Faculty Bibliography
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319
Motor-cognitive aging: The role of motor cortex and its pathways
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.
PMID: 40972830
ISSN: 1095-9572
CID: 5935662
Evaluating Breast Cancer Intravoxel Incoherent Motion MRI Biomarkers across Software Platforms
Purpose To evaluate intravoxel incoherent motion (IVIM) biomarkers across different MRI vendors and software programs for breast cancer characterization in a two-site study. Materials and Methods This institutional review board-approved, Health Insurance Portability and Accountability Act-compliant retrospective study included 106 patients (with 18 benign and 88 malignant lesions) who underwent bilateral diffusion-weighted imaging (DWI) between February 2009 and March 2013. DWI was performed using 1.5-T (n = 6) or 3-T MRI scanners from two vendors using single-shot spin-echo echo-planar imaging or twice-refocused, bipolar gradient single-shot turbo spin-echo readout with multiple b values between 0 and 1000 sec/mm2. IVIM parameters tissue diffusivity (Dt
PMID: 40910883
ISSN: 2638-616x
CID: 5936402
Associations Between Hippocampal Transverse Relaxation Time and Amyloid PET in Cognitively Normal Aging Adults
BACKGROUND:Identifying early neuropathological changes in Alzheimer's disease (AD) is important for improving treatment efficacy. Among quantitative MRI measures, transverse relaxation time (T2) has been shown to reflect tissue microstructure relevant in aging and neurodegeneration; however, findings regarding T2 changes in both normal aging and AD have been inconsistent. The association between T2 and amyloid-beta (Aβ) accumulation, a hallmark of AD pathology, is also unclear, particularly in cognitively normal individuals who may be in preclinical stages of the disease. PURPOSE/OBJECTIVE:To investigate longitudinal hippocampal T2 changes in a cognitively normal cohort of older adults and their association with global Aβ accumulation. STUDY TYPE/METHODS:Retrospective, longitudinal. SUBJECTS/METHODS:56 cognitively normal adults between 55 and 90 years of age (17 males and 39 females). FIELD STRENGTH/SEQUENCE/UNASSIGNED:3 Tesla; multi-echo spin echo sequence for T2 mapping; 18F-florbetaben positron emission tomography for Aβ measurement. ASSESSMENT/RESULTS:Bilateral hippocampal T2 and volume were extracted to relate to Aβ PET measurements. To understand variations in AD risk, participants were separated into Aβ-high and Aβ-low subgroups using a predetermined threshold. STATISTICAL TESTS/METHODS:Linear mixed-effect models and general linear models were used. A p-value < 0.025 was considered significant to account for bilateral comparisons. RESULTS:Older age was associated with increased T2 in the bilateral hippocampus (left: β = 0.30, right: β = 0.25) and smaller hippocampal volume on the left (β = -0.12). In the Aβ-low subgroup, both longitudinal T2 increase rates (β = 0.65) in the left hippocampus and bilateral cross-sectional T2 (left: β = 0.64, right: β = 0.46) were positively correlated with Aβ PET, independent of hippocampal volume. DATA CONCLUSION/CONCLUSIONS:This study provided in vivo evidence linking hippocampal T2 to Aβ accumulation in cognitively normal aging individuals, suggesting that quantitative T2 may be sensitive to microstructural changes accompanying early Aβ pathology, such as neuroinflammation, demyelination, and reduced tissue integrity. EVIDENCE LEVEL/METHODS:3. TECHNICAL EFFICACY/UNASSIGNED:Stage 2.
