Page 14 - Volume 8, Issue 4 - Winter 2012

ments has potential in simplifying array design, as the ele- ments have reduced electrical impedance, which enables the construction of phased arrays without matching circuits. A prototype hemispherical array was constructed in this fash- ion, consisting of 1372 hollowed out cylindrical elements that
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Applications under clinical investigation—thermal tumor therapy
The first procedures undertaken using a clinical proto-
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are capable of operating at 306 kHz or 840 kHz.
The current clinical prototypes (Exablate 4000; Insightec, Haifa, Israel) operate at nominal frequencies of 230 kHz and 650 kHz. The higher frequency system has been used to treat patients with giloblastomas,19 chronic neuro- pathic pain,21 and essential tremor22-24 currently at the clinical
trial stage.
type have been for the treatment of glioblastoma patients. These procedures incorporated patient-specific treatment planning and MR thermometry feedback control, and so demonstrated the clinical feasibility of MR-guided transcra- nial focused ultrasound surgery. Each patient received multi- ple sonications, with focal heating viewable through real- time MR images. Limited by device power available at the time, thermal coagulation was not definitely demonstrated. However, extrapolation of the temperature measurements suggested that thermal ablation would be possible with this device, demonstrating a potential alternative to surgical resection.
Applications under clinical investigation—chronic neuropathic pain
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potential of this treatment.
Future applications of focused ultrasound—blood brain barrier disruption
The ability to disrupt the blood brain barrier (BBB) allows therapeutic agents that would normally be too large for delivery to the brain to be delivered using a method that is localized and non-invasive. It has been demonstrated that, in conjunction with injected microbubbles, ultrasound is
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capable of disrupting the BBB. With microbubbles, the
energy required to cause disruption is roughly two orders of
magnitude smaller than with ultrasound alone allowing the
blood brain barrier to be disrupted without causing harm to
the surrounding tissue. Following sonication, it has been
shown that the barrier is naturally restored 24 hours follow-
ing treatment. BBB disruption within a rat brain is shown in
Fig. 3. Preclinically, Herceptin,27 D4-receptor antibodies,28
doxorubicin,29 and methotrexate30 for cancer treatment; anti-
amyloid-beta antibodies for Alzheimer’s;31 and stem cells for
neuronal regeneration32 have been delivered through the BBB
using focused ultrasound. Figure 4 demonstrates delivery of
neural stem cells through the BBB have ultrasound-induced
disruption. With the goal of eventual clinical use, transcra-
nial BBB disruption studies have recently been completed on
non-human primates, using a single element transducer at
500 kHz33 and the Exablate 4000 clinical prototype at 230
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utilize passively received acoustic signals to adjust sonication
power levels.
The use of high intensity focused ultrasound (HIFU) for
non-invasive neurosurgical procedures has shown great ini-
tial promise, with the chronic neuropathic pain being the
first treated pathology.21 Focused ultrasound was used to per-
form noninvasive central lateral thalamotomies in 12
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patients. The ablations were 3-4 mm in diameter and
achieved peak temperatures of 51–64°C. Treatments could be visualized and guided in real-time through MR thermometry and the lesions were clearly visible on follow-up imaging. At 3 months, patients had a mean pain relief of 49% and 6 patients experienced immediate and persisting improve- ments. Within this initial trial, there was one complication, a bleed at the target and ischemia in thalamus. This lead to the establishment of two safety parameters: the implementation of passive cavitation detection and ensuring the peak tem- perature remained below 60°C. For the remaining patients, the treatments have been well tolerated, producing no side effects or neurological deficits.
Applications under clinical investigation—essential tremor
Treatment of essential tremor, a common movement dis-
order in adults, with focused ultrasound involves the ablation kHz.
of the ventralis intermedius of the thalamus and represents a non-invasive alternative to deep brain stimulation.22 Treatment outcomes can be quite dramatic, giving patients the use of a once uncontrollably shaking hand, after a single
Cognitive testing did not show any negative effects fol- lowing treatment. Furthermore, with a goal of optimizing safe disruption, control algorithms have been developed that
10 Acoustics Today, October 2012
Fig. 3. Visible enhancement regions in the above magnetic resonance (MR) image indicate blood brain disruption of the rat brain induced by focused ultrasound. (Image courtesy of Meaghan O’Reilly)
There are currently ongoing clinical trials at the University of Virginia in the US, Sunnybrook Health Sciences Centre in Canada, the Center of Ultrasound Functional Neurosurgery in Switzerland, and at Yonsei University Medical Centre in Korea to investigate the full
same-day procedure.
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BBB disruption is an exciting area of active