Scholarlink

Background <p>The blood brain barrier (BBB) limits effective treatment for cerebellar diseases. Region-specific parameterization and safety data for MRI-guided focused ultrasound (MRgFUS) BBB opening (BBBO) in the cerebellum are scarce. The goal of this study is to establish safety and feasibility of cerebellar BBBO for antibody delivery.</p> Methods <p>Mice received i.v. AF680 IgG and microbubbles immediately prior to sonication at 0.30 or 0.45&#xa0;MPa peak negative pressure (1.15&#xa0;MHz, 10 ms bursts, 2&#xa0;s burst period, 60 bursts). BBBO was quantified by contrast-enhanced T1-weighted MRI (9.4T) and assessed for recovery at 12&#xa0;h. Radiologic safety was evaluated by T2-weighted MRI. Acoustic emissions were analyzed via real-time passive cavitation detection, and acoustic simulations estimated the derated pressure caused by skull incidence angle. IgG delivery was quantified by ex vivo IVIS epifluorescence imaging and immunofluorescence analysis. Safety assessments included cardio-respiratory monitoring, body weight, motor function, and neuropathology assessment of endpoint H&amp;E.</p> Results <p>Both regimens yielded cerebellar BBBO without radiologic evidence of injury. BBB integrity was restored by 12&#xa0;h. While the higher pressure increased MRI and cavitation signals, IgG delivery was similarly enhanced (&gt; 2-fold vs. sham) by FUS, irrespective of peak negative pressure. Heart rate, respiratory rate, body weight, and motor function were unchanged by FUS, and neuropathologic evaluation revealed no hemorrhage, inflammation, vacuolation, or architectural abnormalities.</p> Conclusions <p>FUS enables safe, transient BBBO in the cerebellum and significantly enhances antibody delivery without measurable physiologic, functional, radiologic, or histologic injury. These findings establish a foundation for expansion of pharmacologic and theranostic delivery strategies directed to the cerebellum.</p> Graphical abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Focused ultrasound-mediated opening of the blood brain barrier for non-invasive drug delivery to the murine cerebellum

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年8月3日

查看全文
  • Stefanyda Maslova,
  • Thomas Sherlock,
  • Andrew T. Thede,
  • Zehra E.F. Demir,
  • Owen Brown,
  • Beyzanur G. Ak,
  • Sarah E. Duclos,
  • Alec J. Batts,
  • Mary Eleanor Hermes,
  • Matthew McCord,
  • Natasha D. Sheybani

摘要

Background

The blood brain barrier (BBB) limits effective treatment for cerebellar diseases. Region-specific parameterization and safety data for MRI-guided focused ultrasound (MRgFUS) BBB opening (BBBO) in the cerebellum are scarce. The goal of this study is to establish safety and feasibility of cerebellar BBBO for antibody delivery.

Methods

Mice received i.v. AF680 IgG and microbubbles immediately prior to sonication at 0.30 or 0.45 MPa peak negative pressure (1.15 MHz, 10 ms bursts, 2 s burst period, 60 bursts). BBBO was quantified by contrast-enhanced T1-weighted MRI (9.4T) and assessed for recovery at 12 h. Radiologic safety was evaluated by T2-weighted MRI. Acoustic emissions were analyzed via real-time passive cavitation detection, and acoustic simulations estimated the derated pressure caused by skull incidence angle. IgG delivery was quantified by ex vivo IVIS epifluorescence imaging and immunofluorescence analysis. Safety assessments included cardio-respiratory monitoring, body weight, motor function, and neuropathology assessment of endpoint H&E.

Results

Both regimens yielded cerebellar BBBO without radiologic evidence of injury. BBB integrity was restored by 12 h. While the higher pressure increased MRI and cavitation signals, IgG delivery was similarly enhanced (> 2-fold vs. sham) by FUS, irrespective of peak negative pressure. Heart rate, respiratory rate, body weight, and motor function were unchanged by FUS, and neuropathologic evaluation revealed no hemorrhage, inflammation, vacuolation, or architectural abnormalities.

Conclusions

FUS enables safe, transient BBBO in the cerebellum and significantly enhances antibody delivery without measurable physiologic, functional, radiologic, or histologic injury. These findings establish a foundation for expansion of pharmacologic and theranostic delivery strategies directed to the cerebellum.

Graphical abstract