Diffusion Tensor Imaging Analysis Research Articles

Assessment of axonal injury in multiple sclerosis: combined analysis of serum light-chain neurofilaments and diffusion tensor imaging

BackgroundMultiple sclerosis (MS) is a chronic neuroinflammatory condition characterised by demyelination and axonal damage in the central nervous system. Diffusion tensor imaging (DTI) enables non-invasive investigation of microstructural white matter...

PLB2Tau mice are impaired in novel and temporal object recognition and show corresponding traits in brain MRI

Recent clinical trials targeting tau protein aggregation have heightened interest in tau-based therapies for dementia. Success of such treatments depends crucially on translation from non-clinical animal models. Here, we present the age profile of the PLB2Tau knock-in model of fronto-temporal dementia in terms of cognition, and by utilising a directly translatable magnetic resonance imaging approach. Separate cohorts of mice aged 3, 6 and 12 months were tested in an object recognition protocol interrogating visual, spatial, and temporal discrimination in consecutive tests. Upon completion of their behavioural testing, animals were recorded in a 7T MRI for brain structural integrity and diffusion tensor imaging (DTI) analysis.We report that PLB2Tau mice presented with an age-dependent deficit in novel object discrimination relative to wild-type controls at 6 and 12 months. Spatial and temporal discrimination, though not significantly different from controls, appeared extremely challenging for PLB2Tau subjects, especially at 12 months, since they explored objects less than controls and were devoid of memory. Controls readily recalled all relevant object-related information. At the same time, the T2 weighted voxel-based image analysis revealed a progressive shrinkage of total brain volumes in 6- and 12-month-old PLB2Tau mice as well as relative striatal, but not hippocampal volumes. A regional DTI analysis yielded only reduced mean diffusivity of the fimbria, but not CA1 or dentate gyrus, amygdala, cingulate cortex, or corpus callosum.These data confirm the PLB2Tau mouse as a translationally useful model for dementia research and suggest the importance of the hippocampal input as a determinant for novel object discrimination.

Relationship between glymphatic system dysfunction and cognitive impairment in patients with mild-to-moderate chronic traumatic brain injury: an analysis of the analysis along the perivascular space (ALPS) index.

Cognitive impairment associated with mild-to-moderate chronic traumatic brain injury (TBI) presents substantial challenges for which the functionality of the brain glymphatic system is a key area of interest. This study aimed to explore the functionality of the brain glymphatic system in patients with chronic cognitive impairment following mild-to-moderate TBI using diffusion tensor image analysis along the perivascular space (DTI-ALPS). This was a prospective cross-sectional study. A total of 56 patients with mild-to-moderate chronic TBI at the Radiology Outpatient Clinic of the First Affiliated Hospital of Hainan Medical University were enrolled in the study between January 2021 and July 2022. Additionally, 20 healthy control (HC) subjects were recruited from the Health Screening Center during the same period as the HC group. Relevant clinical data for all the participants were collected, and cognitive assessments were conducted using cognitive scales. The TBI patients were categorized into the traumatic brain injury cognitive impairment (TBI-CI) and traumatic brain injury cognitively normal (TBI-CN) groups based on their of the Chinese Version of the Montreal Cognitive Assessment-Basic (MoCA-BC) scores. Each group comprised 20 subjects. All three groups of participants underwent diffusion tensor imaging (DTI). The DTI data were processed and analyzed using the MRIcron and FMRIB Software Library (FSL) toolboxes, and the analysis along the perivascular space (ALPS) index was calculated. Differences in the ALPS index among the three groups were examined by an analysis of covariance, adjusted for age and gender. A corrected receiver operating characteristic (ROC) curve analysis was employed to evaluate the diagnostic performance of the ALPS index in identifying patients with traumatic chronic cognitive impairment. Compared with the HC group, both the mild-to-moderate TBI patients with and without cognitive impairment had a decreased ALPS index (HC vs. TBI-CI: 1.629 vs. 1.302, P<0.001; HC vs. TBI-CN: 1.629 vs. 1.523, P=0.003). Moreover, the decrease in the ALPS index was more significant in the mild-to-moderate TBI patients with cognitive impairment (TBI-CN vs. TBI-CI: 1.523 vs. 1.302, P<0.001). The adjusted ROC curve analysis revealed that the area under the curve (AUC) of the ALPS index for diagnosing traumatic chronic cognitive impairment was 0.983 [95% confidence interval (CI): 0.953-1, P<0.001], with a sensitivity of 90% and specificity of 95%. Cognitive impairment in patients with mild-to-moderate chronic TBI may be associated with impairment of the glymphatic system. Additionally, the ALPS index may serve as a potential predictor of the disease. Our findings provide some novel insights into the pathophysiological mechanisms underlying cognitive impairment in mild-to-moderate chronic TBI.

The impact of sleep disorders on glymphatic function in Parkinson’s disease using diffusion-tensor MRI

Rationale and ObjectivesTo investigate the impact of sleep disorders on glymphatic system in Parkinson’s disease (PD) using a non-invasive imaging technique called diffusion tensor image analysis along perivascular space (DTI-ALPS). Materials and MethodsA total of 114 PD patients and 54 healthy controls (HCs) underwent sleep questionnaires and MRI examinations as part of data collection from the Parkinson’s Progression Markers Initiative cohort. An automated pipeline was proposed for ALPS calculation to reduce biases from manually region delineation. ALPS indices were compared between PD and HCs, as well as between PD with and without sleep disorders. Correlation was assessed between ALPS index and clinical characteristics. Furthermore, a 2-year follow-up analysis was performed to explore longitudinal impact of sleep disorders on glymphatic function. ResultsPD patients showed significantly decreased ALPS indices compared with HCs (P=0.038). PD patients with sleep disorders showed slightly but not significantly decreased ALPS index compared with those with normal sleep (P=0.058). However, PD patients who transitioned from normal sleep to sleep disorders showed significantly decreased ALPS index at follow-up compared to baseline (P=0.047). In contrast, patients who maintained normal sleep showed no significant difference in ALPS index between follow-up and baseline (P=0.934). In addition, PD patients who transitioned from normal sleep to sleep disorders showed significantly increased ΔMDS-UPDRS Part I score (P=0.004), ΔMDS-UPDRS total score (P=0.040) and ΔSCOPA-AUT (P=0.048) compared with PD who remained normal sleep. ConclusionSleep disorders accelerate dysfunction of glymphatic system as indicated by ALPS index in PD patients, which may be associated with symptom progression in follow-up analysis. Therefore, more attention should be devoted to prevent sleep disorders in early PD.

Decreased Water Diffusivity Along the Perivascular Space in Older Adults With Poor Sleep Quality.

This study included 52 Japanese older adults with Pittsburgh Sleep Quality Index (PSQI) scores > 5 and 52 healthy controls (HCs) with PSQI score ≤ 5. Diffusion-weighted imaging (DWI) and 3D T1-weighted imaging were acquired using 3T magnetic resonance imaging. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated using preprocessed DWI. The choroid plexus volume (CPV) was calculated using FreeSurfer 6.0. The mean ALPS index and CPV were compared between the older adults with poor sleep quality (PSQ) and HCs using a general linear model, adjusted for covariates including age, sex, years of education, total intracranial volume, systolic blood pressure, hemoglobin A1c, and white matter lesion volume. We also conducted a partial correlation analysis between the mean ALPS index and CPV, Montreal Cognitive Assessment (MoCA), and PSQI scores, adjusting for all the mentioned covariates. The PSQ group had a significantly lower mean ALPS index than HCs. The mean ALPS index in the PSQ group was negatively correlated with CPV and positively correlated with the MoCA score. Therefore, older adults with PSQ may experience dysfunction in the excretory pathway of the perivascular space around the medullary veins. This impairment may be associated with an increase in CPV and cognitive dysfunction.

Deep medullary veins integrity and relationships with small vessel disease and interstitial diffusivity measures in patients with a recent small subcortical infarct.

