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Objectives: The function of choroid plexus is to produce cerebrospinal fluid, which is critical for the glymphatic system function. In this study, we aimed to analyze the differences in choroid plexus volume between patients with obstructive sleep apnea (OSA) and healthy controls, with the goal of discovering the glymphatic system dysfunction in patients with OSA., Methods: We prospectively enrolled 40 patients with OSA confirmed by polysomnography and 38 age- and sex-matched healthy controls. All participants underwent three-dimensional T1-weighted brain imaging, which was suitable for volumetric analysis. We compared choroid plexus volumes between patients with OSA and healthy controls, and analyzed the association between choroid plexus volume and polysomnographic findings in patients with OSA., Results: Choroid plexus volumes were significantly larger in patients with OSA than in healthy controls (2.311 % vs. 2.096 %, p = 0.005). However, no significant association was detected between choroid plexus volume and polysomnographic findings., Conclusion: This study demonstrated enlargement of the choroid plexus in patients with OSA compared with healthy controls. This finding could be related with glymphatic system dysfunction in patients with OSA., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Most myelomeningocele (MMC) cases present with ventriculomegaly or hydrocephalus, yet a comprehensive volumetric assessment of MMC intracranial structures is lacking. This study aimed to provide baseline data on intracranial structural volumes immediately after birth in MMC infants who underwent repair surgeries after birth (postnatal repair)., Methods: In this retrospective single-center study, we analyzed 52 MMC infants undergoing postnatal repair, utilizing head computed tomography scans at birth for volumetric assessment. Intracranial volume (ICV), lateral ventricles volume (LVV), choroid plexus volume (CPV), and posterior cranial fossa volume (PCFV) were measured. Hydrocephalus was classified into no hydrocephalus, progressive hydrocephalus, and hydrocephalus at birth. Comparative analysis employed the Wilcoxon rank-sum test. Receiver operating characteristic (ROC) analysis discriminated cases with and without ventriculoperitoneal shunt (VPS)., Results: The median values were 407.50 mL for ICV, 33.18 mL for LVV, 0.67 mL for CPV, and 21.35 mL for PCFV. Thirty-seven cases (71.15%) underwent VPS. ROC analysis revealed an LVV cut-off value of 6.74 mL for discriminating cases with and without VPS. Progressive hydrocephalus showed no significant difference in ICV but significantly larger LVV compared to no hydrocephalus. Hydrocephalus at birth demonstrated statistically larger ICV and LVV compared to the other two types., Conclusion: Baseline volumetric data were provided, and volumetric analysis exhibited statistical differences among three hydrocephalus types. These findings enhance our understanding of intracranial volumetric changes in MMC, facilitating more objective assessments of MMC cases., (© 2024. The Author(s).)

Background and Purpose: The choroid plexus contains specialized ependymal cells responsible for CSF production. Recent studies have demonstrated volumetric and perfusion changes in the choroid plexus with age and neurodegenerative disorders, however, volumetric changes in the choroid plexus in low pressure states is not known. The purpose of this study is to evaluate volumetric differences in choroid plexus size in patients with spontaneous intracranial hypotension (SIH) resultant from spinal CSF leaks compared with healthy controls., Materials and Methods: This was a retrospective, institutional review board-approved study. Patients with MRI evidence of SIH and a spinal CSF leak diagnosed on myelography and subsequently confirmed at surgery were included in this study. All patients included in this study including age-matched healthy controls had a brain MRI performed on a either a 1.5 or 3T scanner with acquisition of 3D T1 postcontrast (eg, BRAVO, MPRAGE, etc). In all patients, the trigonum ventriculi volume, in the atria of the lateral ventricles, was contoured by using Visage-7 segmentation tools on the volumetric postcontrast T1 sequence. A basic 2-tailed t test was used to compare choroid plexus volumes between the 2 groups., Results: Thirty-four patients were included with 17 patients with SIH with spinal CSF leak and 17 healthy control patients who were age- and sex-matched. The mean age of patients was 45 years, standard deviation 14 years. The mean volume of the choroid plexus for patients with SIH with spinal CSF leak was 1.2 cm 3 (standard deviation = 0.26) compared with 0.63 cm 3 (standard deviation = 0.31) in the control group ( P  < .0001)., Conclusions: Results of this study demonstrate a higher choroid plexus volume in patients with SIH with spinal CSF leak compared with age- and sex-matched healthy controls. This likely reflects compensatory mechanisms to counteract intracranial hypotension by increasing CSF production as well as increased vascularity of the choroid plexus through expansion of the intracranial blood pool., (© 2024 by American Journal of Neuroradiology.)

Background: The choroid plexus (CP) is suggested to be closely associated with the neuroinflammation of multiple sclerosis (MS). Segmentation based on deep learning (DL) could facilitate rapid and reproducible volume assessment of the CP, which is crucial for elucidating its role in MS., Purpose: To develop a reliable DL model for the automatic segmentation of CP, and further validate its clinical significance in MS., Methods: The 3D UX-Net model (3D U-Net used for comparison) was trained and validated on T1-weighted MRI from a cohort of 216 relapsing-remitting MS (RRMS) patients and 75 healthy subjects. Among these, 53 RRMS with baseline and 2-year follow-up scans formed an internal test set (dataset1b). Another 58 RRMS from multi-center data served as an external test set (dataset2). Dice coefficient was computed to assess segmentation performance. Compare the correlation of CP volume obtained through automatic and manual segmentation with clinical outcomes in MS. Disability and cognitive function of patients were assessed using the Expanded Disability Status Scale (EDSS) and Symbol Digit Modalities Test (SDMT)., Results: The 3D UX-Net model achieved Dice coefficients of 0.875 ± 0.030 and 0.870 ± 0.044 for CP segmentation on dataset1b and dataset2, respectively, outperforming 3D U-Net's scores of 0.809 ± 0.098 and 0.601 ± 0.226. Furthermore, CP volumes segmented by the 3D UX-Net model aligned consistently with clinical outcomes compared to manual segmentation. In dataset1b, both manual and automatic segmentation revealed a significant positive correlation between normalized CP volume (nCPV) and EDSS scores at baseline (manual: r = 0.285, p = 0.045; automatic: r = 0.287, p = 0.044) and a negative correlation with SDMT scores (manual: r = -0.331, p = 0.020; automatic: r = -0.329, p = 0.021). In dataset2, similar correlations were found with EDSS scores (manual: r = 0.337, p = 0.021; automatic: r = 0.346, p = 0.017). Meanwhile, in dataset1b, both manual and automatic segmentation revealed a significant increase in nCPV from baseline to follow-up (p < 0.05). The increase of nCPV was more pronounced in patients with disability worsened than stable patients (manual: p = 0.023; automatic: p = 0.018). Patients receiving disease-modifying therapy (DMT) exhibited a significantly lower nCPV increase than untreated patients (manual: p = 0.004; automatic: p = 0.004)., Conclusion: The 3D UX-Net model demonstrated strong segmentation performance for the CP, and the automatic segmented CP can be directly used in MS clinical practice. CP volume can serve as a surrogate imaging biomarker for monitoring disease progression and DMT response in MS patients., Competing Interests: Declaration of competing interest No conflict of interest exists in the submission of this manuscript, and the manuscript is approved by all authors for publication., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Previous studies have shown possible choroid plexus (CP) dysfunction in Alzheimer's disease (AD) and highlighted CP enlargement on magnetic resonance imaging (MRI) as a predictive factor of AD. However, few studies have assessed the relationship between CP volume (CPV) and mild cognitive impairment (MCI). In this large elderly population study, we investigated the changes in CPV in patients with MCI using MRI above 65 years., Methods: This cross-sectional study included 2144 participants (median age, 69 years; 60.9% females) who underwent 3T MRI; they were grouped as 218 MCI participants and 1904 cognitively healthy controls. The total intracranial volume (ICV), total brain volume (TBV), CPV, hippocampal volume (HV), and lateral ventricle volume (LVV) were calculated., Results: CPV/ICV was a significant independent predictor of MCI (p < 0.01) after adjusting for potential confounders (age, sex, hypertension, hyperlipidemia, diabetes, and education level). The CPV/ICV ratio was also a significant independent predictor of MCI after adjusting for the TBV/ICV ratio (p = 0.022) or HV/ICV ratio (p = 0.017), in addition to potential confounders. The CPV was significantly correlated with the LVV (r = 0.97, p < 0.01)., Conclusion: We identified a relationship between CPV and MCI, which could not be explained by the degree of brain atrophy. Our results support CP dysfunction in MCI., Clinical Relevance Statement: Choroid plexus volume measurement may serve as a valuable imaging biomarker for diagnosing and monitoring mild cognitive impairment. The enlargement of the choroid plexus, independent of brain atrophy, suggests its potential role in mild cognitive impairment pathology., Key Points: • The study examines choroid plexus volume in relation to cognitive decline in elderly. • Enlarged choroid plexus volume independently indicates mild cognitive impairment presence. • Choroid plexus volume could be a specific biomarker for early mild cognitive impairment diagnosis., (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Background: The cerebrospinal fluid (CSF), primarily generated by the choroid plexus (ChP), is the major carrier of the glymphatic system. The alternations of CSF production and the ChP can be associated with the Alzheimer's disease (AD). The present work investigated the roles of the ChP in the AD based on a proposed ChP image segmentation pipeline., Methods: A human-in-the-loop ChP image segmentation pipeline was implemented with intermediate and active learning datasets. The performance of the proposed pipeline was evaluated on manual contours by five radiologists, compared to the FreeSurfer and FastSurfer toolboxes. The ChP volume and blood flow were investigated among AD groups. The correlations between the ChP volume and AD CSF biomarkers including phosphorylated tau (p-tau), total tau (t-tau), amyloid-β42 (Aβ42), and amyloid-β40 (Aβ40) was investigated using three models (univariate, multiple variables, and stepwise regression) on two datasets with 806 and 320 subjects., Results: The proposed ChP segmentation pipeline achieved superior performance with a Dice coefficient of 0.620 on the test dataset, compared to the FreeSurfer (0.342) and FastSurfer (0.371). Significantly larger volumes (p < 0.001) and higher perfusion (p = 0.032) at the ChP were found in AD compared to CN groups. Significant correlations were found between the tau and the relative ChP volume (the ChP volume and ChP/parenchyma ratio) in each patient groups and in the univariate regression analysis (p < 0.001), the multiple regression model (p < 0.05 except for the t-tau in the LMCI), and in the step-wise regression model (p < 0.021). In addition, the correlation coefficients changed from - 0.32 to - 0.21 along with the AD progression in the multiple regression model. In contrast, the Aβ42 and Aβ40 shows consistent and significant associations with the lateral ventricle related measures in the step-wise regression model (p < 0.027)., Conclusions: The proposed pipeline provided accurate ChP segmentation which revealed the associations between the ChP and tau level in the AD. The proposed pipeline is available on GitHub ( https://github.com/princeleeee/ChP-Seg )., (© 2024. The Author(s).)

