2286IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 9, SEPTEMBER 2010
A PVDF Receiver for Ultrasound Monitoring of
Transcranial Focused Ultrasound Therapy
Meaghan A. O’Reilly and Kullervo Hynynen*
Abstract—Focused ultrasound (FUS) shows great promise for
use in the area of transcranial therapy. Currently dependent on
MRI for monitoring, transcranial FUS would benefit from a real-
time technique to monitor acoustic emissions during therapy. A
polyvinylidene fluoride receiver with an active area of 17.8 mm2
SNR and allow the long transmission line needed to remove the re-
ceiver electronics outside of the MRI room. The receiver was com-
pared with a 0.5 mm commercial needle hydrophone and focused
and unfocused piezoceramics. The receiver was found to have a
higher sensitivity than the needle hydrophone, a more wideband
response than the piezoceramic, and sufficient threshold for detec-
tion of microbubble emissions. Sonication of microbubbles directly
and through a fragment of human skull demonstrated the ability
of the receiver to detect harmonic bubble emissions, and showed
potential for use in a larger scale array. Monitoring of disruption
of the blood–brain barrier in rats showed functionality in vivo and
the ability to detect subharmonic, harmonic, and wideband emis-
sions during therapy. The receiver shows potential for monitor-
ing acoustic emissions during treatments and providing additional
parameters to assist treatment planning. Future work will focus
on developing a multi-element array for transcranial treatment
Index Terms—Blood–brain barrier (BBB), focused ultrasound
(FUS), polyvinylidene fluoride (PVDF) hydrophone, transcranial
tion of the blood–brain barrier (BBB) –. The complex
geometry of the skull and the high attenuation of sound through
bone create unique challenges for transcranial therapy. Several
sharp transcranial focus. These include low-frequency focused
OCUSED ultrasound (FUS) shows promise in transcranial
applications, including tissue ablation – and disrup-
Manuscript received December 14, 2009; revised March 15, 2010; accepted
April 23, 2010. Date of publication May 27, 2010; date of current version
August 18, 2010. This work was supported by the National Institutes of Health
under Grant EB003268 and Grant EB009032. Asterisk indicates corresponding
M. A. O’Reilly is with the Department of Imaging Research, Sunny-
brook Health Sciences Centre, Toronto, ON, M4N3M5, Canada (e-mail:
*K. Hynynen is with the Department of Imaging Research and the Cen-
tre for Research in Image-Guided Therapeutics, Sunnybrook Health Sciences
Centre, Toronto, ON, M4N3M5, Canada, and also the Department of Medical
Biophysics, University of Toronto, Toronto, ON M4N3M5, Canada (e-mail:
Digital Object Identifier 10.1109/TBME.2010.2050483
transducers , shear wave transmission –, and phased
arrays , , , , .
Transcranial FUS currently relies on MRI to monitor therapy,
which only provides information on the temperature elevation
and the effect of the therapy (such as tissue coagulation and
BBB disruption (BBBD) after the exposure) and does not pro-
vide feedback on the generated sound field itself. Although
MRI-monitored thermal effects are of importance, equally im-
portant are the indicators of nonthermal effects, such as the
interaction of contrast agent microbubbles with the generated
sound field in BBBD . The addition of diagnostic capabili-
non-thermal treatment effects to be monitored, but could also
provide important information regarding the generated sound
Cavitation detection, both active  and passive , ,
is a well-established field of study. Cavitation has been investi-
gated as a means to monitor different ultrasound therapy proce-
dures –. In BBBD, the appearance of harmonic signal
components has been shown to correlate with disruption .
