Special Issue "Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors"

A special issue of Tomography (ISSN 2379-139X). This special issue belongs to the section "Brain Imaging".

Deadline for manuscript submissions: closed (20 April 2023) | Viewed by 4365

Special Issue Editors

Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Interests: primary and secondary brain tumors; molecular therapeutics; imaging; clinical trials
Department of Neurology and Rehabilitation Medicine, University of Cincinnati College of Medicine, Cincinnati, OH 45267, USA
Interests: RNA therapeutics; focused ultrasound; primary and secondary brain tumors
Department of Radiology and Imaging Sciences, Winship Cancer Institute of Emory University, Atlanta, GA 30322, USA
Interests: neuroimaging; brain tumor; MRI; neuro-oncology; tumor response criteria
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Special Issue Information

Dear Colleagues,

Brain tumors encompass a broad range of diagnoses including relatively low-grade lesions, highly aggressive high-grade tumors, and metastases, but a common theme in evaluation and treatment of these tumors is the use of imaging to aid diagnosis, treatment, and patient follow-up. At each step of the way, brain imaging plays a critical role in clinical decision-making, but even the most sophisticated currently available techniques in magnetic resonance imaging (MRI), positron emission tomography (PET), and molecular imaging leave room for improvement. Higher quality imaging is needed to better quantify the scope of disease and to aid decision-making during longitudinal therapy, both of which are currently limited with mainstream clinical techniques. Furthermore, imaging can guide therapy with techniques such as stereotactic radiosurgery, laser ablation, and high-intensity ultrasound. This issue focuses on reviews of current state-of-the-art imaging techniques for improving care of brain tumor patients. Cutting-edge imaging methods as well as guided therapies such as ultrasound technologies that enhance the blood–brain delivery of key therapeutic agents are within the scope of this Special Issue.

Dr. Soma Sengupta
Dr. Daniel Pomeranz Krummel
Dr. Brent Weinberg
Guest Editors

Manuscript Submission Information

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Keywords

  • glioblastoma (GBM)
  • gliomas
  • benign brain tumors
  • brain metastases
  • MRI
  • PET
  • ultrasound

Published Papers (7 papers)

