Inclusion Criteria:
1. Adult male/female patients ≥ 18 years of age.
2. Histologically confirmed glioblastoma at original diagnosis, recurrent after prior radiotherapy and temozolomide chemotherapy.
3. Must have measurable disease ≥ 10mm (according to RANO criteria) .
4. Interval since completion of radiation treatment (including radiation at original diagnosis and/or radiation for recurrent disease) ≥ 12 weeks.
5. If on steroids, must be on a stable dose for ≥ 7 days prior to study treatment.
6. Body mass index (BMI) ≥17 kg / m2.
7. Minimum interval since last drug therapy:
1. 1 week for non-cytotoxic agents (e.g., interferon, tamoxifen), daily chemotherapy (e.g., metronomic temozolomide, cytoxan) or targeted therapies administered daily (e.g., gleevec, tarceva).
2. 4 weeks since last cytotoxic therapy.
3. 6 weeks since the completion of a nitrosourea-containing chemotherapy regimen (e.g., carmustine).
8. Life expectancy ≥ 12 weeks.
9. KPS Score \> 60.
10. Adequate hepatic, renal, coagulation, and hematopoietic function:
1. Hemoglobin ≥ 8 g/dL.
2. Platelets ≥ 100,000/mm3.
3. Neutrophils ≥ 1,500/mm3.
4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN).
5. Urine protein creatinine (UPC) ratio \< 1 or urine dipstick for proteinuria ≤ 2+.
6. Alanine transaminase (ALT) \< 3 x ULN.
7. Aspartate transaminase (AST) \< 3 x ULN.
8. Prothrombin time ≤ 1.2 x ULN.
9. International Normalized Ratio (INR) \< 1.5.
10. Bilirubin \< 2 x ULN.
11. Center of region of interest (ROI) (i.e., tumor site) ≥30mm deep to skull bone.
12. If there is the potential for pregnancy, must agree to follow acceptable birth control methods to avoid conception.
13. Able and willing to have their hair shaved (either whole head or the region where the coupling membrane will touch) and placement of peripheral IV line prior to treatment.
Exclusion Criteria:
* 1\) Previous treatment with an inhibitor of vascular endothelial growth factor (VEGF) or VEGF receptor (VEGFR), including bevacizumab.
2\) New York Heart Association (NYHA) Grade II or greater congestive heart failure requiring hospitalization within 12 months prior to screening.
3\) Hypertension (systolic blood pressure ≥ 160 mmHg and diastolic blood pressure ≥ 100 mmHg).
4\) Uncontrolled intercurrent illness including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, severe cerebral or myocardial infarction, cardiac shunt, heart attack within the previous 12 months, stroke (except for transient ischemic attack; TIA) within the previous 6 months, or psychiatric illness/social situations that would limit compliance with study requirements.
5\) Unstable Pulmonary Disease or Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy at the time of screening.
6\) Implanted pacemaker, defibrillator or deep brain stimulator, or other implanted electronic devices in the brain or documented clinically significant arrhythmias.
7\) Major surgery such as intra-thoracic, intra-abdominal or intra-pelvic (with the exception of craniotomy), open biopsy or significant traumatic injury ≤ 4 weeks prior to screening, or patients who have had minor procedures, percutaneous biopsies or placement of vascular access device ≤ 1 week prior to screening, or who have not recovered from side effects of such procedure or injury.
8\) Known human immunodeficiency virus (HIV) positivity.
9\) Acute bacterial or fungal infection requiring intravenous antibiotics at the time of screening.
10\) Pregnant or breast-feeding women.
11\) Known sensitivity/allergy to MRI contrast agents, CT contrast agents, SonoVue® \[Lumason®\], bevacizumab, or any of their components.
12\) Abnormal baseline findings considered by the Investigator to indicate conditions that might affect study endpoints.
13\) Hemorrhage or cyst within the ROI.
14\) ROI in the deep center brain with crucial brain functions, such as in the region of the brain stem.
15\) The receipt of an investigational drug within a period of 4 weeks prior to the first FUS exposure.
16\) Use of any recreational drugs or a history of drug addiction.
17\) Difficulty lying supine and still for the FUS procedure length.
18\) Any other condition that, in the Investigator's judgment, might increase the risk to the patient or decrease the chance of obtaining satisfactory data needed to achieve the objectives of the study.