This could eventually lead to BBB therapy conducted inde-
pendently of MRI. In that study, a narrow band receiver was
used and low-frequency noise made detection of subharmonics
impossible. A sufficiently wideband receiver would allow for
acquisition of signals with more complete spectral information,
without receiver-induced limitations. Further, in thermal appli-
cations where inertial cavitation is of interest, or of concern, the
receivers would allow monitoring of the bubble activity, which
could be correlated with the tissue-heating information gained
Polyvinylindene fluoride (PVDF) is a piezoelectric polymer
that has been extensively used in medical ultrasound . Al-
though PVDF has been used in high-frequency imaging trans-
PVDF transducers unsuitable for therapeutic purposes. How-
ever, PVDF’s high sensitivity, broadband response, and close
acoustic match to water make it an excellent material choice for
ultrasound receivers, and it has been widely used in needle and
membrane hydrophones , –. PVDF has previously
been used to monitor acoustic cavitation , and we hypoth-
esize that PVDF receivers may be used in combination with
piezoceramic therapy elements to create a therapeutic transcra-
nial array with monitoring capabilities.
The 1372-element phased array presented by Song and
Hynynen  consists of laterally coupled piezoceramic ring
elements operating in extension mode and set within a hemi-
spherical dome of 30 cm diameter. PVDF receivers placed
0018-9294/$26.00 © 2010 IEEE
O’REILLY AND HYNYNEN: PVDF RECEIVER FOR ULTRASOUND MONITORING OF TRANSCRANIAL FOCUSED ULTRASOUND THERAPY2287
in the middle of the rings and aligned with the acoustic axes
of the individual elements would allow the individual hybrid
elements to act in a transmit–receive mode, and would make
use of the available space within the ring elements. Multiple re-
ceivers would allow microbubble harmonic emissions or broad-
band inertial cavitation emissions to be detected and localized
using passive beam-forming techniques – and possibly
used to control the exposure . Unfortunately, commercially
available hydrophones are expensive, not MRI compatible, and
often too large to be used for this purpose with arrays that have
a large number of elements. Therefore, alternatives are required
in order to be able to harness the control potential of the acous-
tic emissions from the oscillating microbubbles in the brain
vasculature. The goal of the current research is to create a low-
cost, MR-compatible wideband receiver with high sensitivity
and a flat response over the frequency range of approximately
100 kHz–1.5 MHz, corresponding to clinically relevant fre-
quencies in transcranial therapy. Further, the receiver must be
designed so as to be contained within and function in combi-
nation with one of the previously described cylindrical transmit
elements to form a dual-purpose pair.
In this paper, a low cost, MRI-compatible, and miniature
PVDF receiver is presented and directly compared with a com-
mercial needle hydrophone. The ability of the PVDF receiver
to function in combination with a ceramic transmit element
is demonstrated. Microbubbles were sonicated through a frag-
to detect transcranial harmonic emissions. Finally, the receiver
was implemented to monitor BBBD in rats and to demonstrate
its ability to detect differences between signals emitted during
sonications producing different biological effects. Preliminary
results from this study have been reported .
II. MATERIALS AND METHODS
A. Receiver Construction
Hundred and ten micrometer thick metalized PVDF film
(Measurement Specialties, Inc., Hampton, VA, USA), with
NiCu electrodes (700 ˚ A Cu, 100 ˚ A Ni) and an active area of
approximately 17.8 mm2, was stretched across brass tubing
having a diameter of 4.76 mm. A thin electrically insulating
layer (Glad Press’n Seal wrap) was applied around the tubing,
leaving the face of the tube exposed. A second length of brass
tubing, which had been worked to create a rim at the top edge,
was used to clamp the PVDF film. Fig. 1 shows the PVDF film
resting between the uninsulated face of the inner tube and the
worked rim of the outer tube, with these two surfaces forming
the electrode connections. The tubes were held together using a
nylon-set screw. Signal and ground connections were made to
the internal and external brass tubes, respectively, as shown in
A small preamplifier with 20 dB of gain was constructed
and enclosed within the brass tubing to improve the receiver
SNR and to drive the long coaxial cables required to reach
outside the MRI. The tubing was sealed to provide air backing,
and the receiver was mounted through a piece of cork-backed
acrylic inside a PZT-4 cylinder element (h = 6 mm; internal
clamped between two brass tubes. (Bottom left) Large receiver and transmit
element pair. (Bottom right) Small receiver and transmit element pair.
