Publications by authors named "Leland Hu"

The dynamic susceptibility contrast (DSC) MRI measures of relative cerebral blood volume (rCBV) play a central role in monitoring therapeutic response and disease progression in patients with gliomas. Previous investigations have demonstrated promise of using rCBV in classifying tumor grade, elucidating tumor viability after therapy, and differentiating pseudoprogression and pseudoresponse. However, the quantification and reproducibility of rCBV measurements across patients, devices, and software remain a critical barrier to routine or clinical trial use of longitudinal DSC MRI in patients with gliomas.

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Background: Older patients (aged ≥65 years) with glioblastoma have a worse prognosis than younger patients and a median overall survival of 6-9 months. 3,4-Dihydroxy-6-[F]fluoro-L-phenylalanine (F-DOPA) PET sensitively and specifically identifies metabolically active glioblastoma for preferential targeting. Proton beam therapy potentially improves quality of life (QOL) by sparing more healthy brain tissue than photon radiotherapy.

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  • Glioblastoma patients typically have a poor prognosis even after standard treatments, prompting research into new combinations of therapy.
  • The study evaluated the effectiveness of veliparib combined with temozolomide for glioblastoma patients with MGMT promoter hypermethylation, hoping to enhance treatment outcomes.
  • Results showed a slight improvement in median overall survival for the veliparib group compared to the placebo, but the difference wasn't significant enough to meet efficacy goals, though the combination treatment was generally well tolerated.
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Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of recurrent glioblastoma. This study addresses the need for non-invasive approaches to map heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient. We developed BioNet, a biologically-informed neural network, to predict regional distributions of two primary tissue-specific gene modules: proliferating tumor (Pro) and reactive/inflammatory cells (Inf).

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  • A national consensus has been established for DSC MRI perfusion data collection to improve comparisons of relative cerebral blood volume (rCBV) maps across different sites and enhance the understanding of brain tumors.
  • This study involved patients with untreated brain metastases, using a standardized MRI technique to generate and analyze rCBV maps, facilitating comparisons with glioblastoma and normal brain tissue.
  • Results showed that the average sRCBV for brain metastases was significantly lower than that of glioblastoma but higher than that of normal appearing white matter, indicating distinct differences in blood volume among these conditions.
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Background And Purpose: DSC-MR imaging can be used to generate fractional tumor burden (FTB) maps via application of relative CBV thresholds to spatially differentiate glioblastoma recurrence from posttreatment radiation effects (PTRE). Image-localized histopathology was previously used to validate FTB maps derived from a reference DSC-MR imaging protocol by using preload, a moderate flip angle (MFA, 60°), and postprocessing leakage correction. Recently, a DSC-MR imaging protocol with a low flip angle (LFA, 30°) with no preload was shown to provide leakage-corrected relative CBV (rCBV) equivalent to the reference protocol.

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Intratumoral heterogeneity poses a significant challenge to the diagnosis and treatment of glioblastoma (GBM). This heterogeneity is further exacerbated during GBM recurrence, as treatment-induced reactive changes produce additional intratumoral heterogeneity that is ambiguous to differentiate on clinical imaging. There is an urgent need to develop non-invasive approaches to map the heterogeneous landscape of histopathological alterations throughout the entire lesion for each patient.

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  • Glioblastoma (GBM) is a highly aggressive cancer characterized by genetic variability within tumors, making it difficult to treat effectively; this study aimed to develop a non-invasive MRI-based machine learning model to analyze this genetic heterogeneity.
  • The research introduced a Weakly Supervised Ordinal Support Vector Machine (WSO-SVM) model, trained on data from 74 patients, to predict alterations in key GBM genes using MRI images, achieving higher accuracy than existing algorithms.
  • Results showed the WSO-SVM model to be effective, with accuracies of 80% for the EGFR gene and comparable results for others; the analysis also highlighted different contributions of MRI images, providing valuable insights into tumor genetics for better treatment planning
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This Expert Panel Narrative Review explores the current status of advanced MRI and PET techniques for the posttherapeutic response assessment of high-grade adult-type gliomas, focusing on ongoing clinical controversies in current practice. Discussed techniques that complement conventional MRI and aid the differentiation of recurrent tumor from posttreatment effects include DWI and diffusion-tensor imaging; perfusion MRI techniques including dynamic susceptibility contrast (DSC), dynamic contrast-enhanced, and arterial spin labeling MRI; MR spectroscopy (MRS) including assessment of 2-hydroxyglutarate (2HG) concentration; glucose- and amino acid (AA)-based PET; and amide proton transfer imaging. Updated criteria for the Response Assessment in Neuro-Oncology are presented.

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  • MRI is commonly used in high-grade glioma treatments to map tumor boundaries and assist in surgery, revealing important tumor biology through its measurements.
  • The study found that specific MRI techniques (like T1+C) not only visualize the tumor's blood flow disruption but also indicate immune cell infiltration, enhancing our understanding of how these factors interact within the tumor environment.
  • The research offers a new, unbiased methodology for linking MRI results with tumor biology, laying the groundwork for future advancements in noninvasive diagnostics and treatment strategies for patients with high-grade gliomas.
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Brain cancers pose a novel set of difficulties due to the limited accessibility of human brain tumor tissue. For this reason, clinical decision-making relies heavily on MR imaging interpretation, yet the mapping between MRI features and underlying biology remains ambiguous. Standard (clinical) tissue sampling fails to capture the full heterogeneity of the disease.

