Novel MRI-Guided Ultrasound Stimulated Microbubble Radiation Treatment for Patients With Head and Neck Cancer

Inclusion Criteria: * Age ≥18 years * All biopsy-confirmed squamous cell carcinoma (SCC) of the H\&N including the following subregions: Larynx, Oropharynx, Hypopharynx, Oral Cavity, Salivary Glands, and Paranasal Sinuses * Stage I-IV H\&N cancers (i.e. cT1-T4, cN0-N3, cM0), per AJCC guidelines (8th Edition). * Assessed by the treating surgeon, and radiation oncologist, and following a multidisciplinary discussion, determined to have unresectable and/or inoperable disease in the head and neck region. * Patients referred for palliative radiotherapy or standard radiotherapy, including the following dose regimens: 70 Gy/35 fractions, 50 Gy/20 fractions, or 35-40 Gy/5 fractions (SBRT, hypofractionation). * Patients treated with concurrent pre-operative chemoradiation, including: Cisplatin (40 mg/m2 q.w.k or Carboplatin 70 mg/m2 / day IV on days 1-4, 22-25 and at days 43-46 of radiation) or referred for palliative radiotherapy. * Able to understand and give informed consent. * Weight \<140kg. * Radiologic evidence of neck lymphadenopathy with at least one target lesion measuring \> 1cm in largest dimension (Recurrent or initial presentation) * Target lesion visible by non-contrast MRI. * Target lesion accessible for MRg-FU procedure. * Able to communicate sensation during MRg-FU treatment. * Creatinine within normal institutional limits or creatinine clearance \>60 mL/min/1.73 m2 for patients with creatinine levels above institutional upper limit of normal Exclusion Criteria: * Pregnant or lactating women may not participate due to the embryotoxic effects of protocol treatment. Women/ men of reproductive potential may not participate unless they have agreed to use an effective contraceptive method. * Unable to have contrast-enhanced MRI scan - standard of care criteria * Head and neck surgery (excluding biopsy) ≤ 6 weeks prior to study enrolment * Chemotherapy or other systemic anti-cancer agents ≤ 1 week prior to enrolment unless cisplatin-based chemotherapy * Previous radiotherapy ≤ 6 weeks prior to enrollment * Target lesion involves the skin surface causing ulceration, bleeding or discharge * Target lesion in contact with hollow viscera * Target lesion located in the skull, spine, or mandible * The fibrotic scar along the proposed FU beam path * Orthopedic implant along proposed FU beam path or at a site of the target lesion. * Severe cardiovascular, neurological, renal or hematological chronic disease * ECOG (Eastern Cooperative Oncology Group) Performance Status ≥ 3. Unable to tolerate required stationary position during treatment * Cardiac disease or unstable hemodynamics including myocardial infarction within six months, unstable angina, congestive heart failure, ejection fraction \< 50%, cardiac shunts, cardiac arrythmia and cardiac pacemaker. * Contraindication to perflutren including subjects with a family or personal history of QT prolongation or taking concomitant medications known to cause QTc prolongation like cisapride, erythromycin, tricyclic antidepressants, Class IA and III antiarrhythmic agents and some antipsychotics like haloperidol, droperidol, quetiapine, thioridazine, ziprasidone. QT prolongation observed on screening ECG (QTc \> 450ms for men or \>470ms for women) * Severe hypertension (diastolic BP \> 100 mmHg) * History of bleeding disorder, coagulopathy * Severely impaired renal function with estimated glomerular filtration rate \< 30ml/min/1.73m2 and/or on dialysis