Advanced Imaging Techniques for Evaluating the Tumor Immune Microenvironment in Glioblastoma Patients

Advanced MRI for Visualization and Quantification of the Tumor Immune Microenvironment (TIME) in Glioblastoma

This phase III trial is evaluating whether a combination of three advanced magnetic resonance imaging (MRI) techniques, including chemical exchange saturation transfer (CEST) MRI, diffusion-relaxation correlation spectrum imaging (DR-CSI), and ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) are effective as non-invasive methods for assessing the cells and proteins that surround and interact with tumor cells (the tumor immune microenvironment) in patients with glioblastoma. Researchers understand that some types of brain tumors are harder to treat than others, but the reasons for this are not known in many cases. CEST MRI uses differences in the tissue microenvironment, like protein concentration or intracellular pH, to generate contrast differences. DR-CSI detects microstructural changes in tissue associated with immune cells infiltrating the tumor. Fe-MRI uses ferumoxytol as a contrast agent with MRI. Contrast agents are substances that are injected into the body and taken up by certain tissues, making the tissues easier to see in imaging scans. More advanced imaging techniques like CEST, DR-CSI, and Fe-MRI may offer less invasive methods than surgery or biopsy for helping researchers understand the tumor immune microenvironment in patients with glioblastoma, which may help researchers determine why some tumors are more resistant to treatment.

Study Overview

• Status: Recruiting
• Conditions: Glioblastoma
• Intervention / Treatment: Procedure: Biospecimen Collection; Drug: Ferumoxytol; Other: Electronic Health Record Review; Procedure: Chemical Exchange Saturation Transfer Magnetic Resonance Imaging; Procedure: Diffusion-Relaxation Correlation Spectrum Imaging; Radiation: Magnetic Resonance Imaging

Detailed Description

PRIMARY OBJECTIVE:

I. To establish the biological validation of advanced MRI as a non-invasive imaging modality for assessing the tumor immune microenvironment (TIME) in glioma.

SECONDARY OBJECTIVES:

I. Conduct more detailed correlation explorations focusing on relevant subpopulations, such as cluster of differentiation 4 (CD4+) versus ( cluster of differentiation 8 (CD8+) T cells and M1- versus M2-like tumor-associated macrophages (TAMs).

II. Perform exploratory correlation analysis between tumor-averaged imaging measures with systemic immunological markers (T cell activation and interferon pathway signaling), to improve our understanding of the relationship between local tissue immune environment and systemic immune response in glioma patients.

OUTLINE:

Patients undergo research CEST MRI and DR-CSI over 30 minutes at research visit 1, up to 28 days before standard of care surgery/biopsy. Following research CEST MRI and DR-CSI at research visit 1, patients receive ferumoxytol intravenously (IV) over 10-15 minutes. Approximately 24-48 hours later, patients undergo Fe-MRI over 15 minutes at research visit 2. Patients also undergo standard of care clinical MRI and collection of blood samples on study.

After completion of study intervention, patients are followed up until death.

• Study Type: Interventional
• Enrollment (Estimated): 15
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095
      • Recruiting
      • UCLA / Jonsson Comprehensive Cancer Center
      • Contact: Jingwen Yao; Phone Number: 310-869-2156; Email: jingwenyao@mednet.ucla.edu
      • Principal Investigator: Jingwen Yao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male or female ≥ 18 years of age
• Documentation of a confirmed or suspected diagnosis of glioblastoma
• The participant is scheduled to undergo standard of care surgical tumor resection and/or biopsy
• The participant has a measurable contrast-enhancing lesion (> 1ml) based on the most recent MRI prior to resection/biopsy

Exclusion Criteria:

• Presence of a condition or abnormality that in the opinion of the investigator would compromise the safety of the patient or the quality of the data
• Individuals who cannot tolerate MRI scan, or with contraindication to 3-Tesla (3T) MRI
• Any abnormalities that would be a contraindication to iron-oxide nanoparticle-based contrast agent. Medical history will be gathered from the patient and clinical chart. The information will be reviewed with medical professionals (Doctor of Medicine [MD]) to determine the eligibility of the patient

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Diagnostic (CEST MRI, DR-CSI, Fe-MRI); Patients undergo research CEST MRI and DR-CSI over 30 minutes at research visit 1, up to 28 days before standard of care surgery/biopsy. Following research CEST MRI and DR-CSI at research visit 1, patients receive ferumoxytol IV over 10-15 minutes. Approximately 24-48 hours later, patients undergo Fe-MRI over 15 minutes at research visit 2. Patients also undergo standard of care clinical MRI and collection of blood samples on study.

Procedure: Biospecimen Collection; Undergo collection of blood samples; Other Names: Biological Sample Collection; Biospecimen Collected; Specimen Collection; Drug: Ferumoxytol; Given IV; Other Names: Feraheme; Ferumoxytol Non-Stoichiometric Magnetite; Other: Electronic Health Record Review; Ancillary studies; Procedure: Chemical Exchange Saturation Transfer Magnetic Resonance Imaging; Undergo CEST MRI; Other Names: Chemical Exchange Saturation Transfer MRI; Procedure: Diffusion-Relaxation Correlation Spectrum Imaging; Undergo DR-CSI; Other Names: Diffusion-Relaxation Correlation Spectroscopic Imaging; DR-CSI; Radiation: Magnetic Resonance Imaging; Undergo MRI; Other Names: MRI; Magnetic Resonance; Magnetic Resonance Imaging Scan; Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance; MR; MR Imaging; MRI Scan; NMR Imaging; NMRI; Nuclear Magnetic Resonance Imaging; Magnetic Resonance Imaging (MRI); sMRI; Magnetic resonance imaging (procedure); MRIs; Structural MRI

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean diffusion-relaxation correlation spectrum imaging (DR-CSI) value	Mean DR-CSI values will be correlated with T cell densities. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.	perioperatively/periprocedurally
Ferumoxytol-enhanced magnetic resonance imaging (Fe-MRI) measures	Fe-MRI measures will be correlated with tumor-associated macrophage densities and iron staining concentration. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.	perioperatively/periprocedurally
Chemical exchange saturation transfer (CEST) values	CEST values will be correlated with tumor burden and immune suppression markers. Pearson's or Spearman's correlation coefficients will be used depending on variable distributions.	perioperatively/periprocedurally

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Center for Advancing Translational Sciences (NCATS)
• Investigators: Principal Investigator: Jingwen Yao, UCLA / Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 27, 2025
• Primary Completion (Estimated): October 27, 2028
• Study Completion (Estimated): October 27, 2028

Study Registration Dates

• First Submitted: December 3, 2025
• First Submitted That Met QC Criteria: March 6, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 6, 2026
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma; Investigative Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Inorganic Chemicals; Chemistry Techniques, Analytical; Spectrum Analysis; Ferric Compounds; Iron Compounds; Ferrous Compounds; Minerals; Ferrosoferric Oxide; Specimen Handling; Magnetic Resonance Spectroscopy
• Other Study ID Numbers: 25-1450; NCI-2025-07966 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); KL2TR001882 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No