Publications by authors named "Ranjit Ittyerah"

Background: Recent advances in automatic face recognition have increased the risk that de-identified research imaging data could be re-identified from face imagery in brain scans.

Method: An ADNI committee of independent imaging experts evaluated 11 published techniques for face-deidentification ("de-facing") and selected four algorithms (FSL-UK Biobank, HCP/XNAT, mri_reface, and BIC) for formal testing using 183 longitudinal scans of 61 racially and ethnically diverse ADNI participants, evaluated by their facial feature removal on 3D rendered surfaces (confirming sufficient privacy protection) and by comparing measurements from ADNI routine image analyses on unmodified vs. de-faced images (confirming negligible side effects on analyses).

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Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-β [Aβ], α-synuclein [α-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

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Background: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a neurodegenerative disease that is often comorbid with Alzheimer's disease (AD) and for which there are no reliable specific chemical or PET biomarkers available. Recent progress in disease-modifying treatments for AD elevates the need for reliable in vivo detection of LATE and other comorbid neurodegenerative diseases. The promise of postmortem and antemortem MRI studies in LATE is that they will lead to the discovery of patterns of neurodegeneration associated with TDP-43 pathology that could be reliably detected in vivo and used as a biomarker of LATE.

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Background: Tau pathology and neurodegeneration in the medial temporal lobe (MTL) are highly associated in Alzheimer's Disease (AD). However, the spatial pattern of neurodegeneration, contribution of individual tau inclusion types, and influence of MTL co-pathologies (i.e.

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Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

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Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

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Background: Postmortem MRI allows brain anatomy to be examined at high-resolution linking pathology with morphometric measurements. However, automated methods for analyzing postmortem MRI are not well developed. We present a deep learning-based framework for automated segmentation of cortical mantle, subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities (WMH), and normal appearing white matter in (n=135) postmortem human brain tissue specimens (Table 1) imaged at 0.

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Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without β-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

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Background: The anterior portion of the MTL is one of the first regions targeted by pathology in sporadic Alzheimer's disease (AD) indicating the potential for imaging metrics from this region to serve as valuable imaging biomarkers. However, most existing automated approaches for MTL segmentation do not incorporate anterior MTL subregions, and the few that do fail to account for its complex anatomical variability. Leveraging a unique postmortem dataset consisting of histology and structural MRI scans we aimed to develop an anatomically valid segmentation protocol for anterior entorhinal cortex (ERC), Brodmann Area (BA) 35, and BA36 and apply it for automated MTL segmentation of in vivo 3 tesla (T) MRI.

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Background: Histopathological analysis of autopsied brains is the gold standard of diagnosis in neurodegenerative disorders. Co-registered histology and MRI scans aid in understanding pathology and structural features. Previous studies focused on the medial temporal lobe (MTL) for atrophy patterns in phosphorylated tau (p-tau) pathology and in whole hemisphere scans with contralateral semi-quantitative p-tau measures.

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Background: Hippocampal Sclerosis of aging (HS) refers to age-related selective neuronal loss and gliosis in hippocampal cornu ammonis 1 (CA1) and subiculum that is out of proportion to tau pathology in Alzheimer's Disease (AD). HS is related to cognitive decline and memory impairments separately from other neurodegenerative pathologies. To date, in vivo imaging biomarkers of HS of aging are non-existent, and their development would greatly improve diagnosis and prognosis in memory clinics.

View Article and Find Full Text PDF

Background: Tau pathology and neurodegeneration in the medial temporal lobe (MTL) are highly associated in Alzheimer's Disease (AD). However, the spatial pattern of neurodegeneration, contribution of individual tau inclusion types, and influence of MTL co-pathologies (i.e.

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Background: The amygdala is a hotspot for neuropathologies; however, it is unclear 1) which neuropathologies lead to amygdala neurodegeneration, 2) what specific amygdala subnuclei are affected, and 3) if the neuropathologies related to amygdala volume are local (inside the amygdala), or distal (in other regions). We investigate the relationships between different neuropathologies (tau, amyloid-ß [Aß], a-synuclein [a-syn], and transactive response DNA-binding protein 43 [TDP-43]) and amygdala volumes.