PMID: 40844208
ISSN: 1522-2586
CID: 5909362
Hippocampal perfusion abnormalities and treatment effects in acute phase of first-episode schizophrenia
BACKGROUND:A subset of first-episode schizophrenia (FES) patients responds poorly to initial antipsychotic therapy. The hippocampus is an early-affected region in schizophrenia, yet neurobiological markers predicting treatment response remain unclear. Arterial spin labeling (ASL) magnetic resonance imaging (MRI) allows non-invasive measurement of cerebral blood flow (CBF), but studies on hippocampal perfusion in acute FES, particularly in those receiving electroconvulsive therapy (ECT) with antipsychotics, are limited. METHODS:Fifty FES patients and 28 age- and sex-matched healthy controls underwent high-resolution ASL MRI to assess hippocampal CBF. Patients received either antipsychotics alone (n = 20) or in combination with ECT (n = 30). MRI Scans were acquired before and after six weeks of treatment. Analysis of covariance and linear mixed-effects models were used to assess group differences and longitudinal effects, adjusting for relevant covariates. RESULTS:At baseline, FES patients exhibited significantly lower hippocampal CBF compared to healthy controls, with no significant difference in hippocampal volume. Longitudinal analysis revealed a significant group × time interaction for hippocampal CBF. Post hoc analysis indicated a significant increase in CBF after treatment in the FES group, while hippocampal volume remained unchanged. CBF changes were not significantly correlated with symptom reduction. We further examined the group differences in longitudinal changes between the ECT + Drug group and the Drug group, however no significant results were found. CONCLUSION/CONCLUSIONS:Our findings suggest that functional, but not structural, hippocampal alterations are present in early schizophrenia and may be responsive to treatment. These preliminary results should be interpreted cautiously and validated in larger samples with extended follow-up and neurochemical assessments.
PMID: 40706394
ISSN: 1573-2509
CID: 5901812
The association between measures of sleepiness and subjective cognitive decline symptoms in a diverse population of cognitively normal older adults
Subjective cognitive decline (SCD) is associated with preclinical Alzheimer's disease (AD). Suboptimal sleep is also a risk factor for cognitive decline, but with unclear relationship to SCD. We conducted a retrospective cross-sectional study in a biracial research cohort of 148 cognitively normal older adults who underwent quantification of SCD (Cognitive Change Index; CCI), sleepiness (Epworth Sleepiness Scale; ESS), depression (Geriatric Depression Scale; GDS), and amyloid/tau PET. ESS score was associated with total, amnestic, and non-amnestic CCI scores, after adjustment for GDS, amyloid/tau burden, and race. This supports future longitudinal work on how sleepiness impacts SCD outcomes.
PMID: 40170406
ISSN: 1875-8908
CID: 5819022
FireVoxel: Interactive Software for Multi-Modality Analysis of Dynamic Medical Images
This article provides an overview of the FireVoxel software for quantitative analysis of medical images and its applications in the field. We describe FireVoxel's user interface, multi-layer design, dynamic parametric models, and several turn-key workflows. Additionally, we discuss its application in recent imaging projects. We outline basic image analysis tools such as segmentation, non-uniformity correction, and coregistration through a pictorial overview, with a focus on deformable coregistration and motion correction. Several example workflows and image-based dynamic modeling are also highlighted. Furthermore, we analyze peer-reviewed studies that utilized FireVoxel for image processing, categorizing published papers based on body structures/organs, image processing methods, and imaging modalities. For comparison, we searched the Ovid MEDLINE database to assess the general use of medical image analysis software. FireVoxel is used by over 3000 users worldwide, with 528 articles, including 413 in English, published in the past 15 years. MRI is the most commonly used imaging modality (78.2%), followed by CT (14.5%) and PET (7.3%). The most frequently used methods are dynamic modeling, segmentation, texture analysis, and coregistration. FireVoxel is commonly used in abdominal and genitourinary imaging studies, where it appears to fill a niche due to the lack of alternative software. The search of the Ovid MEDLINE suggests that quantitative medical imaging studies, on the other hand, focus on the brain and cardiovascular system. FireVoxel offers an effective set of quantitative tools, particularly for abdominal and genitourinary imaging, likely due to its ability to manage patient motion and correct for MR artifacts. The software is especially valuable for processing dynamic studies. The steady increase in publications utilizing FireVoxel reflects growing interest in this software and its relevance for image-based research.
