Keywords: Alzheimer's Disease, Alzheimer's Disease, Cognition

Motivation: Glymphatic function, which eliminates soluble proteins from the brain, is positively associated with cognitive function for patients with Alzheimer’s disease (AD).

Goal(s): To analyze whether the associations between glymphatic function and cognitive function were mediated by regional cortical thickness (CTh) for patients with AD. 

Approach: Mediator analysis was conducted to explore the ALPS index as a predictor, regional CThs as mediators, and cognitive test scores as outcomes.

Results: Mediation analysis showed that regional CTh was a significant mediator between ALPS index and executive function.

Impact: CTh is a key mediator between impaired glymphatic function and cognitive decline. Our findings provide insights regarding associations between decreased glymphatic function and cognitive decline in patients with AD.

Keywords: Neurofluids, Brain, neurofluids

Motivation: While changes of neurofluid dynamic has been observed in CSVD, the potential inter-correlations between them are still unclear.

Goal(s): Our goal was to demonstrate the potential interactive dynamics of neurofluids including the parenchyma perfusion, the glymphatic pathway, and the intracranial CSF in CSVD patients.

Approach: Parenchyma perfusion was assessed with pASL, glymphatic dynamics was assessed with DTI- ALPS, and CSF volume of ventricles was also quantified.

Results: The interactive dynamics of neurofluids of CSVD patients is significantly altered compared with that of normal elderly.

Impact: Disruption of neurofluid dynamics may play an important role in the pathophysiology of CSVD.

Keywords: Alzheimer's Disease, Alzheimer's Disease

Motivation: Glymphatic clearance of toxic proteins, quantified by the “DTI-along-the-perivascular-space” (ALPS) index, is impaired in Alzheimer’s disease (AD)  

Goal(s): We tested the association of the ALPS index to CSF Aβ and tau.

Approach: We used imaging, CSF biomarker, and neuropsychological assessment data from 12 MCI, 21 AD, and 11 other dementia patients. We generated color FA maps and ALPS ROIs, before testing the interaction effects of ALPS × group on each CSF biomarker measure. 

Results: In our sample of AD and mild cognitive impairment patients (n=44), we found significant positive association of CSF tau and phosphorylated tau (but not amyloid-β) with the ALPS index.

Impact: Our study establishes a novel link between brain glymphatic function and CSF phosphorylated tau in AD via the ALPS index.

Keywords: Tumors (Pre-Treatment), Diffusion Tensor Imaging

Motivation: Malignant tumors always metastasize along the blood or meningeal infiltration. We hope to evaluate CSF and blood changes in brain metastases patients through a simple and effective method.

Goal(s): To investigate glymphatic system and inflammation alteration in patients with brain metastases.

Approach: We combined DTI-ALPS and NLR to analyze the differences between healthy controls and patients with brain metastases.

Results: Compared with HCs, the mean ALPS index of patients with brain metastases was significantly decreased, and the NLR was significantly increased.

Impact: ALPS-index and NLR can provide a new perspective for potential assessment of how brain metastasis affects the glymphatic system and inflammatory immune system, and may also support more relevant treatments for patients.

Keywords: White Matter, Diffusion Tensor Imaging

Motivation: The glymphatic function has not yet been explored in non-dialysis,HD and PD patients with ESRD.

Goal(s): Our goal was to explore the pattern of glymphatic function in ESRD patients and its relationship with cognitive decline.

Approach: Diffusion tensor imaging along the perivascular space (DTI-ALPS) index methods was used to investigating brain glymphatic dysfunction in ESRD patients with non-dialysis, HD and PD patients using. The relationship between Montreal Cognitive Assessment (MoCA) and changes in DTI-ALPS index was measured.

Results: Compared with HD and PD, ESRD patients with non-dialysis showed lower DTI-ALPS index.Changed DTI-ALPS index associated with cognitive decline in ESRD patients with non-dialysis.

Impact: Our findings reveal a greater degree of aberrant glymphatic functionality in ESRD patients with non-dialysis than HD and PD, which may offer new insights to the effectiveness of dialysis treatment.

Keywords: Neurofluids, Neurofluids, glymphatics, DTI-ALPS

Motivation: Several parameters affect diffusion tensor imaging along the perivascular spaces (DTI-ALPS) index calculation. However, the impact of ROI size, shape, and relative orientation to the lateral ventricle remains unclear, potentially hindering cross-study comparability.

Goal(s): To investigate the influence of ROI characteristics in estimating the DTI-ALPS index.

Approach: Differences in DTI-ALPS index and correlations among 8 ROI types (size, shape, and orientation) were investigated.

Results: DTI-ALPS index calculation depends on ROI size, shape, and orientation. Single-voxel and parallel rectangular ROIs exhibit strong agreement; parallel-parallel and orthogonal-orthogonal ROIs show excellent correlation. However, larger, rectangular ROIs with orthogonal placement result in significant differences and poor correlation.

