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Distribution and Diffusion of Macromolecule Delivery to the Brain via Focused Ultrasound using Magnetic Resonance and Multispectral Fluorescence Imaging
| Content Provider | Scilit |
|---|---|
| Author | Valdez, Michael A. Fernandez, Elizabeth Matsunaga, Terry Erickson, Robert P. Trouard, Theodore P. |
| Copyright Year | 2019 |
| Description | Journal: Ultrasound in medicine & biology Focused ultrasound (FUS), in combination with microbubble contrast agents, can be used to transiently open the blood–brain barrier (BBB) to allow intravascular agents to cross into the brain. Often, FUS is carried out in conjunction with magnetic resonance imaging (MRI) to evaluate BBB opening to gadolinium-based MRI contrast agents. Although MRI allows direct visualization of the distribution of gadolinium-based contrast agents in the brain parenchyma, it does not allow measurements of the distribution of other molecules crossing the BBB. Therapeutic molecules (e.g., monoclonal antibodies) are much different in size than MRI contrast agents and have been found to have different distributions in the brain after FUS-mediated BBB opening. In the work described here, we combined in vivo MRI and ex vivo multispectral fluorescence imaging to compare the distributions of MRI contrast and dextran molecules of different molecular weights (3, 70 and 500 kDa) after FUS-mediated BBB opening through a range of ultrasound pressures (0.18–0.46 MPa) in laboratory mice. The volume of brain exposed was calculated from the MRI and fluorescence images and was significantly dependent on both molecular weight and ultrasound pressure. Diffusion coefficients of the different-molecular-weight dextran molecules in the brain parenchyma were also calculated from the fluorescence images and were negatively correlated with the molecular weight of the dextran molecules. The results of this work build on a body of knowledge that is critically important for the FUS technique to be used in clinical delivery of therapeutics to the brain. |
| Related Links | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6937597/pdf http://www.umbjournal.org/article/S0301562919314796/pdf |
| Ending Page | 136 |
| Page Count | 15 |
| Starting Page | 122 |
| ISSN | 03015629 |
| e-ISSN | 1879291X |
| DOI | 10.1016/j.ultrasmedbio.2019.08.024 |
| Journal | Ultrasound in medicine & biology |
| Issue Number | 1 |
| Volume Number | 46 |
| Language | English |
| Publisher | Elsevier BV |
| Publisher Date | 2019-10-02 |
| Access Restriction | Open |
| Subject Keyword | Journal: Ultrasound in medicine & biology Blood–brain Barrier Focused Ultrasound Magnetic Resonance Imaging |
| Content Type | Text |
| Resource Type | Article |
| Subject | Radiology, Nuclear Medicine and Imaging Acoustics and Ultrasonics Biophysics Radiological and Ultrasound Technology |
