Keywords: Other Neurodegeneration, Neurodegeneration

Motivation: In bilateral glaucoma, visual field loss often spares complementary regions between eyes to optimize residual vision, but the underlying mechanisms are unknown.

Goal(s): Investigate how brain microstructural environment relates to regional visual field loss patterns in glaucoma.

Approach: Advanced diffusion MRI parameters of optic radiation integrity were correlated with glaucomatous visual field loss patterns using partial correlation and archetypal analyses.

Results: Diffusion MRI metrics generally correlated with overall visual field loss. Complementary archetypal loss patterns were also found between eyes when associating pointwise visual field to certain MRI metrics sensitive to axonal/glial integrity and neuroinflammation, suggesting their involvement in influencing residual binocular vision. 

Impact: Advanced neuroimaging combined with computational analysis can provide insights into the brain’s role in influencing preferential damage to maximize retained binocular vision in glaucoma. Diffusion MRI holds promise for assessing glaucoma progression and brain plasticity for guiding vision preservation.

Keywords: Other Neurodegeneration, Neurodegeneration, non-proton; sodium; ALS

Motivation: ALS is a neurodegenerative disease leading to progressive motor deficit and death within few years. There is an unmet need to identify non-invasive biomarkers at the individual level to predict disease progression.

Goal(s): To study disease severity at the individual level in ALS by mapping abnormal sodium homeostasis using brain ²³Na-MRI.

Approach: 27 ALS patients were explored by brain ²³Na-MRI. Individual map of abnormal total sodium concentration (TSC) was computed for each patient compared to a local database of 62 controls.

Results: This study mapping sodium homeostasis disturbances at the individual level in ALS patients evidenced association between TSC increase and disease severity.

Impact: This pilot study mapping sodium homeostasis disturbances at the individual level in ALS patients through 23Na-MRI evidenced association between TSC increase and disease severity and may be a future biomarker to help stratifying patients and evaluating new therapeutics.

Keywords: Dementia, Blood vessels, MRA

Motivation: Current understanding of dolichoectasia has largely been drawn from patients with clinical need for brain imaging in the cross-sectional settings.

Goal(s): To characterize the longitudinal changes in brain MRA geometry vessel metrics and their associations with demographic variables, imaging biomarkers and cognitive performance.

Approach: Basic demographic and clinical information were compared between two groups w/wo MRI metric measurement change using two-sample t-tests. The associations between MRI metrics and cognitive decline or incidence dementia were tested using logistic regression.

Results: MRA geometry vessel metric change was not associated with the cognitive decline over time (3.6-8 years). Baseline cognitive score can predict future cognitive performance. 

Impact: Clinical predictors of worsening dolichoectasia are unknown. Although MRA geometry vessel metric changes are not significant with cognitive decline, demographic variables show significance on some metric difference. Baseline cognitive score can also predict cognitive change.

Keywords: Other Neurodegeneration, Aging, LATE-NC, TDP-43, Neuropathology, Aging, Postmortem MRI

Motivation: The association of limbic-predominant age-related TDP-43 encephalopathy neuropathological change (LATE-NC) with brain morphometry has not been thoroughly investigated.

Goal(s): To investigate gray and white matter morphometric abnormalities in LATE-NC in a large number of community-based older adults.

Approach: This study combined deformation-based morphometry (DBM) in ex-vivo brain MRI and detailed neuropathological data on the same community-based older adults (N=897), and investigated the association of LATE-NC with brain morphometric characteristics using voxel-wise linear regression models.

Results: LATE-NC was associated with lower volume in gray and white matter areas of temporal and frontal lobes and basal ganglia, consistent with the known pathological distribution of LATE-NC.

Impact: The pattern of morphometric abnormality in LATE-NC that was generated in the present work may potentially be used in combination with other imaging and clinical information towards the development of a marker of this devastating neuropathology.

Keywords: Other Neurodegeneration, Aging, LATE, Alzheimer’s, Neuropathology, Aging, Postmortem MRI

Motivation: Alzheimer’s disease neuropathologic change (AD-NC) and limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC) are common age-related pathologies and are associated with brain atrophy, especially in the medial temporal lobe. However, the difference in atrophy patterns associated with the two pathologies is not well known.

Goal(s): To investigate the difference in brain atrophy patterns associated with AD-NC and LATE-NC.

Approach: Ex-vivo MRI and detailed neuropathology were combined in a large number of community-based older adults that came to autopsy.

Results: LATE-NC stages 2 or 3 are associated with more atrophy in the anterior portion of the hippocampus compared to moderate or severe AD-NC.

Impact: Atrophy in the anterior portion of the hippocampus is more severe with LATE-NC stages 2 or 3 than with moderate or severe AD-NC.