Impact: Our analysis shows that ROI size, shape, and relative orientation to the lateral ventricle impact DTI-ALPS index calculation. Therefore, in addition to imaging parameters, ROI characteristics also need to be considered for comparison among studies.

Keywords: Dementia, Diffusion Tensor Imaging

Motivation: Cognitive reserve (CR) could moderate the cognitive decline. But the association between the glymphatic function and CR in mild cognitive impairment (MCI) remains unclear.

Goal(s): To evaluate the association between CR and glymphatic function. 

Approach: By using diffusion tensor imaging along the perivascular space (DTI-ALPS) to acquire an index (ALPS-index) in MCI and normal controls (NCs). The education level was used as a representation of CR. We used mediator analysis to explore the association among ALPS-index, CR and cognitive function.

Results: MCI exhibited decreased glymphatic activity than NCs and CR mediates the link between the glymphatic system and cognition.

Impact: MCI patients exhibited decreased glymphatic activity compared to NCs. Our study confirms the protective effect of CR in MCI patients, and this protective effect can against the cognitive impairment by improving CR. 

Keywords: Other Neurodegeneration, Diffusion Tensor Imaging, sleep, narcolepsy, glymphatic system

Motivation: The glymphatic system plays an important role in sleep. However, it’s unknown if the glymphatic system was impaired in narcolepsy type1 (NT1) patients.

Goal(s): Investigate if the glymphatic system was impaired and the correlation between dysfunction of glymphatic system and clinical symptom.

Approach: 31 NT1 and 23 healthy controls (HC) were enrolled. DTI-ALPS was used to assess the function of glymphatic system and compared between NT1 and HC. The correlation between DTI-ALPS index and clinical symptom was analyzed.

Results: The DTI-ALPS index was significantly lower in NT1 than in HC and was significantly correlated with the percentage of N3 stage sleep in NT1.

Impact: We firstly reported the dysfunction of glymphatic system in narcolepsy type1 patients and its correlation with clinical symptom. Our study suggested the glymphatic system should be taken into consideration for the treatment of narcolepsy type1 patients.

Keywords: Parkinson's Disease, Parkinson's Disease, Glymphatic Function, Peripheral Inflammation, DTI-ALPS

Motivation: The association between glymphatic system and peripheral inflammation has not been well studied.

Goal(s): Our study aimed to explore the relationship between glymphatic system and peripheral inflammation in PD patients and PD subtypes, and their link to motor symptoms.

Approach: We used DTI to calculate the DTI-ALPS index, a non-invasive measure of glymphatic function, and evaluated the association between the DTI-ALPS index and clinical parameters using multiple linear regression.

Results:  Our study revealed a correlation between peripheral inflammation and glymphatic dysfunction in PD, particularly in TD subtype. Furthermore, the association between peripheral inflammation and clinical severity was observed in PD and PIGD patients.

Impact: This study provides new insights into the pathophysiology of PD and potential therapeutic options.

Keywords: Parkinson's Disease, Parkinson's Disease, Glymphatic dysfunction, Motor symptoms, Imaging biomarkers

Motivation: Growing evidence has shown that glymphatic dysfunction is closely linked to Parkinson’s disease(PD), yet its imaging in glymphatic system with motor symptoms remains unclear.

Goal(s): Using three different imaging metrics to validate the association of the glymphatic system with motor symptoms before and after administration of exogenous levodopa, and levodopa responsiveness  in PD.

Approach: The calculation of DTI-ALPS index, the automated quantification of PVSs of basal ganglia region (BG-PVSs) and choroid plexus volume (CPV) based on MRI. 

Results: When DTI-ALPS index decreases and BG-PVSs and CPV increase, motor symptom gets worsen and levodopa effectiveness diminishes. Significant linear correlations were observed (CPV-DTI-ALPS, CPV-PVSs, DTI-ALPS-PVSs).

Impact: This study employed three distinct imaging metrics (DTI-ALPS index, automated PVSs quantification, and CPV) to provide a more comprehensive characterization of the glymphatic system, affirming a correlation between glymphatic dysfunction and motor symptoms in Parkinson's patients.

Keywords: Epilepsy, Diffusion/other diffusion imaging techniques

Motivation:  Self-limited epilepsy with centrotemporal spikes (SLECTS) is the most prevalent type of idiopathic childhood epilepsy. However, the underlying pathophysiologic mechanisms of SLECTS is largely unknown. 

Goal(s): Studies on the glymphatic system function in SLECTS patients may contribute to better understanding of the associated mechanisms.

Approach: Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) was used to evaluate the glymphatic system function. 

Results: The SLECTS patients exhibited altered DTI-ALPS index. Altered DTI-ALPS index were more severe in ipsilateral than in the contralateral hemisphere. Moreover, RSLECTS (Right SLECTS ) and LSLECTS (Left SLECTS) patients exhibited different change patterns of the glymphatic system.

