Oxygen-Enhanced MRI for Brain Tumors
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: OHSU Knight Cancer Institute
Disqualifiers: Pregnancy, Claustrophobia, Metallic implants, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
This clinical trial evaluates the feasibility of performing oxygen-enhanced magnetic resonance imaging (MRI) to generate hypoxia maps in patients with intracranial tumors. Decreased levels of oxygen (hypoxia) is a hallmark of malignant brain tumors. Chronic hypoxia is a stimulator of blood vessel formation, which is required for tumor growth and spread. Hypoxia also limits the effectiveness of radiation and chemotherapy. MRI is an imaging technique that uses radiofrequency waves and a strong magnetic field rather than x-rays to provide detailed pictures of internal organs and tissues. The administration of inhaled oxygen allows for an increased MRI signal effect size. Oxygen-enhanced MRI may be a non-invasive method that can physiologically estimate tissue hypoxia. With a better understanding of the extent of tumor hypoxia, more effective and patient-specific therapies could be devised to halt malignant tumor growth.
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 Oxygen-Enhanced MRI for Brain Tumors?
Is Oxygen-Enhanced MRI safe for use in humans?
How does the treatment Oxygen-Enhanced MRI for Brain Tumors differ from other treatments for this condition?
Oxygen-Enhanced MRI (OE-MRI) is unique because it uses inhaled oxygen as a contrast agent to non-invasively measure the oxygen levels in brain tumors, which can help in assessing tumor hypoxia (low oxygen levels) and potentially improve treatment planning. This approach is different from traditional methods that may require invasive procedures or contrast agents, offering a safer and more accessible option for evaluating tumor oxygenation.167910
Eligibility Criteria
This trial is for adults over 18 with a suspected or known brain tumor larger than 10 mL. Participants must be able to consent, have a performance score indicating they can carry out daily activities, and may already be receiving treatment for the tumor. It's not suitable for those with sickle cell disease, poor vein access, pregnancy, certain metal implants, severe other illnesses or conditions that make MRI or oxygen therapy risky.Inclusion Criteria
I am planning or have had treatment for a brain tumor.
Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf
I am an adult with a brain tumor.
See 3 more
Exclusion Criteria
Claustrophobia
I should avoid extra oxygen due to my severe lung or breathing condition.
I do not have any serious illnesses that could affect my participation in the study.
See 9 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Diagnostic Imaging
Patients receive supplemental oxygen while undergoing standard of care MRI to generate hypoxia maps
1 hour
1 visit (in-person)
Follow-up
Participants are monitored for progression free survival and other outcomes
Up to 5 years
Treatment Details
Interventions
- Magnetic Resonance Imaging (Procedure)
- Oxygen Therapy (Procedure)
Trial OverviewThe study tests if oxygen-enhanced MRI can create detailed maps of low-oxygen areas in brain tumors. This non-invasive technique could help understand how much of the tumor lacks oxygen which affects treatment effectiveness like radiation and chemotherapy.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Diagnostic (oxygen-enhanced MRI)Experimental Treatment2 Interventions
Patients receive supplemental oxygen while undergoing standard of care MRI.
Magnetic Resonance Imaging is already approved in United States, United States for the following indications:
🇺🇸 Approved in United States as Lumakras (sotorasib) for:
- Non-small cell lung cancer with KRAS G12C mutation
🇺🇸 Approved in United States as Vectibix (panitumumab) for:
- Advanced colorectal cancer that is wild-type RAS
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
OHSU Knight Cancer InstitutePortland, OR
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Who Is Running the Clinical Trial?
