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Item Advanced imaging techniques for neuro-oncologic tumor diagnosis, with an emphasis on PET-MRI imaging of malignant brain tumors(Springer, 2021-02-18) Overcast, Wynton B.; Davis, Korbin M.; Ho, Chang Y.; Hutchins, Gary D.; Green, Mark A.; Graner, Brian D.; Veronesi, Michael C.; Radiology and Imaging Sciences, School of MedicinePurpose of review: This review will explore the latest in advanced imaging techniques, with a focus on the complementary nature of multiparametric, multimodality imaging using magnetic resonance imaging (MRI) and positron emission tomography (PET). Recent findings: Advanced MRI techniques including perfusion-weighted imaging (PWI), MR spectroscopy (MRS), diffusion-weighted imaging (DWI), and MR chemical exchange saturation transfer (CEST) offer significant advantages over conventional MR imaging when evaluating tumor extent, predicting grade, and assessing treatment response. PET performed in addition to advanced MRI provides complementary information regarding tumor metabolic properties, particularly when performed simultaneously. 18F-fluoroethyltyrosine (FET) PET improves the specificity of tumor diagnosis and evaluation of post-treatment changes. Incorporation of radiogenomics and machine learning methods further improve advanced imaging. The complementary nature of combining advanced imaging techniques across modalities for brain tumor imaging and incorporating technologies such as radiogenomics has the potential to reshape the landscape in neuro-oncology. Keywords: Advanced MRI; Amino acid PET; Brain tumor; Chemical exchange saturation transfer; Diffusion-weighted imaging; FET; Glioblastoma; Glioma; High-grade malignancy; Hybrid PET/MRI; MR spectroscopy; Metastasis; Perfusion-weighted imaging; Progression; Pseudoprogression; Pseudoresponse; Radiation necrosis; Radiogenomics; Radiomics; Treatment-related change; Tumor grading.Item The experience of post-craniotomy pain among persons with brain tumors(2018-04-16) Foust, Rebecca Elizabeth; Von Ah, Diane M.; Draucker, Claire B.; Carpenter, Janet S.; Kroenke, Kurt; Stone, CynthiaPost-craniotomy brain tumor patients often experience pain in the post-surgical period which can negatively affect recovery and surgical outcomes. Research with this population has focused on pharmacological treatments of post-craniotomy pain and measurement of pain intensity. Little is known about how these patients experience the quality of their pain and how this pain is managed. The purpose of this dissertation was to provide an in-depth description of the experience of post-craniotomy pain during the post-surgical period. The information gained about how post-craniotomy patients experience pain and pain management will contribute the development of effective, tailored interventions to enhance patient satisfaction and outcomes. This dissertation project was composed of two components. The first component was an integrative review of literature examining the evidence of pain and associated symptoms in adult (aged 21 and older), post-craniotomy brain tumor patients. The review examined studies from the past fourteen years that focused on the incidence and treatment of postcraniotomy pain. It revealed that the majority of post-craniotomy patients experience moderate to severe pain after surgery. This pain is associated with nausea, vomiting, changes in blood pressure, and increased length of hospital stay. The second component was a qualitative descriptive study of a sample of 28 adult (aged 21 and older) post-craniotomy patients hospitalized on an inpatient neurosurgical stepdown unit at a Midwestern urban teaching hospital. During semi-structured interviews, participants described their experiences of post-craniotomy pain and of their experiences of postcraniotomy pain management. Data generated from the qualitative descriptive study were analyzed and resulted in two qualitatively derived products. The first was a description of participants’ experiences of the quality of their post-craniotomy pain during the post-surgical period. The six types of pain quality described were pain as pressure, pain as tender or sore, pain as stabbing, pain as throbbing, pain as jarring, and pain as itching. The second was a description of how post-craniotomy patients experience the management of their pain during the post-surgical period. The four groups of types of pain management experiences described were pain-as-non-salient, routine pain management; pain-as-non-salient, complex pain management; pain-as-salient, routine pain management; and pain-as-salient, complex pain management.Item Human stem cell