Human stem cell-derived neuron

Blood-Brain Barrier Disruption for Liquid Biopsy in Subjects With Glioblastoma


For non-cranial tumors, biomarkers circulate in the peripheral blood and can be easily collected in a blood sample. These liquid biopsies can serve as an alternative to surgical biopsy to identify the type of cancer through genetic sequencing as well as guide treatment options. However, in brain tumors, the blood-brain barrier inhibits the release of tumor-specific biomarkers into the bloodstream. This study is designed to assess the safety and effectiveness of using low intensity focused ultrasound to disrupt the blood-brain barrier using microbubble resonators for the purpose of obtaining liquid biopsies in glioblastoma patients.

Inclusion Criteria
  1. Male or female between ≥ 18-80 years of age able and willing to give informed consent.
  2. Subjects with a suspected glioblastoma tumor on pre-operative brain imaging scans.
  3. Subjects that are scheduled, or will be scheduled within 4 weeks, for surgical resection or biopsy per standard clinical tumor care.
  4. Karnofsky Performance Score ≥70.
  5. Able to communicate sensations during the Exablate blood-brain barrier disruption (BBBD) procedure.
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 antipathy, or macro-hemorrhages.
    3. Intracranial thrombosis, vascular malformation, cerebral aneurysms or vasculitis.
  4. MR non-compatible metallic implants in the skull or brain or the presence of unknown MR unsafe devices.
  5. Significant cardiac disease or unstable hemodynamic status:
    1. Documented myocardial infarction within six months of enrollment
    2. Unstable angina on medication
    3. Left ventricular ejection fraction below the lower limit of normal
    4. History of a hemodynamically unstable cardiac arrhythmia
    5. Cardiac pacemaker
    6. History of hypersensitivity to Perflutren lipid microsphere or its components, e.g., polyethylene glycol
  6. Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)
  7. Unable to discontinue use of an anti-coagulant/antiplatelet therapy as per local standard
  8. History of a liver disease, bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or evidence of increased risk of bleeding
  9. Abnormal coagulation profile (Platelets less than 80,000), PT (>14) or PTT(>36), and INR > 1.3
  10. Known cerebral or systemic vasculopathy.
  11. Significant depression and at potential risk of suicide.
  12. Known sensitivity/allergy to gadolinium or DEFINITY.
  13. Active seizures despite medication treatment (defined as >1 seizure per week) which could be worsened by disruption of the blood brain barrier.
  14. Active drug or alcohol disorder which have a higher risk for seizures, infection and/or poor executive functioning.
  15. Positive HIV status, which can lead to increased entry of HIV into the brain parenchyma leading to HIV encephalitis.
  16. Potential blood-borne infections which can lead to increased entry to brain parenchyma leading to meningitis or brain abscess.
  17. Any contraindication to MRI scanning, including:
    1. Large subjects not fitting comfortably into the scanner
    2. Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia
  18. Impaired renal function with estimated glomerular filtration rate less than 30 mL/min/1.73m2 .
  19. Severe Respiratory Illness: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, subjects with a history of severe drug allergies, asthma or hay fever, and multiple allergies where the benefit/risk of administering Definity® is considered unfavorable by the study physicians in relation to the product labeling for Definity
  20. Currently in a clinical trial involving an investigational product or non-approved use of a drug or device
  21. Pregnancy or lactation.

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