Publications by authors named "Daniel S Marcus"

Background: Glioblastoma is the most aggressive adult primary brain cancer, characterized by significant heterogeneity, posing challenges for patient management, treatment planning, and clinical trial stratification.

Methods: We developed a highly reproducible, personalized prognostication and clinical subgrouping system using machine learning (ML) on routine clinical data, MRI, and molecular measures from 2,838 demographically diverse patients across 22 institutions and 3 continents. Patients were stratified into favorable, intermediate, and poor prognostic subgroups (I, II, III) using Kaplan-Meier analysis (Cox proportional model and hazard ratios [HR]).

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Background: Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD).

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  • Alzheimer's disease (AD) exhibits varied brain atrophy patterns, identified through a semi-supervised learning technique (Surreal-GAN) that distinguishes between "diffuse-AD" (widespread atrophy) and "MTL-AD" (focal atrophy in the medial temporal lobe) dimensions in patients with mild cognitive impairment (MCI) and AD.
  • Only the "MTL-AD" dimension was linked to known AD genetic risk factors like APOE ε4, and both dimensions were later detected in asymptomatic individuals, revealing their association with different genetic and pathological mechanisms.
  • Aside from brain-related genes, up to 77 additional genes were identified in various organs, pointing to broader
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  • - The aging process of the brain is affected by lifestyle, environmental, genetic factors, and age-related diseases, with advanced imaging and AI techniques helping to reveal the complexities of neuroanatomical changes.
  • - A study involving nearly 50,000 participants identified five major patterns of brain atrophy, which are quantified using R-indices to analyze their connections to various biomedical, lifestyle, and genetic factors.
  • - These R-indices not only predict disease progression and mortality but also offer a new, nuanced framework for understanding brain aging, which may enhance personalized diagnostics and improve clinical trial strategies.
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  • A new deep learning model called AmyloidPETNet was developed to classify brain PET scans as amyloid positive or negative, aiming to reduce reliance on radiologist expertise and costly MRI computations.
  • The model was trained on 1538 PET scans and tested on various independent data sets, achieving an impressive area under the receiver operating characteristic curve (AUC) of up to 0.98, indicating strong performance across different tracers.
  • Comparative analyses showed fair to good agreement between the model's classifications and visual assessments made by physicians, providing promising evidence for the model's clinical utility.
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Background: Magnetic resonance imaging (MRI) scans are known to suffer from a variety of acquisition artifacts as well as equipment-based variations that impact image appearance and segmentation performance. It is still unclear whether a direct relationship exists between magnetic resonance (MR) image quality metrics (IQMs) (e.g.

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  • - The study focuses on how brain aging shows various neuroanatomical changes that could hint at early stages of neurodegenerative diseases, especially in individuals without diagnosed cognitive impairment.
  • - Researchers used a deep learning method to analyze structural brain measures from over 27,000 individuals aged 45 to 85 years from 1999 to 2020 to identify common patterns.
  • - Three subgroups were discovered: a typical aging group with minor brain changes, and two accelerated aging groups that exhibited more significant changes after age 65, which may correlate with genetics and risk factors for cognitive decline.
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Brain aging is a complex process influenced by various lifestyle, environmental, and genetic factors, as well as by age-related and often co-existing pathologies. MRI and, more recently, AI methods have been instrumental in understanding the neuroanatomical changes that occur during aging in large and diverse populations. However, the multiplicity and mutual overlap of both pathologic processes and affected brain regions make it difficult to precisely characterize the underlying neurodegenerative profile of an individual from an MRI scan.

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  • Disease heterogeneity poses significant challenges for accurately diagnosing and treating neurologic and neuropsychiatric conditions, as different individuals can exhibit distinct brain phenotypes.
  • The study introduces Gene-SGAN, a method that utilizes phenotypic and genetic data to identify disease subtypes while linking them to genetic factors and biological signatures.
  • Validation results show Gene-SGAN's effectiveness in analyzing data from 28,858 individuals, revealing unique brain phenotypes in Alzheimer's disease and hypertension related to distinct neuroanatomical patterns and genetic determinants.
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Normal and pathologic neurobiological processes influence brain morphology in coordinated ways that give rise to patterns of structural covariance (PSC) across brain regions and individuals during brain aging and diseases. The genetic underpinnings of these patterns remain largely unknown. We apply a stochastic multivariate factorization method to a diverse population of 50,699 individuals (12 studies and 130 sites) and derive data-driven, multi-scale PSCs of regional brain size.

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Background: Resting-state fMRI is increasingly used to study the effects of gliomas on the functional organization of the brain. A variety of preprocessing techniques and functional connectivity analyses are represented in the literature. However, there so far has been no systematic comparison of how alternative methods impact observed results.

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Purpose: While the T2-FLAIR mismatch sign is highly specific for isocitrate dehydrogenase (IDH)-mutant, 1p/19q-noncodeleted astrocytomas among lower-grade gliomas, its utility in WHO grade 4 gliomas is not well-studied. We derived the partial T2-FLAIR mismatch sign as an imaging biomarker for IDH mutation in WHO grade 4 gliomas.

Methods: Preoperative MRI scans of adult WHO grade 4 glioma patients (n = 2165) from the multi-institutional ReSPOND (Radiomics Signatures for PrecisiON Diagnostics) consortium were analyzed.

