Publications by authors named "Sandhitsu Das"

In neuroimaging research, volumetric data contribute valuable information for understanding brain changes during both healthy aging and pathological processes. Extracting these measures from images requires segmenting the regions of interest (ROIs), and many popular methods accomplish this by fusing labels from multiple expert-segmented images called atlases. However, post-segmentation, current practices typically treat each subject's measurement equally without incorporating any information about variation in their segmentation precision.

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Background: Lewy body disorders (LBD), encompassing Parkinson disease (PD), PD dementia (PDD), and dementia with Lewy bodies (DLB), are characterized by alpha-synuclein pathology but often are accompanied by Alzheimer's disease (AD) neuropathological change (ADNC). The medial temporal lobe (MTL) is a primary locus of tau accumulation and associated neurodegeneration in AD. However, it is unclear the extent to which AD copathology in LBD (LBD/AD+) contributes to MTL-specific patterns of degeneration.

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Article Synopsis
  • Alzheimer's disease (AD) involves both neurodegenerative and vascular components, which are linked to lower cerebral blood flow (CBF), but differentiating their specific impacts is still uncertain.
  • A study using advanced MRI techniques examined CBF in 257 participants across the AD spectrum, revealing that vascular risk factors (VRFs) and amyloid positivity have different effects on CBF in various brain regions.
  • The research indicates that specific patterns of reduced CBF can help distinguish between effects caused by Alzheimer’s disease and those related to vascular risk factors, highlighting the role of small vessel disease (SVD) in AD development.
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Alzheimer's disease (AD) is characterized by a long preclinical stage during which molecular markers of amyloid beta and tau pathology rise, but there is minimal neurodegeneration or cognitive decline. Previous literature suggests that measures of brain function might be more sensitive to neuropathologic burden during the preclinical stage of AD than conventional measures of macrostructure, such as cortical thickness. However, among studies that used resting-state functional Magnetic Resonance Imaging (fMRI) acquisitions with Blood Oxygenation Level Dependent (BOLD) contrast, most employed connectivity-based analytic approaches, which discard information about the amplitude of spontaneous brain activity.

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Polypathology is a major driver of heterogeneity in clinical presentation and extent of neurodegeneration (N) in patients with Alzheimer Disease (AD). Beyond amyloid (A) and tau (T) pathologies, over half of patients with AD have concomitant pathology such as α-synuclein (S) in mixed AD with Lewy Body Disease (LBD). Patients with Mixed Etiology Dementia (MED) such as AD+LBD have faster progression and potentially differential responses to targeted treatments, though the diagnosis of AD+LBD can be challenging given overlapping clinical and imaging features.

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Functional magnetic resonance imaging (fMRI) offers an alternative to the traditional Wada test for presurgical language and memory lateralization that carries almost no risk. However, fMRI lateralization of episodic memory remains challenging because the hippocampus, which is fundamental to episodic memory, is smaller, more prone to susceptibility artifact, and harder to functionally modulate than language regions. We previously showed that a complex scene memory task can lateralize memory function in the mesial temporal lobe.

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Introduction: Recent technological advances have increased the risk that de-identified brain images could be re-identified from face imagery. The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a leading source of publicly available de-identified brain imaging, who quickly acted to protect participants' privacy.

Methods: An independent expert committee evaluated 11 face-deidentification ("de-facing") methods and selected four for formal testing.

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MRI allows brain anatomy to be examined at high resolution and to link pathology measures with morphometric measurements. However, automated segmentation methods for brain mapping in postmortem MRI are not well developed, primarily due to limited availability of labeled datasets, and heterogeneity in scanner hardware and acquisition protocols. In this work, we present a high-resolution dataset of 135 postmortem human brain tissue specimens imaged at 0.