The role of the venous compartment in cerebral small vessel disease has yet to be fully understood. As such, we evaluated how deep medullary veins integrity relates to MRI-based small vessel disease severity markers and glymphatic function assessed by DTI measures in patients with a recent small subcortical infarct. We gathered demographic, clinical, and 3 Tesla-MRI imaging data from 50 patients with a recent small subcortical infarct. We evaluate the venular integrity using two visual scales based on their appearance on SWI. We assessed the number of lacunes and microbleeds, white matter hyperintensities volume, perivascular spaces volume in basal ganglia and white matter, summary-small vessel disease score, and brain volume. Diffusivity measures in normal-appearing white matter included free water fraction, mean diffusivity and fractional anisotropy with and without free water correction, and DTI along the perivascular spaces. After categorizing the cohort in quartiles according to both venular scores, we assessed their correlations with small vessel disease markers and diffusivity measures using multivariable ordinal regression analyses adjusting for age, sex, smoking, and summary small vessel disease score. In univariate analysis most of the imaging variables, except for microbleeds, perivascular spaces in white matter and DTI-along the perivascular spaces, were associated with one or both venular scores. In multivariate analysis (OR, 95% CI), free water (1.33, 1.03-1.73), mean diffusivity (4.56, 1.32-15.81), fractional anisotropy (0.77, 0.63-0.93), free water-corrected mean diffusivity and fractional anisotropy (2.39, 1.06-5.39;0.78, 0.65-0.94, respectively), associated with vein appearance, while only brain volume (0.48, 0.25-0.94), fractional anisotropy with and without free water correction (0.82,0.86-0.99; 0.83, 0.7-0.99, respectively) remained significant for vein count. In patients with a recent small subcortical infarct, disruption of the deep medullary veins, increased extracellular water, and white matter injury appear to be associated. SVD=small vessel disease; DMV=deep medullary veins; WMH=white matter hyperintensities; PVS=perivascular spaces; DTI-ALPS=diffusion tensor image analysis along the perivascular spaces; FW=free water; MD=mean diffusivity; FA= fractional anisotropy; BG=basal ganglia.

Unveiling connections between venous disruption and cerebral small vessel disease using diffusion tensor image analysis along perivascular space (DTI-ALPS): A 7-T MRI study.

Cerebral venous disruption is one of the characteristic findings in cerebral small vessel disease (CSVD), and its disruption may impede perivascular glymphatic drainage. And lower diffusivity along perivascular space (DTI-ALPS) index has been suggested to be with the presence and severity of CSVD. However, the relationships between venous disruption, DTI-ALPS index, and CSVD neuroimaging features remain unclear. To investigate the association between venous integrity and perivascular diffusion activity, and explore the mediating role of DTI-ALPS index between venous disruption and CSVD imaging features. In this cross-sectional study, 31 patients (mean age, 59.0 ± 9.9 years) were prospectively enrolled and underwent 7-T magnetic resonance (MR) imaging. DTI-ALPS index was measured to quantify the perivascular diffusivity. The visibility and continuity of deep medullary veins (DMVs) were evaluated based on a brain region-based visual score on high-resolution susceptibility-weighted imaging. White matter hyperintensity (WMH) and perivascular space (PVS) were assessed using qualitative and quantitative methods. Linear regression and mediation analysis were performed to analyze the relationships among DMV scores, DTI-ALPS index, and CSVD features. The DTI-ALPS index was significantly associated with the parietal DMV score (β = -0.573, p corrected = 0.004). Parietal DMV score was associated with WMH volume (β = 0.463, p corrected = 0.013) and PVS volume in basal ganglia (β = 0.415, p corrected = 0.028). Mediation analyses showed that DTI-ALPS index manifested a full mediating effect on the association between parietal DMV score and WMH (indirect effect = 0.115, Pm = 43.1%), as well as between parietal DMV score and PVS volume in basal ganglia (indirect effect = 0.161, Pm = 42.8%). Cerebral venous disruption is associated with glymphatic activity, and with WMH and PVS volumes. Our results suggest cerebral venous integrity may play a critical role in preserving perivascular glymphatic activity; while disruption of small veins may impair the perivascular diffusivity, thereby contributing to the development of WMH and PVS enlargement.

Enlarged choroid plexus related to atrophy of hippocampal subfield volumes and glymphatic dysfunction in benzodiazepine use disorder.

