Towards standardization of the parameters for opening the blood-brain barrier with focused ultrasound to treat glioblastoma multiforme: A systematic review of the devices, animal models, and therapeutic compounds used in rodent tumor models

Rasika Thombre; Griffin Mess; Kelley M Kempski Leadingham; Shivani Kapoor; Andrew Hersh; Molly Acord; Tarana Kaovasia; Nicholas Theodore; Betty Tyler; Amir Manbachi

doi:10.3389/fonc.2022.1072780

Towards standardization of the parameters for opening the blood-brain barrier with focused ultrasound to treat glioblastoma multiforme: A systematic review of the devices, animal models, and therapeutic compounds used in rodent tumor models

Front Oncol. 2023 Feb 16:12:1072780. doi: 10.3389/fonc.2022.1072780. eCollection 2022.

Authors

Rasika Thombre^{1

2

3}, Griffin Mess^{1

2

3}, Kelley M Kempski Leadingham^{1

3}, Shivani Kapoor^{1

3}, Andrew Hersh^{1

3}, Molly Acord^{1

2

3}, Tarana Kaovasia^{1

2

3}, Nicholas Theodore^{1

3}, Betty Tyler¹, Amir Manbachi^{1

2

3

4

5

6}

Affiliations

¹ Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, United States.
² Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD, United States.
³ HEPIUS Innovation Laboratory, School of Medicine, Johns Hopkins University, Baltimore, MD, United States.
⁴ Department of Electrical Engineering and Computer Science, Johns Hopkins University, Baltimore, MD, United States.
⁵ Department of Mechanical Engineering, Johns Hopkins University, Baltimore, MD, United States.
⁶ Department of Anesthesiology, Johns Hopkins University School of Medicine, Baltimore, MD, United States.

Abstract

Glioblastoma multiforme (GBM) is a deadly and aggressive malignant brain cancer that is highly resistant to treatments. A particular challenge of treatment is caused by the blood-brain barrier (BBB), the relatively impermeable vasculature of the brain. The BBB prevents large molecules from entering the brain parenchyma. This protective characteristic of the BBB, however, also limits the delivery of therapeutic drugs for the treatment of brain tumors. To address this limitation, focused ultrasound (FUS) has been safely utilized to create transient openings in the BBB, allowing various high molecular weight drugs access to the brain. We performed a systematic review summarizing current research on treatment of GBMs using FUS-mediated BBB openings in in vivo mouse and rat models. The studies gathered here highlight how the treatment paradigm can allow for increased brain and tumor perfusion of drugs including chemotherapeutics, immunotherapeutics, gene therapeutics, nanoparticles, and more. Given the promising results detailed here, the aim of this review is to detail the commonly used parameters for FUS to open the BBB in rodent GBM models.

Keywords: blood-brain barrier; chemotherapy; focused ultrasound; glioblastoma multiforme; immunotherapy; microbubble; neuro-oncology; non-invasive.

Publication types

Systematic Review

Grants and funding

The authors acknowledge funding support from the National Science Foundation (NSF) STTR Phase 1 Award (#: 1938939), 6 ^© 2021 by ASME Defense Advanced Research Projects Agency (DARPA) Award (#: N660012024075), and Johns Hopkins Institute for Clinical and Translational Research (ICTR)’s Clinical Research Scholars Program (KL2), administered by the National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS).