Faculty Bibliography

PURPOSE/OBJECTIVE:Water-extraction-with-phase-contrast-arterial-spin-tagging (WEPCAST) MRI is a non-contrast method to estimate the blood-brain barrier (BBB) permeability to water. Similar to other arterial-spin-labeling (ASL) based techniques, signal-to-noise ratio is a limitation. This study aims to enhance its reliability via theoretical and experimental improvements. METHODS:scan and investigating its benefit in reducing inter-subject variations. RESULTS:(p = 0.004). VTT estimated from WEPCAST was consistent with that measured with a dedicated sequence (R = 0.757, p = 0.011). CONCLUSION/CONCLUSIONS:.

The choroid plexus (ChP), a highly vascularized epithelial organ within the brain ventricles, sustains cerebrospinal fluid (CSF) production, regulates the blood-CSF barrier (BCSFB), and coordinates neuroimmune responses. Beyond these classical roles, the ChP is increasingly recognized as an active interface within brain clearance pathways, facilitating CSF-interstitial fluid (ISF) exchange and contributing to metabolic waste removal. Structural and functional disruption of the ChP/BCSFB accompanies aging and has been linked to the pathogenesis of neurodegenerative disorders. Magnetic resonance imaging (MRI) provides a powerful, non-invasive platform for in vivo characterization of the ChP. This review summarizes recent advances in MRI techniques tailored to ChP imaging, including quantitative assessments of microstructure, perfusion, permeability, and dynamic water exchange, and highlights their applications in aging and dementia. Converging evidence suggests that MRI-derived indices of ChP integrity are associated with cognitive status and may facilitate early detection and longitudinal monitoring of disease trajectories, particularly in Alzheimer's disease and related dementias (AD/ADRD). Continued development and application of advanced MRI approaches will be essential for further elucidating the role of the ChP in neurodegeneration and for evaluating its potential clinical utility.

INTRODUCTION/BACKGROUND:Though brain fog is common in Long-coronavirus disease 2019 (Long-COVID), the incidence of mild cognitive impairment (MCI) is unknown. METHODS:In an observational cohort study, recovered COVID-positive, Long-COVID, and COVID-negative subjects underwent blinded evaluation using National Alzheimer's Coordinating Center (NACC) and National Institute on Aging (NIA) -Alzheimer's Association diagnostic criteria for dementia and MCI. The cumulative incidence of MCI was calculated for each group, and the hazard of MCI was compared between groups. RESULTS:Among 260 subjects, the cumulative incidence of MCI over 4.4 years was higher with Long-COVID (27%) versus recovered-COVID (5%) or COVID-negative status (1%). There was a higher hazard of MCI for patients with Long-COVID compared to those without (hazard ratio [HR] 3.93, 95% confidence interval [CI] 1.86-8.31, p < 0.001), and specifically for the Alzheimer's disease (AD) -related MCI subtype (HR 3.20, 95% confidence interval [CI] 1.14-9.00, p = 0.027). DISCUSSION/CONCLUSIONS:The cumulative incidence and adjusted hazard of MCI (and specifically AD-related MCI) at 4.4 years was significantly higher among Long-COVID patients compared to recovered-COVID and COVID-negative controls.

PURPOSE/OBJECTIVE:The human brain contains multiple fluid types, including blood, cerebrospinal fluid (CSF), and tissue water. While intravoxel incoherent motion (IVIM) imaging has been used to examine microvascular perfusion, evidence on incoherent flows of CSF is emerging. This study aims to develop in vivo multidimensional MRI methods to investigate potential contributions of CSF in the IVIM regime. METHOD/METHODS:selective IVIM protocols were developed to map incoherent CSF flows in the human brains. RESULTS:-D MRI detected incoherent CSF flow in the brain subarachnoid space. Results from four different relaxation selective IVIM methods further support incoherent CSF flows in these regions. CONCLUSION/CONCLUSIONS:-D MRI within the low b-value regime to probe the heterogeneity of IVIM flow components. Designed based on the 2D MRI spectra, relaxation selective 1D IVIM acquisition can be obtained within clinically feasible time frame.