OHSU Knight Cancer InstituteLead Sponsor
Oregon Health and Science UniversityCollaborator
References
Hypoxia imaging in brain tumors. [2019]Assessment of the oxygenation status of brain tumors has been studied increasingly with imaging techniques in light of recent advances in oncology. Tumor oxygen tension is a critical factor influencing the effectiveness of radiation and chemotherapy and malignant progression. Hypoxic tumors are resistant to treatment, and prognostic value of tumor oxygen status is shown in head and neck tumors. Strategies increasing the tumor oxygenation are being investigated to overcome the compromising [figure: see text] effect of hypoxia on tumor treatment. Administration of nicotinamide and inhalation of various high oxygen concentrations have been implemented. Existing methods for assessment of tissue oxygen level are either invasive or insufficient. Accurate and noninvasive means to measure tumor oxygenation are needed for treatment planning, identification of patients who might benefit from oxygenation strategies, and assessing the efficacy of interventions aimed to increase the radiosensitivity of tumors. Of the various imaging techniques used to assess tissue oxygenation, MR spectroscopy and MR imaging are widely available, noninvasive, and clinically applicable techniques. Tumor hypoxia is related closely to insufficient blood flow through chaotic and partially nonfunctional tumor vasculature and the distance between the capillaries and the tumor cells. Information on characteristics of tumor vasculature such as blood volume, perfusion, and increased capillary permeability can be provided with MR imaging. MR imaging techniques can provide a measure of capillary permeability based on contrast enhancement and relative cerebral blood volume estimates using dynamic susceptibility MR imaging. Blood oxygen level dependent contrast MR imaging using gradient echo sequence is intrinsically sensitive to changes in blood oxygen level. Animal models using blood oxygen level-dependent contrast imaging reveal the different responses of normal and tumor vasculature under hyperoxia. Normobaric hyperoxia is used in MR studies as a method to produce MR contrast in tissues. Increased T2* signal intensity of brain tissue has been observed using blood oxygen level-dependent contrast MR imaging. Dynamic blood oxygen level-dependent contrast MR imaging during hyperoxia is suggested to image tumor oxygenation. Quantification of cerebral oxygen saturation using blood oxygen level-dependent MR imaging also has been reported. Quantification of cerebral blood oxygen saturation using MR imaging has promising clinical applications; however, technical difficulties have to be resolved. Blood oxygen level dependent MR imaging is an emerging technique to evaluate the cerebral blood oxygen saturation, and it has the potential and versatility to assess oxygenation status of brain tumors. Upon improvement and validation of current MR techniques, better diagnostic, prognostic, and treatment monitoring capabilities can be provided for patients with brain tumors.
Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma. [2020]Background Altered metabolism is a characteristic of cancer. Because of a shift in glucose metabolism from oxidative phosphorylation to lactate production for energy generation, malignant tumors are characterized by increased glycolysis followed by lactic acid fermentation, even in the presence of abundant oxygen (the Warburg effect). Purpose To quantitatively investigate dynamic oxygen 17 (17O) MRI in healthy participants and participants with untreated glioma to understand altered cerebral oxygen metabolism in glioma. Materials and Methods In this prospective study conducted from September 2016 to June 2018, individuals with newly diagnosed previously untreated glioma (World Health Organization grade II-IV) and healthy volunteers were included. Dynamic 17O MRI was performed with a 7.0-T whole-body system. 17O2 gas inhalation enabled dynamic measurement of the cerebral metabolic rate of oxygen (CMRO2) consumption. In healthy volunteers and participants with glioma, CMRO2 values in gray matter and white matter volumes were compared by using Wilcoxon signed rank tests. In participants with glioma, the tumor volume and tumor subcompartments were compared with normal-appearing gray matter and white matter by using Friedman test followed by Holm-Sidak post hoc tests. Results Ten participants (mean age, 42 years ± 18 [standard deviation]; nine men) with glioma and three healthy volunteers (mean age, 44 years ± 21; all men) were evaluated. CMRO2 was higher in normal-appearing gray matter compared with white matter in both participants with glioma (2.36 μmol/g/min ± 0.22 vs 0.75 μmol/g/min ± 0.10, respectively) and healthy volunteers (2.38 μmol/g/min ± 0.15 vs 0.63 μmol/g/min ± 0.05, respectively) (P < .001 and P = .03, respectively). In the tumor region, CMRO2 was reduced (high-grade tumor CMRO2, 0.23 μmol/g/min ± 0.07; low-grade tumor CMRO2, 0.39 μmol/g/min ± 0.16; overall CMRO2, 0.34 μmol/g/min ± 0.16) compared with normal-appearing gray matter (P < .001) and normal-appearing white matter (P < .001) in accordance with the Warburg theorem. Conclusion Dynamic oxygen 17 MRI method at 7.0 T as a direct metabolic imaging technique in glioma enabled quantitative visualization of the Warburg effect. A general reduction in oxidative glycolysis was observed in accordance with the Warburg theorem. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Rapalino in this issue.
