Oxygen-Enhanced MRI for Brain Tumors

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: OHSU Knight Cancer Institute

Disqualifiers: Pregnancy, Claustrophobia, Metallic implants, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

20 Participants Needed

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?

Research shows that imaging techniques like MRI can help assess the oxygen levels in brain tumors, which is important because tumors with low oxygen levels are harder to treat. Increasing oxygen levels in tumors can potentially make treatments like radiation and chemotherapy more effective. ^{1 2 3 4 5}

Is Oxygen-Enhanced MRI safe for use in humans?

Oxygen-Enhanced MRI, which involves breathing in high levels of oxygen, has been studied in animal models and is considered a safe, non-invasive method for assessing brain and tumor oxygenation. It does not require injected contrast agents, which can sometimes cause side effects. ^{1 4 6 7 8}

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. ^{1 6 7 9 10}

Research Team

Ramon Barajas

Principal Investigator

OHSU Knight Cancer Institute

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.

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.

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
• Oxygen Therapy

Trial Overview The 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

Group I: Diagnostic (oxygen-enhanced MRI) Experimental Treatment 2 Interventions

Patients receive supplemental oxygen while undergoing standard of care MRI.

Magnetic Resonance Imaging is already approved in 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

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

Tumor oxygenation is crucial for the effectiveness of cancer treatments like radiation and chemotherapy, and hypoxic tumors are known to be resistant to these therapies, highlighting the need for accurate assessment methods.

Noninvasive imaging techniques, particularly blood oxygen level-dependent (BOLD) MR imaging, show promise in evaluating brain tumor oxygenation, which could enhance treatment planning and monitoring by identifying patients who may benefit from oxygenation strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypoxia imaging in brain tumors. Yetkin, FZ., Mendelsohn, D.[2019]

A study involving 10 participants with untreated glioma and 3 healthy volunteers used dynamic 17O MRI to measure cerebral metabolic rate of oxygen (CMRO2), revealing that glioma tumors exhibit significantly reduced CMRO2 compared to normal brain tissue, consistent with the Warburg effect.

The findings confirm that glioma tumors rely less on oxidative metabolism and more on glycolysis for energy, highlighting the potential of 17O MRI as a tool for understanding metabolic changes in brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma. Paech, D., Nagel, AM., Schultheiss, MN., et al.[2020]

Multi-site electron paramagnetic resonance (EPR) oximetry allows for repeated and simultaneous measurements of oxygen levels (pO2) in gliomas and surrounding brain tissue, providing valuable insights into tumor hypoxia over time.

The study found that different glioma types exhibited varying levels of oxygenation, with some tumors being hypoxic, which could inform strategies to optimize oxygen-dependent therapies like chemoradiation by timing treatments when tumor oxygen levels are higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Khan, N., Mupparaju, S., Hou, H., et al.[2021]

Functional MR imaging can effectively visualize changes in tumor oxygenation and blood flow in a rat brain tumor model, indicating its potential as a non-invasive assessment tool for tumor characteristics.

The study demonstrated that fMR imaging can differentiate between viable tumor regions and necrotic areas, providing insights into tumor growth and response to treatments like acetazolamide, which may enhance the evaluation of anti-cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response. Mazurchuk, R., Zhou, R., Straubinger, RM., et al.[2019]

In a study involving eight patients with brain tumors, the response of contrast-enhancing lesions to oxygen was significant, showing a 20.7% increase in T2* values, regardless of the gas administration protocol used.

However, the response to carbogen (a mixture of carbon dioxide and oxygen) was significantly influenced by the order of gas administration, with one protocol showing an increase of 18.6% and the other a decrease of 6.4%, highlighting the importance of gas administration order in interpreting MRI results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dependency of the blood oxygen level dependent-response to hyperoxic challenges on the order of gas administration in intracranial malignancies. Stieb, S., Riesterer, O., Boss, A., et al.[2020]

Hyperoxic BOLD-MRI can effectively differentiate between breast cancer molecular subtypes, such as luminal A, Her2+, and triple-negative, using varying levels of oxygen, with significant differences observed even at 41% oxygen.