models to unravel brain cancer(Springer Nature, 2024-11-28) Dave, Biren; Tailor, Jignesh; Neurological Surgery, School of MedicinePre-clinical animal models of human brain tumors have been invaluable tools for studying cancer pathogenesis and exploring novel treatment modalities. Such models recapitulate important aspects of the human disease such as the stem-progenitor-differentiated cell hierarchy. Although powerful, we argue that animal models are inherently limited in their ability to phenocopy certain important aspects of human brain tumor biology. We specifically highlight the inability of mouse models to generate certain forms aggressive pediatric medulloblastoma likely owing to cellular, anatomic, and genetic differences between the human and mouse brains. Additionally, we review some limitations of human brain tumor derived cell lines and outline why they are a sub-optimal system for purposes of pre-clinical modeling. Below, we present the case for human stem cell-based models of brain tumors, focusing mainly on glioblastoma and medulloblastoma. Drawing on several recently published studies, we review the exciting progress that has been made towards modeling human brain tumors using two-dimensional adherent stem cell cultures and three-dimensional organoids. We identify the important advances arrived at using these human stem cell-based models and suggest opportunities for future work in this direction. In this review article, we aim to highlight the utility and promises of human stem cell-based models of brain tumors as a complementary system to traditional transgenic animal and cell line systems.Item Metabolic Insight into Glioma Heterogeneity: Mapping Whole Exome Sequencing to In Vivo Imaging with Stereotactic Localization and Deep Learning(MDPI, 2024-06-16) Servati, Mahsa; Vaccaro, Courtney N.; Diller, Emily E.; Da Silva, Renata Pellegrino; Mafra, Fernanda; Cao, Sha; Stanley, Katherine B.; Cohen-Gadol, Aaron A.; Parker, Jason G.; Radiology and Imaging Sciences, School of MedicineIntratumoral heterogeneity (ITH) complicates the diagnosis and treatment of glioma, partly due to the diverse metabolic profiles driven by underlying genomic alterations. While multiparametric imaging enhances the characterization of ITH by capturing both spatial and functional variations, it falls short in directly assessing the metabolic activities that underpin these phenotypic differences. This gap stems from the challenge of integrating easily accessible, colocated pathology and detailed genomic data with metabolic insights. This study presents a multifaceted approach combining stereotactic biopsy with standard clinical open-craniotomy for sample collection, voxel-wise analysis of MR images, regression-based GAM, and whole-exome sequencing. This work aims to demonstrate the potential of machine learning algorithms to predict variations in cellular and molecular tumor characteristics. This retrospective study enrolled ten treatment-naïve patients with radiologically confirmed glioma. Each patient underwent a multiparametric MR scan (T1W, T1W-CE, T2W, T2W-FLAIR, DWI) prior to surgery. During standard craniotomy, at least 1 stereotactic biopsy was collected from each patient, with screenshots of the sample locations saved for spatial registration to pre-surgical MR data. Whole-exome sequencing was performed on flash-frozen tumor samples, prioritizing the signatures of five glioma-related genes: IDH1, TP53, EGFR, PIK3CA, and NF1. Regression was implemented with a GAM using a univariate shape function for each predictor. Standard receiver operating characteristic (ROC) analyses were used to evaluate detection, with AUC (area under curve) calculated for each gene target and MR contrast combination. Mean AUC for five gene targets and 31 MR contrast combinations was 0.75 ± 0.11; individual AUCs were as high as 0.96 for both IDH1 and TP53 with T2W-FLAIR and ADC, and 0.99 for EGFR with T2W and ADC. These results suggest the possibility of predicting exome-wide mutation events from noninvasive, in vivo imaging by combining stereotactic localization of glioma samples and a semi-parametric deep learning method. The genomic alterations identified, particularly in IDH1, TP53, EGFR, PIK3CA, and NF1, are known to play pivotal roles in metabolic pathways driving glioma heterogeneity. Our methodology, therefore, indirectly sheds light on the metabolic landscape of glioma through the lens of these critical genomic markers, suggesting a complex interplay between tumor genomics and metabolism. This approach holds potential for refining targeted therapy by better addressing the genomic heterogeneity of glioma tumors.Item