Blood-Brain Barrier Disruption (BBBD) for Liquid Biopsy in Subjects with GlioBlastoma Brain Tumors

Inclusion Criteria:

1. Male or Female subjects18-80 years of age who are able and willing to give informedconsent, or whose legally authorized representative is willing to consent on theirbehalf

2. Subjects with stereotactically-targetable suspected new or recurrent glioblastomatumor on pre-operative brain imaging scans

3. Subjects that are scheduled, or will be scheduled within 4 weeks, for surgicalresection or biopsy per standard clinical tumor care

4. Karnofsky Performance Score >70

5. Able to communicate sensations during the Exablate BBBD procedure

Exclusion Criteria:

1. Subjects with inoperable tumors (e.g., tumor originating from the deep midline,thalamus, midbrain, cerebellum or brainstem)

2. Multifocal tumors

3. Tumor morphology or other imaging findings that precludes the ability to sonicatethe tumor volume (including significant tumor volume outside the treatment envelopeor tumor volume that exceeds the maximum sonication volume allowed, i.e. currently 110 ccs at the treatment volume level). Concern for adequate tumor coverage bysonication based on tumor morphology should be discussed with the Sponsor.

4. MRI or clinical findings of:

5. Active or chronic infection(s) or inflammatory processes

6. Acute or chronic hemorrhages, specifically any lobar microbleeds, and nosiderosis, amyloid angiopathy, or macro-hemorrhages

7. Intracranial thrombosis, vascular malformation, cerebral aneurysm or vasculitis

8. MR non-compatible metallic implants in the skull or the brain or the presence ofunknown MR unsafe devices

9. Significant cardiac disease or unstable hemodynamic status

10. Documented myocardial infarction within six months of enrollment

11. Unstable angina on medication

12. Unstable or worsening congestive heart failure

13. Documented left ventricular ejection fraction below the lower limit of normal

14. History of a hemodynamically unstable cardiac arrhythmia

15. Cardiac pacemaker

16. Uncontrolled hypertension (systolic > 180 and diastolic BP > 120 on medication)

17. Undergoing anti-coagulant or anti-platelet therapy, or using medications known toincrease risk of hemorrhage within washout period prior to treatment (i.e.,antiplatelet or vitamin K inhibitor anticoagulants within 7 days, non-vitamin Kinhibitor anticoagulants within 72 hours, or heparin-derived compounds within 48hours of treatment).

18. History of bleeding disorder, coagulopathy or a history of spontaneous hemorrhage orevidence of increased risk of bleeding

19. Abnormal coagulation profile (Platelets < 80,000, PT >14, PTT >36, or INR > 1.3)

20. Known cerebral or systemic vasculopathy

21. Significant depression and at potential risk of suicide

22. Known sensitivity/allergy to gadolinium or DEFINITY/DEFINITY RT,

23. Active seizures despite medication treatment (defined as >1 seizure per week) whichcould be worsened by disruption of the blood brain barrier

24. Active drug or alcohol disorder which have a higher risk for seizures, infectionand/or poor executive functioning

25. Known positive HIV status, which can lead to increased entry of HIV into the brainparenchyma leading to HIV encephalitis

26. Potential blood-borne infections which can lead to increased entry to brainparenchyma leading to meningitis or brain abscess

27. Any contraindications to MRI scanning, including:

28. Large subjects not fitting comfortably into the scanner

29. Difficulty lying supine and still for up to 3 hours in the MRI unit orclaustrophobia

30. Impaired renal function with estimated glomerular filtration rate <30 mL/min/1.73m2

31. Severe Respiratory Illness: chronic pulmonary disorders (e.g., severe emphysema,pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectionalarea), subjects with a history of severe drug allergies, severe asthma or hay fever,or multiple allergies where the benefit/risk of administering DEFINITY/DEFINITY RTis considered unfavorable by the study physicians in relation to the productlabeling for DEFINITY/DEFINITY RT

32. Currently in a clinical trial involving an investigational product or non-approveduse of a drug or device

33. Pregnancy or Lactation