The aim of this study was to explore the relationship of choroid plexus (CP) volume with hippocampal subregion volume and glymphatic system in patients with benzodiazepine use disorders (BUD). Eighty-four participants were recruited including 23 patients with BUD, 29 patients with chronic insomnia (CI) and 32 healthy controls (HC). The morphological alterations in CP, hippocampal subfield volumes and diffusion tensor image analysis along the perivascular space (DTI-ALPS) index were compared between the three groups and the relationships between CP volume and hippocampal subfield volumes and the glymphatic system were further investigated. Compared with the HC individuals, the CP volumes augmented and hippocampal subfield volumes reduced in patients with BUD (P < .05) but not in patients with CI (P > .05). In patients with BUD, there were extensive relationships between augmented CP volume and decreased hippocampal subfield volumes (P < .05, r = -0.421--0.513). CP volume was negatively related with the DTI-ALPS index (r = -0.582, P = .004) within the BUD group. In patients with BUD, the volume of bilateral cornu ammonis (CA)1 body, molecular layer (ML) body, hippocampal tail, left CA1 head volumes, right dentate gyrus body volumes, and right CA4 body volumes were positively related with the Montreal Cognitive Assessment scores (P < .05, r = 0.422-0.683). Right CA1 and ML body volumes positively related with the Mini-Mental State Examination scores (P < .05, r = 0.503-0.575). The enlarged CP related to atrophy of hippocampal subfield volumes and the glymphatic system dysfunction were shown in BUD patients.

Atrophy-related corticospinal changes in advanced Parkinson's disease are associated with the genetic etiology of the disease

Background Compensatory mechanisms in Parkinson's disease (PD) are thought to explain the temporal delay between the beginning of the neurodegenerative process and the appearance of clinical signs. The enhanced structural integrity of the corticospinal tract was previously suggested as one of these mechanisms. Objective To understand the relations between corticospinal tract integrity and the anatomical, clinical, electrophysiological, and genetic PD characteristics. Methods We analyzed diffusion tensor imaging (DTI) fractional anisotropy (FA) data from 40 genotyped patients with PD (18 without known genetic cause, 11 with LRRK2-PD and 11 with GBA-PD) who were candidates for subthalamic deep brain stimulation (STN-DBS) and from 25 healthy, age-matched, controls. Results PD is associated with higher corticospinal FA values (p &lt; 0.001) that are negatively correlated with the disease duration (p = 0.032), confirming previous results. Higher FA values are negatively correlated with cerebral grey matter volumes (p &lt; 0.001) but not with the motor or cognitive PD characteristics, or with the subthalamic beta-oscillatory activity measured intra-operatively. Increased corticospinal FA values are strongly affected by the genetic etiology of PD, with higher values in the monogenic forms of the disease (p &lt; 0.001). The compensatory index, calculated by dividing the corticostriatal FA value by the cerebral grey matter volume, is highest in GBA-PD (p &lt; 0.001) at the time of evaluation for STN-DBS. Conclusions The genetic etiology of PD strongly shapes corticospinal tract changes along with disease-duration and cerebral grey matter atrophy. The changes may serve as compensatory mechanism.

Evaluating the robustness of DTI-ALPS in clinical context: a meta-analytic parallel on Alzheimer’s and Parkinson’s diseases

In recent years, the glymphatic system has received increasing attention due to its possible implications in biological mechanisms associated with neurodegeneration. In the field of human brain mapping, this led to the development of diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. While this index has been repeatedly used to investigate possible differences between neurodegenerative disorders and healthy controls, a comprehensive evaluation of its stability across multiple measurements and different disorders is still missing. In this study, we perform a Bayesian meta-analysis aiming to assess the consistency of the DTI-ALPS results previously reported for 12 studies on Parkinson’s disease and 11 studies on Alzheimer’s disease. We also evaluated if the measured value of the DTI-ALPS index can quantitatively inform the diagnostic process, allowing disambiguation between these two disorders. Our results, expressed in terms of Bayes’ Factor values, confirmed that the DTI-ALPS index is consistent in measuring the different functioning of the glymphatic system between healthy subjects and patients for both Parkinson’s disease (Log10(BF10) = 30) and Alzheimer’s disease (Log10(BF10) = 10). Moreover, we showed that the DTI-ALPS can be used to compare these two disorders directly, therefore providing a first proof of concept supporting the reliability of taking into consideration this neuroimaging measurement in the diagnostic process. Our study underscores the potential of the DTI-ALPS index in advancing our understanding of neurodegenerative pathologies and enhancing clinical diagnostics.

A Histopathologic Correlation Study Evaluating Glymphatic Function in Brain Tumors by Multiparametric MRI.