Neuroinflammation in Autoimmune Disease and Primary Brain Tumors: The Quest for Striking the Right Balance(Frontiers Media, 2021-08-13) Mitchell, Dana; Shireman, Jack; Potchanant, Elizabeth A. Sierra; Lara-Velazquez, Montserrat; Dey, Mahua; Pediatrics, School of MedicineAccording to classical dogma, the central nervous system (CNS) is defined as an immune privileged space. The basis of this theory was rooted in an incomplete understanding of the CNS microenvironment, however, recent advances such as the identification of resident dendritic cells (DC) in the brain and the presence of CNS lymphatics have deepened our understanding of the neuro-immune axis and revolutionized the field of neuroimmunology. It is now understood that many pathological conditions induce an immune response in the CNS, and that in many ways, the CNS is an immunologically distinct organ. Hyperactivity of neuro-immune axis can lead to primary neuroinflammatory diseases such as multiple sclerosis and antibody-mediated encephalitis, whereas immunosuppressive mechanisms promote the development and survival of primary brain tumors. On the therapeutic front, attempts are being made to target CNS pathologies using various forms of immunotherapy. One of the most actively investigated areas of CNS immunotherapy is for the treatment of glioblastoma (GBM), the most common primary brain tumor in adults. In this review, we provide an up to date overview of the neuro-immune axis in steady state and discuss the mechanisms underlying neuroinflammation in autoimmune neuroinflammatory disease as well as in the development and progression of brain tumors. In addition, we detail the current understanding of the interactions that characterize the primary brain tumor microenvironment and the implications of the neuro-immune axis on the development of successful therapeutic strategies for the treatment of CNS malignancies.Item Pain Management Experiences Among Hospitalized Postcraniotomy Brain Tumor Patients(Wolters Kluwer, 2021) Foust Winton, Rebecca E.; Draucker, Claire B.; Von Ah, Diane; School of NursingBackground: Brain tumors account for the majority of central nervous system tumors, and most are removed by craniotomies. Many postcraniotomy patients experience moderate or severe pain after surgery, but patient perspectives on their experiences with pain management in the hospital have not been well described. Objective: The aim of this study was to describe how patients who have undergone a craniotomy for brain tumor removal experience pain management while hospitalized. Methods: Qualitative descriptive methods using semistructured interviews were conducted with patients on a neurological step-down unit in an urban teaching hospital in the Midwest United States. Interviews focused on how patients experienced postcraniotomy pain and how it was managed. Narratives were analyzed with standard content analytic procedures. Results: Twenty-seven participants (median age, 58.5 years; interquartile range, 26-41 years; range, 21-83 years) were interviewed. The majority were white (n = 25) and female (n = 15) and had an anterior craniotomy (n = 25) with sedation (n = 17). Their pain experiences varied on 2 dimensions: salience of pain during recovery and complexity of pain management. Based on these dimensions, 3 distinct types of pain management experiences were identified: (1) pain-as-nonsalient, routine pain management experience; (2) pain-as-salient, routine pain management experience; and (3) pain-as-salient, complex pain management experience. Conclusions: Many postcraniotomy patients experience their pain as tolerable and/or pain management as satisfying and effective; others experience pain and pain management as challenging. Implications for practice: Clinicians should be attuned to needs of patients with complex pain management experiences and should incorporate good patient/clinician communication.Item Pain Quality Among Hospitalized Postcraniotomy Brain Tumor Patients(Wolters Kluwer, 2021) Foust Winton, Rebecca E.; Draucker, Claire B.; Von Ah, Diane; School of NursingPurpose/aims: The aim of this study was to describe how persons given a diagnosis of a brain tumor who have had a craniotomy describe the quality of their pain after surgery. Design: A qualitative descriptive design was used. Methods: Qualitative descriptive methods as described by Sandelowski guided this study. Semistructured interviews were conducted with patients hospitalized on a neurological step-down unit in an urban teaching hospital in the Midwestern United States. Interviews focused on the quality of participants' pain after surgery. Narratives were analyzed using