Increased choroid plexus (CP) volume has been recently implicated as a potential predictor of worse multiple sclerosis (MS) outcomes. The biomarker signature of CP changes in MS are currently unknown. To determine the blood-based biomarker characteristics of the cross-sectional and longitudinal MRI-based CP changes in a heterogeneous group of people with MS (pwMS), a total of 202 pwMS (148 pwRRMS and 54 pwPMS) underwent MRI examination at baseline and at a 5-year follow-up. The CP was automatically segmented and subsequently refined manually in order to obtain a normalized CP volume. Serum samples were collected at both timepoints, and the concentration of 21 protein measures relevant to MS pathophysiology were determined using the Olink™ platform. Age-, sex-, and BMI-adjusted linear regression models explored the cross-sectional and longitudinal relationships between MRI CP outcomes and blood-based biomarkers. At baseline, there were no significant proteomic predictors of CP volume, while at follow-up, greater CP volume was significantly associated with higher neurofilament light chain levels, NfL (standardized β = 0.373, p = 0.001), and lower osteopontin levels (standardized β = -0.23, p = 0.02). Higher baseline GFAP and lower FLRT2 levels were associated with future 5-year CP % volume expansion (standardized β = 0.277, p = 0.004 and standardized β = -0.226, p = 0.014, respectively). The CP volume in pwMS is associated with inflammatory blood-based biomarkers of neuronal injury (neurofilament light chain; NfL) and glial activation such as GFAP, osteopontin, and FLRT2. The expansion of the CP may play a central role in chronic and compartmentalized inflammation and may be driven by glial changes.

Background: Enlarged choroid plexus (ChP) volume has been reported in patients with Alzheimer's disease (AD) and inversely correlated with cognitive performance. However, its clinical diagnostic and predictive value, and mechanisms by which ChP impacts the AD continuum remain unclear., Methods: This prospective cohort study enrolled 607 participants [healthy control (HC): 110, mild cognitive impairment (MCI): 269, AD dementia: 228] from the Chinese Imaging, Biomarkers, and Lifestyle study between January 1, 2021, and December 31, 2022. Of the 497 patients on the AD continuum, 138 underwent lumbar puncture for cerebrospinal fluid (CSF) hallmark testing. The relationships between ChP volume and CSF pathological hallmarks (Aβ 42 , Aβ 40 , Aβ 42/40 , tTau, and pTau 181 ), neuropsychological tests [Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Neuropsychiatric Inventory (NPI), and Activities of Daily Living (ADL) scores], and multimodal neuroimaging measures [gray matter volume, cortical thickness, and corrected cerebral blood flow (cCBF)] were analyzed using partial Spearman's correlation. The mediating effects of four neuroimaging measures [ChP volume, hippocampal volume, lateral ventricular volume (LVV), and entorhinal cortical thickness (ECT)] on the relationship between CSF hallmarks and neuropsychological tests were examined. The ability of the four neuroimaging measures to identify cerebral Aβ 42 changes or differentiate among patients with AD dementia, MCI and HCs was determined using receiver operating characteristic analysis, and their associations with neuropsychological test scores at baseline were evaluated by linear regression. Longitudinal associations between the rate of change in the four neuroimaging measures and neuropsychological tests scores were evaluated on the AD continuum using generalized linear mixed-effects models., Results: The participants' mean age was 65.99 ± 8.79 years. Patients with AD dementia exhibited the largest baseline ChP volume than the other groups (P < 0.05). ChP volume enlargement correlated with decreased Aβ 42 and Aβ 40 levels; lower MMSE and MoCA and higher NPI and ADL scores; and lower volume, cortical thickness, and cCBF in other cognition-related regions (all P < 0.05). ChP volume mediated the association of Aβ 42 and Aβ 40 levels with MMSE scores (19.08% and 36.57%), and Aβ 42 levels mediated the association of ChP volume and MMSE or MoCA scores (39.49% and 34.36%). ChP volume alone better identified cerebral Aβ 42 changes than LVV alone (AUC = 0.81 vs. 0.67, P = 0.04) and EC thickness alone (AUC = 0.81 vs.0.63, P = 0.01) and better differentiated patients with MCI from HCs than hippocampal volume alone (AUC = 0.85 vs. 0.81, P = 0.01), and LVV alone (AUC = 0.85 vs.0.82, P = 0.03). Combined ChP and hippocampal volumes significantly increased the ability to differentiate cerebral Aβ 42 changes and patients among AD dementia, MCI, and HCs groups compared with hippocampal volume alone (all P < 0.05). After correcting for age, sex, years of education, APOE ε4 status, eTIV, and hippocampal volume, ChP volume was associated with MMSE, MoCA, NPI, and ADL score at baseline, and rapid ChP volume enlargement was associated with faster deterioration in NPI scores with an average follow-up of 10.03 ± 4.45 months (all P < 0.05)., Conclusions: ChP volume may be a novel neuroimaging marker associated with neurodegenerative changes and clinical AD manifestations. It could better detect the early stages of the AD and predict prognosis, and significantly enhance the differential diagnostic ability of hippocampus on the AD continuum., (© 2024. The Author(s).)

Purpose: Mild cognitive impairment (MCI) can be the prodromal phase of Alzheimer's disease (AD) where appropriate intervention might prevent or delay conversion to AD. Given this, there has been increasing interest in using magnetic resonance imaging (MRI) and neuropsychological testing to predict conversion from MCI to AD. Recent evidence suggests that the choroid plexus (ChP), neural substrates implicated in brain clearance, undergo volumetric changes in MCI and AD. Whether the ChP is involved in memory changes observed in MCI and can be used to predict conversion from MCI to AD has not been explored., Method: The current study used data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database to investigate whether later progression from MCI to AD (progressive MCI [pMCI], n = 115) or stable MCI (sMCI, n = 338) was associated with memory scores using the Rey Auditory Verbal Learning Test (RAVLT) and ChP volumes as calculated from MRI. Classification analyses identifying pMCI or sMCI group membership were performed to compare the predictive ability of the RAVLT and ChP volumes., Finding: The results indicated a significant difference between pMCI and sMCI groups for right ChP volume, with the pMCI group showing significantly larger right ChP volume (p = .01, 95% confidence interval [-.116, -.015]). A significant linear relationship between the RAVLT scores and right ChP volume was found across all participants, but not for the two groups separately. Classification analyses showed that a combination of left ChP volume and auditory verbal learning scores resulted in the most accurate classification performance, with group membership accurately predicted for 72% of the testing data., Conclusion: These results suggest that volumetric ChP changes appear to occur before the onset of AD and might provide value in predicting conversion from MCI to AD., (© 2024 The Author(s). Brain and Behavior published by Wiley Periodicals LLC.)

This study aimed to determine whether choroid plexus volume (CPV) could differentiate multiple sclerosis (MS) from its mimics. A secondary analysis of two previously enrolled studies, 50 participants with MS and 64 with alternative diagnoses were included. CPV was automatically segmented from 3T magnetic resonance imaging (MRI), followed by manual review to remove misclassified tissue. Mean normalized choroid plexus volume (nCPV) to intracranial volume demonstrated relatively high specificity for MS participants in each cohort (0.80 and 0.76) with an area under the receiver-operator characteristic curve of 0.71 (95% confidence interval (CI) = 0.55-0.87) and 0.65 (95% CI = 0.52-0.77). In this preliminary study, nCPV differentiated MS from its mimics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: E.L. has no relevant disclosures. Z.R. has relevant disclosures. V.G. has no relevant disclosures. In the last 3 years, Dr C.J.A. has received consulting fees from Horizon Therapeutics, Genentech, Sanofi Genzyme, TG Therapeutics, and EMD Serono. She has received grant support from the National Institutes of Health and the National Multiple Sclerosis Society. P.A.C. is PI on grants to JHU from the Myelin Repair Foundation and Genentech. He has received consulting fees from Lilly, Idorsia, and Novartis. B.A.C.C. has no relevant disclosures. L.F. has received fees for consultancy and/or advisory board participation from Genentech, Novartis, Bristol Myers Squibb, EMD Serono, Sanofi, Horizon Therapeutics, and TG Therapeutics; has received honorarium for participation in educational programs from Medscape, Inc., the MS Association of America and Impact Education; has received program sponsorship from EMD Serono; and grant support from NIH/NINDS, PCORI, Genentech, and EMD Serono through her institution. E.E.L. has received honoraria for consulting from Bristol Myers Squibb, EMD Serono, Genentech, Genzyme, TG Therapeutics, Janssen, and NGM Bio. She has received research from Biogen and Genentech. J.O. is none relevant to this manuscript. M.K.S. has no relevant disclosures. N.L.S. received grant funding from NIH, PCORI, and NMSS. D.S.R. received research funding from Abata and Sanofi. D.O. received research support from the National Institutes of Health, National Multiple Sclerosis Society, Patient Centered Outcomes Research Institute, Race to Erase MS Foundation, Genentech, Genzyme, Bristol Myers Squibb, and Novartis, and also received consulting fees from Biogen Idec, Bristol Myers Squibb, Genentech/Roche, Novartis, Pipeline Therapeutics, and Merck. P.S. received support from the National Institutes of Health, Department of Defense, National Multiple Sclerosis Society and the Erwin Rautenberg Foundation. Q.C. has no relevant disclosures. R.T.S. received consulting income from Octave Bioscience and compensation for scientific reviewing from the American Medical Association. A.J.S. as consulting or advisory board: Genentech, Octave Bioscience, Horizon Therapeutics, Kiniksa Pharmaceuticals, and TG Therapeutics; non-promotional speaking: EMD Serono; research funding: Bristol Meyers Squibb; and contract research: Sanofi, Actelion, Genentech, and Novartis.

