NgFUS NIVO: NeuroNavigation-Guided Focused Ultrasound With Nivolumab in Relapsed and Progressive DMG and Other High Grade Brain Tumors

Inclusion Criteria: * Age ≥ 3 and ≤ 25 years. * Diagnosis of brainstem DMG/DIPG or any high-grade brain tumor. * Group A: Relapsed or progressive brainstem DMG. * Group B: Relapsed or progressive high-grade intracranial brain tumor requiring surgical resection. * Lansky/Karnofsky rating ≥ 60. * Patients must have received at least one line of prior therapy upfront for their disease. * At least four weeks from radiation therapy, prior immunotherapy, or monoclonal antibody therapy. * At least 2 weeks from prior myelosuppressive chemotherapy and post nadir meeting organ function criteria. * At least 1 week or 5 half-lives (whichever is longer) from last targeted therapy. * If on steroids, stable or decreasing dose for at least 7 days prior to study entry and ≤ 0.4 mg/m2/day of dexamethasone or equivalent. * Stable or improving neurological status for 7 days prior to study entry. * Organ function: * Absolute Neutrophil Count (ANC) ≥750/μL. * Absolute Lymphocyte Count (ALC) \>500/μL. * Platelets ≥75K, unsupported. * Coagulation studies: PT and PTT \<1.5 ULN and INR (\<1.5). * Bilirubin ≤1.5x upper limit of normal (ULN). * AST/ALT ≤5x ULN. * Serum creatinine within normal limits for age. * Pulse oximetry \>93% on room air. * Ejection Fraction (EF) above institutional lower limit of normal (LLN). * For females of childbearing potential (FOCBP): negative pregnancy test within 7 days of study entry. * Patients of childbearing or child-fathering potential must agree to use contraceptive measures for at least 5 months following nivolumab infusion. * Patient or parent/guardian capable of providing informed consent. Exclusion Criteria: * Symptoms and signs of increased intracranial pressure. * Patients with metallic ventricular peritoneal shunts. Subjects with nonmetallic VP shunts or similar will have a technical evaluation of the screening non-contrast CT scan of the head. During the mapping of the target area, if the technical NaviFUS specialist determines that the patient cannot be treated within the safety limits of the system, the patient will not be eligible and will be considered a screen failure. * Tumor presenting with the following imaging characteristics: * Evidence of uncal herniation. * Edema and/or mass effect that causes hydrocephalus. * Significant areas of necrosis within the tumor that the neurosurgeon feels cannot be avoided during the ultrasound sonication. * Evidence of a significant new hemorrhage. Area of microhemorrhage (defined as less than 5 mm in diameter) in the treatment area can be acceptable but requires the review of the neurosurgeon. * Containing calcifications in the focused ultrasound sonication beam path and system tools cannot tailor the treatment around these calcification spots. * Patients who are deemed to have overly bulky tumor by the PI of the study. * The sonication pathway to the tumor involves: * More than 30% of the skull area traversed by the sonication pathway is covered by scars, scalp disorders (e.g., eczema), or atrophy of the scalp. * Clips, or other non-MRI compatible metallic implanted objects in the skull or the brain, except for shunts. * Patients receiving anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., ASA, non-steroidal anti-inflammatory drugs \[NSAIDs\], statins). There is no required washout for eligibility assessment, but patients should be off agents for at least 3 days at the time of procedure or until 5 half-lives of the agent, whichever is longer. * History of a bleeding disorder, coagulopathy or with a history of clinically significant spontaneous tumor hemorrhage. * Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis. * Immunosuppression (corticosteroids to prevent/treat brain edema are permitted). * Patients with uncontrolled HIV. * Active seizure disorder or epilepsy (clinically significant seizures despite medical treatment) within four weeks prior to first cycle/NaviFUS BBBO procedure captured by history. * Known sensitivity to gadolinium-based contrast agents. * Known sensitivity to Lumason® ultrasound contrast agent or known hypersensitivity to sulphur hexafluoride microsphere or its components, e.g., polyethylene glycol. * Patients unable to fit comfortably into the MRI scanner (generally \>250 lbs.). * Evidence of cranial or systemic infection.