INTRODUCTION/BACKGROUND:Choroid plexus (ChP) enlargement is a neuroimaging biomarker of neuroinflammation and neurodegeneration. However, evidence of ChP structural and perfusion alterations in long coronavirus disease (COVID) and their clinical relevance remains limited. METHODS:This study included 86 long COVID, 67 recovered COVID, and 26 COVID-negative healthy controls (HCs). ChP volume and cerebral blood flow (CBF) were quantified, and their associations with Alzheimer's disease (AD) symptoms and plasma biomarkers were examined. RESULTS:Both patient groups showed higher ChP volume and lower CBF than HC. Relative to recovered COVID, long COVID patients had a larger ChP volume, but no significant difference in CBF. ChP volume correlated positively with glial fibrillary acidic protein (r = 0.35) and phosphorylated tau217 (p-tau217; r = 0.54), while CBF correlated negatively with p-tau217 (r = -0.56). Both ChP volume and CBF were associated with cognitive decline measured with Mini-Mental State Examination and Clinical Dementia Rating. DISCUSSION/CONCLUSIONS:These findings suggest that ChP differences in long COVID are associated with AD-related cognitive decline and increased plasma biomarkers. HIGHLIGHTS/CONCLUSIONS:Long coronavirus disease (COVID) patients show choroid plexus (ChP) enlargement and reduced cerebral blood flow. ChP alterations are associated with Alzheimer's disease (AD)-related symptoms and plasma biomarker changes. ChP alterations on magnetic resonance imaging may serve as imaging markers for tracking neurological symptoms and AD-related pathology in post-COVID patients.

BACKGROUND:Choroid plexus (ChP) is responsible for producing cerebrospinal fluid, which is increasingly recognized as important in the context of aging and Alzheimer’ disease (AD). However, structural alteration (especially cystic alteration) of ChP across the pathologically confirmed AD continuum remains unclear. MATERIALS AND METHODS:All data used in this study were drawn from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. Aβ and Tau PET were utilized to define the pathologically confirmed AD continuum. The number of ChP cysts on each side were counted and the largest cyst was delineated by experienced neuroradiologist using 3D T2-FLAIR images. The number of ChP cysts was further divided into four grades on each side according to the number of cysts (grade 0 = none, grade 1 = 1–5, grade 2 = 6–10, grade 3 > 10). Then, the ChP cysts rating and the largest cyst volume were compared among subjects across the pathologically confirmed AD continuum. Moreover, correlation analyses were conducted to assess the associations of cystic alteration of ChP with pathological biomarkers, and cognitive performance. RESULTS: < 0.05). DISCUSSION:In addition to volume change, cystic alteration of the ChP may serve as a valuable neuroimaging biomarker for early diagnosing and disease progression monitoring on AD continuum. CLINICAL TRIAL REGISTRATION:Not applicable. SUPPLEMENTARY INFORMATION:The online version contains supplementary material available at 10.1186/s12987-025-00729-7.

BACKGROUND:There is paucity of data on long-term functional and cognitive outcomes after COVID-19 compared to COVID-negative controls. METHODS:We conducted an observational cohort study of patients ≥ 1 year after COVID-19 compared to contemporaneous COVID-19 negative controls (SARS-CoV-2 nucleocapsid IgG negative with no history of COVID-19). Functional (modified Rankin Scale [mRS], Barthel Index), cognitive (telephone MoCA [t-MoCA]), and patient-reported neuropsychiatric symptoms were compared between groups using multivariable logistic regression analysis. In a subgroup of COVID-19 patients who were followed longitudinally, trajectories of recovery were assessed using the paired samples Sign test. RESULTS:Of 145 participants, N = 115 COVID-19 patients (median age 62, 51 % female, 33 % hospitalized for COVID-19, median 2.9 years from index infection), and N = 30 non-COVID-19 controls (median age 75, 70 % female) were enrolled. Neuropsychiatric symptoms were reported in 76 % of COVID-19 patients versus 7 % of controls (aOR 15.0, 95 %CI 3.09-72.47, P < 0.001). Abnormal mRS> 0 occurred in 42 % of COVID-19 patients compared to 11 % of controls (P = 0.002). However, this difference was not significant after adjusting for age, sex, COVID-19 hospitalization and history of mood disorder (aOR 2.10, 95 %CI 0.52-8.51). Rates of abnormal t-MoCA≤ 18 (40 % of COVID-19 versus 41 % of controls, P = 1.00) and Barthel scores< 100 (19 % of COVID-19 versus 14 % in controls, P = 0.785) were similar. Among N = 26 COVID-19 patients with repeated measures, mRS significantly improved between 6-months to 3-years post-COVID (+1.3 points, p = 0.004), while no changes were observed in t-MoCA or Barthel. CONCLUSIONS:Three years after COVID-19, neuropsychiatric symptoms were significantly more frequent compared to controls, however no differences in functional or cognitive status were detected.