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This paper for the 20th anniversary of the Alzheimer's Disease Neuroimaging Initiative (ADNI) provides an overview of magnetic resonance imaging (MRI) of medial temporal lobe (MTL) subregions in ADNI using a dedicated high-resolution T2-weighted sequence. A review of the work that supported the inclusion of this imaging modality into ADNI Phase 3 is followed by a brief description of the ADNI MTL imaging and analysis protocols and a summary of studies that have used these data. This review is supplemented by a new study that uses novel surface-based tools to characterize MTL neurodegeneration across biomarker-defined AD stages.

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The magnetic resonance imaging (MRI) Core has been operating since Alzheimer's Disease Neuroimaging Initiative's (ADNI) inception, providing 20 years of data including reliable, multi-platform standardized protocols, carefully curated image data, and quantitative measures provided by expert investigators. The overarching purposes of the MRI Core include: (1) optimizing and standardizing MRI acquisition methods, which have been adopted by many multicenter studies and trials worldwide and (2) providing curated images and numeric summary values from relevant MRI sequences/contrasts to the scientific community. Over time, ADNI MRI has become increasingly complex.

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Article Synopsis
  • The medial temporal lobe (MTL) is crucial for understanding cognitive decline related to neurodegenerative diseases, but the connection between MTL atrophy and specific proteinopathies remains unclear.
  • Researchers developed two deep learning algorithms to quantitatively measure phosphorylated tau (p-tau) and TDP-43 (pTDP-43) pathology in the MTL, focusing on their roles in Alzheimer's disease and LATE.
  • Their study found that quantitative p-tau measures better correlate with structural changes in the MTL compared to semi-quantitative ratings, revealing significant associations with cortical thickness and volume, especially in severe Alzheimer's cases.
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Background: Excessive daytime sleepiness (EDS) is a disabling symptom of Lewy body disorders (LBD). The hypothalamus is a key sleep-wake regulator, but its contribution to EDS in LBD remains unclear.

Objectives: Use diffusion MRI to evaluate the relationship of hypothalamic microstructure to EDS symptoms in LBD.

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Background: The piriform cortex has been implicated in the initiation, spread and termination of epileptic seizures. This understanding has extended to surgical management of epilepsy, where it has been shown that resection or ablation of the piriform cortex can result in better outcomes. How and why the piriform cortex may play such a crucial role in seizure networks is not well understood.

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The most commonly used neuroimaging biomarkers of brain structure, particularly in neurodegenerative diseases, have traditionally been summary measurements from ROIs derived from structural MRI, such as volume and thickness. Advances in MR acquisition techniques, including high-field imaging, and emergence of learning-based methods have opened up opportunities to interrogate brain structure in finer detail, allowing investigators to move beyond macrostructural measurements. On the one hand, superior signal contrast has the potential to make appearance-based metrics that directly analyze intensity patterns, such as texture analysis and radiomics features, more reliable.

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  • Positron Emission Tomography (FDG-PET) is commonly used to pinpoint seizure onset zones in temporal lobe epilepsy, but it’s expensive and uses a radioactive substance; an alternative, Arterial Spin Labeling (ASL), quantifies brain blood flow via MRI but isn't as effective for the same purpose.
  • This study involved 68 epilepsy patients, comparing FDG-PET with ASL to evaluate their coupling and effectiveness in localizing seizure onset zones, while also developing a deep learning tool called FlowGAN to create PET-like images from ASL data.
  • Results showed that while FDG-PET and ASL demonstrated varying levels of correlation in different brain regions, FDG-PET
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Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield.

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Background: Volumetry of subregions in the medial temporal lobe (MTL) computed from automatic segmentation in MRI can track neurodegeneration in Alzheimer's disease. However, image quality may vary in MRI. Poor quality MR images can lead to unreliable segmentation of MTL subregions.

