Keywords: Alzheimer's Disease, CEST & MT, Alzheimer's Disease

Motivation: Alzheimer's disease(AD) presents a major public health and economic challenge, necessitating reliable early detection of biomarkers such as tau and beta-amyloid protein accumulation. 

Goal(s): Our primary aim was to establish a standardized neuro CEST MRI pipeline, integrating established neuroimaging tools with CEST processing, and applying it to differentiating cognitively impaired(CI) from normal control(NC).

Approach: A pilot study included nine CI and three NC individuals imaged with a mDixon CEST MRI and processed with a proposed pipeline.

Results: The pipeline effectively reduced erroneous signals in CEST maps and identified significant regional differences between CI and NC(p<0.05).

Impact: The successful implementation of CEST-MRI in AD patients could lead to more timely interventions, guide therapeutic strategies, improve patient outcomes, and decrease the overall cost.

Keywords: Other Neurodegeneration, Degenerative, Multiple system atrophy

Motivation: Functional brain network studies of freezing of gait have been extensive in PD in recent years, but are still lacking in MSA, where the disease deteriorate more rapidly.

Goal(s): Investigate the disrupted topology of functional interactions in MSA-FOG. Extend our knowledge of the neurobiological basis of FOG in MSA.

Approach: We constructed and analysed functional network at global, node and modular levels when compared among MSA patients with and without freezing of gait and matched healthy controls.

Results: The aberrations of visual network, DAN and coupling changes between visual network and cerebellum were found in MSA-FOG compared to MSA-nFOG and HC.

Impact: Different from focusing on pairwise brain regions, our study proved MSA-FOG FC alterations in the visual network and the dorsal attention network as well as coupling pattern changes between visual network the other networks at the large-scale network level.

Keywords: Dementia, Neurodegeneration

Motivation: T1 Magnetization Prepared Rapid Acquisition Gradient Echo (MPRAGE) with compress sensing (CS) offers high-contrast 3D images in a short time compared with standard MPRAGE. To utilize this in daily practice, comparison with existing method is essential.

Goal(s): We investigated agreement of volume data obtained by NeuroQuant and test the possibility of CS-MPRAGE as an alternative method to standard-MPRAGE.

Approach: We included 95 patients who underwent both CS-MPRAGE and standard-MPRAGE and compared the volume data.

Results: CS-MPRAGE yields comparable volumes to standard-MPRAGE for large brain region like the entire cortex. However, small structure such as hippocampus tends to measure smaller with CS-MPRAGE.

Impact: CS-MPRAGE offers high-quality 3D images and reliable volume data in significantly less time than standard-MPRAGE. This eliminates need for patients to remain still for extended periods, overcoming a major obstacle in imaging studies.

Keywords: Other Neurodegeneration, Neurodegeneration

Motivation: The emergence of glymphatic system has provided new insights into the mechanisms of cognitive impairment(CI), and cerebral small vessel disease (CSVD) is one of the most frequently diagnosed diseases impairing cognitive function.

Goal(s): We investigated the relationship among the ALPS index, white/gray matter abnormalities and structural network efficiency in CSVD patients.

Approach: The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS)-index and mediation analysis were performed .

Results: Significant differences in the DTI-ALPS index were found  between the HCs and CSVD_CI groups.  Gray matter reserve and white matter integrity may mediates the relationship between glymphatic dysfunction and structural network efficiency in CSVD.

Impact: Our results showed distinct relationships between glymphatic dysfunction and its related abnormalities, Gray matter reserve and white matter integrity may mediate the relationship between glymphatic dysfunction and structural network efficiency.

Keywords: Other Neurodegeneration, fMRI (resting state)

Motivation: Currently, it has been proposed that the occurrence and development of neurodegenerative diseases such as iNPH (idiopathic normal pressure hydrocephalus) are related to the disorder of cerebral microvascular function, neurovascular uncoupling, and blood-brain barrier dysfunction. 

Goal(s): We aimed to explore the impairment of neurovascular coupling in iNPH using multi-types of CBF-BOLD coupling.

Approach:  In this study, we found that the coupling of spontaneous neural function to the corresponding cerebral blood flow was changed in iNPH. 

Results: The results suggest that neurovascular coupling can provide new clues for further exploring the relationship between brain disfunction and disorder progression and outcome in iNPH.

Impact: The three coupling modes can be used to evaluate the potential mechanism of neurovascular coupling injury in iNPH, which may enhance our comprehension of the mechanism underlying neurovascular coupling injury in iNPH.

Keywords: Other Neurodegeneration, Brain, glymphatic system, chronic insomnia

Motivation: Long-term chronic insomnia is considered to be a high risk factor for dementia,but the relationship between insomnia and glymphatic activity is unclear.

Goal(s): Aim to explore the relationship between the changes of DTI-ALPS index and mental and psychological performance in chronic insomnia patients.

Approach: 20 patients diagnosed with chronic insomnia (CR) and 20 control subjects (HC) , MRI scanning, and DTI-ALPS analysis.

