دورية أكاديمية
Cavitation monitoring, treatment strategy, and acoustic simulations of focused ultrasound blood-brain barrier disruption in patients with glioblastoma.
| العنوان: | Cavitation monitoring, treatment strategy, and acoustic simulations of focused ultrasound blood-brain barrier disruption in patients with glioblastoma. |
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| المؤلفون: | McDannold N; Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States of America. Electronic address: njm@bwh.harvard.edu., Wen PY; Department of Neuro-oncology, Dana Farber Cancer Institute, Boston, MA, United States of America., Reardon DA; Department of Neuro-oncology, Dana Farber Cancer Institute, Boston, MA, United States of America., Fletcher SM; Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States of America., Golby AJ; Department of Radiology, Brigham and Women's Hospital, Boston, MA, United States of America; Department of Neurosurgery, Brigham and Women's Hospital, Boston, MA, United States of America. |
| المصدر: | Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2024 Jun 21; Vol. 372, pp. 194-208. Date of Electronic Publication: 2024 Jun 21. |
| Publication Model: | Ahead of Print |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Science Publishers Country of Publication: Netherlands NLM ID: 8607908 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-4995 (Electronic) Linking ISSN: 01683659 NLM ISO Abbreviation: J Control Release Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Amsterdam : Elsevier Science Publishers, 1984- |
| مستخلص: | Purpose: We report our experience disrupting the blood-brain barrier (BBB) to improve drug delivery in glioblastoma patients receiving temozolomide chemotherapy. The goals of this retrospective analysis were to compare MRI-based measures of BBB disruption and vascular damage to the exposure levels, acoustic emissions data, and acoustic simulations. We also simulated the cavitation detectors. Methods: Monthly BBB disruption (BBBD) was performed using a 220 kHz hemispherical phased array focused ultrasound system (Exablate Neuro, InSightec) and Definity microbubbles (Lantheus) over 38 sessions in nine patients. Exposure levels were actively controlled via the cavitation dose obtained by monitoring subharmonic acoustic emissions. The acoustic field and sensitivity profile of the cavitation detection system were simulated. Exposure levels and cavitation metrics were compared to the level of BBBD evident in contrast-enhanced MRI and to hypointense regions in T2*-weighted MRI. Results: Our treatment strategy evolved from using a relatively high cavitation dose goal to a lower goal and longer sonication duration and ultimately resulted in BBBD across the treatment volume with minimal petechiae. Subsonication-level feedback control of the exposure using acoustic emissions also improved consistency. Simulations of the acoustic field suggest that reflections and standing waves appear when the focus is placed near the skull, but their effects can be mitigated with aberration correction. Simulating the cavitation detectors suggest variations in the sensitivity profile across the treatment volume and between patients. A correlation was observed with the cavitation dose, BBBD and petechial hemorrhage in 8/9 patients, but substantial variability was evident. Analysis of the cavitation spectra found that most bursts did not contain wideband emissions, a signature of inertial cavitation, but biggest contribution to the cavitation dose - the metric used to control the procedure - came from bursts with wideband emissions. Conclusion: Using a low subharmonic cavitation dose with a longer duration resulted in BBBD with minimal petechiae. The correlation between cavitation dose and outcomes demonstrates the benefits of feedback control based on acoustic emissions, although more work is needed to reduce variability. Acoustic simulations could improve focusing near the skull and inform our analysis of acoustic emissions. Monitoring additional frequency bands and improving the sensitivity of the cavitation detection could provide signatures of microbubble activity associated with BBB disruption that were undetected here and could improve our ability to achieve BBB disruption without vascular damage. Competing Interests: Declaration of competing interest NM's laboratory has received research support from InSightec. AJG is the site PI for the clinical study supported by InSightec. (Copyright © 2024 Elsevier B.V. All rights reserved.) |
| فهرسة مساهمة: | Keywords: Acoustic simulation; Blood-brain barrier; Brain tumor; Focused ultrasound; MRI |
| تواريخ الأحداث: | Date Created: 20240619 Latest Revision: 20240622 |
| رمز التحديث: | 20240623 |
| DOI: | 10.1016/j.jconrel.2024.06.036 |
| PMID: | 38897294 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1873-4995 |
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| DOI: | 10.1016/j.jconrel.2024.06.036 |