MRI-Guided Focused Ultrasound Feasibility Study for Brain Tumors

In this non-randomized feasibility study, FUS under MRI-guidance and thermometry will be given through intact human skull to brain tumor in up to ten (10) subjects. These subjects will be followed over a 3-month period with contrast MRI and clinical exams.

The objectives are:

• To evaluate the safety of ExAblate TcMRgFUS treatment delivered through intact human skull to the brain, during the treatment, and during the follow-up period of 3 months.
• To evaluate the effect of thermal ablation in the target tumor with contrast MR imaging to identify viable tumor, and non-viable thermally ablated tissue.

Inclusion criteria

• Men or women.
• Age between 18 and 70 years, inclusive.
• Able and willing to give informed consent.
• Subjects with (newly diagnosed or recurrent) metastatic cancer for whom surgery, radiation, or radiosurgery has not been advised by the treating physician.
• The targeted tumor tissue is located in the cerebral hemispheres, > 2.5 cm from the inner table of the skull. Non-targeted parts of the tumor may extend outside the treated tumor limits.
• Tumor(s) are clearly defined on pre-therapy contrast enhanced MRI scans.
• Size of the targeted portion of the tumor (i.e. prescribed Region Of Treatment) is less than 2.5 cm in diameter or 8 cm3 in volume. The non-targeted tumor tissue may exceed the targeted volume.
• Karnofsky rating 70-100 (See Appendix A).
• ASA score 1-2.
• Able to communicate sensations during the ExAblate MRGFUS procedure.
• Able to attend all study visits (i.e. life expectancy of at least 3 months).
• At least 14 days passed since last brain surgery, or intracranial radiation therapy/radiosurgery

Exclusion criteria

• The subject presents with:

• Symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papaedema).

• Unstable hemodynamic status including: i. Documented myocardial infarction within six months of enrollment. ii.Symptomatic coronary artery stenosis. iii. Congestive heart disease requiring medication. iv. Anti-arrhythmic drug medication. v. Cardiac pacemaker. vi. Severe hypertension (diastolic BP > 100 on medication).
• Anti-coagulant therapy, on medications known to increase risk of hemorrhage, (e.g.: non-steroidal anti-inflammatory drugs (NSAIDs), statins
• TIA or stroke in the last 1 month
• Insulin-dependent diabetes mellitus
• Immunosuppression (corticosteroids to prevent brain edema are permitted)
• Known sensitivity to gadolinium-DTPA
• Contraindications to MRI such as non-MRI-compatible implanted devices
• Large subjects not fitting comfortably into the MRI scanner
• Difficulty laying supine and still for up to 4 hours in the MRI unit or claustrophobia
• Untreated, uncontrolled Sleep apnea
• Positive pregnancy test (for pre-menopausal women)
• Known life-threatening systemic disease
• More than 3 metastatic tumors
• History of abnormal bleeding and coagulopathy
• Use of Avastin in the preceding two weeks or planned use in the forthcoming two weeks and VEGF inhibitors within + 30 days of treatment
• Patients with a history of uncontrolled seizures or who are not on anti seizure medication (e.g., Phenytoin 100 mg PO t.i.d. or Keppra 500 mg po bid) before the procedure