Results: The glymphatic function activity of individuals with chronic insomnia is lower compared to the normal control group, and age independently influences this. There were significant correlation between the DTI-ALPS index, the scores of PSQI and MMSE.

Impact:  Chronic insomnia can cause a decrease in brain glymphatic function, and age is an independent factor that affects glymphatic function. Additionally, sleep quality and neuropsychological performance are also related to changes in glymphatic function.

Keywords: Dementia, Diffusion/other diffusion imaging techniques, dementia, CSF, glymphatic

Motivation: Cerebrospinal fluid (CSF) circulation is crucial for removing waste from the brain, and abnormal CSF motion was associated with neurodegenerative diseases. This study aims to use low b-value diffusion MRI to assess the variance of motion of CSF, i.e., pseudodiffusivity, and investigate its association with cognitive impairment.

Goal(s): To quantify CSF pseudodiffusivity within each sulcus, cistern and ventricle.

Approach: In 93 participants from a memory clinic, Intravoxel incoherent motion (IVIM) MRI was performed to measure CSF pseudodiffusivity. Sulci and cisterns were segmented based on gray matter landmarks.

Results: In the third ventricle, CSF pseudodiffusivity was positively correlated with memory performance.

Impact: Our method of quantifying CSF pseudodiffusivity in different CSF regions in an unbiased, automatic fashion enabled discovery of potential novel non-invasive CSF-based imaging biomarkers of cognitive impairment.

Keywords: Dementia, Neurodegeneration, 3D amplified MRI (aMRI), Neurofluids

Motivation: 3D q-aMRI is a method for visualizing and quantifying the pulsatile brain sub-voxel displacement field. Here, we explore the potential of pulsatile brain motion as a biomarker for classification of common neurodegenerative diseases

Goal(s): To explore the ability of 3D q-aMRI to detect abnormal brain motion in patients with common neurodegenerative diseases

Approach: The 3D q-aMRI outputs in 15 patients with different neurodegenerative diseases such mild cognitive impairment (MCI) due to Alzheimer's disease (AD), lewy body dementia (LBD), dementia due to AD were evaluated, and compared with healthy controls. 

Results: 3D q-aMRI revealed abnormal motion in patients with neurodegenerative diseases. 

Impact: 3D quantitative-amplified MRI is a pulsatile brain motion visualization and quantification method. Exploring pulsatile brain motion as a potential biomarker for neurodegenerative diseases classification is of great importance. 3D q-aMRI revealed abnormal pulsatile brain motion in patients with neurodegenerative diseases.

Keywords: Dementia, Dementia, cerebral small vessel disease, glymphatic system

Motivation: Both cerebral small vessel disease (CSVD) and disfunction of glymphatic system contribute to cognition decline, yet the interactions between them remains unclear.

Goal(s): Identify associations of glymphatic function with cognitive function and CSVD.

Approach: 111 CSVD subjects were involved and underwent 7T MRI scans. CSVD makers, neuropsychological test and clinical characteristics were collected. Linear regression and mediation model were used to access the associations.

Results: Age and CSVD markers were associated with glymphatic function in the multivariable model. The relationship between glymphatic function and cognition was mediated by CSVD burden.

Impact: MRI-derived glymphatic features might be utilized to predict early CSVD-induced cognitive decline.

Keywords: Dementia, Dementia, Serum uric acid; Magnetic resonance imaging; Brain tissue volume; White matter microstructural integrity; Cognitive function

Motivation: The longitudinal effects of changes in serum uric acid (SUA) levels on brain health are largely unknown.

Goal(s): This study aimed to evaluate the longitudinal associations of SUA variance with neuroimaging indices and cognitive function.

Approach: The multivariate-adjusted associations of SUA variance with brain MRI markers and cognitive function were examined using generalized linear models and logistic regression models. Mediation analyses were performed to assess whether brain MRI markers mediate the relationship between SUA variance and cognitive function. 

Results: Changes in SUA concentration, particularly elevated SUA levels damages brain health, manifested as smaller brain tissue volume, impaired microstructural integrity, and poorer cognitive performance. 

Impact: In conclusion, our study findings deepen the comprehension of an integrated relationship between SUA variance and neuroimaging indices of brain health. Long-term prevention of SUA fluctuation is essential for protecting brain health and preventing early-stage dementia.

Keywords: Dementia, Blood vessels, Atherosclerosis, Brain, Pathology, Ex-vivo applications, Hippocampus, Neurodegeneration, Vascular

Motivation: Intracranial atherosclerosis is a common and deleterious age-related neuropathology, however, its association with brain morphometry has not been investigated.

Goal(s): To investigate brain morphometric anomalies associated with intracranial atherosclerosis in a large number of community-based older adults.

Approach: Ex-vivo brain MRI and detailed neuropathologic examination were combined on 891 community-based older adults. Deformation-based morphometry (DBM) was used to investigate the association of intracranial atherosclerosis with brain morphometric characteristics voxel-wise.

Results: Intracranial atherosclerosis was associated with lower volume in the posterior body and tail of the hippocampus in linear regression models controlling for all other neuropathologies.

