MRI findings:

1. Active infection/inflammation
2. Acute or chronic hemorrhages, specifically > 4 lobar microbleeds, and no siderosis or macrohemorrhages
3. Tumor/space occupying lesion causing significant mass effect
4. Meningeal enhancement
5. Intracranial hypotension

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

Clips or other metallic implanted objects in the skull or the brain, except shunts

Significant cardiac disease or unstable hemodynamic status including:

1. Documented myocardial infarction within six months of screening
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. Severe hypertension (diastolic BP > 100 on medication)
8. Patient has right-to-left, bidirectional, or transient right-to-left cardiac shunts
9. QT prolongation observed on screening ECG (QTc > 450 for men and > 470 for women)

Uncontrolled hypertension (systolic > 150 and diastolic BP > 100 on medication)

Patients should not take medications known to increase risk of hemorrhage (e.g., aspirin or class I and III anticoagulants) for at least 7 days prior to treatment or lumbar puncture; patients should not take Avastin for 30 days prior to treatment

History of a bleeding disorder, coagulopathy or a history of spontaneous hemorrhage or use of anticoagulants, specifically recent thrombosis or stroke in past 3 months; abnormal coagulation profile (PLT < 100,00/μl), PT (> 14 sec) or PTT (> 36 sec), and INR > 1.3

No more than 1 non-strategic lacune &lt;1.5 cm

Known cerebral or systemic vasculopathy

Significant depression and at potential risk of suicide

Known sensitivity/allergy to gadolinium (an alternative product may be used) and DEFINITY®.

Any contraindications to MRI scanning, including:

1. Large participants not fitting comfortably into the scanner
2. Difficulty lying supine and still for up to 3 hours in the MRI unit or claustrophobia

Any contraindication to lumbar puncture for collection of cerebral spinal fluid, including:

a. Intracranial hypotension

Untreated, uncontrolled sleep apnea

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

IVIg use in the previous 6 months.

Live viral vaccination within the 30 days before study entry

Currently, or in the last 3 months participated in a clinical trial delivering an investigational product or non-approved use of a drug or device or in any other type of medical research.

Respiratory: chronic pulmonary disorders e.g. severe emphysema, pulmonary vasculitis, or other causes of reduced pulmonary vascular cross-sectional area, patients with a history of drug allergies, uncontrolled 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 monograph for DEFINITY®.

Motor cortex atrophy deemed severe enough to limit targeting

Previous major allergic or anaphylactic reaction to IVIg

Known IgA deficiency with anti-IgA.

Known frontotemporal dementia;

Definitely or possibly pregnant (if applicable);

Known auto-immune condition with or without neurological manifestations (e.g., multiple sclerosis (MS), systemic lupus erythematous (SLE), Rheumatoid arthritis).

Current, planned or previous use of oral, intramuscular or intravenous steroid drugs (such as prednisone, prednisolone, dexamethasone, triamcinolone, methylprednisolone, oxandrolone, and others), immunosuppressant drugs (azathioprine, mycophenolate, tacrolimus, sirolimus, cyclophosphamide, and others) or NSAIDs (ibuprofen, naproxen, celecoxib, and others) in the past 30 days;

Other unspecified reasons that, in the opinion of the Investigator or the Sponsor, make the participant unsuitable for enrollment