Background: The choroid plexus (CP), located within the ventricles of the brain and the primary producer of cerebrospinal fluid, has been shown to be enlarged in patients with multiple sclerosis (MS) and linked to periventricular remyelination failure. Atrophied T2-lesion volume (aT2-LV), a promising neurodegenerative imaging marker in progressive MS (PMS), reflects the volume of periventricular lesions subsumed into cerebrospinal fluid over the follow-up., Methods: In a cohort of 143 people with relapsing-remitting MS (RRMS) and 53 with PMS, we used 3T magnetic resonance imaging (MRI) to quantify CP volume (CPV) at baseline and aT2-LV over an average of 5.4 years of follow-up. Partial correlations, adjusting for age and sex, and linear regression analyses were used to assess the relationships between imaging measures., Results: In both cohorts, CPV was associated with aT2-LV in both the RRMS group (r = 0.329, p < 0.001) as well as the PMS group (r = 0.522, p < 0.001). In regression analyses predicting aT2-LV, ventricular volume (final adjusted R2 = 0.407, p < 0.001) explained additional variance beyond age, sex, and T2-lesion volume in the RRMS group while CPV (final adjusted R2 = 0.446, p = 0.009) was retained in the PMS group., Conclusion: Findings from this study suggest that the CP enlargement is associated with future neurodegeneration, with a particularly relevant role in PMS., Competing Interests: Declaration of competing interest Niels Bergsland has nothing to disclose. Michael G. Dwyer received grant support from Novartis, Bristol Myers Squibb, Mapi Pharma, Merck Serono, Keystone Heart Ltd., Protembis GmbH, and V-Wave Ltd., and consulting fees Bristol Myers Squibb, Merck Serono, and Keystone Heart Ltd. Dejan Jakimovski has nothing to disclose. Eleonora Tavazzi has nothing to disclose. Bianca Weinstock-Guttman has participated in speaker's bureaus and/or served as a consultant for Biogen, EMD Serono, Novartis, Genentech, Celgene/Bristol Meyers Squibb, Sanofi Genzyme, Bayer, Janssen, Labcorp and Horizon. Dr. Weinstock-Guttman also has received grant/research support from the agencies listed in the previous sentence. She serves in the editorial board for BMJ Neurology, Children, CNS Drugs, MS International and Frontiers Epidemiology. Robert Zivadinov has received personal compensation from Bristol Myers Squibb, EMD Serono, Sanofi, Janssen, Sanofi, Biogen, Filterlex and Mapi Pharma for speaking and consultant fees. He received financial support for research activities from Novartis, Bristol Myers Squibb, EMD Serono, Octave, Mapi Pharma, CorEvitas, Protembis and V-WAVE Medical., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Some studies have suggested an inflammatory role of the choroid plexus (CP) in the pathophysiology of multiple sclerosis (MS), but mainly in adult patients. We aimed to evaluate clinical and MRI parameters in patients with pediatric-onset multiple sclerosis (POMS). We included 10 patients with POMS and 16 healthy controls (HC), evaluating clinical and neuroimaging variables (cerebral cortex, CP, deep gray matter structures, and demyelinating lesions). Most patients were girls (80%), with a mean age of 15.3 years. POMS individuals had a higher CP volume (p = 0.012) and lower thalamic volume (p = 0.038) compared to HC. This study shows an enlargement of the CP and lower thalamic volume in POMS patients compared to HC., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The choroid plexus (CP) is a vital brain structure essential for cerebrospinal fluid (CSF) production. Moreover, alterations in the CP's structure and function are implicated in molecular conditions and neuropathologies including multiple sclerosis, Alzheimer's disease, and stroke. Our goal is to provide the first characterization of the association between variation in the CP microstructure and macrostructure/volume using advanced magnetic resonance imaging (MRI) methodology, and blood-based biomarkers of Alzheimer's disease (Aß 42/40 ratio; pTau181), neuroinflammation and neuronal injury (GFAP; NfL). We hypothesized that plasma biomarkers of brain pathology are associated with disordered CP structure. Moreover, since cerebral microstructural changes can precede macrostructural changes, we also conjecture that these differences would be evident in the CP microstructural integrity. Our cross-sectional study was conducted on a cohort of 108 well-characterized individuals, spanning 22-94 years of age, after excluding participants with cognitive impairments and non-exploitable MR imaging data. Established automated segmentation methods were used to identify the CP volume/macrostructure using structural MR images, while the microstructural integrity of the CP was assessed using our advanced quantitative high-resolution MR imaging of longitudinal and transverse relaxation times (T 1 and T 2 ). After adjusting for relevant covariates, positive associations were observed between pTau181, NfL and GFAP and all MRI metrics. These associations reached significance (p<0.05) except for CP volume vs. pTau181 (p=0.14), CP volume vs. NfL (p=0.35), and T 2 vs. NFL (p=0.07). Further, negative associations between Aß 42/40 and all MRI metrics were observed but reached significance only for Aß 42/40 vs. T 2 (p=0.04). These novel findings demonstrate that reduced CP macrostructural and microstructural integrity is positively associated with blood-based biomarkers of AD pathology, neurodegeneration/neuroinflammation and neurodegeneration. Degradation of the CP structure may co-occur with AD pathology and neuroinflammation ahead of clinically detectable cognitive impairment, making the CP a potential structure of interest for early disease detection or treatment monitoring.

