Faculty Bibliography

OBJECTIVE:ratio (TPR) imaging approach and evaluates its ability to characterize MS lesions alongside other quantitative MRI (qMRI) metrics. METHODS:and PD values were used to illustrate TPR contrast. Statistical analyses included Wilcoxon rank-sum tests and Spearman correlations (p < 0.05). RESULTS:* (92 ms) values but lower MTR (37.3%) and MTsat (1.57%) compared to hypointense lesions (1085 ms; 0.88 a.u.; 64 ms; 46%; 2.48%, respectively). QSM values varied across lesion types. INTERPRETATION/CONCLUSIONS:, PD, and MT metrics, consistent with demyelination. In contrast, hypointense lesions may reflect tissue changes associated with repair processes such as remyelination.

BACKGROUND/UNASSIGNED:The deep gray matter nuclei (DGMN)-including the thalamus, caudate, putamen, and pallidum-are essential for cognitive, motor, and affective functions and are highly susceptible to age-related degeneration. However, the combined effects of aging and sex on DGMN volume, microstructure, and perfusion remain incompletely characterized. METHODS/UNASSIGNED:Using data from 652 healthy adults (36-89 years) from the Human Connectome Project-Aging cohort, we examined volumetric and perfusion changes across the DGMN. High-resolution T1- and T2-weighted MRI and multi-delay pseudo-continuous arterial spin labeling (pCASL) were used to quantify normalized volume, T1/T2 ratio, cerebral blood flow (CBF), and arterial transit time (ATT) in DGMN regions after perivascular spaces were removed. Age-related trajectories were modeled using linear and quadratic regression, and differences between sexes were examined, with false discovery rate correction applied. RESULTS/UNASSIGNED:Advancing age was associated with significant volumetric decline in all DGMN regions (p < 0.001), prolonged ATT, and reduced CBF, particularly in the caudate and thalamus. The T1/T2 ratio exhibited region-specific nonlinear trajectories, peaking in mid-adulthood and declining thereafter, reflecting its underlying age-related processes of demyelination and iron accumulation. Sex-stratified analyses suggested modest differences in T1/T2, ATT, and CBF trajectories; however, no significant age × sex interactions were observed after correction for multiple comparisons. DGMN volumes correlated negatively with ATT, while T1/T2 ratio correlated inversely with CBF, indicating more complex interactions between structure, tissue properties, and perfusion. CONCLUSIONS/UNASSIGNED:This large-scale quantitative MRI study delineates distinct age-related trajectories of DGMN over adult lifespan. Integrating volumetric, T1/T2 ratio, and multi-delay ASL metrics-while correcting for perivascular spaces-enhances sensitivity to subtle changes and provides normative benchmarks for detecting early neurodegenerative alterations.

Ceramide transporter syndrome (CerTra syndrome) is a rare neurodevelopmental disorder caused by pathogenic variants in CERT1 gene encoding ceramide transporter (CERT). These variants disrupt ceramide transport and sphingolipid homeostasis, leading to a clinical phenotype that includes developmental delay, movement abnormalities, and structural brain anomalies. Despite growing recognition of this condition, detailed neuroimaging and neuropathological characterization remain limited. Here, we present a 12-year-old girl with a pathogenic CERT1 variant complicated by sudden unexplained death, who presented with unreported neuroimaging abnormalities in choroid plexus (ChP) and perivascular space (PVS). Clinical Magnetic Resonance Imaging (MRI) obtained approximately 10 years prior to death, as well as postmortem MRI, revealed bilateral cystic enlargement of the ChP and prominent PVS filled with abundant proteinaceous material in white matter. Neuropathological examination demonstrated marked ChP epithelial disorganization, reduced aquaporin-1 (AQP1) expression, cyst formation, and focal calcifications, which may be associated with disturbances in cerebrospinal fluid (CSF) dynamics. These findings raise the possibility that CERT1 variants may be associated with ChP architectural changes and altered perivascular clearance.

Aging is an important risk factor for Parkinson's disease (PD). Characterizing age-related alterations in the nigrostriatal system may help identify early vulnerability prior to overt neurodegeneration. We aimed to delineate aging trajectories of structure and hemodynamics of the nigrostriatal system and examine their associations with motor and cognitive functions. We analyzed 486 healthy adults from Human Connectome Project-Aging dataset, stratified into younger (≤ 60 years) and older (> 60 years) groups. Motor, cognitive, and motor cognition functions were assessed. Multiparametric MRI included T1- and T2-weighted, multi-delay arterial spin labeling, and multi-shell diffusion imaging. Volumes, T1/T2 ratio, arterial transit time (ATT), and cerebral blood flow (CBF) were quantified in the nigrostriatal nuclei. The nigrostriatal tract (NST) was reconstructed and segmented along the nigra-to-striatum axis. Diffusion metrics and quantitative anisotropy were derived. A composite nigrostriatal aging index (NAI) was generated using principal component analysis. Older adults exhibited reduced substantia nigra and putamen volumes, increased caudate volume, prolonged ATT, and reduced CBF across nigrostriatal nuclei. The NST showed segment-specific age trajectories, with increased diffusivity after age 60. Imaging alterations in nigrostriatal nuclei and tract segments correlated with declines in motor, cognitive, and motor-cognitive performance. The NAI increased more steeply after age 60 and predicted poorer behavioral performance exclusively in older adults. Healthy aging is characterized by coordinated structural and hemodynamic alterations within the nigrostriatal system associated with functional decline. The composite NAI provides a sensitive framework for detecting early nigrostriatal vulnerability in older adults prior to overt neurodegeneration.

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.

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:.

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.