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Research

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Article
Perfusion-Weighted Imaging: The Use of a Novel Perfusion Scoring Criteria to Improve the Assessment of Brain Tumor Recurrence versus Treatment Effects
Tomography 2023, 9(3), 1062-1070; https://doi.org/10.3390/tomography9030087 - 23 May 2023
Viewed by 295
Abstract
Introduction: Imaging surveillance of contrast-enhancing lesions after the treatment of malignant brain tumors with radiation is plagued by an inability to reliably distinguish between tumor recurrence and treatment effects. Magnetic resonance perfusion-weighted imaging (PWI)—among other advanced brain tumor imaging modalities—is a useful adjunctive [...] Read more.
Introduction: Imaging surveillance of contrast-enhancing lesions after the treatment of malignant brain tumors with radiation is plagued by an inability to reliably distinguish between tumor recurrence and treatment effects. Magnetic resonance perfusion-weighted imaging (PWI)—among other advanced brain tumor imaging modalities—is a useful adjunctive tool for distinguishing between these two entities but can be clinically unreliable, leading to the need for tissue sampling to confirm diagnosis. This may be partially because clinical PWI interpretation is non-standardized and no grading criteria are used for assessment, leading to interpretation discrepancies. This variance in the interpretation of PWI and its subsequent effect on the predictive value has not been studied. Our objective is to propose structured perfusion scoring criteria and determine their effect on the clinical value of PWI. Methods: Patients treated at a single institution between 2012 and 2022 who had prior irradiated malignant brain tumors and subsequent progression of contrast-enhancing lesions determined by PWI were retrospectively studied from CTORE (CNS Tumor Outcomes Registry at Emory). PWI was given two separate qualitative scores (high, intermediate, or low perfusion). The first (control) was assigned by a neuroradiologist in the radiology report in the course of interpretation with no additional instruction. The second (experimental) was assigned by a neuroradiologist with additional experience in brain tumor interpretation using a novel perfusion scoring rubric. The perfusion assessments were divided into three categories, each directly corresponding to the pathology-reported classification of residual tumor content. The interpretation accuracy in predicting the true tumor percentage, our primary outcome, was assessed through Chi-squared analysis, and inter-rater reliability was assessed using Cohen’s Kappa. Results: Our 55-patient cohort had a mean age of 53.5 ± 12.2 years. The percentage agreement between the two scores was 57.4% (κ: 0.271). Upon conducting the Chi-squared analysis, we found an association with the experimental group reads (p-value: 0.014) but no association with the control group reads (p-value: 0.734) in predicting tumor recurrence versus treatment effects. Conclusions: With our study, we showed that having an objective perfusion scoring rubric aids in improved PWI interpretation. Although PWI is a powerful tool for CNS lesion diagnosis, methodological radiology evaluation greatly improves the accurate assessment and characterization of tumor recurrence versus treatment effects by all neuroradiologists. Further work should focus on standardizing and validating scoring rubrics for PWI evaluation in tumor patients to improve diagnostic accuracy. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Article
Applying a Radiation Therapy Volume Analysis Pipeline to Determine the Utility of Spectroscopic MRI-Guided Adaptive Radiation Therapy for Glioblastoma
Tomography 2023, 9(3), 1052-1061; https://doi.org/10.3390/tomography9030086 - 21 May 2023
Viewed by 344
Abstract
Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify [...] Read more.
Accurate radiation therapy (RT) targeting is crucial for glioblastoma treatment but may be challenging using clinical imaging alone due to the infiltrative nature of glioblastomas. Precise targeting by whole-brain spectroscopic MRI, which maps tumor metabolites including choline (Cho) and N-acetylaspartate (NAA), can quantify early treatment-induced molecular changes that other traditional modalities cannot measure. We developed a pipeline to determine how spectroscopic MRI changes during early RT are associated with patient outcomes to provide insight into the utility of adaptive RT planning. Data were obtained from a study (NCT03137888) where glioblastoma patients received high-dose RT guided by the pre-RT Cho/NAA twice normal (Cho/NAA ≥ 2x) volume, and received spectroscopic MRI scans pre- and mid-RT. Overlap statistics between pre- and mid-RT scans were used to quantify metabolic activity changes after two weeks of RT. Log-rank tests were used to quantify the relationship between imaging metrics and patient overall and progression-free survival (OS/PFS). Patients with lower Jaccard/Dice coefficients had longer PFS (p = 0.045 for both), and patients with lower Jaccard/Dice coefficients had higher OS trending towards significance (p = 0.060 for both). Cho/NAA ≥ 2x volumes changed significantly during early RT, putting healthy tissue at risk of irradiation, and warranting further study into using adaptive RT planning. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Article
Mutant Isocitrate Dehydrogenase 1 Expression Enhances Response of Gliomas to the Histone Deacetylase Inhibitor Belinostat
Tomography 2023, 9(3), 942-954; https://doi.org/10.3390/tomography9030077 - 04 May 2023
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Abstract
Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic [...] Read more.
Histone deacetylase inhibitors (HDACis) are drugs that target the epigenetic state of cells by modifying the compaction of chromatin through effects on histone acetylation. Gliomas often harbor a mutation of isocitrate dehydrogenase (IDH) 1 or 2 that leads to changes in their epigenetic state presenting a hypermethylator phenotype. We postulated that glioma cells with IDH mutation, due to the presence of epigenetic changes, will show increased sensitivity to HDACis. This hypothesis was tested by expressing mutant IDH1 with a point alteration—converting arginine 132 to histidine—within glioma cell lines that contain wild-type IDH1. Glioma cells engineered to express mutant IDH1 produced D-2-hydroxyglutarate as expected. When assessed for response to the pan-HDACi drug belinostat, mutant IDH1-expressing glioma cells were subjected to more potent inhibition of growth than the corresponding control cells. Increased sensitivity to belinostat correlated with the increased induction of apoptosis. Finally, a phase I trial assessing the addition of belinostat to standard-of-care therapy for newly diagnosed glioblastoma patients included one patient with a mutant IDH1 tumor. This mutant IDH1 tumor appeared to display greater sensitivity to the addition of belinostat than the other cases with wild-type IDH tumors based on both standard magnetic resonance imaging (MRI) and advanced spectroscopic MRI criteria. These data together suggest that IDH mutation status within gliomas may serve as a biomarker of response to HDACis. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Article
Using Brain Tumor MRI Structured Reporting to Quantify the Impact of Imaging on Brain Tumor Boards
Tomography 2023, 9(2), 859-870; https://doi.org/10.3390/tomography9020070 - 18 Apr 2023
Viewed by 599
Abstract
Multidisciplinary tumor boards (TB) are an essential part of brain tumor care, but quantifying the impact of imaging on patient management is challenging due to treatment complexity and a lack of quantitative outcome measures. This work uses a structured reporting system for classifying [...] Read more.
Multidisciplinary tumor boards (TB) are an essential part of brain tumor care, but quantifying the impact of imaging on patient management is challenging due to treatment complexity and a lack of quantitative outcome measures. This work uses a structured reporting system for classifying brain tumor MRIs, the brain tumor reporting and data system (BT-RADS), in a TB setting to prospectively assess the impact of imaging review on patient management. Published criteria were used to prospectively assign three separate BT-RADS scores (an initial radiology report, secondary TB presenter review, and TB consensus) to brain MRIs reviewed at an adult brain TB. Clinical recommendations at TB were noted and management changes within 90 days after TB were determined by chart review. In total, 212 MRIs in 130 patients (median age = 57 years) were reviewed. Agreement was 82.2% between report and presenter, 79.0% between report and consensus, and 90.1% between presenter and consensus. Rates of management change increased with increasing BT-RADS scores (0—3.1%, 1a—0%, 1b—66.7%, 2—8.3%, 3a—38.5%, 3b—55.9, 3c—92.0%, and 4—95.6%). Of 184 (86.8%) cases with clinical follow-up within 90 days after the tumor board, 155 (84.2%) of the recommendations were implemented. Structured scoring of MRIs provides a quantitative way to assess rates of agreement interpretation alongside how often management changes are recommended and implemented in a TB setting. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Article
A Novel Approach to Determining Tumor Progression Using a Three-Site Pilot Clinical Trial of Spectroscopic MRI-Guided Radiation Dose Escalation in Glioblastoma
Tomography 2023, 9(1), 362-374; https://doi.org/10.3390/tomography9010029 - 06 Feb 2023
Cited by 1 | Viewed by 1119
Abstract
Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed [...] Read more.
Glioblastoma (GBM) is a fatal disease, with poor prognosis exacerbated by difficulty in assessing tumor extent with imaging. Spectroscopic MRI (sMRI) is a non-contrast imaging technique measuring endogenous metabolite levels of the brain that can serve as biomarkers for tumor extension. We completed a three-site study to assess survival benefits of GBM patients when treated with escalated radiation dose guided by metabolic abnormalities in sMRI. Escalated radiation led to complex post-treatment imaging, requiring unique approaches to discern tumor progression from radiation-related treatment effect through our quantitative imaging platform. The purpose of this study is to determine true tumor recurrence timepoints for patients in our dose-escalation multisite study using novel methodology and to report on median progression-free survival (PFS). Follow-up imaging for all 30 trial patients were collected, lesion volumes segmented and graphed, and imaging uploaded to our platform for visual interpretation. Eighteen months post-enrollment, the median PFS was 16.6 months with a median time to follow-up of 20.3 months. With this new treatment paradigm, incidence rate of tumor recurrence one year from treatment is 30% compared to 60–70% failure under standard care. Based on the delayed tumor progression and improved survival, a randomized phase II trial is under development (EAF211). Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Review

