Blood Brain Barrier Disruption (BBBD) Using MRgFUS in the Treatment of Her2-positive Breast Cancer Brain Metastases

Inclusion Criteria: * Men and women between 18 and 80 years of age * Able and willing to give informed consent * Metastatic Her2-positive breast cancer with brain metastases * Karnofsky performance score 70-100 * ASA score 1-3 * Able to communicate sensations during the ExAblate BBBD 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 * At least 6 weeks passed since last radiation treatment Exclusion Criteria: * Brain metastases not visible on the pre-therapy imaging * The sonication pathway to the tumour involves: i. Extensive scalp scars ii. Clips or other metallic implanted objects in the skull or the brain, except shunts * The subject presents with symptoms and signs of increased intracranial pressure (e.g., headache, nausea, vomiting, lethargy, and papilledema) * Cardiac disease or unstable hemodynamics including: i. Documented myocardial infarction within six months of enrolment ii. Unstable angina on medication iii. Congestive heart failure iv. Left ventricular ejection fraction \< 50% v. Right-to-left, bidirectional, or transient right-to-left cardiac shunts vi. History of a hemodynamically unstable cardiac arrythmia vii. Cardiac pacemaker viii. Contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation * Severe hypertension (diastolic BP \> 100 on medication) * Anti-coagulant therapy or medications known to increase risk of hemorrhage within washout period prior to treatment (i.e. antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin K inhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48 hours of treatment) * History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage * Abnormal level of platelets (\< 100000) or INR \> 1.3 * Documented cerebral infarction within the past 12 months * Transient Ischemic Attack (TIA) in the last 1 month * Known allergy sensitivity or contraindications to gadolinium-diethylenetriamine penta-acetic acid (DTPA), CT contrast, or perflutren or trastuzumab * Allergy to eggs or egg products * Contraindications to MRI such as non-MRI-compatible implanted devices * Large subjects not fitting comfortably into the MRI scanner (generally \>250 lbs) * Difficulty lying 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 * Severely impaired renal function * Respiratory: chronic pulmonary disorders, e.g. severe emphysema, chronic obstructive pulmonary disease (COPD), pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, subjects with a history of drug allergies * Any illness or medical condition that in the investigator's opinion precludes participation in this study