Biomedical Engineering Reference
In-Depth Information
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Frequency (MHz)
FIGURE 14.10
Example of acoustic emission spectra obtained during microbubble-mediated FUS-induced BBB disruption at 558 kHz. (Top)
fundamental frequency and harmonic emissions, (bottom) fundamental frequency, harmonic emissions, and sub/ultraharmonic emissions.
(Based on data from O'Reilly, M.A., and K. Hynynen,
IEEE Trans Biomed Eng
57, 2010.)
In 1985, a small study of 14 patients was conducted to
examine the feasibility of focused ultrasound surgery for the
treatment of brain tumors [Heimburger, 1985]. Surgery was
performed to create a craniotomy window. After the surgery,
ultrasound lesions were induced in the brain through the
replaced skin flap and the bone window. The study results were
inconclusive.
In 2005, a Korean group presented at conference preliminary
results of focused ultrasound surgery for the treatment of ana-
plastic glioma in a single patient [Park et al., 2006]. Although few
details are available on the study, tumor shrinkage was observed,
along with an improvement in the patient's symptoms.
In 2006, Ram et al. presented initial results from three
patients with recurring gliomas treated using FUS ablation.
The study used the ExAblate 2000 (InSightec Inc., Haifa, Israel)
in-bed FUS system designed for treating uterine fibroids. The
system was not designed for brain FUS, and the small aperture
transducer necessitated the use of a craniotomy window in order
to perform the ablation. Of the three patients in the study, one
did not have any meaningful level of ultrasound energy deposi-
tion in the brain due to a technical malfunction, and one had an
adverse event. In the patient with the adverse event, a secondary
focus was formed in the mid-brain, possibly due to reflections,
which caused hemiparesis. The remaining patient was treated
without adverse event, however, only part of the tumor was
treatable through the craniotomy window and the remaining
section had to be surgically resected.
The preclinical feasibility study results in 10 pigs were reported
after the clinical trial results had been published [Cohen et al.,
2007]. In 10 pigs, the ExAblate 2000 system was used to ablate
tissue through a craniotomy window without any adverse
events. Despite good safety results in the feasibility study, the
clinical trial encountered several problems with the system used.
The secondary focus may have been avoided if tighter focusing
from a larger aperture array had been used. McDannold et al.
[2003] performed ablations in monkey brain using a small aper-
ture transducer through a craniotomy window. When the focus
of the transducer was near the bone, damage was seen in the sur-
rounding tissue. Other large animal,
ex vivo
human skull, and
clinical ablation studies have used larger transducers designed
for transcranial brain therapy [Pernot et al., 2007; Marquet et al.,
2009; McDannold et al., 2010; Martin et al., 2009].
Hynynen et al. [2006] performed the first noninvasive abla-
tions in primates at 650 kHz using a system by InSightec and a
CT-based correction algorithm. Marquet et al. [2006] also pre-
sented transcranial ablation results in primates at 900 kHz and
CT-based aberration correction. More recently the same group
has begun cadaver work validating a 512-element transcranial
therapy array operating at 1 MHz [Aubry et al., 2010].
Results from two transcranial FUS clinical trials have been
published to date. Both trials have used ExAblate transcra-
nial ultrasound systems (InSightec). The first transcranial FUS
trial was conducted in Boston using a 512-element Exablate
system operating at 670 kHz on three patients with recurrent
