Simultaneous Multinuclear Metabolic MRI in Newly Diagnosed or Recurrent Glioma

Study Overview
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Brief Summary
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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.

Detailed Description
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PRIMARY OBJECTIVES: I. Construct and test a novel multinuclear Na+-H+ metabolic MRI sequence with sensitivity to Sodium (Na+) concentration, Potential of Hydrogen (pH), and oxygen (O2). II. Correlate Na+-, pH-, and O2-weighted MR image measurements with sodium-proton exchanger isoform-1 (NHE1) immunohistochemistry (IHC), bioenergetics, and gene expression using stereotactic image-guided biopsies from human brain tumors. III. Quantify changes in Na+-, pH-, and O2-weighted MR images after neoadjuvant anti-PD-1 immunotherapy in recurrent glioblastoma (GBM) and explore associated changes in tumor biology. OUTLINE: 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.

Official Title
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Simultaneous Multinuclear (Na+/H+) Metabolic MRI in Brain Tumors

Conditions
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Glioma, Malignant Glioma, Recurrent Glioma, Recurrent Malignant Glioma

Intervention / Treatment
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* Procedure: Biospecimen Collection
* Procedure: Diagnostic Imaging
* Procedure: Magnetic Resonance Imaging


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: AIM 1: Healthy volunteers with no evidence of brain tumors or neurologic disease AIM 1: Age 18+ AIM 2: Newly diagnosed or recurrent suspected or confirmed glioma (low or high grade) AIM 2: 10 IDH mutant and 10 IDH wild type gliomas AIM 2: Clinically indicated for resective surgery or biopsy AIM 2: Age 18+ AIM 2: Tumor size > 1x1x1 cm (measurable) AIM 3: Recurrent glioma enrolled in an immunotherapy trial or clinically indicated to receive immunotherapy including anti-PD1 AIM 3: Age 18+ Exclusion Criteria: AIM 1: Cannot safely perform an MRI AIM 1: Age < 18 AIM 2: Cannot safely perform an MRI or use of MRI contrast agents AIM 2: Age < 18 AIM 3: Cannot safely perform an MRI or use of MRI contrast agents AIM 3: Age < 18

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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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Interventional Model Description: 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Basic science (MRI, metabolic imaging, tissue collection)<br>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. | Procedure: Biospecimen Collection<br>* Undergo collection of tissue samples<br>* Other names: Biological Sample Collection;Procedure: Diagnostic Imaging<br>* Undergo multinuclear metabolic imaging<br>* Other names: Medical Imaging;Procedure: Magnetic Resonance Imaging<br>* Undergo MRI<br>* Other names: Nuclear Magnetic Resonance Imaging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total sodium concentration | Will calculate NaT using standard methodology and normalize it to ocular Na+ concentration, a constant 135 mmol/l. Will then test whether healthy tissue has a coefficient of variance (COV) of < 10% across all 20 subjects. | Up to 5 years | 
| NHE1 expression | Will create a comprehensive map of genes/pathways and unique cell subsets associated with NHE1 expression. | Up to 5 years | 
| Tumor metabolism | Will examine the correlation between baseline tumor metabolism and change in metabolism with respect to overall survival using Cox multivariable regression. | Up to 5 years |