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

This is an interventional treatment trial for Glioma Read More

Inclusion Criteria:

1. Male or Female between 21-85 years of age who are able and willing to give informed consent
2. Subjects with suspected Grade II, III or IV infiltrating glioma (IG) on pre-operative brain imaging scans who have a non-enhancing component and are planned for surgical resection.
3. Karnofsky Performance Score 70-100
4. Able to communicate sensations during the Exablate 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 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