Repeated assessment of orthotopic glioma pO(2) by multi-site EPR oximetry: a technique with the potential to guide therapeutic optimization by repeated measurements of oxygen. [2021]Tumor hypoxia plays a vital role in therapeutic resistance. Consequently, measurements of tumor pO(2) could be used to optimize the outcome of oxygen-dependent therapies, such as, chemoradiation. However, the potential optimizations are restricted by the lack of methods to repeatedly and quantitatively assess tumor pO(2) during therapies, particularly in gliomas. We describe the procedures for repeated measurements of orthotopic glioma pO(2) by multi-site electron paramagnetic resonance (EPR) oximetry. This oximetry approach provides simultaneous measurements of pO(2) at more than one site in the glioma and contralateral cerebral tissue. The pO(2) of intracerebral 9L, C6, F98 and U251 tumors, as well as contralateral brain, were measured repeatedly for five consecutive days. The 9L glioma was well oxygenated with pO(2) of 27-36 mm Hg, while C6, F98 and U251 glioma were hypoxic with pO(2) of 7-12mm Hg. The potential of multi-site EPR oximetry to assess temporal changes in tissue pO(2) was investigated in rats breathing 100% O(2). A significant increase in F98 tumor and contralateral brain pO(2) was observed on day 1 and day 2, however, glioma oxygenation declined on subsequent days. In conclusion, EPR oximetry provides the capability to repeatedly assess temporal changes in orthotopic glioma pO(2). This information could be used to test and optimize the methods being developed to modulate tumor hypoxia. Furthermore, EPR oximetry could be potentially used to enhance the outcome of chemoradiation by scheduling treatments at times of increase in glioma pO(2).
Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response. [2019]Functional MR (fMR) imaging techniques based on blood oxygenation level dependent (BOLD) effects were developed and applied to a rat brain tumor model to evaluate the potential utility of the method for characterizing tumor growth and regression following treatment. Rats bearing 9L brain tumors in situ were imaged during inhalation of room air and after administration of 100% oxygen + acetazolamide (ACZ) injected 15 mg/kg intravenously. Pixel-to-pixel fMR maps of normalized signal intensity change from baseline values were calculated from T2 weighted spin echo (SE) images acquired pre- and post- oxygen + ACZ administration. Resultant fMR maps were then compared to gross histological sections obtained from corresponding anatomical regions. Regions containing viable tumor with increased cellular density and localized foci of necrotic tumor cells consistent with hypoxia were visualized in the fMR images as regions with decreased signal intensities, indicating diminished oxyhemoglobin concentration and blood flow as compared to normal brain. Histological regions having peritumor edema, caused by increased permeability of tumor vasculature, were visualized in the fMR images as areas with markedly increased signal intensities. These results suggest that fMR imaging techniques could be further developed for use as a non-invasive tool to assess changes in tumor oxygenation/hemodynamics, and to evaluate the pharmacologic effect of anti-neoplastic drugs.
Dependency of the blood oxygen level dependent-response to hyperoxic challenges on the order of gas administration in intracranial malignancies. [2020]Literature reports contradicting results on the response of brain tumors to vascular stimuli measured in T2*-weighted MRI. Here, we analyzed the potential dependency of the MRI-response to (hypercapnic) hyperoxia on the order of the gas administration.
Hyperoxic BOLD-MRI-Based Characterization of Breast Cancer Molecular Subtypes Is Independent of the Supplied Amount of Oxygen: A Preclinical Study. [2023]Hyperoxic BOLD-MRI targeting tumor hypoxia may provide imaging biomarkers that represent breast cancer molecular subtypes without the use of injected contrast agents. However, the diagnostic performance of hyperoxic BOLD-MRI using different levels of oxygen remains unclear. We hypothesized that molecular subtype characterization with hyperoxic BOLD-MRI is feasible independently of the amount of oxygen. Twenty-three nude mice that were inoculated into the flank with luminal A (n = 9), Her2+ (n = 5), and triple-negative (n = 9) human breast cancer cells were imaged using a 9.4 T Bruker BioSpin system. During BOLD-MRI, anesthesia was supplemented with four different levels of oxygen (normoxic: 21%; hyperoxic: 41%, 71%, 100%). The change in the spin-spin relaxation rate in relation to the normoxic state, ΔR2*, dependent on the amount of erythrocyte-bound oxygen, was calculated using in-house MATLAB code. ΔR2* was significantly different between luminal A and Her2+ as well as between luminal A and triple-negative breast cancer, reflective of the less aggressive luminal A breast cancer's ability to better deliver oxygen-rich hemoglobin to its tissue. Differences in ΔR2* between subtypes were independent of the amount of oxygen, with robust distinction already achieved with 41% oxygen. In conclusion, hyperoxic BOLD-MRI may be used as a biomarker for luminal A breast cancer identification without the use of exogenous contrast agents.