This study aimed to elucidate the impact of brain tumors on cerebral edema and glymphatic drainage by leveraging advanced MRI techniques to explore the relationships among tumor characteristics, glymphatic function, and aquaporin-4 (AQP4) expression levels. In a prospective cohort from March 2022 to April 2023, patients with glioblastoma, brain metastases, and aggressive meningiomas, alongside age- and sex-matched healthy controls, underwent 3.0T MRI, including diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index and multiparametric MRI for quantitative brain mapping. Tumor and peritumor tissues were analyzed for AQP4 expression levels via immunofluorescence. Correlations among MRI parameters, glymphatic function (DTI-ALPS index), and AQP4 expression levels were statistically assessed. Among 84 patients (mean age: 55 ± 12 years; 38 males) and 59 controls (mean age: 54 ± 8 years; 23 males), patients with brain tumor exhibited significantly reduced glymphatic function (DTI-ALPS index: 2.315 vs. 2.879; P = 0.001) and increased cerebrospinal fluid volume (201.376 cm³ vs. 115.957 cm³; P = 0.001). A negative correlation was observed between tumor volume and the DTI-ALPS index (r: -0.715, P < 0.001), whereas AQP4 expression levels correlated positively with peritumoral brain edema volume (r: 0.989, P < 0.001) and negatively with proton density in peritumoral brain edema areas (ρ: -0.506, P < 0.001). Our findings highlight the interplay among tumor-induced compression, glymphatic dysfunction, and altered fluid dynamics, demonstrating the utility of DTI-ALPS and multiparametric MRI in understanding the pathophysiology of tumor-related cerebral edema. These insights provide a radiological foundation for further neuro-oncological investigations into the glymphatic system. See related commentary by Surov and Borggrefe, p. 4813.

The Dysregulation of the Glymphatic System in Patients with Psychosis Spectrum Disorders Minimally Exposed to Antipsychotics: La dérégulation du système glymphatique en présence de troubles psychotiques chez des patients peu exposés à des antipsychotiques.

The pathophysiological mechanisms influencing psychosis spectrum disorders are largely unknown. The glymphatic system, which is a brain waste clearance pathway, has recently been implicated in its pathophysiology and has also been shown to be disrupted in various neurodegenerative and vascular diseases. Initial studies examining the glymphatic system in psychosis spectrum disorders have reported disruptions, but the findings have been confounded by medication effects as they included antipsychotic-treated patients. In this study, we used diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as a technique to measure the functionality of the glymphatic system in a sample of antipsychotic-minimally exposed patients with psychosis spectrum disorders and healthy controls. The study included 13 antipsychotic-minimally exposed (2 weeks antipsychotic exposure in the past 3 months/lifetime) patients with psychosis spectrum disorders and 114 healthy controls. We quantified water diffusion metrics along the x-, y-, and z-axes in both projection and association fibres to derive the DTI-ALPS index, a proxy for glymphatic activity. Between-group differences were analyzed using two-way ANCOVA controlling for age and sex. Partial correlations were used to assess the association between the ALPS index and clinical variables. Analyses revealed that antipsychotic-minimally exposed psychosis spectrum disorder patients had a lower DTI-ALPS index value than healthy controls in both hemispheres and the whole brain (all P < 0.005). Significant differences were also observed between the x and y projections/associations between patients and healthy controls (P < 0.001). Furthermore, we did not find any significant correlations (all P > 0.05) between the DTI-ALPS index with age, body mass index, symptomatology, and metabolic parameters. This study shows that the glymphatic system is dysregulated in antipsychotic-minimally exposed patients with psychosis spectrum disorders. Understanding the mechanisms that influence the glymphatic system may help to understand the pathophysiology of psychosis spectrum disorders as proper waste clearance is needed for normal brain functioning.

Glymphatic system dysfunction and risk of clinical milestones in patients with Parkinson disease.

