publications available up to September 2023 describing the development, improvement, or application of computational PVS quantification methods from MRI. We analysed 67 approaches and 60 applications of their implementation, from 112 publications. The two most widely applied were the use of a morphological filter to enhance PVS-like structures, with Frangi being the choice preferred by most, and the use of a U-Net configuration with or without residual connections. Older adults or population studies comprising adults from 18 years old onwards were, overall, more frequent than studies using clinical samples. PVS were mainly assessed from T2-weighted MRI acquired in 1.5T and/or 3T scanners, although combinations using it with T1-weighted and FLAIR images were also abundant. Common associations researched included age, sex, hypertension, diabetes, white matter hyperintensities, sleep and cognition, with occupation-related, ethnicity, and genetic/hereditable traits being also explored. Despite promising improvements to overcome barriers such as noise and differentiation from other confounds, a need for joined efforts for a wider testing and increasing availability of the most promising methods is now paramount.
... For further details we refer to a newly published comprehensive review by Moses et al (45). Advances in both manual and automated ePVS detection methods have widened the investigation of PVS as a biomarker of disease across a range of neurological diseases, enabling quantification from standard clinical MRI protocols with lower quality images than research scans due to motion artifacts ( Figure 2) (46). However, there is still need to optimize ePVS segmentation for typical clinical practice scan qualities (40). ...
Stroke is one of the most common causes of acquired epilepsy, which can also result in disability and increased mortality rates particularly in elderly patients. No preventive treatment for post‐stroke epilepsy is currently available. Development of such treatments has been greatly limited by the lack of biomarkers to reliably identify high‐risk patients. The glymphatic system, including perivascular spaces (PVS), is the brain's waste clearance system, and enlargement or asymmetry of PVS (ePVS) is hypothesized to play a significant role in the pathogenesis of several neurological conditions. In this article, we discuss potential mechanisms for the role of perivascular spaces in the development of post‐stroke epilepsy. Using advanced MR‐imaging techniques, it has been shown that there is asymmetry and impairment of glymphatic function in the setting of ischemic stroke. Furthermore, studies have described a dysfunction of PVS in patients with different focal and generalized epilepsy syndromes. It is thought that inflammatory processes involving PVS and the blood–brain barrier, impairment of waste clearance, and sustained hypertension affecting the glymphatic system during a seizure may play a crucial role in epileptogenesis post‐stroke. We hypothesize that impairment of the glymphatic system and asymmetry and dynamics of ePVS in the course of a stroke contribute to the development of PSE. Automated ePVS detection in stroke patients might thus assist in the identification of high‐risk patients for post‐stroke epilepsy trials.
Plain Language Summary
Stroke often leads to epilepsy and is one of the main causes of epilepsy in elderly patients, with no preventative treatment available. The brain’s waste removal system, called the glymphatic system which consists of perivascular spaces, may be involved. Enlargement or asymmetry of perivascular spaces could play a role in this and can be visualised with advanced brain imaging after a stroke. Detecting enlarged perivascular spaces in stroke patients could help identify those at risk for post‐stroke epilepsy.
... Consistent with our findings, a study found that global cognition and disease severity were associated with PVS burden, a biomarker that may indirectly reflect glymphatic function, in patients with bvFTD. 55 Additionally, higher CP volume was linked with higher NPI and FBI apathy scores. Apathy, the most prevalent core symptom in bvFTD, 56 is defined as a quantitative reduction of goal-directed activity. ...
... Consistent with our findings, a study found that global cognition and disease severity were associated with PVS burden, a biomarker that may indirectly reflect glymphatic function, in patients with bvFTD. 55 Additionally, higher CP volume was linked with higher NPI and FBI apathy scores. Apathy, the most prevalent core symptom in bvFTD, 56 is defined as a quantitative reduction of goal-directed activity. ...
Objectives:
The glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remain unknown.
Method:
A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participant underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. BvFTD-related metabolic pattern was identified using spatial covariance analysis based on l8 F-FDG-PET.
Results:
Patients with bvFTD showed higher CP volume (P < 0.001); anterior and middle DTI-ALPS (P < 0.001); and weaker anterior BOLD-CSF coupling (P < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, P = 0.034) and positively related with regional standardized uptake value ratios of l8 F-FDG-PET in bvFTD-related brain regions (r = 0.49-0.62, P range: 0.017-0.047). Anterior and middle glymphatic function were related to global cognition and disease severity.
Interpretation:
Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. This article is protected by copyright. All rights reserved.
Background: Since the discovery of the glymphatic system in mice with clearance functions distributed throughout the brain, more and more scholars have begun to study the glymphatic system. However, there are a limited number of correlations between glymphatic system and cognition. Therefore, this study aimed to evaluate the research trends, hotspots, and frontiers of glymphatic system in cognition using bibliometric analysis.
Methods: Publications from the Web of Science Core Collection (WoSCC) database spanning 15 years from 1 January 2009 to 31 December 2023 were screened. All eligible publication were included based on our comprehensive search strategy. The analysis of annual publications, countries/regions, institutions, journals, authors, co-cited journals, co-cited authors, and keywords was conducted using CiteSpace and VOSviewer, and the hotspots and major findings of the glymphatic system in cognition were summarised. In addition, ArcGIS software was used to geovisualize the count of publications.
Results: A total of 625 publications were included in this study. Overall, the number of publications has been increasing steadily per year. These publications were published in 59 countries/regions and 149 institutions. Of these, American institutions had the highest number of publications, and their international influence also ranked first. The journal “Neurology” published the most publications and was considered the most co-cited journal. Wardlaw, Joanna M was the author of the most published articles and the most cited authors. The article entitled “The glymphatic pathway in neurological disorders” published in Lancet neurology had the most citations. The keywords with the highest number of occurrences were “Alzheimer disease” and “small vessel disease”, which were regarded as research hotspots. Three main clusters were shown in the keywords clustering network. Alzheimer's disease and perivascular spaces had been a hot topic for a long time and from 2017 research on GS increased. Among 19 emergent terms, “Virchow robin spaces”, “vascular dementia”, and “autosomal dominant arteriopathy” were the first, and “white matter lesions” were the strongest.
Conclusion: Previous research has focused mainly on perivascular spaces, however, with the concept of the glymphatic system was introduced, the correlation of the glymphatic system in cognition have gradually increased. Currently, limited studies have been conducted on the glymphatic system in cognition , and we hope that this study will provide the recommendation for the future research.