Glymphatic dysfunction has been correlated with cognitive decline, with a higher choroid plexus volume (CPV) being linked to a slower glymphatic clearance rate. Nevertheless, the interplay between CPV, glymphatic function, and cognitive impairment in white matter hyperintensities (WMHs) has not yet been investigated. In this study, we performed neuropsychological assessment, T1-weighted three-dimensional (3D-T1) images, and diffusion tensor imaging (DTI) in a cohort of 206 WMHs subjects and 43 healthy controls (HCs) to further explore the relationship. The DTI analysis along the perivascular space (DTI-ALPS) index, as a measure of glymphatic function, was calculated based on DTI. Severe WMHs performed significantly worse in information processing speed (IPS) than other three groups, as well as in executive function than HCs and mild WMHs. Additionally, severe WMHs demonstrated lower DTI-ALPS index and higher CPV than HCs and mild WMHs. Moderate WMHs displayed higher CPV than HCs and mild WMHs. Mini-Mental State Examination, IPS, and executive function correlated negatively with CPV but positively with DTI-ALPS index in WMHs patients. Glymphatic function partially mediated the association between CPV and IPS, indicating a potential mechanism for WMHs-related cognitive impairment. CPV may act as a valuable prognostic marker and glymphatic system as a promising therapeutic target for WMHs-related cognitive impairment., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objectives: To evaluate the the diagnostic yield of chromosomal microarray analysis (CMA) in fetuses with isolated CPC (iCPC)., Methods: A total of 315 fetuses with iCPC (iCPC group) and 364 fetuses without abnormal ultrasound findings (control group) were recruited between July 2014 to March 2018., Results: The overall diagnostic yield of chromosomal abnormalities by CMA and karyotyping in iCPC group was up to 4.1 %, higher than 1.4 % in the control group, p < 0.05. The detection rate of pathogenic or likely pathogenic copy number variants (CNVs) with clinical significance by CMA in iCPC group (1.3 %) was higher than in control group (0 %), p < 0.05. According to the type of chromosome abnormalities, the missed diagnosis rate of non-invasive prenatal testing (NIPT) was 1.6 % in our study., Conclusions: The presence of iCPC on ultrasound examination suggests a potential indication for genetic counseling. Karyotyping and chromosomal microarray analysis may be considered for fetuses with iCPC. It is important to be aware of the limitations of non-invasive prenatal testing, as there is a possibility of residual risk., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: We investigated volumetric alterations in the bilateral choroid plexus (ChP) and brain ventricles of patients during their first episode of major depressive disorder (MDD) prior to antidepressant treatment., Methods: Seventy-one first-episode drug-naïve patients with MDD and seventy-four healthy control (HC) subjects were recruited. MRI data were obtained, and bilateral ChP and brain ventricle volumes were evaluated using segmentation, based on the adaptive multiscale and expectation maximization method. One-way multivariate analysis of covariance was used to calculate volumetric differences in the bilateral ChP and brain ventricles between the groups, and partial Pearson correlation analyses were used to investigate the relationship between the volumes of the bilateral ChP and brain ventricles., Results: First-episode drug-naïve patients with MDD showed enlarged volumes of the bilateral ChP, bilateral lateral ventricle (LV), and third ventricle compared with HCs. The ChP volume positively correlated with the LV and third ventricle, but not with the fourth ventricle in patients with MDD, whereas it correlated with all four brain ventricles in HCs. We did not observe significant correlations between bilateral ChP volume and brain ventricles, HAMD scores, or symptom severity., Limitations: Our study populations differed in age and sex and we did not extensively measure the amount of neuroinflammation in the brain or blood, include a functional assessment, nor evaluate other neural comorbidities or neuropsychiatric conditions., Conclusions: Our study extends the existing research to suggest that illness-related alterations in ChP volume enlargement in first-episode antidepressant-naïve patients with MDD may serve as a trait measure., Competing Interests: Declaration of competing interest The authors declare that this study was conducted in the absence of any commercial or financial relationships that could be construed as potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: Recent studies have suggested an association between dysfunction of the choroid plexus and the glymphatic system. However, information is inconclusive. Following a population-based study design, we aimed to assess the association between choroid plexus calcifications (CPCs)-as a surrogate of choroid plexus dysfunction-and severity and progression of putative markers of glymphatic dysfunction, including white matter hyperintensities (WMH) of presumed vascular origin and abnormally enlarged basal ganglia perivascular spaces (BG-PVS)., Methods: This study recruited community-dwellers aged ≥40 years living in neighboring Ecuadorian villages. Participants who had baseline head CTs and brain MRIs were included in cross-sectional analyses and those who additional had follow-up MRIs (after a mean of 6.4 ± 1.5 years) were included in longitudinal analyses. Logistic and Poisson regression models, adjusted for demographics and cardiovascular risk factors, were fitted to assess associations between CPCs and WMH and enlarged BG-PVS severity and progression., Results: A total of 590 individuals were included in the cross-sectional component of the study, and 215 in the longitudinal component. At baseline, 25% of participants had moderate-to-severe WMH and 27% had abnormally enlarged BG-PVS. At follow-up, 36% and 20% of participants had WMH and enlarged BG-PVS progression, respectively. Logistic regression models showed no significant differences between CPCs volumes stratified in quartiles and severity of WMH and enlarged BG-PVS. Poisson regression models showed no association between the exposure and WMH and enlarged BG-PVS progression. Baseline age remained significant in these models., Conclusions: Choroid plexus calcifications are not associated with putative markers of glymphatic system dysfunction., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Choroid plexus (CP) volume has been recently proposed as a proxy for brain neuroinflammation in multiple sclerosis (MS)., Purpose: To develop and validate a fast automatic method to segment CP using routinely acquired brain T1-weighted and FLAIR MRI., Study Type: Retrospective., Population: Fifty-five MS patients (33 relapsing-remitting, 22 progressive; mean age = 46.8 ± 10.2 years; 31 women) and 60 healthy controls (HC; mean age = 36.1 ± 12.6 years, 33 women)., Field Strength/sequence: 3D T2-weighted FLAIR and 3D T1-weighted gradient echo sequences at 3.0 T., Assessment: Brain tissues were segmented on T1-weighted sequences and a Gaussian Mixture Model (GMM) was fitted to FLAIR image intensities obtained from the ventricle masks of the SIENAX. A second GMM was then applied on the thresholded and filtered ventricle mask. CP volumes were automatically determined and compared with those from manual segmentation by two raters (with 3 and 10 years' experience; reference standard). CP volumes from previously published automatic segmentation methods (freely available Freesurfer [FS] and FS-GMM) were also compared with reference standard. Expanded Disability Status Scale (EDSS) score was assessed within 3 days of MRI. Computational time was assessed for each automatic technique and manual segmentation., Statistical Tests: Comparisons of CP volumes with reference standard were evaluated with Bland Altman analysis. Dice similarity coefficients (DSC) were computed to assess automatic CP segmentations. Volume differences between MS and HC for each method were assessed with t-tests and correlations of CP volumes with EDSS were assessed with Pearson's correlation coefficients (R). A P value <0.05 was considered statistically significant., Results: Compared to manual segmentation, the proposed method had the highest segmentation accuracy (mean DSC = 0.65 ± 0.06) compared to FS (mean DSC = 0.37 ± 0.08) and FS-GMM (0.58 ± 0.06). The percentage CP volume differences relative to manual segmentation were -0.1% ± 0.23, 4.6% ± 2.5, and -0.48% ± 2 for the proposed method, FS, and FS-GMM, respectively. The Pearson's correlations between automatically obtained CP volumes and the manually obtained volumes were 0.70, 0.54, and 0.56 for the proposed method, FS, and FS-GMM, respectively. A significant correlation between CP volume and EDSS was found for the proposed automatic pipeline (R = 0.2), for FS-GMM (R = 0.3) and for manual segmentation (R = 0.4). Computational time for the proposed method (32 ± 2 minutes) was similar to the manual segmentation (20 ± 5 minutes) but <25% of the FS (120 ± 15 minutes) and FS-GMM (125 ± 15 minutes) methods., Data Conclusion: This study developed an accurate and easily implementable method for automatic CP segmentation in MS using T1-weighted and FLAIR MRI., Evidence Level: 1 TECHNICAL EFFICACY: Stage 4., (© 2023 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Objectives: To investigate the potential link among choroid plexus (CP) volume, glymphatic clearance and brain structural change in relapsing-remitting multiple sclerosis (RRMS) patients., Materials and Methods: Sixty-five RRMS patients and 48 healthy controls (HC) underwent MRI examination. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) was calculated to reflect glymphatic system function. The brain structure volume and DTI-ALPS index were compared between RRMS and HC. The mediating effect of the DTI-ALPS index between CP volume and brain structural changes was further investigated. The longitudinal changes of brain structure and DTI-ALPS index were compared in 20 RRMS patients., Results: Compared to HC, CP volume in RRMS was significantly increased (P < 0.001), and DTI-ALPS index was significantly decreased (P = 0.001). The volumes of white matter, thalamus, putamen and pallidum were significantly decreased in RRMS, and the volumes of lateral ventricle and third ventricle were increased. Mediation analysis showed DTI-ALPS index partially mediated the association between CP enlargement and deep gray matter (DGM) atrophy in RRMS, and between CP enlargement and ventricle enlargement. CP volume and DTI-ALPS index were also significantly correlated with Expanded Disability Status Scale (EDSS) (P = 0.006, P = 0.043). Notably, the variation of DTI&#95;ALPS index during the follow-up period were significantly and negatively correlated with the variation of EDSS (P = 0.045)., Conclusion: Enlarged CP volume and decreased DTI&#95;ALPS index may be closely related to DGM atrophy and ventricular enlargement in RRMS, and may be potential imaging markers of clinical disability., Competing Interests: Declaration of competing interest The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2024. Published by Elsevier B.V.)

Background and Objective: We explored dynamic changes in the choroid plexus (CP) in patients with relapsing-remitting multiple sclerosis (RRMS) and assessed its relationship with chronic lesion expansion and atrophy in various brain compartments., Methods: Fifty-seven RRMS patients were annually assessed for a minimum of 48 months with 3D FLAIR, pre- and post-contrast 3D T1 and diffusion-weighted magnetic resonance imaging (MRI). The CP was manually segmented at baseline and last follow-up., Results: The volume of CP significantly increased by 1.4% annually. However, the extent of CP enlargement varied considerably among individuals (ranging from -3.6 to 150.8 mm 3 or -0.2% to 6.3%). The magnitude of CP enlargement significantly correlated with central ( r = 0.70, p < 0.001) and total brain atrophy ( r = -0.57, p < 0.001), white ( r = -0.61, p < 0.001) and deep grey matter atrophy ( r = -0.60, p < 0.001). Progressive CP enlargement was significantly associated with the volume and extent of chronic lesion expansion ( r = 0.60, p < 0.001), but not with the number or volume of new lesions., Conclusion: This study provides evidence of progressive CP enlargement in patients with RRMS. Our findings also demonstrate that enlargement of the CP volume is linked to the expansion of chronic lesions and neurodegeneration of periventricular white and grey matter in RRMS patients., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article.

