This phase III trial compares pH weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI)-based surgical resections to standard of care surgical resections for the treatment of patients with glioblastoma. Standard of care therapy for glioblastoma is surgery to remove tumor tissue that enhances on standard MRI imaging, however, it has been shown that significant tumor burden exists in the region around the tumor tissue that does not enhance with standard MRI. MRI is a procedure in which radio waves and a powerful magnet linked to a computer are used to create detailed pictures of areas inside the body. These pictures can show the difference between normal and tumor tissue. CEST MRI is a technique that uses differences in the tissue environment, like protein concentration or intracellular pH, to generate contrast differences. CEST MRI may identify tumor tissue that does not enhance with standard of care MRI. PH weighted CEST MRI based surgical resection may be more effective compared to standard of care surgical resection in treating patients with glioblastoma.

PRIMARY OBJECTIVE:

I. To assess the efficacy of potential of hydrogen (pH) sensitive MRI based resections of glioblastoma.

SECONDARY OBJECTIVE:

I. To find surgical and adjuvant therapies to treat infiltrating glioblastoma cells.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients undergo surgical resection with standard intraoperative guidance using contrast-enhanced MRI. Patients also undergo post operative standard of care radiation therapy over 30 fractions and receive standard of care temozolomide orally (PO) for 6 weeks. Additionally, patients undergo MRI during follow up.

GROUP II: Patients undergo surgical resection with intraoperative guidance using CEST MRI. Patients also undergo post operative standard of care radiation therapy over 30 fractions and receive standard of care temozolomide PO for 6 weeks. Additionally, patients undergo MRI during follow up.

After completion of study treatment, patients are followed up at months 3, 6, 12, and 24.

Inclusion Criteria:

• Male or female ≥ 18 years of age
• Documentation of a newly diagnosed World Health Organization (WHO) grade IV glioblastoma as evidenced by clinical features and imaging data
• Written informed consent (and assent when applicable) obtained from subject or subject's legal representative and ability for subject to comply with the requirements of the study

Exclusion Criteria:

• Male or female < 18 years of age
• 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
• Not medically cleared for surgery
• Previous treatment (any chemotherapy, molecular therapy, immunotherapy, or radiation therapy)

The patient, investigators and research staff will be blinded.