Publications by authors named "Kristin R Swanson"

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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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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Many cancers, including glioblastoma (GBM), have a male-biased sex difference in incidence and outcome. The underlying reasons for this sex bias are unclear but likely involve differences in tumor cell state and immune response. This effect is further amplified by sex hormones, including androgens, which have been shown to inhibit anti-tumor T cell immunity.

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Article Synopsis
  • 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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  • The study compares volumetric measurements of pediatric low-grade gliomas (pLGG) to simpler 2D methods traditionally used in clinical trials, aiming to determine which is more effective for assessing tumor response.
  • An expert neuroradiologist assessed both solid and whole tumor volumes from MRI scans, finding that 3D volumetric analysis significantly outperformed 2D assessments in classifying tumor progression based on the BT-RADS criteria.
  • Results showed that using 3D volume thresholds provided strong sensitivity for detecting tumor progression, suggesting that volumetric methods could enhance clinical management of pLGG.
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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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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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Background: Glioblastoma is an extraordinarily heterogeneous tumor, yet the current treatment paradigm is a "one size fits all" approach. Hundreds of glioblastoma clinical trials have been deemed failures because they did not extend median survival, but these cohorts are comprised of patients with diverse tumors. Current methods of assessing treatment efficacy fail to fully account for this heterogeneity.

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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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Purpose: Quantify in vivo biomechanical tissue properties in various breast densities and in average risk and high-risk women using Magnetic Resonance Imaging (MRI)/MRE and examine the association between breast biomechanical properties and cancer risk based on patient demographics and clinical data.

Methods: Patients with average risk or high-risk of breast cancer underwent 3.0 T breast MR imaging and elastography.

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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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Lacunarity, a quantitative morphological measure of how shapes fill space, and fractal dimension, a morphological measure of the complexity of pixel arrangement, have shown relationships with outcome across a variety of cancers. However, the application of these metrics to glioblastoma (GBM), a very aggressive primary brain tumor, has not been fully explored. In this project, we computed lacunarity and fractal dimension values for GBM-induced abnormalities on clinically standard magnetic resonance imaging (MRI).

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Objective: Recent studies have proposed resection of the T2 FLAIR hyperintensity beyond the T1 contrast enhancement (supramarginal resection [SMR]) for IDH-wild-type glioblastoma (GBM) to further improve patients' overall survival (OS). GBMs have significant variability in tumor cell density, distribution, and infiltration. Advanced mathematical models based on patient-specific radiographic features have provided new insights into GBM growth kinetics on two important parameters of tumor aggressiveness: proliferation rate (ρ) and diffusion rate (D).

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The most commonly-used omics databases are a compilation of results from primarily male-only and sex-agnostic studies. The pervasive use of these databases critically hinders progress towards fully accounting for the biology of sex differences.

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Radiogenomics uses machine-learning (ML) to directly connect the morphologic and physiological appearance of tumors on clinical imaging with underlying genomic features. Despite extensive growth in the area of radiogenomics across many cancers, and its potential role in advancing clinical decision making, no published studies have directly addressed uncertainty in these model predictions. We developed a radiogenomics ML model to quantify uncertainty using transductive Gaussian Processes (GP) and a unique dataset of 95 image-localized biopsies with spatially matched MRI from 25 untreated Glioblastoma (GBM) patients.

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Glioblastoma (GBM) is the most aggressive primary brain tumor and can have cystic components, identifiable through magnetic resonance imaging (MRI). Previous studies suggest that cysts occur in 7-23% of GBMs and report mixed results regarding their prognostic impact. Using our retrospective cohort of 493 patients with first-diagnosis GBM, we carried out an exploratory analysis on this potential link between cystic GBM and survival.

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Glioblastoma (GBM) is the most aggressive primary brain tumor with a short median survival. Tumor recurrence is a clinical expectation of this disease and usually occurs along the resection cavity wall. However, previous clinical observations have suggested that in cases of ischemia following surgery, tumors are more likely to recur distally.

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The influence of biological sex differences on human health and disease, while being increasingly recognized, has long been underappreciated and underexplored. While humans of all sexes are more alike than different, there is evidence for sex differences in the most basic aspects of human biology and these differences have consequences for the etiology and pathophysiology of many diseases. In a disease like cancer, these consequences manifest in the sex biases in incidence and outcome of many cancer types.

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Glioblastomas (GBMs) are the most aggressive primary brain tumours and have no known cure. Each individual tumour comprises multiple sub-populations of genetically-distinct cells that may respond differently to targeted therapies and may contribute to disappointing clinical trial results. Image-localized biopsy techniques allow multiple biopsies to be taken during surgery and provide information that identifies regions where particular sub-populations occur within an individual GBM, thus providing insight into their regional genetic variability.

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Article Synopsis
  • * A database of 741 MRI exams from 729 unique patients was compiled, where 641 exams were used for training the DL system, and 100 were set aside for testing through a blinded assessment platform.
  • * Neuroradiologists rated the mean scores of DL segmentations higher than those from technicians (7.31 vs 6.97), and the DL method demonstrated a strong overlap in segmentations with a Dice coefficient of 0.87, indicating its potential to outperform human segmentations.
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Many drugs investigated for the treatment of glioblastoma (GBM) have had disappointing clinical trial results. Efficacy of these agents is dependent on adequate delivery to sensitive tumor cell populations, which is limited by the blood-brain barrier (BBB). Additionally, tumor heterogeneity can lead to subpopulations of cells with different sensitivities to anti-cancer drugs, further impacting therapeutic efficacy.

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Equation learning methods present a promising tool to aid scientists in the modeling process for biological data. Previous equation learning studies have demonstrated that these methods can infer models from rich datasets; however, the performance of these methods in the presence of common challenges from biological data has not been thoroughly explored. We present an equation learning methodology comprised of data denoising, equation learning, model selection and post-processing steps that infers a dynamical systems model from noisy spatiotemporal data.

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