Blood Brain Barrier (BBB) Disruption Using Exablate Focused Ultrasound With Doxorubicin for Treatment of Pediatric DIPG

Inclusion Criteria: Age between 5 and 21 years, inclusive Patient diagnosed with DIPG At least 4-week and not greater than 12 weeks from completion of radiation therapy Post-radiation imaging does not show evidence of necrosis/ hemorrhage or other features that contraindicate MRgFUS If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable If on steroids, stable or decreasing dose for at least 7 days prior to study entry Stable or improving neurologic status for 7 days prior to study entry Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so Able to attend all study visits and with life expectancy of at least 6 months Exclusion Criteria: Tumor not visible on any pre-therapy or post-radiation imaging Previous participation in other chemotherapy, molecularly targeted therapy, or immunotherapy treatment-related phase 1 or 2 trials Symptoms and signs of increased intracranial pressure Subject with metastatic disease Subject with ventricular peritoneal shunt Subject receiving bevacizumab (Avastin) therapy or increasing doses of steroids Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs [NSAIDs], statins) within washout period prior to treatment History of a bleeding disorder, coagulopathy or with a history of spontaneous tumor hemorrhage. Hypertension per age Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis Immunosuppression (corticosteroids to prevent/treat brain edema are permitted). Patients with positive HIV status Active seizure disorder or epilepsy (seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by history Known sensitivity to gadolinium-based contrast agents Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol Contraindication to Doxorubicin Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones Severely impaired renal function with estimated glomerular filtration rate <2 standard deviations for age Patients that may require trastuzumab during the study Patients that may require inhibitors and inducers of CYP3A4, CYP2D6, and/or P-gp during the study