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Review
Advances in Focused Ultrasound for the Treatment of Brain Tumors
Tomography 2023, 9(3), 1094-1109; https://doi.org/10.3390/tomography9030090 - 29 May 2023
Viewed by 186
Abstract
Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood–brain and blood–tumor barriers. In physiologic states, the blood–brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits [...] Read more.
Employing the full arsenal of therapeutics to treat brain tumors is limited by the relative impermeability of the blood–brain and blood–tumor barriers. In physiologic states, the blood–brain barrier serves a protective role by passively and actively excluding neurotoxic compounds; however, this functionality limits the penetrance of therapeutics into the tumor microenvironment. Focused ultrasound technology provides a method for overcoming the blood–brain and blood–tumor barriers through ultrasound frequency to transiently permeabilize or disrupt these barriers. Concomitant delivery of therapeutics has allowed for previously impermeable agents to reach the tumor microenvironment. This review details the advances in focused ultrasound in both preclinical models and clinical studies, with a focus on its safety profile. We then turn towards future directions in focused ultrasound-mediated therapies for brain tumors. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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Review
Labeling T Cells to Track Immune Response to Immunotherapy in Glioblastoma
Tomography 2023, 9(1), 274-284; https://doi.org/10.3390/tomography9010022 - 30 Jan 2023
Viewed by 852
Abstract
While the advent of immunotherapy has revolutionized cancer treatment, its use in the treatment of glioblastoma (GBM) has been less successful. Most studies using immunotherapy in GBM have been negative and the reasons for this are still being studied. In clinical practice, interpreting [...] Read more.
While the advent of immunotherapy has revolutionized cancer treatment, its use in the treatment of glioblastoma (GBM) has been less successful. Most studies using immunotherapy in GBM have been negative and the reasons for this are still being studied. In clinical practice, interpreting response to immunotherapy has been challenging, particularly when trying to differentiate between treatment-related changes (i.e., pseudoprogression) or true tumor progression. T cell tagging is one promising technique to noninvasively monitor treatment efficacy by assessing the migration, expansion, and engagement of T cells and their ability to target tumor cells at the tumor site. Full article
(This article belongs to the Special Issue Current Trends in Diagnostic and Therapeutic Imaging of Brain Tumors)
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