Objective: This study aims to determine the link between choroid plexus (CP) volume and cognitive decline in patients with early-stage Parkinson's disease (PD) and to test whether pathological proteins in the cerebrospinal fluid (CSF) are involved in the modulation of any detrimental effects from CP volume., Methods: Data on 95 early-stage PD patients with 5 years of follow-up were collected from the Parkinson's Progression Marker Initiative cohort. The patients were separated into three groups based on tertiles of baseline CP volume. We then used a linear mixed model for longitudinal analysis and conducted path analysis to investigate mediating effects., Results: At baseline, the patients in both the upper and middle tertile group were older and had lower concentrations of CSF Aβ 1-42 than those in the lowest tertile group. Longitudinal analysis showed that the upper tertile group suffered from a more rapid cognitive decline in the Symbol Digit Modalities test, Hopkins Verbal Learning Test (HVLT)-retention, and HVLT delayed recalled score. Furthermore, path analysis showed that the pathological effects of CP volume on the 5-year decline in memory might be partly mediated by the CSF Aβ 1-42 /αsyn ratio., Conclusion: CP enlargement could be an independent risk factor for decreased cognition in patients with early-stage PD, and this risk may be mediated by CSF pathological proteins., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Background: Choroid plexus (ChP) enlargement exists in first-episode and chronic psychosis, but whether enlargement occurs before psychosis onset is unknown. This study investigated whether ChP volume is enlarged in individuals with clinical high-risk (CHR) for psychosis and whether these changes are related to clinical, neuroanatomical, and plasma analytes., Methods: Clinical and neuroimaging data from the North American Prodrome Longitudinal Study 2 (NAPLS2) was used for analysis. 509 participants (169 controls, 340 CHR) were recruited. Conversion status was determined after 2-years of follow-up, with 36 psychosis converters. The lateral ventricle ChP was manually segmented from baseline scans. A subsample of 31 controls and 53 CHR had plasma analyte and neuroimaging data., Results: Compared to controls, CHR (d = 0.23, p = 0.017) and non-converters (d = 0.22, p = 0.03) demonstrated higher ChP volumes, but not in converters. In CHR, greater ChP volume correlated with lower cortical (r = -0.22, p < 0.001), subcortical gray matter (r = -0.21, p < 0.001), and total white matter volume (r = -0.28,p < 0.001), as well as larger lateral ventricle volume (r = 0.63,p < 0.001). Greater ChP volume correlated with makers functionally associated with the lateral ventricle ChP in CHR [CCL1 (r = -0.30, p = 0.035), ICAM1 (r = 0.33, p = 0.02)], converters [IL1β (r = 0.66, p = 0.004)], and non-converters [BMP6 (r = -0.96, p < 0.001), CALB1 (r = -0.98, p < 0.001), ICAM1 (r = 0.80, p = 0.003), SELE (r = 0.59, p = 0.026), SHBG (r = 0.99, p < 0.001), TNFRSF10C (r = 0.78, p = 0.001)]., Conclusions: CHR and non-converters demonstrated significantly larger ChP volumes compared to controls. Enlarged ChP was associated with neuroanatomical alterations and analyte markers functionally associated with the ChP. These findings suggest that the ChP may be a key an important biomarker in CHR., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: The dysregulation of the gut-brain axis in chronic inflammatory bowel diseases can cause neuro-psychological disturbances, but the underlying mechanisms are still not fully understood. The choroid plexus (CP) maintains brain homeostasis and nourishment through the secretion and clearance of cerebrospinal fluid. Recent research has demonstrated the existence of a CP vascular barrier in mice which is modulated during intestinal inflammation. This study investigates possible correlations between CP modifications and inflammatory activity in patients with Crohn's disease (CD)., Methods: In this prospective study, 17 patients with CD underwent concomitant abdominal and brain 3 T MRI. The volume and permeability of CP were compared with levels of C-reactive protein (CRP), fecal calprotectin (FC), sMARIA and SES-CD scores., Results: The CP volume was negatively correlated with CRP levels (R = -0.643, p-value = 0.024) and FC (R = -0.571, p-value = 0.050). DCE metrics normalized by CP volume were positively correlated with CRP (K-trans: R = 0.587, p-value = 0.045; Vp: R = 0.706, p-value = 0.010; T1: R = 0.699, p-value = 0.011), and FC (Vp: R = 0.606, p-value = 0.037)., Conclusions: Inflammatory activity in patients with CD is associated with changes in CP volume and permeability, thus supporting the hypothesis that intestinal inflammation could affect the brain through the modulation of CP vascular barrier also in humans., Competing Interests: Declaration of competing interest The following authors disclose conflicts of interest: Federica Furfaro received consulting fees from Amgen, AbbVie and lecture fees from Janssen and Pfizer; Mariangela Allocca received consulting fees from Nikkiso Europe, Mundipharma, Janssen, AbbVie and Pfizer; Gionata Fiorino received consultancy fees from Ferring, MSD, AbbVie, Takeda, Janssen, Amgen, Sandoz, Samsung Bioepis, Celltrion; Silvio Danese served as a speaker, consultant, and advisory board member for Schering-Plow, Abbott (AbbVie) Laboratories, Merck, UCB Pharma, Ferring, Cellerix, Millenium Takeda, Nycomed, Pharmacosmos, Actelion, Alfa Wasserman, Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, Vifor, and Johnson and Johnson; Alessandro Armuzzi has received consulting and/or advisory board fees from AbbVie, Allergan, Amgen, Arena, Biogen, Boehringer Ingelheim, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mylan, Pfizer, Protagonist Therapeutics, Roche, Samsung Bioepis, Sandoz, and Takeda; lecture and/or speaker bureau fees from AbbVie, Amgen, Arena, Biogen, Bristol-Myers Squibb, Celltrion, Eli-Lilly, Ferring, Galapagos, Gilead, Janssen, MSD, Mitsubishi Tanabe, Novartis, Pfizer, Roche, Samsung Bioepis, Sandoz, Takeda, and Tigenix; and research grants from MSD, Pfizer, Takeda and Biogen; Maria Rescigno reports payment or honoraria for speaking engagements from Fondazione Internazionale Menarini; Riccardo Levi has received funds from Esaote. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. All remaining authors declare no financial or non-financial competing interests. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Chronic inflammation may contribute to cognitive dysfunction and fatigue in patients with multiple sclerosis (MS). Paramagnetic rim lesions (PRLs) and choroid plexus (CP) enlargement have been proposed as markers of chronic inflammation in MS being associated with a more severe disease course. However, their relation with cognitive impairment and fatigue has not been fully explored yet. Here, we investigated the contribution of PRL number and volume and CP enlargement to cognitive impairment and fatigue in patients with MS., Methods: Brain 3T MRI, neurologic evaluation, and neuropsychological assessment, including the Brief Repeatable Battery of Neuropsychological Tests and Modified Fatigue Impact Scale, were obtained from 129 patients with MS and 73 age-matched and sex-matched healthy controls (HC). PRLs were identified on phase images of susceptibility-weighted imaging, whereas CP volume was quantified using a fully automatic method on brain three-dimensional T1-weighted and fluid-attenuated inversion recovery MRI sequences. Predictors of cognitive impairment and fatigue were identified using random forest., Results: Thirty-six (27.9%) patients with MS were cognitively impaired, and 31/113 (27.4%) patients had fatigue. Fifty-nine (45.7%) patients with MS had ≥1 PRLs (median = 0, interquartile range = 0;2). Compared with HC, patients with MS showed significantly higher T2-hyperintense white matter lesion (WM) volume; lower normalized brain, thalamic, hippocampal, caudate, cortical, and WM volumes; and higher normalized CP volume ( p from <0.001 to 0.040). The predictors of cognitive impairment (relative importance) (out-of-bag area under the curve [OOB-AUC] = 0.707) were normalized brain volume (100%), normalized caudate volume (89.1%), normalized CP volume (80.3%), normalized cortical volume (70.3%), number (67.3%) and volume (66.7%) of PRLs, and T2-hyperintense WM lesion volume (64.0%). Normalized CP volume was the only predictor of the presence of fatigue (OOB-AUC = 0.563)., Discussion: Chronic inflammation, with higher number and volume of PRLs and enlarged CP, may contribute to cognitive impairment in MS in addition to gray matter atrophy. The contribution of enlarged CP in explaining fatigue supports the relevance of immune-related processes in determining this manifestation independently of disease severity. PRLs and CP enlargement may contribute to the pathophysiology of cognitive impairment and fatigue in MS, and they may represent clinically relevant therapeutic targets to limit the impact of these clinical manifestations in MS.

Background: The choroid plexus functions as the blood-cerebrospinal fluid (CSF) barrier, plays an important role in CSF production and circulation, and has gained increased attention in light of the recent elucidation of CSF circulation dysfunction in neurodegenerative conditions. However, methods for routinely quantifying choroid plexus volume are suboptimal and require technical improvements and validation. Here, we propose three deep learning models that can segment the choroid plexus from commonly-acquired anatomical MRI data and report performance metrics and changes across the adult lifespan., Methods: Fully convolutional neural networks were trained from 3D T 1 -weighted, 3D T 2 -weighted, and 2D T 2 -weighted FLAIR MRI using gold-standard manual segmentations in control and neurodegenerative participants across the lifespan (n = 50; age = 21-85 years). Dice coefficients, 95% Hausdorff distances, and area-under-curve (AUCs) were calculated for each model and compared to segmentations from FreeSurfer using two-tailed Wilcoxon tests (significance criteria: p < 0.05 after false discovery rate multiple comparisons correction). Metrics were regressed against lateral ventricular volume using generalized linear models to assess model performance for varying levels of atrophy. Finally, models were applied to an expanded cohort of adult controls (n = 98; age = 21-89 years) to provide an exemplar of choroid plexus volumetry values across the lifespan., Results: Deep learning results yielded Dice coefficient = 0.72, Hausdorff distance = 1.97 mm, AUC = 0.87 for T 1 -weighted MRI, Dice coefficient = 0.72, Hausdorff distance = 2.22 mm, AUC = 0.87 for T 2 -weighted MRI, and Dice coefficient = 0.74, Hausdorff distance = 1.69 mm, AUC = 0.87 for T 2 -weighted FLAIR MRI; values did not differ significantly between MRI sequences and were statistically improved compared to current commercially-available algorithms (p < 0.001). The intraclass coefficients were 0.95, 0.95, and 0.96 between T 1 -weighted and T 2 -weighted FLAIR, T 1 -weighted and T 2 -weighted, and T 2 -weighted and T 2 -weighted FLAIR models, respectively. Mean lateral ventricle choroid plexus volume across all participants was 3.20 ± 1.4 cm 3 ; a significant, positive relationship (R 2  = 0.54-0.60) was observed between participant age and choroid plexus volume for all MRI sequences (p < 0.001)., Conclusions: Findings support comparable performance in choroid plexus delineation between standard, clinically available, non-contrasted anatomical MRI sequences. The software embedding the evaluated models is freely available online and should provide a useful tool for the growing number of studies that desire to quantitatively evaluate choroid plexus structure and function ( https://github.com/hettk/chp&#95;seg )., (© 2024. The Author(s).)

We compared choroid plexus (ChP) manual segmentation on non-contrast-enhanced (non-CE) sequences and reference standard CE T1- weighted (T1w) sequences in 61 multiple sclerosis patients prospectively included. ChP was separately segmented on T1w, T2-weighted (T2w) fluid-attenuated inversion-recovery (FLAIR), and CE-T1w sequences. Inter-rater variability assessed on 10 subjects showed high reproducibility between sequences measured by intraclass correlation coefficient (T1w 0.93, FLAIR 0.93, CE-T1w 0.99). CE-T1w showed higher signal-to-noise ratio and contrast-to-noise ratio (CE-T1w 23.77 and 18.49, T1w 13.73 and 7.44, FLAIR 13.09 and 10.77, respectively). Manual segmentation of ChP resulted 3.073 ± 0.563 mL (mean ± standard deviation) on T1w, 3.787 ± 0.679 mL on FLAIR, and 2.984 ± 0.506 mL on CE-T1w images, with an error of 28.02 ± 19.02% for FLAIR and 3.52 ± 12.61% for T1w. FLAIR overestimated ChP volume compared to CE-T1w (p < 0.001). The Dice similarity coefficient of CE-T1w versus T1w and FLAIR was 0.67 ± 0.05 and 0.68 ± 0.05, respectively. Spatial error distribution per slice was calculated after nonlinear coregistration to the standard MNI152 space and showed a heterogeneous profile along the ChP especially near the fornix and the hippocampus. Quantitative analyses suggest T1w as a surrogate of CE-T1w to estimate ChP volume.Relevance statement To estimate the ChP volume, CE-T1w can be replaced by non-CE T1w sequences because the error is acceptable, while FLAIR overestimates the ChP volume. This encourages the development of automatic tools for ChP segmentation, also improving the understanding of the role of the ChP volume in multiple sclerosis, promoting longitudinal studies.Key points • CE-T1w sequences are considered the reference standard for ChP manual segmentation.• FLAIR sequences showed a higher CNR than T1w sequences but overestimated the ChP volume.• Non-CE T1w sequences can be a surrogate of CE-T1w sequences for manual segmentation of ChP., (© 2024. The Author(s).)