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Article Synopsis
  • MRI tests for brain changes usually miss early signs of diseases like Alzheimer's.
  • Using a special type of MRI called diffusion MRI may help find these early signs by looking at brain structures.
  • The study found that certain brain changes are linked to Alzheimer's even before other symptoms show up, showing that this new method is really useful.
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Introduction: We investigate pathological correlates of plasma phosphorylated tau 181 (p-tau), glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) across a clinically diverse spectrum of neurodegenerative disease, including normal cognition (NormCog) and impaired cognition (ImpCog).

Methods: Participants were NormCog (n = 132) and ImpCog (n = 461), with confirmed β-amyloid (Aβ+/-) status (cerebrospinal fluid, positron emission tomography, autopsy) and single molecule array plasma measurements. Logistic regression and receiver operating characteristic (ROC) area under the curve (AUC) tested how combining plasma analytes discriminated Aβ+ from Aβ-.

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Objective: Epilepsy patients are often grouped together by clinical variables. Quantitative neuroimaging metrics can provide a data-driven alternative for grouping of patients. In this work, we leverage ultra-high-field 7-T structural magnetic resonance imaging (MRI) to characterize volumetric atrophy patterns across hippocampal subfields and thalamic nuclei in drug-resistant focal epilepsy.

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We used indirect brain mapping with virtual lesion tractography to test the hypothesis that the extent of white matter tract disconnection due to white matter hyperintensities (WMH) is associated with corresponding tract-specific cognitive performance decrements. To estimate tract disconnection, WMH masks were extracted from FLAIR MRI data of 481 cognitively intact participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) and used as regions of avoidance for fiber tracking in diffusion MRI data from 50 healthy young participants from the Human Connectome Project. Estimated tract disconnection in the right inferior fronto-occipital fasciculus, right frontal aslant tract, and right superior longitudinal fasciculus mediated the effects of WMH volume on executive function.

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Objective: Clinicians use intracranial electroencephalography (iEEG) in conjunction with noninvasive brain imaging to identify epileptic networks and target therapy for drug-resistant epilepsy cases. Our goal was to promote ongoing and future collaboration by automating the process of "electrode reconstruction," which involves the labeling, registration, and assignment of iEEG electrode coordinates on neuroimaging. We developed a standalone, modular pipeline that performs electrode reconstruction.

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Introduction: Variability in relationship of tau-based neurofibrillary tangles (T) and neurodegeneration (N) in Alzheimer's disease (AD) arises from non-specific nature of N, modulated by non-AD co-pathologies, age-related changes, and resilience factors.

Methods: We used regional T-N residual patterns to partition 184 patients within the Alzheimer's continuum into data-driven groups. These were compared with groups from 159 non-AD (amyloid "negative") patients partitioned using cortical thickness, and groups in 98 patients with ante mortem MRI and post mortem tissue for measuring N and T, respectively.

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Article Synopsis
  • The medial temporal lobe is crucial for episodic memory and is affected differently by aging and Alzheimer's disease, with each condition showing distinct patterns of vulnerability.
  • In preclinical Alzheimer's, there's an increase in functional connectivity in the medial temporal lobe, which declines as the disease progresses into its symptomatic phase.
  • Normal aging leads to decreased connectivity in both the Anterior-Temporal and Posterior-Medial networks, indicating a decline in memory-related brain functions across age.
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Synopsis of recent research by authors named "Sandhitsu Das"

  • - Sandhitsu Das's recent research primarily focuses on advanced neuroimaging techniques and their applications in understanding neurodegenerative diseases, particularly through the use of MRI and deep learning methods to enhance segmentation and analysis of brain structures.
  • - Key findings include the development and validation of face de-identification methods to protect participant privacy in Alzheimer's research, as well as the use of high-resolution imaging to investigate specific brain regions like the medial temporal lobe and their correlation with cognitive decline.
  • - Das's work also explores microstructural changes in various brain regions associated with symptoms in Lewy body disease and emphasizes the importance of beyond-macrostructure assessments, leveraging innovative imaging and analytical techniques to assess pathologies in neurodegenerative conditions.