The Use of Focused Ultrasound and DCE K-trans Imaging to Evaluate Permeability of the Blood-Brain Barrier

Study Overview
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Brief Summary
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The limitation of treating intrinsic brain pathologies has been circumvented with neurosurgical techniques; however, less invasive approaches may be desirable particularly for widespread or multifocal disease and when long term and repetitive administration is required. This study seeks to investigate the efficacy of focused ultrasound. Patients with either low grade gliomas or neurodegenerative dementias will be evaluated for study candidacy. There are no immediate benefits for patients who choose to participate; however, the information gained from this study will contribute to the research base and help patients in similar situations in the future.

Detailed Description
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Treatment of intrinsic brain diseases is challenging because brain barrier (BBB) limits the delivery of drugs, particulates and cellular elements such as stem cells to the central nervous system (CNS). This limitation is often circumvented with neurosurgical techniques, however, less invasive approaches may be desirable particularly for widespread or multifocal disease and when long term and repetitive administration is required. The diagnosis for the participants will be either low grade gliomas. A baseline fMRI and follow up routine fMRI's will be taken and evaluated for any changes in perfusion. During the scans, The ultrasound placement will last for one hour. This study seeks to investigate the efficacy of focused ultrasound in opening the blood brain barrier. This physiological effect would have significant clinical applications. The ability to open the blood brain barrier has the potential to revolutionize the delivery of therapeutic agents to the brain, allowing for more localized and efficient delivery. There are no immediate benefits for patients who choose to participate; however, the information gained from this study will contribute to the research base and help patients in similar situations in the future.

Official Title
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The Use of Focused Ultrasound and DCE K-trans Imaging to Evaluate Permeability of the Blood-Brain Barrier

Conditions
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Low Grade Glioma of Brain

Intervention / Treatment
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* Other: Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects undergoing routine, repetitive MRI scanning for monitoring low grade gliomas 18 or older Exclusion Criteria: • Cognitive decline with mild cognitive impairment (Clinical Dementia Rating stage 0.5) through moderate dementia CDR stages 1 and 2

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Focused Ultrasound<br>The ultrasound treatment will last either 1 hour or 20 minutes total time for the DWL device or Brainsonix Focused Ultrasound Device, respectively. | Other: Focused Ultrasound<br>* With focused ultrasound, there is an expected accentuation of local perfusion and potential temporary opening of the blood brain barrier with the aim is to provide better delivery of therapeutic agents including medication, particulates and cellular elements for treatment of neoplastic, inflammatory and degenerative brain diseases. The present study seeks to investigate differences in perfusion between areas treated and untreated by this modality in order to further explore its use in clinical application for the treatment of brain disease.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Event (AE) & Serious Adverse Event (SAE) Reporting | Per protocol, any suspected adverse events possibly related to the study protocol (e.g., itching, dizziness, headache, or neurological problems) will be tracked and monitored. In the event of a high-grade or serious adverse event, such event will be reported immediately and the study will be discontinued. | 24 hours | 
| functional Magnetic Resonance Imaging (fMRI) | Some functional neuroimaging scans (e.g., high resolution T1-weighted images; Arterial Spin Labeling [ASL]; Dynamic Contrast Enhanced [DCE] perfusion sequences; post-contrast T1-weighted images, Susceptibility Weighted Imaging [SWI], T2 weighted imaging, and T2 Flair) will be used to evaluate longitudinal changes in perfusion as an efficacy measure. The scans will be acquired within one hour before and after the study procedures of focused transcranial ultrasound and infusion of definity microbubbles. Voxel-based comparisons showing perfusion values relative to the acquired data range will be used for quantification and comparison of baseline and post-procedure scans. | 3 hours |