Impact: This study indicating that the glymphatic system may be a separate system in the left and right hemispheres. Patients with RSLECTS and LSLECTS exhibited different pattern of glymphatic system changes. Our research may contribute to elucidating the pathophysiologic of SLECTS.  

Keywords: Structural Connectivity, Diffusion/other diffusion imaging techniques, ALPS; GABA; hepatic encephalopathy

Motivation: Hepatic encephalopathy (HE) is a severe complication of decompensated cirrhosis. Understanding the pathogenesis is crucial for developing effective treatments and improving outcomes.

Goal(s): This study delved into the HE pathogenesis by employing diffusion tensor imaging analysis focused on the perivascular space (DTI-ALPS), alongside the quantification of GABA levels in the thalamus of patients with cirrhosis.

Approach: 48 patients with decompensated cirrhosis were enrolled, with all of them undergoing DTI and MRS assessments.

Results: We found that patients with HE exhibited impaired glymphatic system function and increased levels of the inhibitory neurotransmitter GABA in the thalamus, with a noteworthy correlation found between them.

Impact: The discovery of decreased glymphatic system activity and increased GABA levels may hold significant promise in understanding the potential mechanisms behind HE patients. These findings could contribute to the development of targeted therapies for HE and improve patient care and outcomes.

Keywords: White Matter, Inflammation, Inflammatory Bowel Disease

Motivation: The mechanisms underlying brain structural changes and its relationship with neuropsychological symptoms in inflammatory bowel disease (IBD) remain unclear.

Goal(s): To explore the relationship between the function of the glymphatic system, changes in white matter microstructure, and clinical symptoms in patients with IBD.

Approach: Diffusion along perivascular spaces (DTI-ALPS) and tract-based spatial statistics (TBSS) techniques were used.

Results: The observed alterations in white matter microstructure and decreased clearance rate of the glymphatic system in IBD may be an external manifestation of neuroinflammation. These abnormalities are related to sleep disorders and pain in IBD patients.

Impact: Neuroinflammation is known to have adverse effects on glymphatic flow. The changes in diffusion MRI indicators suggest glymphatic dysfunction in IBD. Chronic visceral pain reduces the diffusion rate. The changes in diffusion MRI indicators are associated with poor cognitive performance.

Keywords: Neurofluids, Diffusion Tensor Imaging, glymphatic system, cerebral small vessel disease (cSVD), vascular cognitive impairment and dementia (VCID))

Motivation: To test the validity of the ALPS index as a biomarker for VCID

Goal(s): To test our hypothesis that ALPS index is an independent biomarker for the cognitive decline in cSVD.

Approach: Participants from MarkVCID consortium underwent baseline and follow-up MRI examinations and clinical evaluations of cognitive function

Results: We found the baseline ALPS index was correlated with the existing biomarkers of cSVD and VCID, and was independently associated with the baseline cognitive performance

Impact: Our study provides the clinical validation of the ALPS index as a sensitive and independent biomarker for the cognitive function of cSVD related VCID.

Keywords: Neurofluids, Psychiatric Disorders, Glymphatic system

Motivation: Our previous study revealed abnormalities in aquaporin 4, which works at the cerebrospinal–interstitial fluid exchange in the postmortem brains of patients with bipolar disorder (BP). However, glymphatic system (GS) alterations in BP are still unclear.

Goal(s): This study aims to assess GS function in BP patients.

Approach: We used diffusion tensor image analysis along the perivascular space (DTI–ALPS) method in BP subjects and healthy controls (HCs).

Results: The ALPS index of BP subjects was significantly lower than that of HCs. We also found associations between the ALPS index and BP risk. Thus, per our findings, BP patients could have GS dysfunction.

Impact: This study suggests the potential for GS dysfunction in BP patients. Our findings could support the fact that BP patients are more likely to experience dementia since they have an Alzheimer’s disease-like pathology that causes amyloid β accumulation.

Keywords: Vessels, Diffusion/other diffusion imaging techniques, MUSE, PROPELLER, Meningeal lymphatics vessels

Motivation: Is it possible to water diffusion be measured in meningeal lymphatic vessels (MLVs)?

Goal(s): Diffusion-weighted MRI is employed to assess the circulatory condition of MLVs, eliminating the need for MRI with contrast agent administration, which typically requires monitoring for over 4 hours.

Approach: Water diffusion measurements in MLVs were conducted using MUSE DWI and PROPELLER DWI, which offer low image distortion and high resolution.

Results: Our results indicate that MLVs were clearly visible on high spatial resolution DWI and ADC maps, and the ADC values of MLVs are higher than those of GM and WM but lower than CSF.

Impact: Since evaluating the circulatory condition of meningeal lymphatic vessels takes over 4 hours by contrast agent injection, our study investigates the feasibility of assessing the ADC of meningeal lymphatic vessels using high-resolution MUSE DWI and PROPELLER DWI.