Amyloid, Tau, and APOE in Alzheimer's Disease: Impact on White Matter Tracts.

Alzheimer's disease (AD) is characterized by cognitive decline and memory loss due to the abnormal accumulation of amyloid-beta (Aß) plaques and tau tangles in the brain; its onset and progression also depend on genetic factors such as the apolipoprotein E (APOE) genotype. Understanding how these factors affect the brain's neural pathways is important for early diagnostics and interventions. Tractometry is an advanced technique for 3D quantitative assessment of white matter tracts, localizing microstructural abnormalities in diseased populations in vivo. In this work, we applied BUAN (Bundle Analytics) tractometry to 3D diffusion MRI data from 730 participants in ADNI3 (phase 3 of the Alzheimer's Disease Neuroimaging Initiative; age range: 55-95 years, 349M/381F, 214 with mild cognitive impairment, 69 with AD, and 447 cognitively healthy controls). Using along-tract statistical analysis, we assessed the localized impact of amyloid, tau, and APOE genetic variants on the brain's neural pathways. BUAN quantifies microstructural properties of white matter tracts, supporting along-tract statistical analyses that identify factors associated with brain microstructure. We visualize the 3D profile of white matter tract associations with tau and amyloid burden in Alzheimer's disease; strong associations near the cortex may support models of disease propagation along neural pathways. Relative to the neutral genotype, APOE ϵ3/ϵ3, carriers of the AD-risk conferring APOE ϵ4 genotype show microstructural abnormalities, while carriers of the protective ϵ2 genotype also show subtle differences. Of all the microstructural metrics, mean diffusivity (MD) generally shows the strongest associations with AD pathology, followed by axial diffusivity (AxD) and radial diffusivity (RD), while fractional anisotropy (FA) is typically the least sensitive metric. Along-tract microstructural metrics are sensitive to tau and amyloid accumulation, showing the potential of diffusion MRI to track AD pathology and map its impact on neural pathways.

Microstructural Mapping of Neural Pathways in Alzheimer's Disease using Macrostructure-Informed Normative Tractometry.

Introduction: Diffusion MRI is sensitive to the microstructural properties of brain tissues, and shows great promise in detecting the effects of degenerative diseases. However, many approaches analyze single measures averaged over regions of interest, without considering the underlying fiber geometry. Methods: Here, we propose a novel Macrostructure-Informed Normative Tractometry (MINT) framework, to investigate how white matter microstructure and macrostructure are jointly altered in mild cognitive impairment (MCI) and dementia. We compare MINT-derived metrics with univariate metrics from diffusion tensor imaging (DTI), to examine how fiber geometry may impact interpretation of microstructure. Results: In two multi-site cohorts from North America and India, we find consistent patterns of microstructural and macrostructural anomalies implicated in MCI and dementia; we also rank diffusion metrics' sensitivity to dementia. Discussion: We show that MINT, by jointly modeling tract shape and microstructure, has potential to disentangle and better interpret the effects of degenerative disease on the brain's neural pathways.

Sex Differences in the Brain's White Matter Microstructure during Development assessed using Advanced Diffusion MRI Models.

Typical sex differences in white matter (WM) microstructure during development are incompletely understood. Here we evaluated sex differences in WM microstructure during typical brain development using a sample of neurotypical individuals across a wide developmental age (N=239, aged 5-22 years). We used the conventional diffusion-weighted MRI (dMRI) model, diffusion tensor imaging (DTI), and two advanced dMRI models, the tensor distribution function (TDF) and neurite orientation dispersion density imaging (NODDI) to assess WM microstructure. WM microstructure exhibited significant, regionally consistent sex differences across the brain during typical development. Additionally, the TDF model was most sensitive in detecting sex differences. These findings highlight the importance of considering sex in neurodevelopmental research and underscore the value of the advanced TDF model.

Deep Normative Tractometry for Identifying Joint White Matter Macro- and Micro-structural Abnormalities in Alzheimer's Disease.

This study introduces the Deep Normative Tractometry (DNT) framework, that encodes the joint distribution of both macrostructural and microstructural profiles of the brain white matter tracts through a variational autoencoder (VAE). By training on data from healthy controls, DNT learns the normative distribution of tract data, and can delineate along-tract micro-and macro-structural abnormalities. Leveraging a large sample size via generative pre-training, we assess DNT's generalizability using transfer learning on data from an independent cohort acquired in India. Our findings demonstrate DNT's capacity to detect widespread diffusivity abnormalities along tracts in mild cognitive impairment and Alzheimer's disease, aligning closely with results from the Bundle Analytics (BUAN) tractometry pipeline. By incorporating tract geometry information, DNT may be able to distinguish disease-related abnormalities in anisotropy from tract macrostructure, and shows promise in enhancing fine-scale mapping and detection of white matter alterations in neurodegenerative conditions.

Vitrectomía en el agujero macular senil / Vitrectomy for senile macular hole

Se ha estudiado la eficacia del uso de aceite de silicón y de la remoción del epitelio pigmentario de la base del agujero macular durante la vitrectomía para el agujero macular senil en 8 ojos de 7 siete pacientes. Se obtuvo la resolución anatómica de todos los casos luego de la primera intervención y 5 casos mostraron una mejoría visual. Se confirma que el uso de aceite de silicón y la remoción del epitelio pigmentario producen buenos resultados anatómicos y visuales en casos seleccionados de agujero macular senil

Doppler color orbitario en la enfermedad obstructiva carotídea / Color Doppler imaging of the orbit in carotid occlusive disease

Objetivo: evaluar las características hemodinámicas de las arterias oftálmica (AO), central de la retina (ACR), y ciliares posteriores (ACP) nasal y temporal, en 20 ojos de 17 pacientes con síndrome isquémico ocular (SIO) por compromiso hemodinámico significativo de la arteria carótida interna extracraneana (estenosis mayor del 70 por ciento). Material y métodos: estudio prospectivo realizado desde enero de 1996 a marzo de 2000. Se realizaron 2741 Doppler de vasos de cuello. En 153 pacientes se registró estenosis carotídea mayor del 70 por ciento. En éste grupo de pacientes se estudiaron, con Doppler Duplex Color (DDC), las velocidades sistólica e índice de resistencia (IR) de las AO, ACR y ACP. Se encontraron 17 pacientes (20 ojos) con signos Doppler de SIO. Once pacientes fueron evaluados clínicamente y por funduscopía en Oftalmología. Resultados: se demostró disminución de las velocidades de flujo sistólico y diastólico, con aumento del IR en ACR y ACP homolateral a la lesión en todos los pacientes; en 3 pacientes el hallazgo fue bilateral. La AO mostró patrón de flujo colateral, en general con flujo invertido; sólo en un paciente fue de dirección anterógrada con hipoflujo, y en dos pacientes no fue hallada (se confirmó trombosis por angiografía digital). Sólo 3 pacientes mostraron signos por funduscopía. Dos de 3 pacientes con disección carotídea tuvieron repermeabilización completa al mes y revirtieron los síntomas y signos de SIO. Conclusión: el DDC cuantifica la hemodinamia en los ojos con SIO. La desaparición de los hallazgos de SIO en pacientes con repermeabilización de disección carotídea sugiere que el tratamiento de la enfermedad obstructiva carotídea podría mejorar el estado de la circulación orbitaria. El DDC precede los hallazgos clínicos. Sugerimos realizar DDC oftálmico como complemento del DVC en pacientes con enfermedad carotídea obstructiva