The permeabilization of the BBB to deliver therapeutics with MR-guided FUS redefines therapeutic strategies as it improves patient outcomes. To ensure the best translation towards clinical treatment, the evaluation of hemodynamic modifications in the CNS is necessary to refine treatment parameters. MR-guided FUS was applied at 1.5 MHz with a 50 ms burst every 1 s to open the BBB. CBF, BVf and ADC parameters were monitored with MRI. Cavitation was monitored with a PCD during the FUS sequence and classified with the IUD index into three cavitation levels. We distinctly applied the FUS in the cortex or the striatum. After the BBB permeabilization, neuroinflammation markers were quantified longitudinally. The BBB was successfully opened in all animals in this study and only one animal was classified as "hard" and excluded from the rest of the study. 30 min after FUS-induced BBB opening in the cortex, we measured a 54% drop in CBF and a 13% drop in BVf compared to the contralateral side. After permeabilization of the striatum, a 38% drop in CBF and a 15% drop in BVf were measured. CBF values rapidly returned to baseline, and 90 min after BBB opening, no significant differences were observed. We quantified the subsequent neuroinflammation, noting a significant increase in astrocytic recruitment at 2 days and microglial activation at 1 day after FUS. After 7 days, no more inflammation was visible in the brain. FUS-induced BBB opening transiently modifies hemodynamic parameters such as CBF and BVf, suggesting limited nutrients and oxygen supply to the CNS in the hour following the procedure.
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http://dx.doi.org/10.7150/thno.96721 | DOI Listing |
Biomed Pharmacother
December 2024
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address:
The technology of focused ultrasound-mediated disruption of the blood-brain barrier (FUS-BBB opening) has now been used in over 20 Phase 1 clinical trials to validate the safety and feasibility of BBB opening for drug delivery in patients with brain tumors and neurodegenerative diseases. The primary treatment parameters, FUS intensity and microbubble dose, are chosen to balance sufficient BBB disruption to achieve drug delivery against potential acute vessel damage leading to microhemorrhage. However, other safety considerations due to second order effects caused by BBB disruption, such as inflammation and alteration of neurovascular function, are only beginning to be understood.
View Article and Find Full Text PDFPhys Med Biol
December 2024
Department of Medical Physics and Bioengineering, University College London, Gower Street, London, WC1E 6BT, UNITED KINGDOM OF GREAT BRITAIN AND NORTHERN IRELAND.
Transcranial ultrasound is used in a variety of treatments, including neuromodulation, opening the blood-brain barrier (BBB), and high intensity focused ultrasound (HIFU) therapies. To ensure safety and efficacy of these treatments, numerical simulations of the ultrasound field within the brain are used for treatment planning and evaluation. This study investigates the accuracy of numerical modelling of the propagation of focused ultrasound through cranial bones.
View Article and Find Full Text PDFJ Control Release
December 2024
School of Chemistry and Molecular Bioscience, Molecular Horizons, Faculty of Science, Medicine and Health, University of Wollongong, Wollongong, NSW 2522, Australia. Electronic address:
Asian J Pharm Sci
December 2024
State Key Laboratory of Fine Chemicals, Department of Pharmaceutical Engineering, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China.
Parkinson's disease (PD) poses a significant therapeutic challenge, mainly due to the limited ability of drugs to cross the blood-brain barrier (BBB) without undergoing metabolic transformations. Levodopa, a key component of dopamine replacement therapy, effectively enhances dopaminergic activity. However, it encounters obstacles from peripheral decarboxylase, hindering its passage through the BBB.
View Article and Find Full Text PDFExpert Opin Drug Deliv
December 2024
Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
Introduction: Central nervous system (CNS) disorders present major therapeutic challenges due to the presence of the blood - brain barrier (BBB) and disease heterogeneity. The BBB impedes most therapeutic agents, which restricts conventional treatments. Focused ultrasound (FUS) -assisted delivery offers a novel solution by temporarily disrupting the BBB and thereby enhancing drug delivery to the CNS.
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