Biomedical Engineering Reference
In-Depth Information
effort into applying HIFU in the field of ophthalmology. They
constructed the first FDA-approved HIFU device (Sonocare
C S T-10 0) to investigate the possibility of using HIFU to treat
glaucoma, choroidal melanomas, and capsular tears, and clini-
cal results looked very exciting [10-13]. However, the advent of
medical lasers for use in ophthalmology occurred simultane-
ously. Due to the ease of its use, the laser has superseded HIFU
in most ophthalmological applications.
Based on their experience with extracorporeal shock wave litho-
tripsy, Guy Vallancien and colleagues at the institute Mutualiste
Montsouris in Paris, France, constructed an extracorporeal HIFU
device in the 1990s. His team used this ultrasound-guided pyro-
therapy device to treat superficial bladder tumors in clinical trials.
Five patients were enrolled in the phase I trial, and cystoscopy was
performed before and after HIFU treatment. The disappearance of
the tumor in two cases and coagulation necrosis in the remaining
patients was noted [14].
In the phase II trial, a total of 25 patients
with low-grade superficial bladder tumors were recruited. After
treatment, 67% of the patients were tumor free at one year and
no invasion or metastasis was detected with follow-up of 3-21
months [15].
However, when two patients with metastatic liver
cancer were treated with the same device prior to surgical resec-
tion, the results looked unsatisfactory. There was no visible effect
in one case, and in another there was extensive tissue laceration
and patchy necrosis [16].
Gail ter Haar and colleagues at the Royal
Marsden Hospital in London, United Kingdom, built a prototype of
an ultrasound-guided HIFU (USgHIFU) device in the 1990s. This
device employed a spherical ceramic transducer of 10 cm diameter
and 15 cm focal length. It was driven at a frequency of 1.7 MHz and
operated at free field spatial intensities between 1000 W cm
−2
and
4660 W. cm
−2
[17].
In the phase I trial, a total of 68 patients were
treated with this device. The results demonstrated that HIFU treat-
ment of liver cancer was well tolerated; some moderate local pain
was observed, but only in a few patients [18].
My group at the Institute of Ultrasonic Engineering in
Medicine, Chongqing Medical University in Chongqing, China,
started USgHIFU research in 1988. Laboratory and animal stud-
ies including goat, pig, and monkey were mostly carried out
from 1988 to 1997, and an extracorporeal HIFU prototype was
designed and constructed in 1997 for clinical trials. It employed
real-time ultrasound imaging to guide and monitor the procedure
of HIFU ablation. On December 10, 1997, we used it to perform
the first HIFU treatment in China for a boy with tibia osteosar-
coma. The treatment was very successful and without any compli-
cations. After treating 1038 patients with solid tumors from 1997
to 2001 in 10 Chinese hospitals [19], the device (Model-JC HIFU
system, Chongqing HAIFU, China) became the first HIFU system
approved by the State Food and Drug Administration in China, an
organization similar to the FDA in the United States. Solid malig-
nancies treated with HIFU included primary and metastatic liver
cancer, malignant bone tumor, breast cancer, soft tissue sarcoma,
kidney cancer, pancreatic cancer, and advanced local tumors.
Benign tumors, such as uterine fibroid, benign breast tumor, and
hepatic hemangioma, were also treated. The same device was then
introduced in the United Kingdom in 2002, and four clinical trials
were performed at the Churchill Hospital, University of Oxford,
for the treatment of liver and kidney cancer.
The clinical results
were very promising, indicative that HIFU could be safe, feasible,
and effective for the treatment of solid malignancies, leading to a
CE approval in Europe for the device in 2005 [20].
Although the purpose of this chapter is to describe extracor-
poreal USgHIFU treatment, it is necessary to introduce some
clinical experiences of using a transrectal USgHIFU device
in the treatment of patients with prostate cancer. Up to now,
two commercially available devices have been reported to treat
prostate cancer in clinical practice. One transrectal device
(Sonablate, Focused Surgery, United States) uses a 4 MHz
PZT transducer for both imaging and treatment,
and another
(Ablatherm, EDAP, France) uses a 2.25-3.0 MHz rectangular
transducer for treatment and a retractable 7.5 MHz probe for
imaging guidance [21].
These devices have been widely used
in the treatment of patients with prostate cancer, and clini-
cal results are very promising [22]. In addition, Hynynen and
colleagues at the Brigham and Women's Hospital in Boston,
Massachusetts, did a lot of work incorporating HIFU into an
MRI system and constructed an MRI-guided HIFU device in
the 1990s [23].
With MRI thermometry techniques, the device
can record focal temperature rises on the anatomical images
during treatment procedure. This MRI-guided HIFU has been
used clinically to treat uterine fibroids and breast neoplasms,
and the results indicate successful ablation of targeted tumors
[24, 25]. It has been approved by the FDA for the treatment of
patients with uterine fibroids.
15.2 physical principles of HIFU
ablation
Ultrasound is a form of vibrational energy. It propagates as
a mechanical wave by the motion of particles in the medium.
The wave propagation leads to compressions and rarefactions
of the particles, so that a pressure wave is transmitted along with
the mechanical movement of the particles. As an ultrasound
beam propagates through the body, it loses energy due to ultra-
sonic attenuation in tissue, which is caused by both scattering
and absorption. The absorption of ultrasonic energy causes a
local temperature rise in tissue if the rate of heating exceeds the
rate of cooling. In HIFU, the absorption is greatest in the focus,
where the acoustic intensity is at its highest. Additionally, dur-
ing the rarefaction of the pressure wave, gas can be drawn out of
the solution, and the subsequently formed bubbles may be acted
on by the acoustic wave. When they reach the size of resonance,
these bubbles suddenly collapse, causing mechanical stresses on
surrounding tissues.
Two major effects are directly involved in the tissue damage
induced by HIFU exposure. The first is a thermal effect from
the conversion of mechanical energy into heat in the tissue, and
the second is through cavitation. The thermal effect depends
on the temperature achieved and the length of HIFU expo-
sure. If the temperature rise is above a threshold of 56°C and
