Safety and Effectiveness of Blood-Brain Barrier Disruption (BBBD) in Subjects With Suspected Infiltrating Glioma

Exclusion Criteria

• •1. Tumor originating from the deep midline, thalamus, midbrain, cerebellum or brainstem.
• •2. Multifocal tumors
• •3. MRI or clinical findings of:
• •1. Active or chronic infection(s) or inflammatory processes
• •2. Acute or chronic hemorrhages, specifically any lobar microbleeds, and no siderosis, amyloid angiopathy, or macro-hemorrhages
• •3. Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis
• •4. 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
• •5. MR non-compatible metallic implants in the skull or the brain or the presence of unknown MR unsafe devices
• •6. Significant cardiac disease or unstable hemodynamic status
• •1. Documented myocardial infarction within six months of enrollment
• •2. Unstable angina on medication
• •3. Unstable or worsening congestive heart failure
• •4. Left ventricular ejection fraction below the lower limit of normal
• •5. History of a hemodynamically unstable cardiac arrhythmia
• •6. Cardiac pacemaker
• •7. Patient has right-to-left, bidirectional, or transient right-to-left cardiac shunts
• •8. Subjects with relative contraindications to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation,
• •9. Perflutren sensitivity or allergy ii. QT prolongation observed on screening ECG (QTc \> 450 for men and \>470 for women)
• •7. Uncontrolled hypertension (systolic \> 180 and diastolic BP \> 120 on medication)
• •8. Unable to discontinue use of anti-coagulant/antiplatelet therapy as per local standard.
• •9. History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding
• •10. Abnormal coagulation profile (Platelets \< 80,000), PT (\>14) or PTT (\>36), and INR \> 1.3.
• •11. Large lacunar lesions that cannot be navigated around
• •12. Known cerebral or systemic vasculopathy
• •13. Significant depression and at potential risk of suicide
• •14. Known sensitivity/allergy to gadolinium, or other intravascular contrast agents
• •15. Active seizures despite medication treatment (defined as \>1 seizure per week) which could be worsened by disruption of the blood brain barrier
• •16. History of anaphylactic shock
• •17. Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning
• •18. Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis
• •19. Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess
• •20. Any contraindications to MRI scanning,
• •21. Impaired renal function with estimated glomerular filtration rate \<30 mL/min/1.73m2
• •22. Severe Respiratory Illness
• •23. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
• •24. Pregnancy or Lactation