Method: We analyzed postmortem data from 73 individuals with and without neurodegenerative diseases (age: 77±11 [45-101] years; 26 [36%] females; 51 [70%] cognitively impaired).

View Article and Find Full Text PDF

Background: Recent advances in automatic face recognition have increased the risk that de-identified research imaging data could be re-identified from face imagery in brain scans.

Method: An ADNI committee of independent imaging experts evaluated 11 published techniques for face-deidentification ("de-facing") and selected four algorithms (FSL-UK Biobank, HCP/XNAT, mri_reface, and BIC) for formal testing using 183 longitudinal scans of 61 racially and ethnically diverse ADNI participants, evaluated by their facial feature removal on 3D rendered surfaces (confirming sufficient privacy protection) and by comparing measurements from ADNI routine image analyses on unmodified vs. de-faced images (confirming negligible side effects on analyses).

View Article and Find Full Text PDF

Background: The medial temporal lobe (MTL) is the epicenter of both primary and concomitant molecular pathologies in Alzheimer's disease (AD). The intricate anatomy of the MTL has been the subject of extensive study over the past two centuries. However, current PET and MRI AD biomarkers use often crude parcellations of the MTL that have not been sufficiently validated vis-à-vis anatomical ground truth.

View Article and Find Full Text PDF

Background: Postmortem MRI allows brain anatomy to be examined at high-resolution linking pathology with morphometric measurements. However, automated methods for analyzing postmortem MRI are not well developed. We present a deep learning-based framework for automated segmentation of cortical mantle, subcortical structures (caudate, putamen, globus pallidus, and thalamus), white matter hyperintensities (WMH), and normal appearing white matter in (n = 135) postmortem human brain tissue specimens (Table 1) imaged at 0.

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Background: The medial temporal lobe's (MTL) early involvement in tau pathology makes it a key focus in the development of preclinical Alzheimer's disease (AD) biomarkers. ROI analyses in prior studies reported significant MTL structural differences in cognitively normal individuals with and without ß-amyloid (A+/-CN). Pointwise analysis, offering spatial information of early neurodegeneration, has potential to pinpoint "signature regions" of pathological change, but has been underexplored in the MTL.

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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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Article Synopsis
  • The paper reviews the introduction of high-resolution T2-weighted MRI scans to the Alzheimer's Disease Neuroimaging Initiative (ADNI) Phase 3, focusing on the medial temporal lobe (MTL) subregions and hippocampal areas.
  • It discusses the application of new surface-based analysis techniques to assess neurodegeneration patterns related to Alzheimer's disease (AD), highlighting the correlation with amyloid and tau biomarkers.
  • The study concludes with insights into the future of high-resolution MTL imaging efforts in ADNI Phase 4, emphasizing the relationship between tau pathology and cortical thinning.
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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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Article Synopsis
  • Current understanding of tau neurofibrillary tangles (NFTs) in Alzheimer's Disease is hindered by other non-AD pathologies and limitations of conventional two-dimensional histological methods.
  • The study combines ex vivo MRI and serial histological imaging from 25 human medial temporal lobe specimens to create a high-resolution 3-D atlas that maps the distribution of NFT burden.
  • Findings reveal a gradient in NFT distribution from anterior to posterior in the medial temporal lobe, with highest concentrations in specific regions, suggesting certain areas may serve as early biomarkers for neurodegeneration in Alzheimer's Disease.
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Article Synopsis
  • The medial temporal lobe (MTL) cortex, essential for memory and vulnerable to diseases like Alzheimer's, consists of various subregions with distinct functions and structures.
  • This study compares the cytoarchitectonic definitions of specific areas within the MTL cortex provided by four different neuroanatomists to assess overlapping and differing delineations among them.
  • Findings revealed more consensus on the entorhinal cortex and Brodmann area 35, while there was less agreement on Brodmann area 36 and the parahippocampal cortex, particularly in transitional zones where defining features are not as clear.
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