(Top) Cut section showing receiver construction. The PVDF film is
resonance frequency f = 306 kHz), similar to the ones used in
an existing 1372-element transcranial array  [see Fig. 1(b)].
In air-backing the receiver, some bandwidth was sacrificed in
order to be able to enclose the preamplifier entirely within the
device and to prevent corrosion. A second smaller receiver with
a diameter of 2.4 mm was constructed using the same method in
order to examine the feasibility of reducing the receiver’s active
area to improve the field of view.
B. Preamplifier Design and Characterization
To minimize the electrical noise introduced to the system,
the preamplifier had to be contained within the grounded brass
tubing, limiting the circuit-board dimensions. Additionally, an
op-amp with a large bandwidth was desired to avoid narrowing
the bandwidth of the receiver beyond the range of interest. The
selected op-amp (FHP3131, Fairchild Semiconductor Corpora-
tion, California, USA) has a unity gain bandwidth of 70 MHz
and component dimensions of 1.45 × 1.00 × 0.55 mm (6 Lead
MicroPak). The circuit, shown in Fig. 2, provides 20 dB of
gain. The resulting single-sided circuit board was constructed
in-house and had board dimensions of 7.1 × 1.8 mm.
The response of the preamplifier circuit over a range of fre-
quencies (0.1–5 MHz), rail voltages, and coaxial cable lengths
C. MRI Compatibility
The receiver was imaged in an 1.5 T MRI (Signa 1.5 T,
General Electric, Fairfield, Connecticut, USA) to determine the
level of interference, if any, with the MRI. A sonication was
performed during MR image acquisition to demonstrate func-
tionality of the device in the MRI.
2288 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 9, SEPTEMBER 2010
Fig. 2.(Top) Preamplifier circuit diagram. (Bottom) Populated circuit board.
D. Receiver Characterization
The receiver sensitivity was measured at the fundamental
frequency and third harmonic of the transmit element using a
characterized element and was compared with both a 0.5 mm
commercial needle hydrophone (Precision Acoustics Ltd.,
existing, in-house constructed, calibrated transducer. Both the
transmit element and calibrated transducer were calibrated us-
Polytec, Waldbronn, Germany) to measure the particle veloc-
ity of a membrane placed normal to the acoustic axis and at a
fixed distance from the transducer . The peak pressures re-
sulting from different excitation voltages were then calculated.
The SNR of the receiver and the hydrophone were compared
when each device was used in receive mode only, by placing the
receiver and hydrophone in the field, and when acting in a trans-
mit/receive pair. For this comparison, the needle hydrophone
was mounted through the center of the transmit element in the
same configuration, as the constructed receiver. A function gen-
erator (AFG3102, Tektronix, TX, USA) was used to send a
pulse train to a power amplifier (KAA2030, AR, Washington,
USA), and then to the transmit element. The receiver signal was
received using a signal amplifier (DA1820 A, LeCroy, Chestnut
Ridge, NY, USA) and digital oscilloscope (TDS3014B, Tek-
tronix). The signals were transferred from the oscilloscope to
the computer using a general purpose interface bus (GPIB) in-
terface and LABVIEW software (National Instruments, TX,
USA). Data analysis was performed in MATLAB (Mathworks,
The thresholds for detection of various microbubble emis-
sions were established by sonicating a solution of Definity
contrast agent (Lantheus Medical Imaging, MA, USA) in a
thin-walled tube (0.0152–0.0203 mm double-wall thickness,
2 mm diameter medical balloon; Advanced Polymers, Inc., NH,
USA) using a 0.548 MHz spherically focused therapy trans-
bubble excitation setup.
(a) Experimental setup, receiver characterization. (b) Transcranial
ducer (5 cm aperture, f-number = 1), as shown in Fig. 3(a).
A focused passive transducer (5 cm aperture, f-number = 2)
with a center frequency of 0.270 MHz was cofocused with the
therapy transducer at the tubing. Focusing was achieved using
a 0.10 µm planar fiber-optic hydrophone (Precision Acoustics
Ltd.). The PVDF receiver was then aligned with the tubing
opposite the passive receiver. Ten millsecond bursts were de-
livered with increasing focal pressure until wideband emission
LeCroy WavePro 715Zi oscilloscope (LeCroy) and transferred
to computer for analysis in MATLAB.