PMID: 39900865
ISSN: 2948-2933
CID: 5783792
-Penalized Multinomial Regression: Estimation, Inference, and Prediction, With an Application to Risk Factor Identification for Different Dementia Subtypes
High-dimensional multinomial regression models are very useful in practice but have received less research attention than logistic regression models, especially from the perspective of statistical inference. In this work, we analyze the estimation and prediction error of the contrast-based
PMID: 39532663
ISSN: 1097-0258
CID: 5751462
Quantitative Characterization of Respiratory Patterns on Dynamic Higher Temporal Resolution MRI to Stratify Postacute Covid-19 Patients by Cardiopulmonary Symptom Burden
BACKGROUND:Postacute Covid-19 patients commonly present with respiratory symptoms; however, a noninvasive imaging method for quantitative characterization of respiratory patterns is lacking. PURPOSE/OBJECTIVE:To evaluate if quantitative characterization of respiratory pattern on free-breathing higher temporal resolution MRI stratifies patients by cardiopulmonary symptom burden. STUDY TYPE/METHODS:Prospective analysis of retrospectively acquired data. SUBJECTS/METHODS:A total of 37 postacute Covid-19 patients (25 male; median [interquartile range (IQR)] age: 58 [42-64] years; median [IQR] days from acute infection: 335 [186-449]). FIELD STRENGTH/SEQUENCE/UNASSIGNED:0.55 T/two-dimensional coronal true fast imaging with steady-state free precession (trueFISP) at higher temporal resolution. ASSESSMENT/RESULTS:Patients were stratified into three groups based on presence of no (N = 11), 1 (N = 14), or ≥2 (N = 14) cardiopulmonary symptoms, assessed using a standardized symptom inventory within 1 month of MRI. An automated lung postprocessing workflow segmented each lung in each trueFISP image (temporal resolution 0.2 seconds) and respiratory curves were generated. Quantitative parameters were derived including tidal lung area, rates of inspiration and expiration, lung area coefficient of variability (CV), and respiratory incoherence (departure from sinusoidal pattern) were. Pulmonary function tests were recorded if within 1 month of MRI. Qualitative assessment of respiratory pattern and lung opacity was performed by three independent readers with 6, 9, and 23 years of experience. STATISTICAL TESTS/METHODS:Analysis of variance to assess differences in demographic, clinical, and quantitative MRI parameters among groups; univariable analysis and multinomial logistic regression modeling to determine features predictive of patient symptom status; Akaike information criterion to compare the quality of regression models; Cohen and Fleiss kappa (κ) to quantify inter-reader reliability. Two-sided 5% significance level was used. RESULTS:; CV: 0.072, 0.067, and 0.058). Respiratory incoherence was significantly higher in patients with two or more symptoms than in those with one or no symptoms (0.05 vs. 0.043 vs. 0.033). There were no significant differences in patient age (P = 0.19), sex (P = 0.88), lung opacity severity (P = 0.48), or pulmonary function tests (P = 0.35-0.97) among groups. Qualitative reader assessment did not distinguish between groups and showed slight inter-reader agreement (κ = 0.05-0.11). DATA CONCLUSION/CONCLUSIONS:Quantitative respiratory pattern measures derived from dynamic higher-temporal resolution MRI have potential to stratify patients by symptom burden in a postacute Covid-19 cohort. LEVEL OF EVIDENCE/METHODS:3 TECHNICAL EFFICACY: Stage 3.
