Publications by authors named "Michael T Duong"

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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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 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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We report the first description of spinal cord mycobacterial spindle cell pseudotumor. A patient with newly diagnosed advanced HIV presented with recent-onset bilateral leg weakness and was found to have a hypermetabolic spinal cord mass on structural and molecular imaging. Biopsy and cultures from blood and cerebrospinal fluid confirmed spindle cell pseudotumor due to Mycobacterium avium-intracellulare.

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To gauge the safety and utility of extended tecovirimat/cidofovir for severe mpox, here we report our experience caring for 4 patients with mpox and advanced human immunodeficiency virus (HIV) at the Hospitals of the University of Pennsylvania during the 2022 global outbreak. Three patients had recurrent courses complicated by superinfections, coinfections and insufficient nutrition/housing, requiring extended tecovirimat (5-16 weeks) and cidofovir (1-12 doses) with probenecid and fluids. At follow-up, patients had undetectable HIV RNA on antiretrovirals, improved ulcers and stable renal function on antivirals.

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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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Recent therapeutic advances provide heightened motivation for accurate diagnosis of the underlying biologic causes of dementia. This review focuses on the importance of clinical recognition of limbic-predominant age-related TDP-43 encephalopathy (LATE). LATE affects approximately one-quarter of older adults and produces an amnestic syndrome that is commonly mistaken for Alzheimer's disease (AD).

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Cholesterol is stored as cholesteryl esters by the enzymes acyl-CoA:cholesterol acyltransferases/sterol O:acyltransferases (ACATs/SOATs). ACAT1 blockade (A1B) ameliorates the pro-inflammatory responses of macrophages to lipopolysaccharides (LPS) and cholesterol loading. However, the mediators involved in transmitting the effects of A1B in immune cells is unknown.

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Variability in the relationship of tau-based neurofibrillary tangles (T) and degree of neurodegeneration (N) in Alzheimer's Disease (AD) is likely attributable to the non-specific nature of N, which is also modulated by such factors as other co-pathologies, age-related changes, and developmental differences. We studied this variability by partitioning patients within the Alzheimer's continuum into data-driven groups based on their regional T-N dissociation, which reflects the residuals after the effect of tau pathology is "removed". We found six groups displaying distinct spatial T-N and thickness patterns despite similar tau burden.

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Neuroimaging provides rapid, noninvasive visualization of central nervous system infections for optimal diagnosis and management. Generalizable and characteristic imaging patterns help radiologists distinguish different types of intracranial infections including meningitis and cerebritis from a variety of bacterial, viral, fungal, and/or parasitic causes. Here, we describe key radiologic patterns of meningeal enhancement and diffusion restriction through profiles of meningitis, cerebritis, abscess, and ventriculitis.

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Purpose Of Review: Limbic-predominant age-related TDP-43 encephalopathy (LATE) is a recently defined neurodegenerative disease characterized by amnestic phenotype and pathological inclusions of TAR DNA-binding protein 43 (TDP-43). LATE is distinct from rarer forms of TDP-43 diseases such as frontotemporal lobar degeneration with TDP-43 but is also a common copathology with Alzheimer's disease (AD) and cerebrovascular disease and accelerates cognitive decline. LATE contributes to clinicopathologic heterogeneity in neurodegenerative diseases, so it is imperative to distinguish LATE from other etiologies.

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Alzheimer's disease (AD) is defined by amyloid (A) and tau (T) pathologies, with T better correlated to neurodegeneration (N). However, T and N have complex regional relationships in part related to non-AD factors that influence N. With machine learning, we assessed heterogeneity in F-flortaucipir vs.

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Purpose: To assess how well a brain MRI lesion segmentation algorithm trained at one institution performed at another institution, and to assess the effect of multi-institutional training datasets for mitigating performance loss.

