Biology subjects

Aizenstein, H. J.

Publications and source records attributed to Aizenstein, H. J..

7 recordsLinked to original sources

bioRxiv2026

An open-source stereotaxic container with an integrated cutting guide for human brain fixation during magnetic resonance imaging and sectioning for histology

IntroductionPostmortem imaging at ultrahigh field strengths, such as 7 Tesla (7T) magnetic resonance imaging (MRI), enables unprecedented visualization of fine brain structures and pathology. However, precise registration between MRI and histology is often compromised by tissue deformation and lack of standardized tools for preserving anatomical orientation. A reliable, high-resolution MRI-to-histology workflow is essential for MRI-guided sampling to investigate neurodegenerative diseases. MethodsWe developed a human postmortem brain container composed of stereotaxic enclosure and cutting guide system using iterative 3D printing. The final design is constructed from Victrex AM 200, a polyaryletherketone material engineered with MRI compatibility, high mechanical strength, and high resistance to fixatives. Human brains were embedded in an agar/sucrose mixture within the container and scanned at 7T using high-contrast and high-resolution imaging sequences. The cutting guide enables reproducible sectioning at defined tissue coronal slab thicknesses (9.2 {+/-} 0.6 mm). Block face photographs of each coronal slab were then co-registered with MRI for targeted tissue sampling. ResultsTo date, 215 human postmortem brains have been imaged ex vivo using this container. The container maintains consistent spatial orientation from imaging through sectioning, supporting correlation between MR-visible features and histological findings. Imaging-visible abnormalities, such as white matter hyperintensities and cerebral microbleeds, were localized and sampled with minimal deformation. The container enables single-scan workflows, avoiding custom cutting templates or repeat imaging. It supports deep learning-based lesion segmentation and MRI-guided histology registration, facilitating large-scale neuropathological investigations. ConclusionThe stereotaxic cutting guide system addresses a critical gap in postmortem imaging by integrating MRI-compatible materials, precision-guided sectioning, and high-throughput imaging. It has enabled multimodal studies of aging and neurodegeneration and is being adopted in neuropathological workflows. This platform provides a reproducible, scalable, and anatomically precise solution for aligning ultrahigh field MRI with histology, enhancing both clinical research and digital pathology efforts.

bioengineering↗

bioRxiv2025

Differential Cerebral White Matter Tract Alterations in Generalized Anxiety Disorder Revealed by Ultra-High Field 7T Diffusion-Weighted Imaging

BackgroundGeneralized anxiety disorder (GAD) is characterized by chronic worry and emotional dysregulation, yet its underlying white matter (WM) architecture remains inconsistent in previous neuroimaging studies. This study aimed to delineate microstructural WM alterations in GAD using ultra-high field (7T) diffusion tensor imaging (DTI) and advanced correlational tractography, evaluating their associations with symptom severity and diagnostic-aided value. MethodsEighty-eight participants (27 GAD, 61 healthy controls, HCs) underwent 7T DTI scanning with 1.5-mm isotropic resolution. Whole-brain correlational tractography was applied to identify tracts exhibiting significant group-related differences in diffusion indices while controlling for demographic covariates. Associations with Hamilton Anxiety Rating Scale (HAM-A) and Penn State Worry Questionnaire (PSWQ) scores were examined, and machine learning-based models were used to assess the diagnostic-aided utility of identified WM features. ResultsTwo tract bundles showed significant fractional anisotropy (FA) alterations in GAD: decreased FA in the right prefrontal pathway (PFDR = 0.039) and increased FA in the right cingulum (PFDR < 0.001). The anterior portions of both tracts exhibited stronger effects of GAD. FA in the right cingulum positively correlated with HAM-A and PSWQ scores, indicating that greater microstructural coherence was associated with higher anxiety and worry severity (both PFDRs < 0.001). Inclusion of WM features could improve classification performance beyond neuropsychological measures alone. ConclusionsUltra-high field 7T tractometry revealed a differential pattern of WM abnormalities in GAD, suggesting weakened prefrontal control and hyper-integrated cingulate connectivity as structural correlates of emotional dysregulation. These findings indicate the potential of 7T DTI markers for advancing mechanistic and diagnostic understanding of GAD.