The directivity of the receiver was measured using a ring
transmit element that was mounted at the end of a rotational
arm and was used to sonicate the receiver at the center of
rotation. The signal strength was measured for 180◦of inci-
dence in 5◦steps. This was performed for the fundamental
frequency (306 kHz) and the third harmonic of the transmit
element (830 kHz). The measured results were compared with
the theoretical values obtained using the normalized far-field
directivity function for a circular piston 
D(θ) =2J1[(2πa/λ)sin θ]
where J1is the first-order Bessel function of the first kind, a is
the radius of the receiver, and λ is the wavelength.
E. Transcranial Bubble Excitation
The transmit/receive pair was used to excite a solution of
rectly and in the presence of a fragment of human skull. The
experimental setup is illustrated in Fig. 3(b). The thin-walled
tube was mounted in a tank filled with degassed, deionized wa-
ter. Rubber (Neoprene 70 durometer, Global Rubber Products
Ltd., Toronto, ON, Canada), with approximately 4.5% reflected
intensity at 1 MHz based on tests conducted in this laboratory,
O’REILLY AND HYNYNEN: PVDF RECEIVER FOR ULTRASOUND MONITORING OF TRANSCRANIAL FOCUSED ULTRASOUND THERAPY2289
tank walls and bottom. To further reduce the impact of reflec-
tions, short bursts were used. All sonications consisted of ten
cycle bursts at 10 ms intervals. The transmit/receive pair was
mounted on a three-axis stage and was aligned with the thin-
walled tube by maximizing the reflection from the tube when
it was filled with air. After alignment, the tube was filled with
degassed water and a reference sonication was performed. The
captured reference waveform was subtracted from subsequent
sonications to remove the reflections from the tubing, tubing
mount, and other parts of the tank, as well as reduce the effects
of coupling with the transmit element. Attempts were made to
repeat the experiment with the commercial hydrophone; how-
ever, alignment of the hydrophone with the tubing was impossi-
ble, as the reflected signal was completely lost in the electrical
coupling with the transmit element.
The acoustic pressure at the tubing was measured using the
0.5 mm needle hydrophone. The waveforms captured using the
needle hydrophone were analyzed to confirm that no harmonic
signals were present in the outgoing therapy pulse. The hy-
drophone was then removed and 25:1 and 100:1 solutions of
Definity contrast agent were injected into the tubing, which
was then sonicated using the transmit element. Reflected wave-
forms detected with the PVDF receiver for each solution were
recorded. Pulse inversion techniques  were used to amplify
the harmonic components of the reflected waveform. A frag-
ment of human skull was placed between the transmit/receive
pair and the tubing, and the alignment, hydrophone pressure
measurements, and reference waveform acquisition procedures
were repeated. Sonications were performed for 100:1, 25:1, and
10:1 Definity solutions. A second transmit element was used
to increase the pressure at the tubing and sonications were re-
of the second transmit element had increased the local acoustic
pressure rather than causing phase cancellations.
F. In Vivo Monitoring of BBBD
to examine its effectiveness in monitoring transcranial therapy,
given more realistic concentrations of microbubbles and realis-
tic therapeutic pressures. Disruption of the BBB was performed
in six rats using a 558 kHz spherically focused transducer (10
cm diameter and 78 mm focal length), and the three-axis po-
sitioning system described by Chopra et al. . To avoid in-
troducing harmonic components to the transmitted pulse, the
therapy transducer was matched to 50 Ω at 558 kHz using an
external matching circuit, and the power input to the RF power
were delivered at a repetition frequency of 1 Hz for 2 min. The
applied electrical power was kept constant during the bursts of
each sonication, but it was varied from sonication to sonication
which corresponds to an applied acoustic power range of 0.18–
0.88 W. The corresponding peak-negative pressure amplitudes
Fig. 4.Positioning system arm with transducer and PVDF receiver.
in situ were estimated to be 0.14–0.33 MPa taking the attenua-
tion in the brain to be approximately 5 (Np·m−1)/MHz  and
73%, based on previous measurements taken in this laboratory.
