Trial Summary
What is the purpose of this trial?This clinical trial constructs and tests a novel multinuclear metabolic magnetic resonance imaging (MRI) sequence in patients with glioma (brain tumor) that is newly diagnosed or has come back (recurrent). This trial aims to develop new diagnostic imaging technology that may bridge gaps between early detection and diagnosis, prognosis, and treatment in brain cancer.
Will I have to stop taking my current medications?
The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.
What data supports the effectiveness of the treatment Simultaneous Multinuclear Metabolic MRI, Multinuclear Metabolic MRI, Metabolic MRI for brain tumors?
Research shows that magnetic resonance spectroscopy (MRS), a part of metabolic MRI, can help understand tumor metabolism and monitor treatment response in brain tumors. It has been used to detect metabolic changes and assess therapeutic responses, making it a valuable tool in managing brain tumors.
12345Is Metabolic MRI safe for use in humans?
In a study involving 18 patients with glioblastoma, Metabolic MRI was used to guide radiation therapy, and no severe toxicities were observed, suggesting it is generally safe.
678910How is Simultaneous Multinuclear Metabolic MRI different from other treatments for brain tumors?
Simultaneous Multinuclear Metabolic MRI is unique because it uses advanced magnetic resonance spectroscopy to noninvasively analyze the metabolism of brain tumors, providing detailed insights into tumor biology and treatment response. This approach allows for the detection of metabolic changes in tumors, which can help in understanding tumor growth and monitoring treatment effectiveness, unlike traditional imaging methods that primarily focus on structural changes.
1571112Eligibility Criteria
This trial is for adults over 18 with newly diagnosed or recurrent glioma, a type of brain tumor. Healthy volunteers are also needed for part of the study. Participants must be able to safely undergo MRI scans and have tumors measurable at least 1cm in size. Those receiving immunotherapy for recurrent glioma can join too.Inclusion Criteria
I am 18 or older with a suspected or confirmed glioma, indicated for surgery, and my tumor is larger than 1cm³.
I am over 18 and do not have any brain tumors or neurological diseases.
I am 18 or older with recurrent glioma and am in an immunotherapy trial or need immunotherapy.
Exclusion Criteria
I am under 18 or cannot safely have an MRI with contrast.
I am under 18 or cannot safely have an MRI with contrast.
I am under 18 and cannot safely have an MRI.
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Imaging and Tissue Collection
Patients undergo MRI and collection of tissue samples for IHC analysis
Up to 5 years
Metabolic Imaging and Immunotherapy
Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection
Up to 5 years
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Participant Groups
The trial is testing a new multinuclear metabolic MRI sequence designed to improve early detection, diagnosis, prognosis, and treatment planning in brain cancer patients. It involves biospecimen collection and diagnostic imaging using this novel technology.
1Treatment groups
Experimental Treatment
Group I: Basic science (MRI, metabolic imaging, tissue collection)Experimental Treatment3 Interventions
AIM 1: Previous scan data from healthy subjects is collected and analyzed.
AIM 2: Patients undergo MRI. Patients also undergo collection of tissue samples for IHC analysis.
AIM 3: Patients undergo multinuclear metabolic imaging before and after immunotherapy and prior to surgical resection.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UCLA / Jonsson Comprehensive Cancer CenterLos Angeles, CA
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Who Is Running the Clinical Trial?
Jonsson Comprehensive Cancer CenterLead Sponsor
United States Department of DefenseCollaborator
References
Magnetic resonance spectroscopy of neoplasms. [2015]MRS made especially versatile with current technology of multinuclear coils and time interlacing of signals is appropriately suited to multifaceted tumor biochemistry, where growth is a key metabolic feature. The established results that bioenergetics and lipid metabolite concentrations show a variety of responses in tumor growth and remission in response to anticancer procedures add a further novel dimension to tumor studies by MRS. Finally, the versatility of the multinuclear MRS approach seems most appropriate to the varied nature of cancer.
Metabolic mapping of gliomas using hybrid MR-PET imaging: feasibility of the method and spatial distribution of metabolic changes. [2016]The most powerful adjunct to histopathology for the grading of gliomas seems to be the metabolic imaging using positron emission tomography and magnetic resonance spectroscopy (MRS). The purposes of this study were to examine the feasibility of simultaneous acquisition of both techniques for purposes of tumor grading in a newly launched hybrid magnetic resonance positron emission tomography (MR-PET) and to examine the spatial distributions of metabolic changes in gliomas.
