To learn if drawing blood directly from veins inside the brain is safe and can effectively provide the same kind of detailed information about high-grade glioma as traditional surgical biopsy.

Primary Objectives The primary objective is to evaluate the safety and efficacy of intracranial venous sampling with or without BBB disruption with administration of intraarterial mannitol in participants with high grade gliomas.

• The study will determine if intracranial venous blood sampling for liquid biopsy can facilitate accurate and precise molecular diagnosis in participants with high grade gliomas that is comparable to molecular diagnosis obtained during surgical brain biopsy.
• The study will determine if intracranial venous blood sampling for liquid biopsy requires concomitant temporary blood brain barrier disruption with endovascular selective intraarterial infusion of mannitol for accurate and precise molecular diagnosis of high-grade gliomas.

Secondary Objectives

• The study will determine if intracranial venous blood sampling in participants with high grade gliomas results in higher yield of ctDNA and other biomarkers than peripheral venous blood sampling, and if this is further augmented by BBB disruption.

Eligibility Criteria

1. Subjects over the age of 18 with suspected or confirmed, recently diagnosed, previously treated or recurrent high-grade glioma (WHO grade III and IV) in whom a diagnostic cerebral Angiogram is indicated as standard of care may be approached for participation in this study.

2. Subjects are eligible if review of relevant intracranial cerebrovascular anatomy by cross sectional imaging such as CTA head and MRI brain, is deemed suitable for endovascular intracranial venous sampling.

3. For subjects with suspected or recently diagnosed glioma, subjects are eligible if they have or are scheduled to undergo surgical biopsy or surgical resection of the tumor within 4 weeks (+/- 1 week) of the planned liquid biopsy.

4. For subjects with previously treated or recurrent glioma in whom tissue diagnosis and molecular profiling had been previously performed on surgical specimens at any time in the past, a planned surgical biopsy/resection is desirable but not necessary for inclusion in the study.

   • Ability to understand and the willingness to sign an informed consent document.

5. For participants with known history of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy within 6 months, if indicated.

6. Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load within 6 months.

7. Participants with a known history of human immunodeficiency virus (HIV on effective antiretroviral therapy with undetectable viral load within 6 months are eligible for this trial.

8. Karnofsky Performance Scale ≥ 60%

9. Participants must have adequate organ and marrow function as defined below:

hemoglobin ≥ 7mg/dL absolute neutrophil count ≥ 1,000/mcL platelets ≥ 100,000/mcL International Normalized Ratio ≤ 1.7 AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN creatinine ≤ 1.5mg/dL

Exclusion Criteria

1. Subjects with suspected glioma or other brain cancers who do not have a tissue diagnosis and no surgical biopsy or resection is anticipated.

2. Subjects in whom diagnostic cerebral angiogram is contra-indicated defined as:

   • Severe contrast allergy
   • Acute/chronic renal dysfunction with eGFR < 45 ml/min and Cr ≤ 1.5 mg/dL

3. For participants undergoing surgery, refractory coagulopathy or thrombocytopenia which cannot be corrected defined as:

   • Platelets ≤100,000/mcL
   • International Normalized Ratio ≤ 1.7

4. Subjects that have a known high risk in monitored anesthetic care or general anesthesia assessed by the treating physician.

5. Anatomic considerations: based on cross-sectional imaging such as CT angiogram of the head and neck, the anatomy for arterial and venous vascular access is deemed unsuitable for endovascular access such as high-grade carotid artery stenosis, absent or occluded internal jugular veins, sigmoid sinuses and/or transverse sinuses.

6. Participants with clinical cerebral edema evidenced from altered mental status

7. Pregnant women due to risk of radiation exposure to the fetus, as determined by pregnancy urinalysis or serum analysis test during screening.

8. Subjects with psychiatric illness/social situations that would limit compliance with study requirements at the physician's discretion.

MD Anderson Cancer Center