While hippocampal atrophy in Alzheimer's disease is well-documented, research on microstructural integrity of hippocampal pathways to selected cortical regions in healthy aging populations remains limited. Four hundred seventy-five healthy individuals aged 36-90 from the Human Connectome Project Aging (HCP-A) dataset were analyzed. Hippocampal fiber pathways, including the "Papez," "Prefrontal," "Occipital," and "Parietal" pathways, were extracted from whole-brain tractography and characterized by fractional anisotropy (FA) and mean diffusivity (MD), neurite density index (NDI), and orientation distribution index (ODI). Partial linear and quadratic nonlinear correlation analyses were conducted to examine the relationship between age, cognition, and diffusion metrics, adjusted by hippocampus volumes. While FA, MD, and ODI demonstrated linear age-related changes, NDI exhibited a quadratic pattern. MD was identified as the most age-sensitive parameter. Among all pathways, the "Prefrontal" pathway showed the most pronounced microstructural changes in both males and females, characterized by reduced FA and NDI and increased MD and ODI with age (FA: r = -0.31 to -0.40; NDI: r² = 0.30-0.31; MD/ODI: r = 0.23-0.48; p < 0.01). Similar changes were observed in the "Occipital" pathway (FA: r = -0.28 to -0.39; MD/ODI: r = 0.32-0.50; p < 0.01), with NDI reduction present only in females (r² = 0.18, p < 0.01). In the "Parietal" pathway, changes were detected only in females, with lower FA (r = -0.29, p < 0.01) and higher ODI (r = 0.24, p < 0.01). Additionally, age-related cognitive decline was significantly associated with microstructural changes in the "Occipital" (FA: r = 0.29; MD: r = -0.28; ODI: r = -0.25; p < 0.001) and "Prefrontal" pathways (FA: r = 0.27; MD: r = -0.25; NDI: r = 0.25; ODI: r = -0.22; p < 0.01) in females. This study revealed age- and cognition-related changes in hippocampal pathways across the adult lifespan. These findings provide normative references for hippocampal-cortical connectivity changes associated with healthy aging and its potential relevance to Alzheimer's disease and related dementias.

The choroid plexus (ChP) is critical to the glymphatic system of the human brain through its primary function as the source of cerebrospinal fluid (CSF) production, which plays an important role in brain waste clearance. Developing noninvasive imaging techniques to assess ChP is crucial for studying its function and age-related neurofluid dynamics. In this study, we developed a relaxation-selective intravoxel incoherent motion (IVIM) technique to assess tissue and fluid compartments in the ChP of 83 middle-aged to elderly participants (age: 61.5 ± 17.1 years) and 15 young controls (age: 30.7 ± 2.9 years). Using a 3-T MRI scanner, we implemented T1- and T2-selective IVIM approaches, including Fluid-Attenuated Inversion Recovery IVIM (FLAIR-IVIM), LongTE-IVIM, and Vascular Space Occupancy-LongTE-IVIM (VASO-LongTE-IVIM), to measure diffusivity and volume fractions of fluid compartments in ChP. Our results showed that FLAIR-IVIM identified an additional interstitial fluid (ISF) compartment with free-water-like diffusivity in ChP. We then evaluated the aging effects on microvascular perfusion and ISF in ChP. Compared to younger adults, older adults exhibited increased ChP volume, reduced perfusion, decreased ISF volume fraction, and lower tissue diffusivity. Relaxation-selective IVIM may offer enhanced specificity for characterizing age-related changes in ChP structure and fluid dynamics.

BACKGROUND:Motor and cognitive decline are hallmark features of aging. In the primary motor cortex (M1), pyramidal neurons project to the corticospinal tract (CST), a well-established motor pathway, and send collaterals to the ipsilateral striatum, forming the corticostriatal tract (CStrT). While the CST has been extensively studied, the role of the CStrT in motor and cognitive aging remains poorly understood. METHODS:We analyzed T1- and T2-weighted MRI, multi-delay arterial spin labeling, and multi-shell diffusion MRI data from 339 right-handed healthy adults (aged 36-90 years) in the Human Connectome Project-Aging dataset. Age-related trajectories of M1 structure and hemodynamics, as well as CST and CStrT microstructure, were assessed. Segment-wise along-tract analyses were conducted to identify localized tract degeneration. Mediation analyses were performed to examine whether tract integrity linked M1 atrophy to motor and cognitive performance. RESULTS:With age, M1 exhibited reduced volume and hemodynamics, altered T1/T2 ratio, and increased cortical curvature, reflecting structural and hemodynamic alterations. Along-tract analyses revealed localized microstructural degeneration in the CST adjacent to M1, whereas the CStrT showed more extensive degeneration along its trajectory. These tract changes were associated with structural and hemodynamic alterations in M1. Furthermore, integrity of the dominant (left) CST and CStrT mediated the relationship between ipsilateral M1 atrophy and motor decline. Notably, CStrT integrity also mediated the association between M1 atrophy and motor cognition decline. CONCLUSION/CONCLUSIONS:These findings establish age-related structural and functional degeneration of M1 and its pathways, highlighting the CStrT as a critical mediator between motor cortical atrophy and both motor and cognitive decline. These normative imaging markers of healthy aging may help inform the early detection of neurodegenerative diseases.