Glymphatic dysfunction may play a significant role in the development of neurodegenerative diseases. We aimed to evaluate the association between glymphatic dysfunction and the risk of malignant event/clinical milestones in Parkinson disease (PD). This study included 236 patients from August 2014 to December 2020. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) index was calculated as an approximate measure of glymphatic function. The primary outcomes were four clinical milestones including recurrent falls, wheelchair dependence, dementia, and placement in residential or nursing home care. The associations of DTI-ALPS with the risk of clinical milestones were examined using multivariate Cox proportional hazards regression models. Then, logistic regression was repeated using clinical variables and DTI-ALPS index individually and in combination of the two to explore the ability to distinguish patients who reached clinical milestones within a 5-year period. A total of 175 PD patients with baseline DTI-ALPS index and follow-up clinical assessments were included. A lower DTI-ALPS was independently associated with increased risk of recurrent falls, wheelchair dependence, and dementia. Additionally, in 103 patients monitored over 5 years, a logistic regression model combining clinical variables and DTI-ALPS index showed better performance for predicting wheelchair dependence within 5 years than a model using clinical variables or DTI-ALPS index alone. Glymphatic dysfunction, as measured by the DTI-ALPS index, was associated with increased risk of clinical milestones in patients with PD. This finding implies that therapy targeting the glymphatic system may serve as a viable strategy for slowing down the progression of PD.

Association of glymphatic system dysfunction with cognitive impairment in temporal lobe epilepsy.

To explore the relationship between glymphatic dysfunction and cognitive impairment in unilateral temporal lobe epilepsy (TLE). This study retrospectively included 38 patients with unilateral TLE and 26 age- and gender-matched healthy controls (HCs). The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index, choroid plexus volume (CPV), and cognitive assessment were obtained for each participant. Neuropsychological test batteries included Montreal Cognitive Assessment (MoCA), Minimum Mental State Examination, Arithmetic Test (AT), Digit Symbol Substitution Test (DSST), Digit Span Test (DST), Boston Naming Test, Block design, Phonological Fluency Test (PFT), and Semantic Verbal Fluency (SVF). Compared to HCs, TLE patients had lower scores of MoCA, AT, DSST, DST, Block design, PFT and SVF (all p < 0.05) and lower values of mean DTI-ALPS index (1.491 ± 0.142 vs. 1.642 ± 0.123, p < 0.001). Significantly lower DTI-ALPS index values were observed in the ipsilateral hemisphere than in the contralateral hemisphere (1.466 ± 0.129 vs. 1.517 ± 0.175, p = 0.013) for patients with unilateral TLE. Correlation analyses found that SVF performance was significantly or borderline significantly associated with glymphatic function (FDR-corrected p < 0.05 for all DTI-ALPS index and FDR-corrected p = 0.057 for CPV) in TLE patients. Linear regression analyses showed that increased CPV and decreased DTI-ALPS index were independent risk factors for semantic fluency impairment (all p < 0.05). Furthermore, mediation analyses found the mediator role of the mean DTI-ALPS index in the relationship between choroid plexus enlargement and semantic fluency impairment (indirect effect: β = -0.182, 95%CI = -0.486 to -0.037). These findings reveal the important role of the DTI-ALPS index and CPV in SVF performance in unilateral TLE. Decreased DTI-ALPS index and increased CPV are the independent risk factors for semantic fluency impairment. The DTI-ALPS index may fully mediate the relationship between CP enlargement and SVF performance. These insights provide a radiological foundation for further investigations into the mechanism of the glymphatic system in TLE pathophysiology.

Choroid plexus enlargement in patients with end-stage renal disease: implications for glymphatic system dysfunction.

The choroid plexus plays a role in eliminating detrimental metabolites from the brain as an integral component of the glymphatic system. This study aimed to investigate alterations in choroid plexus volume in patients with end-stage renal disease (ESRD) compared with healthy controls. We enrolled 40 patients with ESRD and 42 healthy controls. They underwent brain magnetic resonance imaging (MRI), specifically using three dimensional T1-weighted imaging. We analyzed choroid plexus volumes and compared them between patients with ESRD and healthy controls. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated. We compared the DTI-ALPS index between the ESRD patients and healthy controls. Additionally, we evaluated the association between choroid plexus volume and neuropsychological tests results in patients with ESRD. There were significant differences in choroid plexus volumes between patients with ESRD and healthy controls. The choroid plexus volumes in patients with ESRD were higher than those in healthy controls (1.392 vs. 1.138%, p < 0.001). The DTI-ALPS index in patients with ESRD was lower than that in healthy controls (1.470 ± 0.239 vs. 1.641 ± 0.266, p = 0.005). There were no differences in choroid plexus volumes between patients with ESRD, regardless of the presence of cognitive impairment. However, among the neuropsychological tests, the scores for word-list recognition in verbal memory were negatively correlated with the choroid plexus volume (r = -0.428, p = 0.006). We demonstrated a significant enlargement of the choroid plexus volume in patients with ESRD compared to healthy controls. This finding suggests that patients with ESRD have glymphatic system dysfunction, which may be related to cognitive impairment.

