Page 15 - JCTR-11-2

Journal of Clinical and
Translational Research US-mediated drug delivery

for therapeutic delivery. The exposure of brain tissue biocompatible implant containing a 1-MHz planar
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to FUS is generally guided by MRI or neuronavigation US transducer, 64,65 while SonoCloud-9 consists of
systems, enabling more precise and safe treatments. For nine 1-MHz planar US transducers arranged on an
63
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several years, lab-made US devices have been paired with implantable grid (Figure 9). SonoCloud-9 safely and
PCD devices to monitor and manage acoustic intensity in efficiently disrupts the BBB over a large volume of brain
real-time during FUS exposure, ensuring safe and effective tissue and significantly increases the i.c. bioavailability
treatment within the brain tissue. 29 of therapeutics in the brain compared to SonoCloud-1 .
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This US protocol is fully compatible with conventional
4.2. Clinically approved devices pharmacological treatments and does not require patient
At present, three clinically approved US devices— anesthesia. In addition, BBB disruption can be monitored
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SonoCloud , NaviFUS , and ExAblate Neuro —are available using dynamic contrast-enhanced MRI (DCE-MRI)
for i.c. delivery of therapeutics. Below, their distinct following the i.v. administration of an MRI contrast
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characteristics are described. agent. These SonoCloud devices are currently being
evaluated in clinical trials for treating brain tumors 66-68
4.2.1. SonoCloud ® and AD. 69
CarThera (Lyon, France) has designed innovative 4.2.2. NaviFUS ®
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therapeutic US-based medical devices known as
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SonoCloud for delivering therapeutics into the brain. NaviFUS Corp. (Taipei, Taiwan) has developed a
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SonoCloud is an intracranial US implant that transmits neuronavigation-guided transcranial FUS system known
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US waves to a target brain region, bypassing the skull as NaviFUS . This custom-designed system features a
and transiently opening the BBB before or after i.v. multichannel hemispherical FUS-phased array operating
administration of therapeutics. The device is implanted at a frequency of 0.5 MHz. It delivers FUS to brain tissue in
in a skull window, positioned beneath the skin, and a transcranial, non-invasive manner (Figure 9). Before the
remains invisible externally. After an i.v. injection of MBs, FUS intervention, a personalized treatment plan is designed
SonoCloud is activated through a transdermal needle for each patient based on cranial bone data obtained
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connected to an external control unit. Low-intensity pulsed from their MRI and/or CT scans. Physicians determine
US exposure to the targeted brain area disrupts the BBB the target brain regions and specify the positioning of
for several hours (typically 4 – 6 h), thereby increasing the the transducers. The intervention is conducted on an
effective concentration of therapeutics in this brain area. outpatient basis, with the patient remaining awake and
This acoustically mediated BBB disruption can be repeated seated in a chair for the duration of the procedure which
with each cycle of pharmacological therapy. typically lasts <30 min. After i.v. administration of MBs,
a neuronavigation tracking device guides the FUS to
CarThera has developed and validated two MRI- the targeted brain regions, ensuring precise treatment
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compatible SonoCloud devices: SonoCloud-1 and delivery. 70
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SonoCloud-9 . SonoCloud-1 is an 11.5-mm diameter
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Figure 9. Illustration of the different models of clinically approved US
Figure 8. An example of lab-made ultrasound device. Created with devices—NaviFUS , SonoCloud-1 and ExAblate Neuro . Created with
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BioRender.com. BioRender.com.
Volume 11 Issue 2 (2025) 9 doi: 10.36922/jctr.24.00061