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The translation of AI-generated brain metastases (BM) segmentation into clinical practice relies heavily on diverse, high-quality annotated medical imaging datasets. The BraTS-METS 2023 challenge has gained momentum for testing and benchmarking algorithms using rigorously annotated internationally compiled real-world datasets. This study presents the results of the segmentation challenge and characterizes the challenging cases that impacted the performance of the winning algorithms.

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Background: Patients with glioblastoma (GBM) and high-grade glioma (HGG, World Health Organization [WHO] grade IV glioma) have a poor prognosis. Consequently, there is an unmet clinical need for accessible and noninvasively acquired predictive biomarkers of overall survival in patients. This study evaluated morphological changes in the brain separated from the tumor invasion site (ie, contralateral hemisphere).

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Background: IDH mutation and 1p/19q codeletion status are important prognostic markers for glioma that are currently determined using invasive procedures. Our goal was to develop artificial intelligence-based methods to noninvasively determine molecular alterations from MRI.

Methods: Pre-operative MRI scans of 2648 glioma patients were collected from Washington University School of Medicine (WUSM; = 835) and publicly available Brain Tumor Segmentation (BraTS; = 378), LGG 1p/19q ( = 159), Ivy Glioblastoma Atlas Project (Ivy GAP; = 41), The Cancer Genome Atlas (TCGA; = 461), and the Erasmus Glioma Database (EGD; = 774) datasets.

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Purpose: Efforts to use growing volumes of clinical imaging data to generate tumor evaluations continue to require significant manual data wrangling, owing to data heterogeneity. Here, we propose an artificial intelligence-based solution for the aggregation and processing of multisequence neuro-oncology MRI data to extract quantitative tumor measurements.

Materials And Methods: Our end-to-end framework (1) classifies MRI sequences using an ensemble classifier, (2) preprocesses the data in a reproducible manner, (3) delineates tumor tissue subtypes using convolutional neural networks, and (4) extracts diverse radiomic features.

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Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors.

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Modern neuro-oncology workflows are driven by large collections of high-dimensional MRI data obtained using varying acquisition protocols. The concomitant heterogeneity of this data makes extensive manual curation and pre-processing imperative prior to algorithmic use. The limited efforts invested towards automating this curation and processing are fragmented, do not encompass the entire workflow, or still require significant manual intervention.

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Glioma is the most common form of brain tumor with a high degree of heterogeneity in imaging characteristics, treatment-response, and survival rate. An important factor causing this heterogeneity is the mutation of isocitrate dehydrogenase (IDH) enzyme. The current clinical gold-standard for identifying IDH mutation status involves invasive procedures that involve risk, may fail to capture intra-tumoral spatial heterogeneity or can be inaccessible in low-resource settings.

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An automated quality control (QC) system is essential to ensure streamlined head computed tomography (CT) scan interpretations that do not affect subsequent image analysis. Such a system is advantageous compared to current human QC protocols, which are subjective and time-consuming. In this work, we aim to develop a deep learning-based framework to classify a scan to be of usable or unusable quality.

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Article Synopsis
  • Prior studies have used different methods to explore functional connectivity in aging and Alzheimer’s disease, but they often overlook how signal amplitude impacts results.
  • This study compares covariance-based and correlation-based functional connectivity, finding that aging leads to a loss of resting state fMRI signal amplitude while Alzheimer’s disease causes both amplitude loss and disrupted correlation structure.
  • The results highlight a distinction between aging and Alzheimer’s effects on brain activity, emphasizing the significance of signal amplitude in understanding these conditions.
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Background: Hyperphosphorylation of tau leads to conformational changes that destabilize microtubules and hinder axonal transport in Alzheimer's disease (AD). However, it remains unknown whether white matter (WM) decline due to AD is associated with specific Tau phosphorylation site(s).

Methods: In autosomal dominant AD (ADAD) mutation carriers (MC) and non-carriers (NC) we compared cerebrospinal fluid (CSF) phosphorylation at tau sites (pT217, pT181, pS202, and pT205) and total tau with WM measures, as derived from diffusion tensor imaging (DTI), and cognition.

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As prevention trials advance with autosomal dominant Alzheimer disease (ADAD) participants, understanding the similarities and differences between ADAD and "sporadic" late-onset AD (LOAD) is critical to determine generalizability of findings between these cohorts. Cognitive trajectories of ADAD mutation carriers (MCs) and autopsy-confirmed LOAD individuals were compared to address this question. Longitudinal rates of change on cognitive measures were compared in ADAD MCs (n = 310) and autopsy-confirmed LOAD participants (n = 163) before and after symptom onset (estimated/observed).

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Background: Malignant cerebral edema is a devastating complication of stroke, resulting in deterioration and death if hemicraniectomy is not performed prior to herniation. Current approaches for predicting this relatively rare complication often require advanced imaging and still suffer from suboptimal performance. We performed a pilot study to evaluate whether neural networks incorporating data extracted from routine computed tomography (CT) imaging could enhance prediction of edema in a large diverse stroke cohort.

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  • Chronic traumatic encephalopathy (CTE) is a serious brain disease caused by repeated head impacts and can only be diagnosed after death; the DIAGNOSE CTE Research Project aims to develop diagnostic methods for this condition.
  • Funded by the National Institute of Neurological Disorders and Stroke, the project includes 240 male participants, focusing on former football players and asymptomatic individuals, to study various risk factors and biomarkers related to CTE.
  • The research involves extensive evaluations such as neurological exams, brain imaging, and biological sample collection, with a focus on refining clinical criteria and sharing data with the broader research community.
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