Effects of sleep on the glymphatic functioning and multimodal human brain network affecting memory in older adults.

Understanding how sleep affects the glymphatic system and human brain networks is crucial for elucidating the neurophysiological mechanism underpinning aging-related memory declines. We analyzed a multimodal dataset collected through magnetic resonance imaging (MRI) and polysomnographic recording from 72 older adults. A proxy of the glymphatic functioning was obtained from the Diffusion Tensor Image Analysis along the Perivascular Space (DTI-ALPS) index. Structural and functional brain networks were constructed based on MRI data, and coupling between the two networks (SC-FC coupling) was also calculated. Correlation analyses revealed that DTI-ALPS was negatively correlated with sleep quality measures [e.g., Pittsburgh Sleep Quality Index (PSQI) and apnea-hypopnea index]. Regarding human brain networks, DTI-ALPS was associated with the strength of both functional connectivity (FC) and structural connectivity (SC) involving regions such asthe middle temporal gyrus and parahippocampal gyrus, as well as with the SC-FC coupling ofrich-club connections. Furthermore, we found that DTI-ALPS positively mediated the association between sleep quality and rich-club SC-FC coupling. The rich-club SC-FC coupling further mediated the association between DTI-ALPS and memory function in good sleepers but not in poor sleepers. The results suggest a disrupted glymphatic-brain relationship in poor sleepers, which underlies memory decline. Our findings add important evidence that sleep quality affects cognitive health through the underlying neural relationships and the interplay between the glymphatic system and multimodal brain networks.

The association between structural connectivity and anti-seizure medication response in patients with temporal lobe epilepsy.

This study aimed to investigate the differences in structural connectivity and glymphatic system function between patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS) and healthy controls. Additionally, we analyzed the association between structural connectivity, glymphatic system function, and antiseizure medication (ASM) response. We retrospectively enrolled patients with TLE and HS and healthy controls who underwent diffusion tensor imaging at our hospital. We assessed structural connectivity in patients with TLE and HS and healthy controls by calculating network measures using graph theory and evaluated glymphatic system function using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) index. Patients with TLE and HS were categorized into two groups: ASM poor and good responders. We enrolled 55 patients with TLE and HS and 53 healthy controls. Of the 55 patients with TLE and HS, 39 were ASM poor responders, and 16 were ASM good responders. The assortativity coefficient in patients with TLE and HS was higher than that in healthy controls (0.004 vs. -0.007, p = 0.004), and the assortativity coefficient in ASM poor responders was lower than that in ASM good responders (-0.001 vs. -0.197, p = 0.003). The DTI-ALPS index in patients with TLE and HS was lower than that in healthy controls (1.403 vs. 1.709, p < 0.001); however, the DTI-ALPS index did not differ between ASM poor and good responders (1.411 vs. 1.385, p = 0.628). The DTI-ALPS index had a significant negative correlation with age in patients with TLE and HS (r = -0.267, p = 0.049). We confirmed increased assortativity coefficient in structural connectivity and decreased DTI-ALPS index in patients with TLE and HS compared with healthy controls. Additionally, we demonstrated an association between decreased assortativity coefficient in structural connectivity and ASM poor response in patients with TLE patients and HS. This study investigates the relationship between brain connectivity changes and glymphatic system function with antiseizure medication response in patients with temporal lobe epilepsy and hippocampal sclerosis. The research reveals that these patients show altered brain connectivity and glymphatic function compared to healthy individuals. A key finding is the strong link between a specific connectivity measure (assortativity coefficient) and antiseizure medication response, providing valuable insights that could influence epilepsy treatment and future research directions.

