Blood-Brain Barrier Disruption Using Exablate Magnetic Resonance-Guided Low Intensity Focused Ultrasound With Microbubbles in Combination With T-Cell Infusion in Patients With Newly Diagnosed Diffuse Midline Glioma (LIFT)

Inclusion Criteria: Inclusion Criteria for Screening and Procurement: * Age ≥ 3 and ≤ 25 years * Diagnosis of pontine or thalamic DMG * Group A: newly diagnosed pontine DMG after completion of standard radiation therapy; radiographic diagnosis is defined as tumors with a pontine epicenter and diffuse intrinsic involvement of the pons - tissue diagnosis is not required * Group B: newly diagnosed thalamic DMG after completion of standard radiation therapy; tissue diagnosis is required NOTE: Tumor extending outside of the pons or the thalamus can remain eligible if the LIFU treatment is not contraindicated based on the neurosurgeon's assessment and the tumor does not meet any of the exclusion criteria below * The first procurement blood draw must occur between 4 and 14 weeks after completion of radiation therapy for Group A, and between 4 and 22 weeks after completion of radiation therapy for Group B * Lansky/Karnofsky rating ≥ 60 (participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status) * Head circumference ≥ 49 cm * Organ function: * Hemoglobin ≥ 8 g/dL, unsupported * Absolute Neutrophil Count (ANC) ≥750/μL * Absolute Lymphocyte Count (ALC) \>500/μL * Platelets ≥75K, unsupported * Total Bilirubin ≤3x upper limit of normal (ULN) * AST/ALT ≤5x ULN * Serum creatinine ≤1.0 mg/dL or ≤1.5x ULN for age (whichever is higher) * Pulse oximetry \>90% on room air * If the participant is on corticosteroids, the dose must be stable or decreasing for at least 7 days prior to procurement, and the treating investigator must anticipate that steroids can be weaned to ≤ 0.4 mg/m2/day of dexamethasone or equivalent by the start of the first LIFT protocol therapy cycle * Deemed to be of sufficient size (≥10 kg) to provide the necessary blood volume for TAA-T generation with no contra-indications to research blood draw, as determined by the treating PI/Sub-I * Adult participant or LAR of minor participant demonstrates willingness to have intracerebroventricular access device placed prior to initiation of LIFT protocol therapy, if a suitable Rickham, Ommaya, or accessible VP shunt is not already in place at study entry * For females of childbearing potential (FOCBP): negative pregnancy test within 7 days prior to procurement (urine or serum) * Adult participant or LAR of minor participant capable of providing informed consent. When appropriate, pediatric participants ≥7 years of age will participate in an age-appropriate discussion and provide assent, unless an IRB-approved waiver of assent applies and documentation of the participant's eligibility for the waiver is maintained Inclusion Criteria for BBBD Procedure and TAA-T Infusion: * Lansky/Karnofsky rating ≥ 60 (participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for purposes of assessing performance status) * Group A: must have their initial planned LIFU and TAA-T infusion within 20 weeks from completion of radiation therapy; Group B: must have their initial planned LIFU and TAA-T infusion within 28 weeks from completion of radiation therapy * For participant with a history of prior intracranial surgery, at least 14 days must have elapsed since surgery and the participant must have fully recovered from acute surgical effects * For participant with a history of bevacizumab (Avastin) exposure, at least 28 days must have elapsed since the last dose * If on steroids, stable or decreasing dose ≤ 0.4 mg/m2/day of dexamethasone or equivalent on the date of eligibility confirmation for LIFT treatment * Stable or improving neurological status for ≥14 days prior to the date of eligibility confirmation for the first LIFU and TAA-T infusion, and for ≥7 days prior to the date of eligibility confirmation for subsequent cycles * Intracerebroventricular access device (such as an Ommaya or Rickham reservoir and catheter) or VP shunt present, and in a location that does not interfere with Exablate BBBD procedure * Organ function: * Hemoglobin ≥ 8 g/dL, unsupported * Absolute Neutrophil Count (ANC) ≥750/μL * Platelets ≥75K, unsupported * Normal coagulation studies: PT (\<14 sec) or PTT (\<36 sec), and INR (\<1.2) * Total Bilirubin ≤3x upper limit of normal (ULN) * AST/ALT ≤5x ULN * Serum creatinine ≤1.0mg/dL or ≤1.5x ULN for age (whichever is higher) * Pulse oximetry \>90% on room air * For FOCBP: negative pregnancy test (urine or serum) * Agree to use contraceptive measures for at least 6 months following final TAA-T infusion (when age appropriate) * Suitability for prolonged anesthesia for LIFU procedure, in the opinion of treating PI or qualified Sub-I * Agree to a brief course of steroids or bevacizumab or anti-cytokine agent/s if the treating investigator deems it clinically necessary in the context of clinical deterioration that may be attributed to the LIFT protocol therapy * Adult participant or LAR of a minor participant capable of providing informed consent. When appropriate, pediatric participants ≥7 years of age will participate in an age-appropriate discussion and provide assent, unless an IRB-approved waiver of assent applies and documentation of the participant's eligibility for the waiver is maintained * Adult participant or LAR of a minor participant must attest to the participant's ability to remain in close geographic proximity to CNH (within 60-mile radius) for the initial dose limiting toxicity (DLT) monitoring period, and for the first 14 days after each subsequent infusion Exclusion Criteria: Exclusion Criteria for Screening and Procurement: * Tumor not visible on any pre-LIFT therapy imaging * Previous participation in other conventional or investigational chemotherapy, molecularly targeted therapy, or immunotherapy (Exceptions: Temozolomide during radiation in Group B patients is allowed; Bevacizumab use is allowed) * Disseminated disease * Primary disease in the spinal cord * Clinical or radiologic evidence of increased intracranial pressure * For a participant with a ventricular peritoneal (VP) shunt or similar device: presence of a device that, in the judgment of the institutional neurosurgeon (based on a technical evaluation of the screening non-contrast CT imaging and Exablate system target mapping), would interfere with safe delivery of the Exablate BBBD procedure * Previous or current uncontrolled infection/s * Known HIV infection * Pregnant or lactating females * Prior allogeneic stem cell transplantation (patients who have received autologous stem cell infusions will remain eligible) * Unable to fit comfortably into the MRI scanner (generally greater than 114 kg) * History of a bleeding disorder or clinically significant coagulopathy at treating PI/Sub-I's discretion * Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis * Known hypersensitivity to gadolinium-based contrast agents that, in the judgment of the PI or Sub-I in consultation with Radiology, is not expected to be safely mitigated with standard premedication and supportive care measures * Known hypersensitivity to DEFINITY®, or its components (e.g., polyethylene glycol), or to other perflutren microsphere agent/s * History of severe allergy or hypersensitivity to a study product excipient (e.g., DMSO) that, in the judgment of the PI or Sub-I, cannot be adequately managed with standard supportive measures and would pose an unacceptable risk to the participant * Cardiac disease, anomalies, or unstable hemodynamics * Left ventricular ejection fraction below the lower limit of normal, as defined by age per institutional standards * History of a hemodynamically unstable cardiac arrhythmia * The planned 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 * "Overly bulky tumor", defined as follows: * Group A: tumor \>5 cm in a single maximal dimension, or clinically significant swallowing dysfunction/dysphagia or prominent medullary dysfunction as determined by the clinical investigator; * Group B: tumor \>6 cm in a single maximal dimension, or tumor causing uncal herniation * Tumor presenting with the following imaging characteristics: * Edema and/or mass effect that causes hydrocephalus * Necrosis within the tumor and the neurosurgeon cannot ensure that all areas of necrosis within the ultrasound sonication beam path can be avoided * Evidence of a significant new hemorrhage following radiation therapy. 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 Exclusion Criteria for BBBD Procedure and TAA-T Infusion: * Tumor not visible on most recent pre-LIFT therapy imaging * Previous participation in other conventional or investigational chemotherapy, molecularly targeted therapy, or immunotherapy. (Exceptions: Temozolomide during radiation in Group B patients is allowed; Bevacizumab use is allowed) * Disseminated disease * Clinical and radiographic evidence of increased intracranial pressure * For a participant with a ventricular peritoneal (VP) shunt or similar device: presence of a device that, in the judgment of the institutional neurosurgeon (based on a technical evaluation of the screening non-contrast CT imaging and Exablate system target mapping), would interfere with safe delivery of the Exablate BBBD procedure * "Overly bulky tumor", defined as follows: * Group A: tumor \>5 cm in a single maximal dimension, or clinically significant swallowing dysfunction/dysphagia or prominent medullary dysfunction as determined by the clinical investigator; * Group B: tumor \>6 cm in a single maximal dimension, or tumor causing uncal herniation * Tumor presenting with the following imaging characteristics: * Edema and/or mass effect that causes hydrocephalus. * Necrosis within the tumor and the neurosurgeon cannot ensure that all areas of necrosis within the ultrasound sonication beam path can be avoided * Evidence of a significant new hemorrhage following radiation therapy. 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. * Confirmed radiographic progressive disease (for subsequent cycles, participants with pseudoprogression may continue to be eligible if they demonstrate radiographic stability relative to prior indeterminate scan) * 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 * Anti-coagulant therapy, or medications known to increase risk of hemorrhage, (e.g., acetylsalicylic acid \[ASA/aspirin\], non-steroidal anti-inflammatory drugs \[NSAIDs\], statins) within washout period prior to treatment (There is no required washout for eligibility assessment, but patients should be off agents for at least 3 days at the time of LIFU procedure or until 5 half-lives of the agent, whichever is longer) * Immunosuppression (corticosteroids to prevent/treat brain edema are permitted) * Active seizure disorder or epilepsy (clinically significant seizures despite medical treatment) for a minimum of 4 weeks prior to first cycle/Exablate BBBD procedure captured by history * Evidence of cranial or systemic infection * Known HIV infection * For participants for whom PI or medically licensed sub-I have suspicion of changed cardiac function since their prior pre-treatment echocardiogram/ECG: Repeat echo/ECG is indicative of cardiac disease, anomalies, or unstable hemodynamics (including left ventricular ejection fraction below the lower limit of normal, as defined by age per institutional standards OR hemodynamically unstable cardiac arrhythmia) * History of a bleeding disorder or clinically significant coagulopathy at treating PI/Sub-I's discretion * Cerebral or systemic vasculopathy, including intracranial thrombosis, vascular malformation, cerebral aneurysm, or vasculitis * Known hypersensitivity to gadolinium-based contrast agents that, in the judgment of the PI or Sub-I in consultation with Radiology, is not expected to be safely mitigated with standard premedication and supportive care measures * Known hypersensitivity to DEFINITY®, or its components (e.g., polyethylene glycol), or to other perflutren microsphere agent/s * History of severe allergy or hypersensitivity to a study product excipient (e.g., DMSO) that, in the judgment of the PI or Sub-I, cannot be adequately managed with standard supportive measures and would pose an unacceptable risk to the participant * Pregnant or lactating females