Applications of magnetic resonance in model systems: cancer therapeutics. [2019]The lack of information regarding the metabolism and pathophysiology of individual tumors limits, in part, both the development of new anti-cancer therapies and the optimal implementation of currently available treatments. Magnetic resonance [MR, including magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), and electron paramagnetic resonance (EPR)] provides a powerful tool to assess many aspects of tumor metabolism and pathophysiology. Moreover, since this information can be obtained nondestructively, pre-clinical results from cellular or animal models are often easily translated into the clinic. This review presents selected examples of how MR has been used to identify metabolic changes associated with apoptosis, detect therapeutic response prior to a change in tumor volume, optimize the combination of metabolic inhibitors with chemotherapy and/or radiation, characterize and exploit the influence of tumor pH on the effectiveness of chemotherapy, characterize tumor reoxygenation and the effects of modifiers of tumor oxygenation in individual tumors, image transgene expression and assess the efficacy of gene therapy. These examples provide an overview of several of the areas in which cellular and animal model studies using MR have contributed to our understanding of the effects of treatment on tumor metabolism and pathophysiology and the importance of tumor metabolism and pathophysiology as determinants of therapeutic response.
Magnetic resonance spectroscopy for the study of cns malignancies. [2021]Despite intensive research, brain tumors are amongst the malignancies with the worst prognosis; therefore, a prompt diagnosis and thoughtful assessment of the disease is required. The resistance of brain tumors to most forms of conventional therapy has led researchers to explore the underlying biology in search of new vulnerabilities and biomarkers. The unique metabolism of brain tumors represents one potential vulnerability and the basis for a system of classification. Profiling this aberrant metabolism requires a method to accurately measure and report differences in metabolite concentrations. Magnetic resonance-based techniques provide a framework for examining tumor tissue and the evolution of disease. Nuclear Magnetic Resonance (NMR) analysis of biofluids collected from patients suffering from brain cancer can provide biological information about disease status. In particular, urine and plasma can serve to monitor the evolution of disease through the changes observed in the metabolic profiles. Moreover, cerebrospinal fluid can be utilized as a direct reporter of cerebral activity since it carries the chemicals exchanged with the brain tissue and the tumor mass. Metabolic reprogramming has recently been included as one of the hallmarks of cancer. Accordingly, the metabolic rewiring experienced by these tumors to sustain rapid growth and proliferation can also serve as a potential therapeutic target. The combination of 13C tracing approaches with the utilization of different NMR spectral modalities has allowed investigations of the upregulation of glycolysis in the aggressive forms of brain tumors, including glioblastomas, and the discovery of the utilization of acetate as an alternative cellular fuel in brain metastasis and gliomas. One of the major contributions of magnetic resonance to the assessment of brain tumors has been the non-invasive determination of 2-hydroxyglutarate (2HG) in tumors harboring a mutation in isocitrate dehydrogenase 1 (IDH1). The mutational status of this enzyme already serves as a key feature in the clinical classification of brain neoplasia in routine clinical practice and pilot studies have established the use of in vivo magnetic resonance spectroscopy (MRS) for monitoring disease progression and treatment response in IDH mutant gliomas. However, the development of bespoke methods for 2HG detection by MRS has been required, and this has prevented the wider implementation of MRS methodology into the clinic. One of the main challenges for improving the management of the disease is to obtain an accurate insight into the response to treatment, so that the patient can be promptly diverted into a new therapy if resistant or maintained on the original therapy if responsive. The implementation of 13C hyperpolarized magnetic resonance spectroscopic imaging (MRSI) has allowed detection of changes in tumor metabolism associated with a treatment, and as such has been revealed as a remarkable tool for monitoring response to therapeutic strategies. In summary, the application of magnetic resonance-based methodologies to the diagnosis and management of brain tumor patients, in addition to its utilization in the investigation of its tumor-associated metabolic rewiring, is helping to unravel the biological basis of malignancies of the central nervous system.
Magnetic Resonance (MR) Metabolic Imaging in Glioma. [2023]This review is focused on describing the use of magnetic resonance (MR) spectroscopy for metabolic imaging of brain tumors. We will first review the MR metabolic imaging findings generated from preclinical models, focusing primarily on in vivo studies, and will then describe the use of metabolic imaging in the clinical setting. We will address relatively well-established (1) H MRS approaches, as well as (31) P MRS, (13) C MRS and emerging hyperpolarized (13) C MRS methodologies, and will describe the use of metabolic imaging for understanding the basic biology of glioma as well as for improving the characterization and monitoring of brain tumors in the clinic.
A multi-institutional pilot clinical trial of spectroscopic MRI-guided radiation dose escalation for newly diagnosed glioblastoma. [2023]Glioblastomas (GBMs) are aggressive brain tumors despite radiation therapy (RT) to 60 Gy and temozolomide (TMZ). Spectroscopic magnetic resonance imaging (sMRI), which measures levels of specific brain metabolites, can delineate regions at high risk for GBM recurrence not visualized on contrast-enhanced (CE) MRI. We conducted a clinical trial to assess the feasibility, safety, and efficacy of sMRI-guided RT dose escalation to 75 Gy for newly diagnosed GBMs.