Glymphatic System Assessment Using DTI-ALPS in Age-Dependent Neurodegenerative Diseases

Introduction. Dysfunction of the glymphatic system glymphatic system of the brain is considered a pathogenetic factor in some age-dependent neurodegenerative diseases, including Alzheimer's disease (AD), dementia with Lewy bodies (DLB), Parkinson's disease (PD), and normal pressure hydrocephalus (NPH). The innovative method for calculating DTI-ALPS (Diffusion Tensor Image Analysis ALong the Perivascular Space) allows non-invasive assessment of the glymphatic system status using magnetic resonance imaging (MRI). The aim of the study is to compare DTI-ALPS in patients with AD, DLB, PD, and NPH and to evaluate its potential use as a biomarker of the glymphatic system status in these diseases. Materials and methods. The study included 116 subjects: 32 patients with AD, 15 patients with DLB, 31 patients with PD, 11 patients with NPH, and 27 healthy volunteers. Cognitive testing was performed for patients in the main groups using the Montreal Cognitive Assessment (MoCA) score. All subjects underwent diffusion tensor imaging (DTI) of the brain. DTI-ALPS was then calculated. Results. DTI-ALPS index significantly differed across groups (p 0.001). Patients with AD, DLB, and NPH had a significantly lower DTI-ALPS index on both sides compared to the PD group and healthy volunteers (p 0.01). Analysis of the entire sample showed a direct correlation between MoCA score and DTI-ALPS index (p 0.05). Conclusion. This is the first comparison of DTI-ALPS across such a broad range of age-dependent neurodegenerative diseases. Since our DTI-ALPS results were comparable to previously reported data, we believe that this parameter can be used as an indirect marker of the glymphatic system status.

Early Improvement in Interstitial Fluid Flow in Patients With Severe Carotid Stenosis After Angioplasty and Stenting.

This study aimed to investigate early changes in interstitial fluid (ISF) flow in patients with severe carotid stenosis after carotid angioplasty and stenting (CAS). We prospectively recruited participants with carotid stenosis ≥80% undergoing CAS at our institute between October 2019 and March 2023. Magnetic resonance imaging (MRI), including diffusion tensor imaging (DTI), and the Mini-Mental State Examination (MMSE) were performed 3 days before CAS. MRI with DTI and MMSE were conducted within 24 hours and 2 months after CAS, respectively. The diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was calculated from the DTI data to determine the ISF status. Increments were defined as the ratio of the difference between post- and preprocedural values to preprocedural values. In total, 102 participants (age: 67.1±8.9 years; stenosis: 89.5%±5.7%) with longitudinal data were evaluated. The DTI-ALPS index increased after CAS (0.85±0.15; 0.85 [0.22] vs. 0.86±0.14; 0.86 [0.21]; P=0.022), as did the MMSE score (25.9±3.7; 24.0 [4.0] vs. 26.9±3.4; 26.0 [3.0]; P<0.001). Positive correlations between increments in the DTI-ALPS index and MMSE score were found in all patients (rs=0.468; P<0.001). An increased 24-hour post-CAS DTI-ALPS index suggests early improvement in ISF flow efficiency. The positive correlation between the 24-hour DTI-ALPS index and 2-month MMSE score increments suggests that early ISF flow improvement may contribute to long-term cognitive improvement after CAS.

Glymphatic dysfunction in multiple sclerosis and its association with disease pathology and disability.

The role of the glymphatic system in multiple sclerosis (MS)-related disability remains underexplored. Diffusion-tensor image analysis along the perivascular space (DTI-ALPS) offers a non-invasive method to assess glymphatic function. To evaluate glymphatic function in MS patients with lower and higher disability. This study included 118 MS patients who underwent structural, diffusion-weighted imaging, and clinical assessment. The participants were divided into lower (MS-L, n = 57) and higher disability (MS-H, n = 61) subgroups. Brain parenchymal fraction (BPF), lesion load (LL), and DTI-ALPS index were measured. Subgroup differences and correlations between DTI-ALPS index and other measures were explored. Logistic regression was performed to evaluate BPF, LL, and DTI-ALPS index in classifying lower and higher disability patients. Significant differences in DTI-ALPS index between MS-H and MS-L (d = -0.71, false discovery rate-corrected p-value (p-FDR) = 0.001) were found. The DTI-ALPS index correlated significantly with disease duration (rp = -0.29, p-FDR = 0.002) and EDSS (rsp = -0.35, p-FDR = 0.0002). It also showed significant correlations with BPF and LL. DTI-ALPS index and LL were significant predictors of disability subgroup (DTI-ALPS: odds ratio (OR) = 1.77, p = 0.04, LL: OR = 0.94, p = 0.02). Our findings highlight DTI-ALPS index as an imaging biomarker in MS, suggesting the involvement of glymphatic impairment in MS pathology, although further research is needed to elucidate its role in contributing to MS-related disability.