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  • Purpose of the study was to standardize quantitative imaging methods for tumors, specifically using DCE-MRI, through the OSIPI-DCE challenge to benchmark these methods.
  • Methods involved creating a framework for evaluating DCE-MRI analysis submissions from the perfusion MRI community, focusing on glioblastoma quantification and requiring detailed reporting of procedures and software.
  • Results showed significant variability in software performance, with scores indicating differences in accuracy, repeatability, and reproducibility, while highlighting the importance of standardized procedures for improving analysis consistency.
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Imaging is central to the clinical surveillance of brain tumors yet it provides limited insight into a tumor's underlying biology. Machine learning and other mathematical modeling approaches can leverage paired magnetic resonance images and image-localized tissue samples to predict almost any characteristic of a tumor. Image-based modeling takes advantage of the spatial resolution of routine clinical scans and can be applied to measure biological differences within a tumor, changes over time, as well as the variance between patients.

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Sampling restrictions have hindered the comprehensive study of invasive non-enhancing (NE) high-grade glioma (HGG) cell populations driving tumor progression. Here, we present an integrated multi-omic analysis of spatially matched molecular and multi-parametric magnetic resonance imaging (MRI) profiling across 313 multi-regional tumor biopsies, including 111 from the NE, across 68 HGG patients. Whole exome and RNA sequencing uncover unique genomic alterations to unresectable invasive NE tumor, including subclonal events, which inform genomic models predictive of geographic evolution.

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  • Glioblastoma treatment currently uses a generic approach, leading to many failed clinical trials due to the tumor's vast diversity among patients.
  • An image-based modeling technique was applied to predict T-cell levels from MRI scans of patients in a dendritic cell vaccine trial, focusing on different tumor regions over time.
  • The study identified previously unrecognized patients who responded positively to the vaccine, suggesting that machine learning can improve clinical trial assessments and move towards personalized treatment strategies.
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Primary central nervous system lymphoma (PCNSL) is a diffuse large B cell lymphoma in which the brain, spinal cord, leptomeninges and/or eyes are exclusive sites of disease. Pathophysiology is incompletely understood, although a central role seems to comprise immunoglobulins binding to self-proteins expressed in the central nervous system (CNS) and alterations of genes involved in B cell receptor, Toll-like receptor and NF-κB signalling. Other factors such as T cells, macrophages or microglia, endothelial cells, chemokines, and interleukins, probably also have important roles.

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Introduction: Resting-state functional magnetic resonance imaging (fMRI) graph theory may help detect subtle functional connectivity changes affecting memory prior to impairment.

Methods: Cognitively normal apolipoprotein E (APOE) ε4 carriers/noncarriers underwent longitudinal cognitive assessment and one-time MRI. The relationship of left/right hippocampal connectivity and memory trajectory were compared between carriers/noncarriers.

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Background: Relative cerebral blood volume (rCBV) obtained from dynamic susceptibility contrast (DSC) MRI is widely used to distinguish high grade glioma recurrence from post treatment radiation effects (PTRE). Application of rCBV thresholds yield maps to distinguish between regional tumor burden and PTRE, a biomarker termed the fractional tumor burden (FTB). FTB is generally measured using conventional double-dose, single-echo DSC-MRI protocols; recently, a single-dose, dual-echo DSC-MRI protocol was clinically validated by direct comparison to the conventional double-dose, single-echo protocol.

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  • CE-MRI is the preferred imaging method for diagnosing and monitoring primary central nervous system lymphoma, but it may not accurately reflect the true tumor size due to its reliance on specific anatomical measurements.
  • While standard T1 and T2 MRI techniques are commonly used, incorporating additional methods like diffusion-weighted and perfusion-weighted imaging could enhance understanding of tumor behavior and response to treatment.
  • There is a pressing need for standardizing imaging practices and reporting, as current inconsistencies hinder effective treatment planning and clinical trial outcomes for patients with PCNSL.
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  • The paper discusses the need for spatial predictions of molecular markers in cancer treatment to enhance precision medicine, particularly in matching therapies to tumors based on their unique markers.
  • It highlights the challenges in obtaining accurate measurements of these markers due to the limitations of existing methods like biopsies and MRI imaging.
  • The authors introduce a new machine learning approach, the Knowledge-Infused Global-Local Data Fusion (KGL) model, which successfully combines biopsy data, MRI images, and biological models to improve predictions of tumor cell density in brain cancer patients, achieving superior accuracy.
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Brain metastases occur commonly in patients with advanced solid malignancies. Yet, less is known about brain metastases than cancer-related entities of similar incidence. Advances in oncologic care have heightened the importance of intracranial management.

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Automatic brain tumor segmentation is particularly challenging on magnetic resonance imaging (MRI) with marked pathologies, such as brain tumors, which usually cause large displacement, abnormal appearance, and deformation of brain tissue. Despite an abundance of previous literature on learning-based methodologies for MRI segmentation, few works have focused on tackling MRI skull stripping of brain tumor patient data. This gap in literature can be associated with the lack of publicly available data (due to concerns about patient identification) and the labor-intensive nature of generating ground truth labels for model training.

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In the follow-up treatment of high-grade gliomas (HGGs), differentiating true tumor progression from treatment-related effects, such as pseudoprogression and radiation necrosis, presents an ongoing clinical challenge. Conventional MRI with and without intravenous contrast serves as the clinical benchmark for the posttreatment surveillance imaging of HGG. However, many advanced imaging techniques have shown promise in helping better delineate the findings in indeterminate scenarios, as posttreatment effects can often mimic true tumor progression on conventional imaging.

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