The peak-negative acoustic pressure amplitude was calibrated
using a scanning laser vibrometer (PSV-400 Scanning Vibrom-
eter, Polytec) and the acoustic power output using a radiation
force measurement system with an absorbing target . The
PVDF receiver was mounted on the positioning arm, directed
toward the focus, as illustrated in Fig. 4. The signal was ampli-
fier, and captured using a LeCroy WavePro 715Zi oscilloscope
(LeCroy). Waveforms were captured and stored approximately
every 3 s for the duration of the sonications.
Six animals (Wistar; 303–380 g) were anesthetized using a
jected intraperitoneally. Their heads were shaved and depilated
to remove hair from the ultrasound path. The animals were
placed supine on the positioning system table with their heads
over the transducer, in contact with the water. Single-point son-
ications were performed at four separate locations in each rat.
Sonication locations were selected from T2-weighted MR im-
ages taken in a 1.5-T MRI (Signa 1.5 T, General Electric). A
bolus of Definity contrast agent (0.02 mL/kg) was injected, via
a tail vein catheter, immediately before the start of sonication.
A minimum delay of 4 min was allowed between sonications to
allow the contrast agent to clear from the system. Opening was
confirmed via contrast-enhanced (OmniScan, 0.2 mL/kg) T1-
weighted MRI images, and T2-weighted images were used to
check for edema (see Table I). In two rats, sonication of the first
location was performed at low power, and when BBBD was not
a higher power. A total of 26 sonications were performed at 24
separate locations. Waveforms were analyzed using MATLAB
and results were compared with the captured MR images.
Thorough reviews of acoustic emissions during cavitation
exist ,  and will therefore not be covered in depth
in this paper. During analysis, the presence of harmonics,
2290 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 9, SEPTEMBER 2010
Fig. 5. Frequency response of the preamplifier.
subharmonics, and ultraharmonics were considered to mark mi-
crobubble presence and stable cavitation, whereas inertial cavi-
tation was identified by a sharp rise in broadband emissions. To
and water, harmonic signal strengths were considered relative
to the waveform acquired at time t = 0 s, when contrast agent
would not be present.
The preamplifier produced high gain over a reasonable fre-
quency range. The −3 dB point of the gain occurred around
4 MHz, with roll-off beginning around 1 MHz (see Fig. 5).
Supplied rail voltages and load had little effect on the gain
of the amplifier, which was able to drive loads across coaxial
cable lengths of 8.5 m without loss of signal strength (81 mV
cable), sufficient to drive the signal outside the MRI.
Imaging of the device revealed small artifacts near solder
points (see Fig. 6). The artifacts did not extend far from the
surface of the device and would therefore not interfere with
imaging of the brain during therapy. Waveforms captured while
in or near the MRI bore while the MRI was not imaging showed
little or no distortion (see Fig. 6). Acquiring MR images while
simultaneously operating the device in pulse–echo mode added
some distortion to the ultrasound signal (see Fig. 6). However,
and even at low amplitudes the reflected waveforms were still
The sensitivity of the PVDF receiver (1.62 ± 0.09 V/MPa at
306 kHz and 1.38 ± 0.16 V/MPa at 830 kHz) was 6.8 times and
4.1 times that of the 0.5 mm commercial hydrophone (0.24 ±
0.01 V/MPa at 306 kHz and 0.34 ± 0.03 V/MPa at 830 kHz)
at 306 and 830 kHz, respectively. By comparison, the smaller
in MRI bore with MRI off. (c) Frequency spectrum from 0 to 1 MHz while in
(e) Frequency spectrum from 0 to 1 MHz while in MRI bore while acquiring
(a) MR images of receive/transmit pair in water. (b) Pulse echo while
acteristics and sensitivity of a PZT-4 reciever with the same effective area. Error
bars indicate one standard deviation.
