The use of ultrasound to break down the blood brain barrier & the role of imaging- a review of both human & preclinical studies.
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- Background: At the turn of the 21" century, improvement in focussed ultrasound (FUS) technology has overcome the barriers of the skull to disrupt the blood brain barrier (BBB), and to deliver molecules to the brain. This has led to a surge in research to combine FUS with advanced imaging tools to improve the accuracy, precision and safety of this technique. This study aims to review the methods used in the literature by looking at the different contrast agents, ultrasound parameters and imaging techniques used to localise the area of insonation in both preclinical and human studies.
- Methods: The PRISMA guideline was followed in this literature review. A database search was conducted on OVID using MEDLINE and EMBASE, and optimized with additional hand searching. Critical appraisal was performed according to the ARRIVE and SYRCLE guidelines for preclinical research and the CASP guideline for clinical research.
- Results: There were a total of 124 hits with no human clinical study published at the time of the database search. Studies had found that an infusion of monodispersed microbubbles given before sonication at a long pulse length (PL), low acoustic pressure, and a moderate pulse repetition frequency (PRF) for a short duration could open the BBB safely and consistently with a more homogenous distribution. Imaging modalities, such as magnetic resonance imaging (MRI), and detection method, such as passive cavitation detectors with microbubble mapping, were able to increase the accuracy, precision and safety of the technology. However, the internal validity of individual studies was low and was at risk of bias.
- Conclusion: This technology still has much to be optimized in terms of its effectiveness and safety. Further understanding of microbubble behaviour in the vasculature during sonication will help in this optimization and its application in different neurological conditions in the brain. The success of this technology will open a realm of therapeutic options for patients with different brain disorders and change the way they are treated.
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