Impact: Intracranial atherosclerosis is the third age-related neuropathology after Alzheimer’s and limbic-predominant age-related TDP-43 encephalopathy (LATE) that is shown to be independently associated with lower volume of the hippocampus.

Keywords: Dementia, Dementia

Motivation: Brain damage in end-stage renal disease patients with mild cognitive impairment (ESRD-MCI) has not yet been elucidated.

Goal(s): Our goal was to determine the characteristics of alterations in gray matter (GM) structure and the neurobiological mechanisms in ESRD-MCI patients.

Approach: We utilized voxel-based morphology to analyze GM volume alterations in ESRD-MCI patients.

Results: Results demonstrated that MCI in ESRD patients was predominantly impaired in the left middle temporal gyrus, completely mediating the effect of serum phosphorus on MCI.

Impact: Our demonstration of a detectable volume decline in the left middle temporal gyrus utilizing structural MRI provides a quantitative metric to be utilized within clinical therapy trials for intervention of MCI in ESRD patients.

Keywords: Dementia, Neuroscience, volumetry analysis, verbal fluency test

Motivation: To investigate whether there are correlations between regional brain volume and the categorical verbal fluency test (CFT).

Goal(s): While the relationship between CFT and the region of cerebral infarction or brain function has been investigated, it remains uncertain whether they also correlate with local brain volume.

Approach: We used a multiple regression analysis with age, gender, and total brain volume as covariates to examine the relationship between 267 community residents' cortical volume and CFT scores. A 3D high-resolution brain MRI captured the images.

Results: The volume of the left inferior frontal gyrus had a significant correlation with the CFT.

Impact: This result suggests a potential association between brain volume and various neuropsychological impairments. Furthermore, it motivates the exploration of a novel time-based examination of the manifestation of changes in brain metabolism, function, and volume in the context of neuropsychological alterations.

Keywords: Dementia, Alzheimer's Disease, Aging, TAR DNA-binding protein 43, TDP-43, Neurodegeneration, PET, MRI

Motivation: TDP-43, a 43kDa protein in the brain, plays a crucial role in neurodegenerative disorders and is a potential target for clinical trials. Confirmation currently requires an autopsy.

Goal(s): To explore potential antemortem biomarkers for early-stage TDP-43 detection using conventional MRI and ¹⁸F-FDG-PET scans.

Approach: Blinded visual evaluations of MRI and ¹⁸F-FDG-PET scans were performed utilizing specialized rating scales.

Results: TDP-43(+) cases exhibited more medial temporal atrophy on MRI, though influenced by age. Visual inspection of MRI and ¹⁸F-FDG-PET changes could aid early TDP-43 prediction, although further research employing advanced neuroimaging and statistical techniques is essential to identify more robust early-stage TDP-43 neuroimaging biomarkers.

Impact: Predicting TDP-43 status holds substantial diagnostic and clinical significance. TDP-43 could emerge as a promising therapy target in neurodegenerative disorders and a critical consideration in clinical trials. Early-stage TDP-43 prediction offers valuable insights into disease prognosis and progression.

Keywords: Aging, Diffusion Tensor Imaging, Other diffusion models

Motivation: The glymphatic system is presumed to be associated with perivascular space (PVS). 

Goal(s): To identify the relationship between the glymphatic system (ALPS index), PVS, and cerebral white matter hyperintensities (WMH) according to age.

Approach: Participants indicated for brain MRI for cognitive decline (n=611) were retrospectively included. The glymphatic function was assessed by ALPS index calculated from diffusion tensor imaging along the perivascular space (DTI-ALPS). PVS volumes were automatically quantified via deep learning segmentation model. FLAIR WMH were also automatically quantified.

Results: ALPS index showed a significant negative correlation with WMH and PVS in the age group of 50–59. 

Impact: WMH show a negative correlation with ALPS index, indicating poor glymphatic function.  However, only age group of 50–59 shows such relationship. This suggests that aging and enlarged PVS might have diminished glymphatic function as reflected in decreased ALPS index. 

Keywords: Alzheimer's Disease, Aging, cerebrovascular reactivity, BOLD

Motivation: Cerebrovascular disruptions are associated with Alzheimer’s Dementia and can precede cognitive decline; therefore, studying the progression of cerebrovascular dysfunction in healthy aging versus cognitive decline is a promising opportunity for early therapeutic interventions.

Goal(s): In this study, we aimed to determine if there were differences in cerebrovascular health metrics between young and old healthy cohorts.

Approach: Using a novel MR pulse sequence, we quantified cerebrovascular reactivity (CVR), resting state blood-oxygen level dependent signal (BOLD), and cerebral blood flow (CBF) in both cohorts.

Results: We found an age-dependent decrease in CBF and BOLD CVR.

Impact: Age related changes in cerebrovascular health metrics assessed by quantitative MRI methods can help us characterize differences between healthy aging and cognitive decline thus offering unique opportunities for early therapeutic interventions in neurodegenerative diseases like Alzheimer's dementia.