standard content analysis. Results: Twenty-seven participants were interviewed. Most were White and female. Most underwent a craniotomy using an anterior approach with sedation. Participants described the quality of their pain with 6 different types of descriptors: pain as pressure, pain as tender or sore, pain as stabbing, pain as throbbing, pain as jarring, and pain as itching. Conclusions: Participants' descriptions of their pain quality after surgery provide a different understanding than do numerical pain ratings. Clinicians should use questions to explore patients' individual pain experiences, seeking to understand the quality of patients' pain and their perceptions.Item Recent advances in Tumor Treating Fields (TTFields) therapy for glioblastoma(Oxford University Press, 2025) Khagi, Simon; Kotecha, Rupesh; Gatson, Na Tosha N.; Jeyapalan, Suriya; Abdullah, Huda Ismail; Avgeropoulos, Nicholas G.; Batzianouli, Eleni T.; Giladi, Moshe; Lustgarten, Leonardo; Goldlust, Samuel A.; Neurology, School of MedicineTumor Treating Fields (TTFields) therapy is a locoregional, anticancer treatment consisting of a noninvasive, portable device that delivers alternating electric fields to tumors through arrays placed on the skin. Based on efficacy and safety data from global pivotal (randomized phase III) clinical studies, TTFields therapy (Optune Gio) is US Food and Drug Administration-approved for newly diagnosed (nd) and recurrent glioblastoma (GBM) and Conformité Européenne-marked for grade 4 glioma. Here we review data on the multimodal TTFields mechanism of action that includes disruption of cancer cell mitosis, inhibition of DNA replication and damage response, interference with cell motility, and enhancement of systemic antitumor immunity (adaptive immunity). We describe new data showing that TTFields therapy has efficacy in a broad range of patients, with a tolerable safety profile extending to high-risk subpopulations. New analyses of clinical study data also confirmed that overall and progression-free survival positively correlated with increased usage of the device and dose of TTFields at the tumor site. Additionally, pilot/early phase clinical studies evaluating TTFields therapy in ndGBM concomitant with immunotherapy as well as radiotherapy have shown promise, and new pivotal studies will explore TTFields therapy in these settings. Finally, we review recent and ongoing studies in patients in pediatric care, other central nervous system tumors and brain metastases, as well as other advanced-stage solid tumors (ie, lung, ovarian, pancreatic, gastric, and hepatic cancers), that highlight the broad potential of TTFields therapy as an adjuvant treatment in oncology.Item Trends in the Management Paradigms of Intracranial Meningioma(Thieme, 2021) Aljuboori, Zaid; Alhourani, Ahmad; Woo, Shiao; Hattab, Eyas; Yusuf, Mehran; Nelson, Megan; Andaluz, Norberto; Ding, Dale; Savage, Jesse; Williams, Brian; Neurological Surgery, School of MedicineObjective: Intracranial meningiomas are the most common primary brain tumor. Treatment paradigms have evolved over time. There are limited number of population-based studies that examine this modern evolution. Here, we describe the trends of management of intracranial meningiomas using a national database. Methods: The data were obtained from the National Cancer Database for the years 2004 to 2015, the collected variables included: patients' age, gender, insurance type, income, comorbidity score, the tumor size and grade, and treatment modality (observation, surgery, radiotherapy, or combination therapy). We performed statistical analyses to detect association between unique variables and outcomes. In addition, we performed mortality analyses for various treatment modalities. Results: A total of 199,096 patients with a diagnosis of intracranial meningioma were included, the majority of patients were white females, mean age of 61 years, and half of the tumors were ≤ 3 cm. Observation was the most commonly used management modality followed by surgical resection, radiotherapy, and combination therapy. For the entire time period, there was an increased use of observation as a primary management method. Predictors of mortality included increased age, larger tumor size, higher tumor grade, treatment at a community hospital, and higher comorbidity scores. Conclusion: Population-based studies of intracranial meningiomas are uncommon; our study is one of the few reports that examine the changes in the modern management paradigms of meningioma in the United States over time. Additionally, we shed light on the factors that affected survival of patients with this condition.