Materials And Methods: In this retrospective study, a three-dimensional U-Net for brain MRI abnormality segmentation was trained on data from 293 patients from one institution (IN1) (median age, 54 years; 165 women; patients treated between 2008 and 2018) and tested on data from 51 patients from a second institution (IN2) (median age, 46 years; 27 women; patients treated between 2003 and 2019). The model was then trained on additional data from various sources: 285 multi-institution brain tumor segmentations, 198 IN2 brain tumor segmentations, and 34 IN2 lesion segmentations from various brain pathologic conditions.

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Article Synopsis
  • The study investigates the relationship between tau neurofibrillary tangles and neurodegeneration in Alzheimer's disease, highlighting that this relationship can vary significantly between individuals.
  • Researchers analyzed brain scans from 104 cognitively impaired individuals, calculating a metric to identify discrepancies in expected atrophy based on tau levels, which linked to factors like age and white matter lesions.
  • Findings suggest that these variations reveal different biological phenotypes, indicating that other contributors beyond tau might influence neurodegeneration, potentially aiding in cohort selection for clinical trials.
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Background: Neuroinflammation is a well-known feature of early Alzheimer disease (AD) yet astrocyte activation has not been extensively evaluated with in vivo imaging in mild cognitive impairment (MCI) due to amyloid plaque pathology. Unlike neurons, astrocytes metabolize acetate, which has potential as a glial biomarker in neurodegeneration in response to AD pathologic features. Since the medial temporal lobe (MTL) is a hotspot for AD neurodegeneration and inflammation, we assessed astrocyte activity in the MTL and compared it to amyloid and cognition.

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Automated quantitative and probabilistic medical image analysis has the potential to improve the accuracy and efficiency of the radiology workflow. We sought to determine whether AI systems for brain MRI diagnosis could be used as a clinical decision support tool to augment radiologist performance. We utilized previously developed AI systems that combine convolutional neural networks and expert-derived Bayesian networks to distinguish among 50 diagnostic entities on multimodal brain MRIs.

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Purpose: To develop and validate a system that could perform automated diagnosis of common and rare neurologic diseases involving deep gray matter on clinical brain MRI studies.

Materials And Methods: In this retrospective study, multimodal brain MRI scans from 212 patients (mean age, 55 years ± 17 [standard deviation]; 113 women) with 35 neurologic diseases and normal brain MRI scans obtained between January 2008 and January 2018 were included (110 patients in the training set, 102 patients in the test set). MRI scans from 178 patients (mean age, 48 years ± 17; 106 women) were used to supplement training of the neural networks.

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Vascular contributions to cognitive impairment and dementia (VCID) are a common cause of cognitive decline, yet limited therapies exist. This cerebrovascular disease results in neurodegeneration acute, chronic, local, and systemic mechanisms. The etiology of VCID is complex, with a significant impact from atherosclerosis.

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Recent advances in artificial intelligence (AI) and deep learning (DL) hold promise to augment neuroimaging diagnosis for patients with brain tumors and stroke. Here, the authors review the diverse landscape of emerging neuroimaging applications of AI, including workflow optimization, lesion segmentation, and precision education. Given the many modalities used in diagnosing neurologic diseases, AI may be deployed to integrate across modalities (MR imaging, computed tomography, PET, electroencephalography, clinical and laboratory findings), facilitate crosstalk among specialists, and potentially improve diagnosis in patients with trauma, multiple sclerosis, epilepsy, and neurodegeneration.

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Background Although artificial intelligence (AI) shows promise across many aspects of radiology, the use of AI to create differential diagnoses for rare and common diseases at brain MRI has not been demonstrated. Purpose To evaluate an AI system for generation of differential diagnoses at brain MRI compared with radiologists. Materials and Methods This retrospective study tested performance of an AI system for probabilistic diagnosis in patients with 19 common and rare diagnoses at brain MRI acquired between January 2008 and January 2018.

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In the era of personalized medicine, the emphasis of health care is shifting from populations to individuals. Artificial intelligence (AI) is capable of learning without explicit instruction and has emerging applications in medicine, particularly radiology. Whereas much attention has focused on teaching radiology trainees about AI, here our goal is to instead focus on how AI might be developed to better teach radiology trainees.

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