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:.

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.

Sex differences in hippocampal aging have been increasingly recognized, with females showing greater vulnerability to neurodegeneration, particularly after menopause. However, the underlying neurobiological mechanisms remain unclear, especially at the level of hippocampal subfields. Leveraging high-resolution T1-, T2-weighted, and multi-delay arterial spin labeling MRI from 650 adults in the Human Connectome Project-Aging dataset, we examined sex-specific alterations in hippocampal subfield volume, arterial transit time (ATT), and cerebral blood flow (CBF) across the adult lifespan. All hippocampal subfields showed age-related atrophy and ATT prolongation. An age × sex interaction effect on ATT was observed in CA1 and CA2, indicating that age-related increases in ATT were more pronounced in females than in males in these subfields. Moreover, females exhibited more pronounced hippocampal subfields CBF reductions with aging and atrophy, while males showed relatively preserved CBF, with an increase in subiculum perfusion. Furthermore, CA1 showed the lowest perfusion and the strongest association with atrophy among hippocampal subfields. To investigate the potential impact of menopausal hormonal changes on sex-specific patterns, we explored the hypothalamic structure and hemodynamic alterations during aging and their effects on the hippocampus, given that hypothalamus regulates gonadal hormone secretion through the hypothalamic-pituitary-gonadal axis. We found significant hypothalamic atrophy during aging in both sexes, accompanied by ATT prolongation exclusively in females, which was associated with hippocampal atrophy and impaired hemodynamics. Our study highlights the intricate interplay between hippocampal structure and vascular function, revealing sex- and subfield-specific aging trajectories. These findings provide a normative quantitative imaging reference to age-related neurodegenerative diseases such as Alzheimer's Disease.

Sodium magnetic resonance imaging (MRI) is highly sensitive to cellular ionic balance due to tenfold difference in sodium concentration across membranes, actively maintained by the sodium-potassium (Na⁺-K⁺) pump. Disruptions in this pump or membrane integrity, as seen in neurological disorders like epilepsy, multiple sclerosis, bipolar disease, and mild traumatic brain injury, lead to increased intracellular sodium. However, this cellular-level alteration is often masked by the dominant extracellular sodium signal, making it challenging to distinguish sodium populations with mono- vs. bi-exponential transverse (T₂) decays-especially given the low signal-to-noise ratio (SNR) even at an advanced clinical field of 3 Tesla. Here, we propose a novel technique that leverages intrinsic difference in T₂ decays by acquiring single-quantum images at multiple echo times (TEs) and applying voxel-wise matrix inversion for accurate signal separation. Using numerical models, agar phantoms, and human subjects, we achieved high separation accuracy in phantoms (95.8% for mono-T₂ and 72.5-80.4% for bi-T₂) and demonstrated clinical feasibility in humans. This approach may enable early detection of neurological disorders and early assessment of treatment responses at the cellular level using sodium MRI at 3 T.

INTRODUCTION/UNASSIGNED:White matter hyperintensity (WMH) is a hallmark imaging biomarker of cerebral small vessel disease and are strongly associated with vascular cognitive impairment in the elderly. Morphological changes in large extracranial brain-feeding arteries, such as the internal carotid (ICA) and vertebral arteries (VA), may alter intracranial hemodynamics and contribute to WMH development. This study examined the relationship between arterial tortuosity and WMHs using magnetic resonance angiography (MRA). METHODS/UNASSIGNED:Seventy-eight participants underwent time-of-flight (TOF) MRA and phase-contrast (PC) MRI to assess arterial morphology and blood flow. After excluding three for poor image quality, 75 subjects were analyzed. Arterial tortuosity was quantified using the inflection count metric (ICM) and ICA angle. Global cerebral blood flow (CBF) was estimated with PC-MRI and compared against pseudo-continuous arterial spin labeling (pCASL) to determine whether it could be a reliable surrogate measurement to reflect intracranial blood supply. RESULTS/UNASSIGNED:Participants with severe WMHs (Fazekas ≥2) demonstrated greater tortuosity (higher ICM and larger ICA angles) and lower blood flow than those with mild WMHs. Females showed more tortuous arteries, greater WMH burden, and higher susceptibility to hypoperfusion. Correlation analyses revealed a positive association between tortuosity and WMH volume. DISCUSSION/UNASSIGNED:These findings highlight the role of extracranial arterial tortuosity in WMH burden and reveal sex-specific differences in vascular vulnerability. The results underscore the need for further investigation into how age-related vascular remodeling contributes to WMH development and cognitive decline.