Objective: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS)., Methods: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons., Results: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r 2  = 0.25, p = 0.0002), disease duration (r 2  = 0.30, p = 0.01), and T2 lesion volume (r 2  = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001)., Conclusions: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS., Competing Interests: Declaration of competing interest The authors declared no conflict of interest relevant to this manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Enlargement of the choroid plexus (CP) is reported to associate with inflammatory activity and contribute to brain atrophy in patients with multiple sclerosis (pwMS). However, a recent study in healthy volunteers (HVTs) has suggested that CP enlargement can be attributed to ventriculomegaly., Objectives: To clarify the pathological significance of the enlargement of CP in multiple sclerosis (MS)., Methods: A total of 102 pwMS (89 with relapsing-remitting MS and 13 with secondary progressive MS) and 41 HVTs were cross-sectionally evaluated using brain volumetry. The CP volume was compared between disease groups and investigated for the relationships with other brain regional volumes., Results: CP volume was significantly larger in pwMS than in HVTs in the univariate analysis, but not in multivariable analysis. Meanwhile, the CP and lateral ventricle (LV) volumes were significantly correlated. CP enlargement was significantly associated with increased lesion load and cerebral white matter (WM) atrophy, even after adjusting for LV volume. In contrast, multivariable analyses revealed that LV enlargement, but not CP enlargement, was associated with total gray matter (GM) atrophy., Conclusion: CP enlargement was closely associated with LV enlargement. After adjusting for LV volume, CP enlargement in pwMS was associated with increased lesion load and WM atrophy but not GM atrophy., Competing Interests: Declaration of Competing Interest I. Nakashima serves on the scientific advisory boards for Biogen Japan and Novartis Pharma and receives honoraria for speaking engagements with Biogen Japan, Mitsubishi Tanabe Pharma, Novartis Pharma, Takeda Pharmaceutical, and Eisai. T. Akaishi and J. Fujimori have no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Choroid plexus (CP) enlargement is proposed as a marker of neuroinflammation in immune-mediated conditions. CP involvement has also been hypothesized in the immunopathology of systemic lupus erythematosus (SLE). We investigated whether CP enlargement occurs in SLE patients and its association with neuropsychiatric involvement. Additionally, we explored abnormalities along the glymphatic system in SLE patients through enlarged perivascular space (PVS) quantification. Clinical assessment and 3 Tesla brain dual-echo and T1-weighted MRI scans were obtained from 32 SLE patients and 32 sex and age-matched healthy controls (HC). CPs were manually segmented on 3D T1-weighted sequence and enlarged PVS (ePVS) were assessed through Potter's score. Compared to HC, SLE patients showed higher normalized CP volume (nCPV) (p = 0.023), with higher CP enlargement in neuropsychiatric SLE (NPSLE) (n = 12) vs. non-NPSLE (p = 0.027) patients. SLE patients with antiphospholipid antibodies (APA) positivity (n = 18) had higher nCPV compared to HC (p = 0.012), while APA negative ones did not. SLE patients also had higher Potter's score than HC (p < 0.001), with a tendency towards a higher number of basal ganglia ePVS in NPSLE vs. non-NPSLE patients. Using a random forest analysis, nCPV emerged as a significant predictor of NPSLE, together with T2-hyperintense white matter (WM) lesion volume (LV) and APA positivity (out-of-bag AUC 0.81). Our findings support the hypothesis of a role exerted by the CP in SLE physiopathology, especially in patients with neuropsychiatric involvement. The higher prevalence of ePVS in SLE patients, compared to HC, suggests the presence of glymphatic system impairment in this population., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The Hindbrain Choroid Plexus is a complex, cerebrospinal fluid-secreting tissue that projects into the 4th vertebrate brain ventricle. Despite its irreplaceability in the development and homeostasis of the entire central nervous system, the research of Hindbrain Choroid Plexus and other Choroid Plexuses has been neglected by neuroscientists for decades. One of the obstacles is the lack of tools that describe the complex shape of the Hindbrain Choroid Plexus in the context of brain ventricles. Here we introduce an effective tool, termed Ch O P-CT, for the noninvasive, X-ray micro-computed tomography-based, three-dimensional visualization and subsequent quantitative spatial morphological analysis of developing mouse Hindbrain Choroid Plexus. Ch O P-CT can reliably quantify Hindbrain Choroid Plexus volume, surface area, length, outgrowth angle, the proportion of the ventricular space occupied, asymmetries and general shape alterations in mouse embryos from embryonic day 13.5 onwards. We provide evidence that Ch O P-CT is suitable for the unbiased evaluation and detection of the Hindbrain Choroid Plexus alterations within various mutant embryos. We believe, that thanks to its versatility, quantitative nature and the possibility of automation, Ch O P-CT will facilitate the analysis of the Hindbrain Choroid Plexus in the mouse models. This will ultimately accelerate the screening of the candidate genes and mechanisms involved in the onset of various Hindbrain Choroid Plexus-related diseases., (© 2024. The Author(s).)

A woman in her 20s, who was pregnant, underwent a routine antenatal ultrasound revealing organised intraventricular haemorrhage and a vascular area in the left thalamic region. Fetal MRI raised suspicion of arteriovenous malformation (AVM). The baby was delivered at 36 weeks via C-section, and initial brain MRI suggested a possible neoplastic lesion.Cerebral angiography confirmed a large AVM involving the left choroid plexus with arterial feeders from the left anterior and posterior choroidal arteries and a large venous varix draining into the vein of Galen. Both arterial feeders were successfully embolised with Onyx and glue, achieving complete occlusion.Choroid plexus AVMs are rare and often lead to intraventricular or intraparenchymal haemorrhage. Surgical treatment has shown success, but endovascular management is effective, especially for small, deep-seated AVMs, offering a better prognosis., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Multiple sclerosis (MS) is a central nervous system (CNS) disease associated with inflammation, demyelination, and neurodegeneration. It affects more than 2 million people globally, and usually occurs in young adults, three-quarters of whom are women. Importantly, accurate diagnosis and treatment are essential, as this disease can lead to the rapid development of disability. The choroid plexus (CP) is a structure widely known as the main cerebrospinal fluid source. However, it is also involved in immune cell trafficking to the cerebrospinal fluid, which is increased in different neurological disorders, particularly those associated with neuroinflammation. As MS is generally thought to be caused by an autoimmune process, it has been suggested that the choroid plexus may play a significant role in its pathogenesis, manifesting via changes in imaging characteristics., Material and Methods: Although research regarding this topic has been very limited, the results of the available studies appear promising. To further investigate this subject, we performed a systematic literature review according to the PRISMA 2020 guidelines. The PubMed and Embase databases were searched for relevant articles, and after thorough analysis, 16 studies were included in our review., Results: CP volume was significantly increased in MS patients compared to healthy individuals. Furthermore, some studies found that CP enlargement occurs even before a definite diagnosis. Moreover, a few articles reported correlations between CP volume and brain atrophy, or even disease severity., Conclusions: Our findings show that CP imaging has the potential to become a novel and valuable tool in multiple sclerosis management.

Background and Purpose: Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy., Methods: We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time = 35 ms; spatial resolution = 3.5 × 3.5 × 3.5 mm, repetition time = 2000 ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n = 53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p < .05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories., Results: In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p ≤ .01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population., Conclusions: Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress., (© 2023 American Society of Neuroimaging.)

Purpose: Our aims were to investigate the presence of choroid plexus (CP) inflammation in chronic-phase intracerebral hemorrhage (ICH) patients and to characterize any inflammatory cells in the CP., Patients and Methods: An in vivo 18 F-DPA714 PET study was undertaken in 22 chronic-phase ICH patients who were admitted to the First Affiliated Hospital of Fujian Medical University or Tianjin Medical University General Hospital from April 2017 to June 2020. Ten control participants with nonhemorrhagic central nervous system diseases were included. Choroid plexus 18 F-DPA714 uptake was calculated as the average SUVR. To aid the interpretation of the 18 F-DPA714 uptake results at the CP level, Cy5-DPA714 in vivo imaging and immunofluorescence staining were used to show the presence of CP inflammation in an ICH mouse model during the chronic phase (14 weeks after ICH). Then immunofluorescence staining against translocator protein and other specific biomarkers was used to characterize the cells present in the inflamed CP of ICH mice in the chronic phase., Results: PET imaging showed that CP DPA714 SUVRs in chronic-phase ICH patients were higher than in controls (mean CP SUVR ± SD; ICH group: 1.05 ± 0.35; control group: 0.81 ± 0.21; P = 0.006). Immunofluorescence staining of the CP in ICH model mice identified a population of CD45 + immune cells, peripheral monocyte-derived CD14 + cells, CD68 + phagocytes, and CD11b + resident microglia/macrophages expressing translocator protein, possibly contributing to the increased 18 F-DPA714 uptake., Conclusions: Our study shows that CP DPA714 uptake in chronic-phase ICH patients was higher than that of participants with nonhemorrhagic central nervous system diseases, which means that CP inflammation is still active in chronic-phase ICH patients., Competing Interests: Conflicts of interest and sources of funding: The authors declared no conflicts of interest. The study was supported by the National Natural Science Foundation of China (grant no. 82171327, 82171982, and 82371466), the Stroke Prevention and Treatment Project of the National Health Commission–Research and Popularization of Appropriate Intervention Technology for the Stroke High Risk Group in China (GN2018R002), the Fujian Science and Technology Innovation Joint Fund Project (2019Y9118), the Technology Platform Construction Project of Fujian Province (2020Y2003 and 2021Y2001), the Major Scientific Research Specialty Project of Fujian Province (2022ZD01003), and the Natural Science Foundation of Fujian Province (2023J01590 and 2023J06031). The funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the article; and decision to submit the article for publication., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

The choroid plexus has been implicated in neurodevelopment and a range of brain disorders. Evidence demonstrates that the choroid plexus is critical for brain maturation, immune/ inflammatory regulation, and behavioral/cognitive functioning. However, current automated neuroimaging segmentation tools are poor at accurately and reliably segmenting the lateral ventricle choroid plexus. Furthermore, there is no existing tool that segments the choroid plexus located in the third and fourth ventricles of the brain. Thus, a protocol delineating how to segment the choroid plexus in the lateral, third, and fourth ventricle is needed to increase the reliability and replicability of studies examining the choroid plexus in neurodevelopmental and brain disorders. This protocol provides detailed steps to create separately labeled files in 3D Slicer for the choroid plexus based on DICOM or NIFTI images. The choroid plexus will be manually segmented using the axial, sagittal, and coronal planes of T1w images making sure to exclude voxels from gray or white matter structures bordering the ventricles. Windowing will be adjusted to assist in the localization of the choroid plexus and its anatomical boundaries. Methods for assessing accuracy and reliability will be demonstrated as part of this protocol. Gold standard segmentation of the choroid plexus using manual delineations can be used to develop better and more reliable automated segmentation tools that can be openly shared to elucidate changes in the choroid plexus across the lifespan and within various brain disorders.