Sensitivity of the PVDF receiver corrected for the preamplifier char-
receiver sensitivities were 0.88 ± 0.03 V/MPa at 306 kHz and
1.12 ± 0.09 V/MPa at 830 kHz. As expected, the PZT-4 had
a much higher sensitivity than the PVDF (see Fig. 7); how-
ever, it also had a greater variation in sensitivity over the range
examined. At higher frequencies, the receiver displayed a sim-
ilar frequency response to the preamplifier, rolling-off around
1 MHz. Correcting for the response of the preamplifier, a flat
trend was obtained (see Fig. 7). The sensitivity variations in
the corrected response are consistent with the variations at low
frequency observed in needle-type polymer hydrophones ,
, although the expected periodic nature of these fluctuations
due to finite-aperture effects and reflections along the brass tub-
ing may be not be completely visible, given only a few data
points. Since frequencies above 1.5 MHz are not expected to be
detected through the human skull due to the large attenuation
O’REILLY AND HYNYNEN: PVDF RECEIVER FOR ULTRASOUND MONITORING OF TRANSCRANIAL FOCUSED ULTRASOUND THERAPY2291
Fig. 8. Response of the receiver during sonication into free field.
receiver with increasing pressure for (a) second harmonic 1096 kHz ± 200 Hz,
and 325–450 kHz). Area under the FFT curve from the ceramic receiver with
increasing pressure for (a) second harmonic 1096 kHz ± 200 Hz, (b) half-
harmonic 274 kHz ± 200 Hz, and (c) wideband emissions (100–225 kHz and
Area under the fast Fourier transform (FFT) curve from the PVDF
through the skull associated with higher frequencies , the
response of the receiver was accepted.
that of the commercial hydrophone was 90.8 ± 6.2. However,
transmit element. In this instance, the SNR of the hydrophone
receiver. A single waveform was used for this comparison, as it
with the needle hydrophone.
When placed inside the transmit element, the receiver was
also subject to acoustic coupling with the transmit element (see
Fig. 8). This signal component was removable through filter-
ing of the fundamental frequency during post-processing. In the
intended application of monitoring therapy, this would leave
the signal components of interest, namely the microbubble har-
monic emissions and any wideband emissions.
The PVDF receiver was able to detect different types of mi-
crobubble emissions at the same time as the 5 cm aperture
passive detector (see Fig. 9). The focused detector with a center
frequency near the transmit subharmonic and harmonics near
the transmit ultraharmonic frequencies had stronger sub- and
ultraharmonic signal components than the PVDF. However, the
transmit harmonic frequencies detected by the PVDF receiver
and (bottom) 830 kHz. Calculated theoretical values are shown with a dashed
Measured and theoretical directivity of the receiver at (top) 306 kHz
a 25:1 solution of Definity contrast agent. (c) Waveform and (d) frequency
spectrum for through-skull sonication of a 10:1 solution of Definity contrast
agent. The timing shown in (a) and (c) are to show scale, and time t = 0 marks
the start of the waveform capture.
(a) Waveform and (b) frequency spectrum for direct sonication of
were an order of magnitude stronger than those detected by the
The measured directivity of the receiver was a close match to
of the transmit element (see Fig. 10). At a distance of 15 cm,
the fundamental frequency can be detected to approximately
±7 cm from the acoustic axis (3 dB point). However, this range
decreases to approximately ±2.6 cm at 830 kHz.
When directly sonicating the thin-walled tubing, a peak pres-
sure of approximately 46 kPa was measured using the needle
hydrophone. The reflected waveforms for both the 25:1 and
100:1 solutions of Definity showed an increase in signal am-
plitude over the reference sonication, and the presence of har-
monic components indicated the detection of the microbubbles
(see Fig. 11).
After the addition of the skull fragment, the pressure at the
tubing decreased to 22 kPa. An increase in received waveform
amplitude was seen for Definity concentrations of 10:1 and
25:1; however, harmonic signal components were not detected
(see Fig. 11). The peak received pressures were approximately
respectively. At a concentration of 100:1, no distinct difference
from the reference waveform was visible.