Comparison study of oxygen-induced MRI-signal changes and pO2 changes in murine tumors. [2019]The purpose of this study was to compare the results from oxygen-induced MR-signal intensity changes with polarographic pO2 measurements in tumors. Balb-c mice with an intramuscular transplanted osteosarcoma were examined. To study the response of tumors to changes in oxygen supply, hyperoxia was induced by breathing pure oxygen for a short period. The examination of each animal started with T2* weighted MRI followed by the pO2 measurements (Eppendorf Histograph). During oxygen inhalation in all tumors, when the hypoxic tumor fraction drops, both areas of significant MR-signal intensity increase and decrease were observed in each animal.
Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice. [2020]Advanced MR imaging methods have an essential role in classification, grading, follow-up and therapeutic management in patients with brain tumors. With the introduction of new therapeutic options, the challenge for better tissue characterization and diagnosis increase, calling for new reliable non-invasive imaging methods. In the current study we evaluated the added value of a combined protocol of blood oxygen level dependent (BOLD) imaging during hyperoxic challenge (termed hemodynamic response imaging (HRI)) in an orthotopic mouse model for glioblastoma under anti-angiogenic treatment with B20-4.1.1, an anti-VEGF antibody. In glioblastoma tumors, the elevated HRI indicated progressive angiogenesis as further confirmed by histology. In the current glioblastoma model, B20-treatment caused delayed tumor progression with no significant changes in HRI yet with slightly reduced tumor vascularity as indicated by histology. Furthermore, fewer apoptotic cells and higher proliferation index were detected in the B20-treated tumors compared to control-treated tumors. In conclusion, HRI provides an easy, safe and contrast agent free method for the assessment of the brain hemodynamic function, an additionally important clinical information.
Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager. [2023]Label="PURPOSE" NlmCategory="OBJECTIVE">Spatial heterogeneity in tumor hypoxia is one of the most important factors regulating tumor growth, development, aggressiveness, metastasis, and affecting treatment outcome. Most solid tumors are known to have hypoxia or low oxygen levels (pO2 ≤10 torr). Electron paramagnetic resonance oxygen imaging (EPROI) is an emerging oxygen mapping technology. EPROI utilizes the linear relationship between the relaxation rates of the injectable OX071 trityl spin probe and the partial oxygen pressure (pO2). However, most of the EPROI studies have been limited to mouse models of solid tumors because of the instrument-size limitations. The purpose of this work was to develop a human-sized 9-mT (250 MHz resonance frequency, 60 cm bore size) pulse EPROI instrument and evaluate its performance with rabbit VX-2 tumor oxygen imaging.
Radiosensitizing oxygenation changes in murine tumors treated with VEGF-ablation therapy are measurable using oxygen enhanced-MRI (OE-MRI). [2023]There is a significant need for a widely available, translatable, sensitive and non-invasive imaging biomarker for tumor hypoxia in radiation oncology. Treatment-induced changes in tumor tissue oxygenation can alter the sensitivity of cancer tissues to radiation, but the relative difficulty in monitoring the tumor microenvironment results in scarce clinical and research data. Oxygen-Enhanced MRI (OE-MRI) uses inhaled oxygen as a contrast agent to measure tissue oxygenation. Here we investigate the utility of dOE-MRI, a previously validated imaging approach employing a cycling gas challenge and independent component analysis (ICA), to detect VEGF-ablation treatment-induced changes in tumor oxygenation that result in radiosensitization.