Background: The choroid plexus (CP) is involved in the clearance of harmful metabolites from the brain, as a part of the glymphatic system. This study aimed to investigate the association between CP volume (CPV), nigrostriatal dopaminergic degeneration and motor outcomes in Parkinson's disease (PD)., Methods: We retrospectively searched drug-naïve patients with early-stage PD who underwent dopamine transporter (DAT) scanning and MRI. Automatic CP segmentation was performed, and the CPV was calculated. The relationship between CPV, DAT availability and Unified PD Rating Scale Part III (UPDRS-III) scores was assessed using multivariate linear regression. We performed longitudinal analyses to assess motor outcomes according to CPV., Results: CPV was negatively associated with DAT availability in each striatal subregion (anterior caudate, β=-0.134, p=0.012; posterior caudate, β=-0.162, p=0.002; anterior putamen, β=-0.133, p=0.024; posterior putamen, β=-0.125, p=0.039; ventral putamen, β=-0.125, p=0.035), except for the ventral striatum. CPV was positively associated with the UPDRS-III score even after adjusting for DAT availability in the posterior putamen (β=0.121; p=0.035). A larger CPV was associated with the future development of freezing of gait in the Cox regression model (HR 1.539, p=0.027) and a more rapid increase in dopaminergic medication in the linear mixed model (CPV×time, p=0.037), but was not associated with the risk of developing levodopa-induced dyskinesia or wearing off., Conclusion: These findings suggest that CPV has the potential to serve as a biomarker for baseline and longitudinal motor disabilities in PD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To assess the role of the choroid plexus (CP) of the fourth ventricle (4V) in fetuses with an open 4V and a normal cerebellar vermis., Methods: Two groups of patients were recruited in two fetal medicine referral centers. The prospectively collected control group included singleton pregnancies with a normal sonographic examination after first-trimester combined screening for chromosomal abnormalities and normal outcome, recruited in the period between 2019 and 2022. The study group was selected retrospectively by searching our databases to identify all cases with an isolated open 4V and normal anatomy and size of the cerebellar vermis. The inclusion criteria of the study group were: (1) gestational age between 20 and 22 weeks; (2) a brainstem-vermis angle ≥ 18° in the midsagittal plane with an otherwise normal cerebellum and vermis; (3) 4V-CP visible and seen separately from the vermis; (4) absence of other intra- and extracranial anomalies; and (5) available prenatal and/or postnatal magnetic resonance imaging (MRI) data., Results: In 169 cases of the control group, the 4V-CP was seen separately from the cerebellar vermis and was noticed to progressively fill the space caudal to the 4V, between the vermis and brainstem. From 12 to 22 weeks, the surface areas of the vermis and medial portion of the 4V-CP increased progressively with advancing gestation (P < 0.0001). Intra- and interobserver correlation analysis showed good reproducibility for the measurements. Among the cases with an open 4V and a normal vermis, it was retrospectively feasible to visualize the 4V-CP separately from the inferior part of the vermis in 41 fetuses. In five of these cases, the open 4V was due to a small CP. In all 41 fetuses, the diagnosis on MRI was isolated upward rotation of the cerebellar vermis, and no additional anomaly was found., Conclusions: Closure of the 4V is dependent on the 4V-CP and not only the cerebellar vermis. In fact, a small CP may represent another cause of an open 4V. Therefore, separate visualization of the 4V-CP and cerebellar vermis is crucial to improve discrimination between the different causes of an open 4V at the anomaly scan and its clinical implications. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Purpose: The glymphatic system is a fluid exchange pathway that clears waste products that is crucial for the maintenance of brain homeostasis. However, the exact role it plays in the emergence of fibromyalgia (FM) is still not fully understood. Here, we explored the changes in non-invasive MRI proxy probably related to the glymphatic function in FM patients, and explored brain-behavior relationships., Methods: A total of 40 participants, consisting of 20 individuals with FM and 20 healthy controls (HCs), were included in the study. The participants underwent structural T1-weighted MRI, diffusion tensor imaging (DTI), and clinical assessment. The data was obtained from an open access dataset. The study compared non-invasive MRI indices, including choroid plexus (CP) volume and DTI analysis along the perivascular space (ALPS), between the FM and HC groups. Furthermore, correlation analysis was conducted to determine the correlation between clinical parameters and both CP volume and DTI-ALPS index., Results: Patients with FM had significantly higher CP volume and a lower DTI-ALPS index than HCs adjusting for age and intracranial volume. Higher CP volume was associated with lower DTI-ALPS index, and longer disease duration., Conclusion: Our findings demonstrate aberrant glymphatic function in FM, and that dysfunction in the brain glymphatic system may play a role in the neural mechanisms underlying FM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: Choroid plexus cysts (CPCs) are incidental findings on ultrasound examination of the fetal brain. It is not known if isolated CPCs are associated with any adverse health or neurodevelopmental outcomes during the life course. This systematic review aimed to collate and synthesize the evidence on whether or not isolated choroid plexus cysts are associated with an increased risk of adverse health or developmental outcomes during childhood and adolescence., Methods: A search strategy was developed specifically for this study and applied to four electronic databases Medline (Ovid), Embase (Ovid), Web of Science, and Google Scholar. Studies were assessed and selected for inclusion if there was a measurement of CPC (including single or multiple; unilateral or bilateral; isolated or presenting alongside other markers) during the antenatal or early neonatal period (<7 days) with follow-up of children and adolescents for health and developmental outcomes measured at any time from age 1 month onwards. Study quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Due to heterogeneity in the types of outcome measures included and the timing of measurement of outcomes across the studies, it was not possible to pool data across studies and a narrative description of findings was presented., Results: Eight studies (three cohorts and five case series) met the inclusion criteria. Different methods were used for outcome assessment, such as in-person assessment, parent questionnaires, medical records, and telephone interviews with parents. Six studies measured outcomes only once during the specified duration of follow-up; two studies carried out paediatric reviews of the children several times during follow-up. There were no differences in developmental outcomes or physical health between babies with CPCs reported in the three cohort studies, and no abnormalities were detected in the children that were followed up in four of the five case series studies. Most of the included studies were graded as low quality due to the small sample size, high risk of selection bias, unclear definitions of CPC or lack of a comparison group., Conclusions: The studies conducted to date do not provide evidence of adverse physical health outcomes or neurodevelopmental delays in babies with CPCs. However, most of these studies were small and included a narrow range of outcomes. Further research is needed to explore the relative incidence of outcomes such as ASD, ADHD, epilepsy and educational attainment in children with CPCs., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aim: Elevated inflammation and larger choroid plexus (ChP) volume has been previously identified in mood disorders. Connections between inflammation, ChP, and clinical symptoms in bipolar II depression (BDII-D) are unclear. Data-driven clustering based on neuroanatomical phenotypes may help to elucidate neurobiological associations in BDII-D., Methods: Inflammatory cytokines, clinical symptoms, and neuroanatomical features were assessed in 150 BDII-D patients. Sixty-eight cortical surface area (SA) and 19 subcortical volumes were extracted using FreeSurfer. The ChP volume was segmented manually using 3D Slicer. Regularized canonical correlation analysis was used to identify significantly correlated components between cortical SA and subcortical volumes (excluding the ChP), followed by k-means clustering to define brain-derived subgroups of BDII-D. Low-grade inflammation was derived by averaging the standardized z scores of interleukin (IL)-6, IL-1β, and tumor necrosis factor-α (TNF-α), which were computed to create a composite z-value score. Partial Pearson correlations followed by multiple comparison correction were conducted to explore associations between inflammation, clinical symptoms, and ChP volume., Results: Subgroup I demonstrated smaller subcortical volume and cortical SA, higher inflammation, and larger ChP volume compared with subgroup II. Greater ChP volume was associated with a higher low-grade inflammation (mean r = 0.289, q = 0.003), CRP (mean r = 0.249, q = 0.007), IL-6 (left r = 0.200, q = 0.03), and TNF-α (right r = 0.226, q = 0.01), while greater IL-1β was significantly associated with severe depressive symptoms in BDII-D (r = 0.218, q = 0.045)., Conclusions: Neuroanatomically-derived subgroups of BDII-D differed in their inflammation levels and ChP volume. These findings suggest an important role of elevated peripheral inflammation and larger ChP in BDII-D., (© 2023 The Authors. Psychiatry and Clinical Neurosciences © 2023 Japanese Society of Psychiatry and Neurology.)