neuroscience↗

bioRxiv2025

Patterns of Brain Activation and Hippocampal Functional Connectivity Supporting Verbal Memory in Midlife Women

Women show declines in verbal memory across the menopause transition that may persist into the postmenopause. The goal of the present study was to characterize the patterns of brain activity and hippocampal functional connectivity that support verbal memory performance in midlife postmenopausal women. The study sample included 171 midlife postmenopausal women from the MsBrain I study (mean age = 59.3 years, mean education= 15.7 years, 87.7% white). All participants were cognitively normal, native English speakers, not taking menopausal hormone therapy. Participants completed neuropsychological (California Verbal Learning Test [CVLT]) and neuroimaging assessments, including an fMRI task of verbal encoding and recognition. Findings indicated that during verbal encoding, greater activation of bilateral prefrontal and medial temporal regions, as well as the precuneus, cuneus, caudate, and cerebellar regions, was associated with better performance on CVLT measures, including learning, short- and long-delay recall, and semantic clustering. Functional connectivity from both hippocampi to primarily right prefrontal regions during verbal encoding associated with better CVLT performance. In-scanner word recognition accuracy was more strongly associated with activation of parietal and occipital regions, and with functional connectivity between the right hippocampus and bilateral parietal and temporal regions. Our findings characterize the patterns underlying verbal memory abilities in midlife postmenopausal women. The patterns identified here may act as a foundation for better interpreting the effects of hormonal changes and menopausal symptoms on cognition at midlife, and for identifying neural targets for pharmacological and lifestyle interventions aimed at sustaining womens memory function.

neuroscience↗

bioRxiv2025

Community Socioeconomic Disadvantage relates to White Matter Hyperintensity Burden in Mid-to-Late Life Adults

BackgroundResiding in communities characterized by socioeconomic disadvantage may confer risk for neurodegenerative brain changes and future neuropathology. Based on prior evidence, this study tested the hypotheses that (1) community-level disadvantage would relate independently of individual-level socioeconomic position to white matter hyperintensities (WMHs), which reflect subclinical brain pathology that may presage later dementia; and (2) this association would be partly explained by blood pressure, cardiometabolic risk, and/or systemic levels of inflammation. These hypotheses were examined among otherwise healthy middle- and older-aged adults without clinical dementia at testing. MethodsParticipants were 388 adults aged 40-72 years (53% female; 12% non-White) whose street addresses were entered into the Neighborhood Atlas to compute Area Deprivation Index scores by census block. Participants also underwent high resolution (7 Tesla) brain imaging to assess total WMH volume normalized for intracranial volume, and assessment of blood pressure, cardiometabolic (adiposity, lipids, glucose and insulin), and inflammatory (interleukin-6 and C-reactive protein) risk factors. ResultsLinear regression models showed that higher community deprivation on the ADI associated with greater WMH volume, independently of age, sex, years of education and smoking. This association was largely independent of blood pressure, cardiometabolic risk and systemic inflammation. ConclusionThe present novel findings add to growing evidence that community disadvantage relates to preclinical neurodegenerative changes, which may contribute to accelerated brain and cognitive aging. Future work is warranted to better understand pathways that link residential environments to brain health and to identify targets for community and public policy interventions.

neuroscience↗

bioRxiv2025

Periventricular Diffusivity Reflects APOE4-modulated Amyloid Accumulation and Cognitive Impairment in Alzheimers Continuum

