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

Inclusion Criteria:

* Age between 5 and 18 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
* Able to attend all study visits and with life expectancy of at least 6 months
* Able and willing to give consent and/or assent or have a legal guardian who is able and willing to do so
* If on steroids, stable or decreasing dose for at least 7 days prior to study entry
* If brain surgery occurred, at least 14 days passed since last brain surgery and the patient is fully recovered and neurologically stable

Exclusion Criteria:

* Evidence of cranial or systemic infection
* Known life-threatening systemic disease
* Previous treatment with complete cumulative doses of Doxorubicin, daunorubicin, idarubicin, and/or other anthracyclines and anthracenediones
* Contraindication to Doxorubicin. - Known sensitivity to DEFINITY® ultrasound contrast agent or known hypersensitivity to perflutren microsphere or its components, e.g., polyethylene glycol. - Known sensitivity to gadolinium-based contrast agents
* 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
* Patients with positive HIV status. - Immunosuppression (corticosteroids to prevent/treat brain edema are permitted)
* Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis
* Hypertension per age
* History of a bleeding disorder, coagulopathy or with a history of spontaneous tumour hemorrhage
* 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
* Patient receiving bevacizumab (Avastin) therapy or increasing doses of steroids
* Symptoms and signs of increased intracranial pressure
* Previous participation in other chemotherapy, molecularly targeted therapy or immunotherapy treatment-related phase 1 or 2 trials
* Tumor not visible on any pre-therapy or post-radiation imaging