Assessment of Safety and Feasibility of ExAblate Blood-Brain Barrier (BBB) Disruption

Prior treatment

• The sonication pathway to the tumor involves:
  • Extensive scalp sores. ii. Clips or other metallic implanted objects in the skull or the brain (brain implants)
• Significant depression not adequately controlled with medication and at potential risk of suicide.
• Patient receiving bevacizumab (Avastin) therapy.
• Patients receiving treatment with corticosteroid doses greater than dexamethasone 24 mg daily (or equivalent).
• Patients undergoing other concurrent therapies such as chemotherapy wafers, immunotoxins delivered by convection-enhanced delivery, regionally administered gene and viral therapies, immunotherapies, focal irradiation with brachytherapy, stereotactic radiosurgery, laser interstitial thermotherapy, and tumor treatment fields therapy.
• Anti-coagulant therapy, or medications known to increase risk of hemorrhage within washout period prior to treatment.

Other illness

• Patients presenting with the following imaging characteristics:
  • Evidence of acute intracranial hemorrhage.
• Patients with positive HIV status.
• Severe hypertension (diastolic BP \> 100 on medication).
• History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage.
• Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis.
• History of drug or alcohol use disorder.
• Active seizure disorder or epilepsy (seizures despite medical treatment).
• Cardiac shunt.
• Subjects with evidence of cranial or systemic infection.
• Subjects with significant liver dysfunction, e.g., history of cirrhosis or active hepatitis.

Lab values

• Cardiac disease or unstable hemodynamics including:
  • Documented myocardial infarction within six months of enrollment. ii. Unstable angina on medication. iii. Congestive heart failure. iv. Left ventricular ejection fraction \<50%. v. History of a hemodynamically unstable cardiac arrhythmia. vi. Cardiac pacemaker.

Other

• The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema).
• Patients with cerebellar or brainstem tumors.
• Known sensitivity to gadolinium-based contrast agents.
• Known sensitivity to DEFINITY® ultrasound contrast agent or perflutren.
• Contraindications to MRI such as non-MRI-compatible implanted devices.
• Large subjects not fitting comfortably into the MRI scanner.
• Difficulty lying supine and still for up to 4 hours in the MRI unit or claustrophobia.
• Positive pregnancy test (women of childbearing potential).
• Severely impaired renal function or on dialysis.

• Patient is eligible for adjuvant temozolomide (TMZ) treatment based on the current standard of care.
• Men or women age between 18 and 80 years, inclusive.
• Able and willing to give informed consent.
• Grade IV glioma (GBM)
• Combined radiation/TMZ treatment is completed based on the prescribed standard of care regimen.
• Karnofsky rating 70-100.
• Able to communicate during the ExAblate BBBD (Blood Brain Barrier Disruption) procedure.
• Able to attend all study visits (i.e., life expectancy of at least 3 months).