BackgroundAltered glymphatic-related fluid dynamics are increasingly recognized as a key feature of Alzheimers disease (AD). We generalized an established diffusion imaging technique to estimate periventricular diffusivity (PVeD), hypothesizing that fast diffusion signals in the periventricular region can reflect amyloid-beta (A{beta}) deposition across the Alzheimers continuum. MethodsParticipants from two multi-site cohorts (n = 440 and 414), comprising cognitively unimpaired individuals, those with mild cognitive impairment, and patients with AD, were included. We tested and validated the association of PVeD with A{beta} burden and core AD characteristics. ResultsLower PVeD was extensively associated with greater A{beta} burden, neurodegeneration, cognitive impairment, and clinical severity. Importantly, the relationship between PVeD and A{beta} burden was significantly modulated by APOE4 status, with APOE4 carriers showing a stronger negative association. Baseline PVeD also predicted longitudinal cognitive decline. DiscussionThese findings suggest that periventricular fast diffusion signals can reflect APOE4-modulated A{beta} burden and cognitive decline in AD. Research-in-ContextO_ST_ABSSystematic reviewC_ST_ABSA comprehensive PubMed literature search indicates that fluid movement related to glymphatic activity assessed by diffusion tensor image analysis along the perivascular space (DTI-ALPS) is associated with amyloid-beta deposition in Alzheimers disease (AD). However, recent evidence underscores certain limitations of DTI-ALPS, suggesting that it may not fully capture the diffusion processes involved in amyloid clearance. Moreover, no previous studies have investigated the role of APOE4 in modulating the relationship between glymphatic-related fast diffusion signals and amyloid-beta deposition. InterpretationThe transverse diffusion process along the perivenous space in the periventricular region appears to reflect glymphatic-related dysfunction manifested by amyloid-beta deposition. Reduced periventricular diffusivity is associated with greater amyloid burden across the AD continuum. This association is notably enhanced in APOE4 carriers, who exhibit higher amyloid accumulation for a given reduction in the periventricular diffusivity. Besides, periventricular diffusivity is related to other pathological markers of AD, including clinical symptom severity and neurodegeneration, and may also predict subsequent cognitive decline. Future directionsAlthough diffusion-based neuroimaging metrics hold promise as surrogate imaging biomarkers for glymphatic-related activity, they do not comprehensively capture the complex fluid dynamics such as convective bulk flow within the glymphatic system. By leveraging multimodal neuroimaging techniques and advanced analytic approaches, future research can refine these metrics into more sensitive, non-invasive tools capable of evaluating fluid dynamics related to glymphatic dysfunction in AD.

neuroscience↗

bioRxiv2020

Analysis of Hippocampal Subfields in Sickle Cell Disease Using Ultrahigh Field MRI

Sickle cell disease (SCD) is an inherited hemoglobinopathy that causes organ dysfunction, including cerebral vasculopathy and neurological complications. Hippocampal segmentation with newer and advanced 7 Tesla (7T) MRI protocols has revealed atrophy in specific subregions in other neurodegenerative and neuroinflammatory diseases, however, there is limited evidence of hippocampal involvement in SCD. Thus, we explored whether SCD may be also associated with abnormalities in hippocampal subregions. We conducted 7T MRI imaging in individuals with SCD, including the HbSS, HbSC and HbS/beta thalassemia genotypes (n=37), and healthy race and age-matched controls (n=40), using a customized head coil. Both T1 and T2 weighted images were used for automatic segmentation of the hippocampus subfields. Individuals with SCD had significantly smaller volume of the Dentate Gyrus and Cornu Ammonis (CA) 2 and 3 as compared to the control group. Other hippocampal subregions also showed a trend towards smaller volumes in the SCD group. These findings support previous reports of reduced volume in the temporal lobe in SCD patients. Further studies are necessary to investigate the mechanisms that lead to structural changes in the hippocampus subfields and their relationship with cognitive performance in SCD patients.

neuroscience↗

bioRxiv2020

Improved 7 Tesla Transmit Field Homogeneity with Reduced Electromagnetic Power Deposition Using Coupled Tic Tac Toe Antennas

Recently cleared by the FDA, 7 Tesla (7T) MRI is a rapidly growing technology that can provide higher resolution and enhanced contrast in human MRI images. However, the increased operational frequency (~297 MHz) hinders its full potential since it causes inhomogeneities in the images and increases the power deposition in the tissues. This work describes the optimization of an innovative radiofrequency (RF) head coil coupled design, named Tic Tac Toe, currently used in large scale human MRI scanning at 7T; to date, this device was used in more than 1,300 patient/volunteer neuro 7T MRI scans. Electromagnetic simulations were performed for each of the coils antennas using the finite-difference time-domain method. Numerical optimizations were used to combine the calculated electromagnetic fields produced by these antennas, based on the superposition principle, and successfully produced homogeneous magnetic field distributions at low levels of power deposition in the tissues. The simulations were then successfully validated in-vivo using the Tic Tac Toe RF head coil system on a 7T MRI scanner.

bioengineering↗