PMCID:11399317
PMID: 38485244
ISSN: 1522-2586
CID: 5692222
Retrospective analysis of Braak stage- and APOE4 allele-dependent associations between MR spectroscopy and markers of tau and neurodegeneration in cognitively unimpaired elderly
PURPOSE/OBJECTIVE:The pathological hallmarks of Alzheimer's disease (AD), amyloid, tau, and associated neurodegeneration, are present in the cortical gray matter (GM) years before symptom onset, and at significantly greater levels in carriers of the apolipoprotein E4 (APOE4) allele. Their respective biomarkers, A/T/N, have been found to correlate with aspects of brain biochemistry, measured with magnetic resonance spectroscopy (MRS), indicating a potential for MRS to augment the A/T/N framework for staging and prediction of AD. Unfortunately, the relationships between MRS and A/T/N biomarkers are unclear, largely due to a lack of studies examining them in the context of the spatial and temporal model of T/N progression. Advanced MRS acquisition and post-processing approaches have enabled us to address this knowledge gap and test the hypotheses, that glutamate-plus-glutamine (Glx) and N-acetyl-aspartate (NAA), metabolites reflecting synaptic and neuronal health, respectively, measured from regions on the Braak stage continuum, correlate with: (i) cerebrospinal fluid (CSF) p-tau181 level (T), and (ii) hippocampal volume or cortical thickness of parietal lobe GM (N). We hypothesized that these correlations will be moderated by Braak stage and APOE4 genotype. METHODS:We conducted a retrospective imaging study of 34 cognitively unimpaired elderly individuals who received APOE4 genotyping and lumbar puncture from pre-existing prospective studies at the NYU Grossman School of Medicine between October 2014 and January 2019. Subjects returned for their imaging exam between April 2018 and February 2020. Metabolites were measured from the left hippocampus (Braak II) using a single-voxel semi-adiabatic localization by adiabatic selective refocusing sequence; and from the bilateral posterior cingulate cortex (PCC; Braak IV), bilateral precuneus (Braak V), and bilateral precentral gyrus (Braak VI) using a multi-voxel echo-planar spectroscopic imaging sequence. Pearson and Spearman correlations were used to examine the relationships between absolute levels of choline, creatine, myo-inositol, Glx, and NAA and CSF p-tau181, and between these metabolites and hippocampal volume or parietal cortical thicknesses. Covariates included age, sex, years of education, Fazekas score, and months between CSF collection and MRI exam. RESULTS:There was a direct correlation between hippocampal Glx and CSF p-tau181 in APOE4 carriers (Pearson's r = 0.76, p = 0.02), but not after adjusting for covariates. In the entire cohort, there was a direct correlation between hippocampal NAA and hippocampal volume (Spearman's r = 0.55, p = 0.001), even after adjusting for age and Fazekas score (Spearman's r = 0.48, p = 0.006). This relationship was observed only in APOE4 carriers (Pearson's r = 0.66, p = 0.017), and was also retained after adjustment (Pearson's r = 0.76, p = 0.008; metabolite-by-carrier interaction p = 0.03). There were no findings in the PCC, nor in the negative control (late Braak stage) regions of the precuneus and precentral gyrus. CONCLUSIONS:Our findings are in line with the spatially- and temporally-resolved Braak staging model of pathological severity in which the hippocampus is affected earlier than the PCC. The correlations, between MRS markers of synaptic and neuronal health and, respectively, T and N pathology, were found exclusively within APOE4 carriers, suggesting a connection with AD pathological change, rather than with normal aging. We therefore conclude that MRS has the potential to augment early A/T/N staging, with the hippocampus serving as a more sensitive MRS target compared to the PCC.
PMCID:11404707
PMID: 39029606
ISSN: 1095-9572
CID: 5695972
Sensitivity of unconstrained quantitative magnetization transfer MRI to Amyloid burden in preclinical Alzheimer's disease
Magnetization transfer MRI is sensitive to semi-solid macromolecules, including amyloid beta, and has previously been used to discriminate Alzheimer's disease (AD) patients from controls. Here, we fit an unconstrained 2-pool quantitative MT (qMT) model, i.e., without constraints on the longitudinal relaxation rate
PMCID:11065014
PMID: 38699343
CID: 5806382