Background and Purpose: The choroid plexus (CP) clears harmful metabolites from the central nervous system as part of the glymphatic system. We investigated the association of CP volume (CPV) with baseline and longitudinal cognitive decline in patients with Parkinson disease (PD)., Methods: We retrospectively reviewed the medical records of 240 patients with newly diagnosed PD who had undergone detailed neuropsychological tests and high-resolution T1-weighted structural magnetic resonance imaging during the initial assessment. The CPV of each patient was automatically segmented, and the intracranial volume ratio was used in subsequent analyses. The relationship between CPV and baseline composite scores of each cognitive domain was assessed using multivariate linear regression analyses. A Cox proportional hazards model was used to compare the risk of dementia conversion with CPV., Results: CPV negatively correlated with composite scores of the frontal/executive function domain (β = -0.375, p = 0.002) after adjusting for age, sex, years of education, and parkinsonian symptom duration. The Cox regression model revealed that a larger CPV was associated with a higher risk of dementia conversion (hazard ratio [HR] = 1.509, p = 0.038), which was no longer significant after adjusting for the composite scores of the frontal/executive function domain. A mediation analysis demonstrated that the effect of CPV on the risk of dementia conversion was completely mediated by frontal/executive function (direct effect: HR = 1.203, p = 0.396; indirect effect: HR = 1.400, p = 0.015)., Conclusions: Baseline CPV is associated with baseline frontal/executive function, which subsequently influences dementia conversion risk in patients with PD., (© 2023 European Academy of Neurology.)

Background and Objectives: Choroid plexus (ChP) is emerging as a key brain structure in the pathophysiology of neurodegenerative disorders. In this observational study, we investigated ChP volume in a large cohort of patients with frontotemporal lobar degeneration (FTLD) spectrum to explore a possible link between ChP volume and other disease-specific biomarkers., Methods: Participants included patients meeting clinical criteria for a probable syndrome in the FTLD spectrum. Structural brain MRI imaging, serum neurofilament light (NfL), serum phosphorylated-Tau 181 (p-Tau 181 ), and cognitive and behavioral data were collected. MRI ChP volumes were obtained from an ad-hoc segmentation model based on a Gaussian Mixture Models algorithm., Results: Three-hundred and sixteen patients within FTLD spectrum were included in this study, specifically 135 patients diagnosed with behavioral variant frontotemporal dementia (bvFTD), 75 primary progressive aphasia, 46 progressive supranuclear palsy, and 60 corticobasal syndrome. In addition, 82 age-matched healthy participants were recruited as controls (HCs). ChP volume was significantly larger in patients with FTLD compared with HC, across the clinical subtype. Moreover, we found a significant difference in ChP volume between HC and patients stratified for disease-severity based on CDR plus NACC FTLD, including patients at very early stage of the disease. Interestingly, ChP volume correlated with serum NfL, cognitive/behavioral deficits, and with patterns of cortical atrophy. Finally, ChP volume seemed to discriminate HC from patients with FTLD better than other previously identified brain structure volumes., Discussion: Considering the clinical, pathologic, and genetic heterogeneity of the disease, ChP could represent a potential biomarker across the FTLD spectrum, especially at the early stage of disease. Further longitudinal studies are needed to establish its role in disease onset and progression., Classification of Evidence: This study provides Class III evidence that choroid plexus volume, as measured on MRI scan, can assist in differentiating patients with FTLD from healthy controls and in characterizing disease severity., (© 2023 American Academy of Neurology.)

Objective: Pediatric hydrocephalus requires evaluation while accounting for growth of the intracranial structures, but information on choroid plexus growth in children is lacking. This study aimed to create normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Additionally, the authors aimed to objectively assess the degree of hydrocephalus caused by choroid plexus hyperplasia (CPH) and to examine the impact of surgical procedures., Methods: This retrospective study analyzed the head CT scans of pediatric patients with minor head trauma treated at Osaka Women's and Children's Hospital between March 2006 and May 2023. The study segmented and calculated intracranial, choroid plexus, and lateral ventricles volumes. The study also calculated the correlation coefficients among these 3 parameters. Patients aged 0 to 10 years were divided into 15 age-related clusters, and mean ± SD values were calculated for each cluster. Growth curves were created by plotting mean values sequentially. Volume obtained from patients with CPH were z-normalized using mean and SD values and compared., Results: A total of 229 CT scans (94 from females) were analyzed, and positive correlations were observed among intracranial volume, choroid plexus volume, and lateral ventricles volume, with the strongest correlation between the choroid plexus and lateral ventricles volumes. The growth rate of intracranial volume was rapid until approximately 20 months of age, while those of choroid plexus volume and lateral ventricles volume increased rapidly until approximately 1 year of age. Subsequently, choroid plexus volume and lateral ventricles volume plateaued at 1.5 ml and 10 ml, respectively. Three patients with CPH were enrolled and quantitatively evaluated on the basis of the z-normalized volume. Notable abnormal volumes of the choroid plexus (range z-normalized values 24.11-51.17) and lateral ventricles (46.78-122.36) were observed. In 2 patients, improvements in the z-normalized values of intracranial volume and lateral ventricles volume were observed after surgical interventions. Additionally, in 1 patient, choroid plexus volume was reduced by approximately 24% (range z-normalized values 51.17-38.93) after bilateral endoscopic plexus coagulation., Conclusions: This study provides normal growth curves for intracranial volume, choroid plexus volume, and lateral ventricles volume. Knowledge of these normal values holds the potential for objective assessment of abnormal values associated with hydrocephalus and choroid plexus diseases such as CPH.

Objectives: Glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remains 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 participants 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. The 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 range: 0.49 to 0.62, p range: 0.017 to 0.047). Anterior and middle glymphatic functions 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. ANN NEUROL 2023;94:442-456., (© 2023 The Authors. Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Tau protein accumulation in the brain is thought to be one of the causes of Alzheimer's disease (AD). Recent studies found that the choroid plexus (CP) has a role in β-amyloid and tau protein clearance in the brain. We evaluated the relationships between CP volume and the ß-amyloid and tau protein depositions. Participants were 20 patients with AD and 35 healthy subjects who underwent MRI and PET scanning using the ß-amyloid tracer 11C-PiB and the tau/inflammatory tracer 18F-THK5351. We computed the volume of the CP and estimated the relationships between the CP volume and ß-amyloid and tau protein/inflammatory deposition by Spearman's correlation test. The CP volume was significantly positively correlated with both the standardized uptake value ratio (SUVR) of 11C-PiB and the SUVR of 18F-THK5351 in all participants. The CP volume was also significantly positively correlated with the SUVR of 18F-THK5351in patients with AD. Our data suggested that the volume of the CP was a good biomarker for the evaluation of tau deposition and neuroinflammation., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

We report a 4-year-old male who presented with a blocked ventriculoperitoneal (VP) shunt inserted post excision of a WHO Grade 1 cerebellar pilocytic astrocytoma complicated post-operatively by pseudo meningocoele formation. Imaging revealed choroid plexus that had herniated along the shunt tract. Subsequent MRI showed development of cystic changes around the tract. The ectopic choroid plexus was still in continuity with the ventricular ependyma and was producing CSF in the left parietal lobe.

Objective: Ventriculomegaly can be associated with long-term neurodevelopmental impairment. Prenatal diagnosis of ventriculomegaly is most commonly made at the routine second-trimester anomaly scan. The value of first-trimester ultrasound has expanded to early diagnosis and screening of fetal abnormalities. The objective of this study was to assess the predictive accuracy of first-trimester choroid-plexus-to-lateral-ventricle-or-head ratios for development of ventriculomegaly at a later gestational age., Methods: This was a case-control study of fetuses with isolated ventriculomegaly diagnosed after 16 weeks' gestation and a control group of normal fetuses (without ventriculomegaly). The exclusion criteria included aneuploidy, genetic syndrome and/or other brain abnormality. Stored two-dimensional first-trimester ultrasound images were analyzed blindly offline and fetal biometry was performed in the axial view of the fetal head. The ratios of choroid plexus area (PA) to lateral ventricular area (VA), choroid plexus length (PL) to lateral ventricular length (VL), choroid plexus diameter (PD) to lateral ventricular diameter (VD) and PA to biparietal diameter (BPD) were measured at 11 + 0 to 13 + 6 weeks' gestation. Intra- and interobserver variability of measurement of these fetal head biometric parameters at 11 + 0 to 13 + 6 weeks' gestation were assessed in 20 normal fetuses using intraclass correlation coefficients with 95% CI. The accuracy of first-trimester biometric measurements for prediction of ventriculomegaly was assessed using the area under the receiver-operating-characteristics curves (AUC)., Results: The analysis included 683 singleton pregnancies, of which 102 fetuses were diagnosed with ventriculomegaly. Ventriculomegaly was mild in 86 (84.3%) cases and severe in the other 16 (15.7%). All first-trimester fetal choroid-plexus-to-lateral-ventricle/head ratios were significantly lower in cases with ventriculomegaly compared with controls (P < 0.001), with good inter- and intraobserver agreement (≥ 0.95) for the majority of the fetal head biometric parameters assessed. On adjusting for crown-rump length, optimism-adjusted AUC values obtained after cross-validation showed that both PL/VL ratio (AUC, 0.87 (95% CI, 0.73-0.98)) and PA/VA ratio (AUC, 0.90 (95% CI, 0.82-0.98)) had good predictive accuracy for severe ventriculomegaly. The PA/BPD ratio (AUC, 0.73 (95% CI, 0.54-0.90)) had modest predictive ability, which was significantly lower compared with that of the PA/VA ratio and PL/VL ratio (P = 0.003 and P = 0.001, respectively). The predictive accuracy of PD/VD ratio was low with an AUC of 0.65 (95% CI, 0.47-0.84). Optimism-adjusted AUC values obtained after cross-validation showed that PA/VA ratio offered the highest predictive accuracy for mild ventriculomegaly with an AUC of 0.84 (95% CI, 0.79-0.89), followed by PL/VL ratio (AUC, 0.82 (95% CI, 0.76-0.88)), PA/BPD ratio (AUC, 0.76 (95% CI, 0.69-0.82)) and PD/VD ratio (AUC, 0.75 (95% CI, 0.67-0.81)). Calibration plots showed that both PA/VA and PL/VL ratios had good calibration., Conclusion: First-trimester prediction of ventriculomegaly using ratios of fetal choroid plexus to lateral ventricle/head appears promising. Future prospective studies are needed to validate the predictive accuracy of these ultrasound markers as a screening tool for ventriculomegaly. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.)