Interrogating Metabolism in Brain Cancer. [2018]This article reviews existing and emerging techniques of interrogating metabolism in brain cancer from well-established proton magnetic resonance spectroscopy to the promising hyperpolarized metabolic imaging and chemical exchange saturation transfer and emerging techniques of imaging inflammation. Some of these techniques are at an early stage of development and clinical trials are in progress in patients to establish the clinical efficacy. It is likely that in vivo metabolomics and metabolic imaging is the next frontier in brain cancer diagnosis and assessing therapeutic efficacy; with the combined knowledge of genomics and proteomics a complete understanding of tumorigenesis in brain might be achieved.
Functional and metabolic magnetic resonance imaging and positron emission tomography for tumor volume definition in high-grade gliomas. [2021]Although the addition of concurrent and adjuvant temozolomide (TMZ) to standard-dose radiation (60 Gy) improves survival, the pattern of failure continues to be local. Conventional contrast enhanced T1-weighted and T2-weighted magnetic resonance imaging (MRI) used for radiation planning reflect anatomic rather than molecular or functional, properties of the tumor. Functional and metabolic MRI and positron emission tomography are able to detect metabolic and functional abnormalities beyond the tumor volume seen on conventional MRI, assess early response to treatment, and delineate the regions of high risks for failure in high-grade gliomas. This article focuses on the potential of these functional and metabolic imaging techniques to refine our clinical target volumes.
The Brain Imaging Collaboration Suite (BrICS): A Cloud Platform for Integrating Whole-Brain Spectroscopic MRI into the Radiation Therapy Planning Workflow. [2021]Glioblastoma has poor prognosis with inevitable local recurrence despite aggressive treatment with surgery and chemoradiation. Radiation therapy (RT) is typically guided by contrast-enhanced T1-weighted magnetic resonance imaging (MRI) for defining the high-dose target and T2-weighted fluid-attenuation inversion recovery MRI for defining the moderate-dose target. There is an urgent need for improved imaging methods to better delineate tumors for focal RT. Spectroscopic MRI (sMRI) is a quantitative imaging technique that enables whole-brain analysis of endogenous metabolite levels, such as the ratio of choline-to-N-acetylaspartate. Previous work has shown that choline-to-N-acetylaspartate ratio accurately identifies tissue with high tumor burden beyond what is seen on standard imaging and can predict regions of metabolic abnormality that are at high risk for recurrence. To facilitate efficient clinical implementation of sMRI for RT planning, we developed the Brain Imaging Collaboration Suite (BrICS; https://brainimaging.emory.edu/brics-demo), a cloud platform that integrates sMRI with standard imaging and enables team members from multiple departments and institutions to work together in delineating RT targets. BrICS is being used in a multisite pilot study to assess feasibility and safety of dose-escalated RT based on metabolic abnormalities in patients with glioblastoma (Clinicaltrials.gov NCT03137888). The workflow of analyzing sMRI volumes and preparing RT plans is described. The pipeline achieved rapid turnaround time by enabling team members to perform their delegated tasks independently in BrICS when their clinical schedules allowed. To date, 18 patients have been treated using targets created in BrICS and no severe toxicities have been observed.
Detection and measurement of neurofibromatosis-1 mouse optic glioma in vivo. [2018]One of the major limitations to preclinical mouse therapeutic evaluation is the inherent difficulty in imaging small tumors in vivo. We present a rapid and reliable method to detect optic glioma (OPG) in a mouse neurofibromatosis-1 model (Nf1(flox/mut)GFAP-Cre mice) in vivo using Manganese-Enhanced Magnetic Resonance Imaging (MEMRI). In a blinded study, 23 mice were chosen randomly from a cohort of Nf1(flox/mut)GFAP-Cre mice and two sets of age-matched controls. In all cases, OPG presence or absence was correctly identified. In addition, the OPG size and shape were accurately measured in vivo, facilitating the use of this model for preclinical drug studies.
Prognostic factor from MR spectroscopy in rat with astrocytic tumour during radiation therapy. [2018]To investigate the relationship between the tumour volume and metabolic rates of astrocytic tumours using MR spectroscopy (MRS) during radiation therapy (RT).
Spatially localized in vivo 1H magnetic resonance spectroscopy of an intracerebral rat glioma. [2019]Surface coil MRI combined with spatially localized spectroscopy was used to noninvasively detect 1H signals from metabolites within an intracerebral malignant glioma in rats. The MRS pulse sequence was based upon two-dimensional ISIS, which restricted 1H signals to a column-shaped volume, combined with one-dimensional spectroscopic imaging, which further resolved the signals into 8 or 16 slices along the major axis of the column. All experiments were executed with adiabatic pulses which induced uniform spin excitation despite the inhomogeneous radiofrequency field distribution produced by the surface coil transmitter. Surface coil MRI and MRS experiments were performed on phantom samples, normal rat brains, and rat brains harboring malignant gliomas. Spatially resolved in vivo 1H spectra of intracerebral gliomas revealed significantly decreased concentrations of N-acetyl-aspartate and creatine and increased lactic acid (or lipids) as compared to the contralateral hemisphere. These results demonstrate that metabolic abnormalities in intracerebral rat gliomas can be spatially resolved in a noninvasive manner using localized in vivo 1H MRS.