2292 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 9, SEPTEMBER 2010
noise level. (b) Fundamental frequency and second harmonic. (c) Harmonics
and sub/ultraharmonics. (d) Harmonics and broadband noise. (e) Harmonics,
sub/ultraharmonics and broadband noise.
FFTs showing different signal types received. (a) Receive baseline
After the addition of a second transmit element, a small
second-harmonic component was detected for a concentration
In vivo, opening of the BBB was observed for 23 of 26 soni-
cations. Harmonic signal components were detected for all son-
ications. Sub- and ultraharmonics were detected for 12 loca-
tions, all of which showed edema in the T2-weighted images.
Only one sonication produced edema without the detection of
were detected at locations where edema had not occurred. Iner-
icated at high power (four locations at 0.27 MPa peak-negative
pressure and one location at 0.33 MPa peak-negative pressure),
all of which experienced notable edema. Fig. 12 shows sample
spectra from the in vivo work displaying the different types of
signal components observed: baseline noise, harmonics, sub-
and ultraharmonics, and wideband emissions. Fig. 13 shows T1
and T2 images of a rat brain sonicated in four locations with
(f). Opening of the BBB at three locations can be seen on the
T1-weighted image, of which edema is visible in two locations
in the corresponding T2-weighted image. Spurious peaks were
seen on the frequency spectra from some sonications. These
seem to be an artifact of the MRI and may be dependent on the
receiver position within the field.
The presented receiver shows great potential for use in ultra-
sound monitoring of transcranial therapy. Positive results were
achieved in bench-top work and in vivo, and comparison with a
commercial hydrophone demonstrated the performance advan-
application in a large-scale, MRI-guided array. The manufac-
turing cost of the PVDF receiver was less than $15 (CAD) in
parts. This is a small fraction of the cost of commercial needle
sonication locations 2, 3, and 4. (b) Corresponding T2-weighted image showing
1 (0.15 MPa), (d) location 2 (0.18 MPa peak-negative pressure), (e) location 3
(0.22 MPa peak-negative pressure), and (f) location 4 (0.27 MPa peak-negative
(a) Contrast-enhanced T1-weighted image showing enhancements at
hydrophones, and would make construction of a large re-
ceiver array more economically feasible than if commercial
hydrophones were used.
Due to the nature of therapeutic ultrasound and, more specifi-
transmit and receive components than in diagnostic ultrasound.
The ability to receive while transmitting is necessary to al-
low for real-time monitoring. For transcranial therapy, lower
frequencies are also desired as the attenuation and phase aber-
ration through the skull increases greatly with increasing fre-
quency . It should be noted that while low frequencies can
give rise to complications, such as standing waves in the skull
cavity, their use is a necessary compromise to ensure ultrasound
transmission transcranially while minimizing focal distortion.
The resulting long outgoing pulses may interact both electri-
cally and acoustically with the receiver, and some degree of
interaction between transmit and receive sides may be present
when the reflected waveform is detected. If isolation of the de-
vice is poor, the reflected waveforms may be indiscernible from
the coupling contributions. Gating the therapy pulses to reduce
the interference between transmit and receive elements may be
possible. However, investigation of the effects of a reduced duty
cycle on BBBD would be required to ensure that this did not
influence treatment efficacy. The proposed use of the receivers
in a hemispherical array would add the additional complication
of signals emanating from facing transmit elements in the ar-
ray and from multiple reflections caused by the skull. In the
proposed application, filtering of the fundamental frequency
would eliminate these, leaving only the generated harmonics
and wideband emissions. While reflections of the microbubble
O’REILLY AND HYNYNEN: PVDF RECEIVER FOR ULTRASOUND MONITORING OF TRANSCRANIAL FOCUSED ULTRASOUND THERAPY2293
emissions within the skull, as well as harmonics generated by
the nonlinearities of tissue and water, must be still considered,
elimination of the transmit frequency substantially simplifies
the signal analysis.