Keywords: Other Neurodegeneration, Neurodegeneration, Wilson's disease; 7T MRI; biomarker; metal deposition pattern

Motivation: Excessive subcortical metal deposition seen on susceptibility imaging has suggested a characteristic pattern in neurological Wilson’s disease (NWD).

Goal(s): To develop a novel imaging biomarker of NWD using 7T SWI.

Approach: WD patients, monoallelic ATP7B variant carriers, health controls, and patients with comparable clinical or imaging manifestations were recruited for development of a novel biomarker of NWD and  exploratory comparative analysis. All underwent 7T SWI with quantitative susceptibility mapping and principal component analysis performed.

Results: The novel biomarker of NWD termed "hyperintense globus pallidus rim sign" showed high diagnostic accuracy. It revealed a special metal deposition pattern in the lenticular nucleus in NWD.

Impact: A novel imaging biomarker of neurological Wilson’s disease (NWD) termed "hyperintense globus pallidus rim sign" could aid the diagnosis and monitoring of NWD.

Keywords: Dementia, Alzheimer's Disease, Biomarker's, Novel contrast mechanisms

Motivation: Magnetic resonance elastography (MRE) is typically used to assess shear mechanical properties of a tissue. A new measure related to the compressibility of a tissue could provide new insights into disease processes.

Goal(s): To test a new measure related to the tissue compressibility in application to neurological disorders.

Approach: A measure of compressibility was defined as the ratio of the magnitude of the divergence over the magnitude of the curl of displacements.

Results: Normal pressure hydrocephalus and Alzheimer’s disease displayed distinct patterns of compressibility measure compared to the control group.

Impact: An MRE-based compressibility measure demonstrates unique patterns in normal pressure hydrocephalus and Alzheimer’s disease. This may provide new insights into disease processes and guides future research.  

Keywords: Other Neurodegeneration, Quantitative Susceptibility mapping, Myotonic Dystrophy type 1

Motivation: QSM is a valuable tool for investigating neurodegenerative conditions, including DM1, a genetic multisystem disorder affecting the central nervous system. 

Goal(s): The objective of this research is to identify biomarkers of clinical impairment by exploring magnetic susceptibility in sub-cortical areas of DM1 brains. 

Approach: We developed an automated pipeline for segmenting various structures and their sub-units. DM1 susceptibility values were compared to healthy controls and correlated with clinical and laboratory data. 

Results: Thalamus and brainstem were identified as key structures, showing increased iron concentration and correlation with disability and polysomnography scores, contributing to a comprehensive understanding of DM1 and its symptomathology. 

Impact: Examining iron accumulation in sub-cortical structures through QSM contributes to a complete understanding of DM1 as a neurodegenerative disorder.  Thalamus and brainstem, crucial in autonomic functions, exhibit alterations and correlations with clinical measurements, suggesting central origins of DM1 symptomatology.

Keywords: Dementia, Blood vessels, MRA

Motivation: We aimed to address the gap in understanding the neurovascular contributions to dementia risk in a US community-based study, recognizing the need to consider arterial geometry factors and cerebral small vessel disease (CSVD).

Goal(s): Our study sought to investigate the relationship between brain arterial remodeling and incident dementia risk, focusing on how arterial geometry and CSVD factor into this complex equation.

Approach: Our approaches involved analyzing data from a US community-based study to assess the impact of arterial remodeling, arterial geometry, and CSVD on dementia risk.

Results: Our study's core findings indicate an increased risk of incident dementia associated with brain arterial remodeling.

Impact: Our model is promising for the prediction of cognitive decline and dementia diagnosis based on the MRA measurements.

Keywords: Neurofluids, Alzheimer's Disease

Motivation: Beta-amyloid (Aβ) in Alzheimer’s disease (AD) is caused by decreased glymphatic clearance function. As the main source of CSF in glymphatic system, the mechanism of CSF dynamic in ventricle system is of great importance.

Goal(s): Use dynamic ¹⁸F-MK-6240 PET and PC-MRI to study the relationship of CSF clearance in lateral ventricle (LV) and aqueduct.

Approach: CSF turnover rate in LV is derived from dynamic 18F-MK-6240 PET. Aqueduct parameters were calculated using PC-MRI data. Linear regression analysis was performed between PET and PC-MRI measurements.

Results: The CSF clearance measurements from both PET and MRI are consistent and show diagnostic group difference. 

Impact: ¹⁸F-MK-6240 PET derived CSF turnover rate and phase-contrast MRI produced aqueduct CSF measurements are highly correlated. The data reveals diagnostic group difference after controlling for age and sex, indicating that the decreased CSF clearance is associated with Alzheimer’s disease.