This imaging technique shows promise as a non-invasive biomarker for identifying luminal A breast cancer without the need for injected contrast agents, highlighting its potential for safer diagnostic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hyperoxic BOLD-MRI-Based Characterization of Breast Cancer Molecular Subtypes Is Independent of the Supplied Amount of Oxygen: A Preclinical Study. Bartsch, SJ., Ehret, V., Friske, J., et al.[2023]

The study compared MRI signal changes with direct pO2 measurements in tumors of Balb-c mice with osteosarcoma, revealing that hyperoxia (breathing pure oxygen) affects tumor oxygen levels.

During oxygen inhalation, both increases and decreases in MR-signal intensity were observed, indicating a complex response of tumors to changes in oxygen supply, particularly as the hypoxic tumor fraction decreased.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison study of oxygen-induced MRI-signal changes and pO2 changes in murine tumors. Weissfloch, L., Peller, M., Weber, J., et al.[2019]

The study demonstrated that hemodynamic response imaging (HRI) using BOLD imaging during hyperoxic challenge is a safe and effective non-invasive method for assessing brain hemodynamic function in glioblastoma, providing valuable clinical information.

In an orthotopic mouse model, the anti-VEGF antibody B20-4.1.1 delayed tumor progression without significantly altering HRI results, while histological analysis showed reduced tumor vascularity and increased cell proliferation in treated tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice. Laufer, S., Mazuz, A., Nachmansson, N., et al.[2020]

A new human-sized pulse EPROI instrument was successfully developed and tested for oxygen imaging in a rabbit model, marking a significant advancement in tumor hypoxia research.

The study demonstrated that systemic intravenous injection of the oxygen-sensitive spin probe OX071 can effectively cover tumors, paving the way for potential clinical applications in cancer therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager. Epel, B., Viswakarma, N., Sundramoorthy, SV., et al.[2023]

Oxygen-Enhanced MRI (dOE-MRI) effectively detects changes in tumor oxygenation following VEGF-ablation therapy, indicating its potential as a non-invasive biomarker for monitoring treatment response in radiation oncology.

The study demonstrated that dOE-MRI can reveal increased tissue oxygenation and reduced hypoxia in tumors, which correlates with enhanced sensitivity to radiation, suggesting that this imaging technique could improve cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Radiosensitizing oxygenation changes in murine tumors treated with VEGF-ablation therapy are measurable using oxygen enhanced-MRI (OE-MRI). Baker, JHE., Moosvi, F., Kyle, AH., et al.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Hypoxia imaging in brain tumors. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

Quantitative Dynamic Oxygen 17 MRI at 7.0 T for the Cerebral Oxygen Metabolism in Glioma. [2020]

3. Netherlands pubmed.ncbi.nlm.nih.gov

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]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Functional magnetic resonance (fMR) imaging of a rat brain tumor model: implications for evaluation of tumor microvasculature and therapeutic response. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

Dependency of the blood oxygen level dependent-response to hyperoxic challenges on the order of gas administration in intracranial malignancies. [2020]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Hyperoxic BOLD-MRI-Based Characterization of Breast Cancer Molecular Subtypes Is Independent of the Supplied Amount of Oxygen: A Preclinical Study. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Comparison study of oxygen-induced MRI-signal changes and pO2 changes in murine tumors. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Monitoring brain tumor vascular heamodynamic following anti-angiogenic therapy with advanced magnetic resonance imaging in mice. [2020]

9. United States pubmed.ncbi.nlm.nih.gov

Oxygen Imaging of a Rabbit Tumor Using a Human-Sized Pulse Electron Paramagnetic Resonance Imager. [2023]

10. Ireland pubmed.ncbi.nlm.nih.gov

Radiosensitizing oxygenation changes in murine tumors treated with VEGF-ablation therapy are measurable using oxygen enhanced-MRI (OE-MRI). [2023]