though less sensitive than PZT-4 of equivalent size, the broad-
band response of PVDF is desirable, and comparison with a
highly sensitive passive transducer demonstrated that the PVDF
receiver is sufficiently sensitive for the proposed application. Its
both on the bench-top and in vivo, shows promise for use in a
large-scale array. The superior sensitivity of the PVDF is also
important, as in practice, reflected pressures can be less than
1% of the transmitted-signal strength . While the reflected
signal strength was low for the bubble excitation experiments,
the experiments utilized only a single element, and therefore,
the excitation pressure was low. The absence of harmonic sig-
nal components in the single-element through-skull sonications
pressureatthe contrast agent was insufficient tocause nonlinear
the skull, as above 600 kHz the attenuation of sound through
adult skull bone begins to increase . Nonlinear effects were
restored with the addition of a second transmit element, which
implies feasibility for use within a multielement array. The con-
to those used in vivo. Thus, the in vivo experiments served not
only to confirm the ability of the receiver to detect realistic mi-
crobubble concentrations while transmitting the therapy pulse,
but also showed that the sensitivity of the receiver was sufficient
to detect differences in the waveforms at different powers and
given different biological effects.
One fall back of the current design is the directivity of the
has an effective beam steering range of ±50 mm in the lateral
direction and ±30 mm in the depth direction. At 306 kHz, with
of the maximum receiver signal strength. However, at 830 kHz,
only signals originating ±26 mm from the geometric focus can
be detected without significant signal loss, and at 918 kHz,
the approximate third harmonic generated by the microbubbles,
this range is even further reduced. The smaller receiver that was
successfully constructed without sacrificing signal strength and
that has a PVDF film diameter of 2.4 mm will be able to detect
the third harmonic over the whole beam steering range.
Having demonstrated the feasibility of using the PVDF re-
ceiver in combination with a therapy array element, and in vivo,
future work will focus on expanding to a multielement array, as
well as identifying the control parameters necessary to realize
real-time monitoring of therapy.
A compact, MRI-compatible PVDF receiver for use in com-
bination with a transcranial array element has been presented.
for the proposed application than a commercial hydrophone,
with greater sensitivity and rejection of electrical coupling. The
receiver was able to function in combination with a transmit
element to sonicate a transcranial target and detect the result-
ing low-pressure microbubble oscillations. Preliminary in vivo
work further demonstrated the functionality of the receiver and
demonstrated the possibility of correlating ultrasound signals
with biological effects of treatment. Future work will focus on
developing a multielement receiver array and its acquisition
system, and their testing for brain treatment monitoring.
M. A. O’Reilly would like to thank S. Gunaseelan for his
technical assistance and support on the electronics, as well as
Dr. Y. Huang, P. Wu, S. Rideout-Gros, and A. Garces, for their
assistance withthe in vivo work. She would also like tothank D.
Biancolin for his assistance in characterizing the preamplifier,
and Dr. J. Song for his general assistance and advice.
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New York: Academic, 1994,
Meaghan A. O’Reilly received the B.Sc. degree
in mechanical engineering from Queen’s University,
Kingston, ON, Canada, in 2007, and the M.Sc. de-
gree in biomedical engineering from the University
of Oxford, Oxford, U.K., in 2008.
Since 2009, she has been a Research Engineer
in the Focused Ultrasound Laboratory, Sunnybrook
Health Sciences Centre, Toronto, ON.
Kullervo Hynynen received the Ph.D. degree from
the University of Aberdeen, Aberdeen, U.K.
In 1984, after completing his postdoctoral train-
Aberdeen, he accepted a faculty position at the Uni-
ulty at the Harvard Medical School and Brigham and
Women’s Hospital, Boston, MA. There he reached
the rank of Full Professor, and founded and directed
the Focused Ultrasound Laboratory, Brigham and
Women’s Hospital. Since 2006, he has been at the
University of Toronto, Toronto, ON, Canada. He is currently a Professor in
the Department of Medical Biophysics at the University of Toronto, and is the
Director of Imaging Research and the Centre for Research in Image-Guided
Therapeutics at the Sunnybrook Health Sciences Centre.
Dr. Hynynen is the Tier 1 Canada Research Chair in imaging systems and
image-guided therapy awarded by the Government of Canada.