Oxygen-Enhanced MRI for Generating Hypoxia Maps in Patients With Intracranial Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVE: I. Determine the feasibility of generating hypoxia maps from oxygen MRI. SECONDARY OBJECTIVES: I. Evaluate the association between oxygen MRI hypoxia maps generated using T2* and T1 MRI sequences. II. Evaluate the association between oxygen MRI hypoxia maps and progression free survival. OUTLINE: Patients receive supplemental oxygen while undergoing standard of care MRI.

Official Title
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Feasibility of Oxygen Enhanced MRI in Assessment of Malignant Brain Tumors

Conditions
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Intracranial Neoplasm

Intervention / Treatment
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* Procedure: Magnetic Resonance Imaging
* Procedure: Oxygen Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients (18 years of age or older) with a known or suspected intracranial tumor Able to provide informed written consent and/or acceptable surrogate capable of providing consent on the patient's behalf Legally authorized representative (LAR)-signed informed consent and assent obtained for those subjects identified as decisionally impaired Intracranial lesion known or suspected to be neoplastic greater than 10 mL as assessed by T2/fluid attenuated inversion recovery (FLAIR) magnetic resonance (MR) imaging Karnofsky performance score > 60 or Eastern Cooperative Oncology Group (ECOG) < 3 as assessed by referring clinician Planning to undergo or previously received therapeutic intervention for the intracranial tumor Exclusion Criteria: Pregnant or breastfeeding Contraindication to supplemental oxygen administration, MRI, or intravenous gadolinium based contrast agents. Claustrophobia Weight greater than modality maximum capacity Presence of metallic foreign body or implanted medical devices in body not documented as MRI safe according to the Oregon Health & Science University (OHSU) Department of Radiology guidelines (including but not limited to cardiac pacemaker, aneurysm clips, surgical clips, prostheses, artificial hearts, valves with steel parts, metal fragments, shrapnel, tattoos near the eye, or steel implants) Sickle cell disease Unsure of pregnancy status as assessed by Department of Radiology and Advanced Imaging Research Center (AIRC) guidelines Subjects for whom supplemental oxygen could be harmful such as people with potential for hypoventilation or chronic respiratory insufficiency (end-stage chronic obstructive pulmonary disease [COPD], obstructive sleep apnea [OSA] on continuous positive airway pressure [CPAP]/biphasic positive airway pressure [Bi-PAP], etc) Subjects with a relative contraindication to supplemental oxygen administration will not be provided oxygen but may still participate in the study Presence of any other co-existing condition that, in the judgment of the principal investigator, might increase the risk to the subject (i.e., plans for hospice or end of life care) Poor peripheral intravenous access evaluated by patient history Presence of other serious systemic illnesses, including: uncontrolled infection, other uncontrolled malignancy, uncontrolled diabetes type II, or psychiatric/social situations which might impact the endpoint of the study or limit compliance with study requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Diagnostic (oxygen-enhanced MRI)<br>Patients receive supplemental oxygen while undergoing standard of care MRI. | Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;Procedure: Oxygen Therapy<br>* Receive supplemental oxygen<br>* Other names: supplemental oxygen therapy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Generation of whole brain oxygen magnetic resonance imaging (MRI) data set | Evaluated to determine the feasibility of obtaining oxygen MRI hypoxia maps. Following completion of cohort enrollment, the generation of each hypoxia map will be independently scored as a dichotomous variable; successful or non-successful. The successful generation of a hypoxia map from either a T1 or T2* approach in 85% of the cohort of patients will need to be achieved for the imaging modality to be deemed feasible for the purposes of this study. Will provide the estimated proportion of success rate for each metric along with the corresponding 95% exact confidence interval. | One hour of diagnostic imaging | 
| Quantification of hypoxic tumor volume | Evaluated to determine the feasibility of obtaining oxygen MRI hypoxia maps. | One hour of diagnostic imaging | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between T1 and T2* sequence hypoxia volume | Will determine the association between oxygen MRI hypoxia maps generated using T2* and T1 MRI sequences. Assessed using Pearson's correlation coefficient. | One hour of diagnostic imaging | 
| Progression free survival | Will perform Kaplan Meier analysis of progression free survival stratified by median T1 and T2* hypoxic volume to determine the association between oxygen MRI hypoxia maps and progression free survival. A Cox regression model will also be explored by treating hypoxic volume as a continuous variable. | Clinical follow up for up to 5 years |