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.
2294 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 57, NO. 9, SEPTEMBER 2010
 S. Pichardo and K. Hynynen, “Treatment of near-skull brain tissue with a
focused device using shear-mode conversion: A numerical study,” Phys.
Med. Biol., vol. 52, pp. 7313–7332, 2007.
 S. C. Tang, G. T. Clement, and K. Hynynen, “A computer-controlled
ultrasound pulser-receiver systme for transskull fluid detection using a
shear wave transmission technique,” IEEE Trans. Ultrason. Ferroelectr.,
Freq. Control, vol. 54, no. 9, pp. 1772–1783, Sep. 2007.
 J. Song and K. Hynynen, “Feasibility of using lateral mode coupling
method for a large scale ultrasound phased array for noninvasive transcra-
nial therapy,” IEEE Trans. Biomed. Eng., vol. 57, no. 1, pp. 124–133, Jan.
 R. A. Roy, S. I. Mandashetty, and R. E. Apfel, “An acoustic backscat-
tering technique for the detection of transient cavitation produced by
microsecond pulses of ultrasound,” J. Acoust. Soc. Amer., vol. 87, no. 6,
pp. 2451–2458, 1990.
 A. A. Atchley, L. A. Frizzell, R. E. Apfel, C. K. Holland, S. Madanshetty,
and R. A. Roy, “Thresholds for cavitation produced in water by pulsed
ultrasound,” Ultrasonics, vol. 26, pp. 280–285, 1988.
 S. I. Madanshetty, R. A. Roy, and R. E. Apfel, “Acoustic microcavitation:
Its active and passive acoustic detection,” J. Acoust. Soc. Amer., vol. 90,
no. 3, pp. 1515–1526, 1991.
 C. H. Farny, R. G. Holt, and R. A. Roy, “Monitoring the development of
HIFU-induced cavitation activity,” in AIP Conf. Proc 5th Int. Symp. Ther.
Ultrasound, 2006, vol. 829, pp. 348–352.
 C. C. Coussios, C. H. Farny, G. Ter Harr, and R. A. Roy, “Role of
acoustic cavitation in the delivery and monitoring of cancer treatment by
high-intensity focused ultrasound (HIFU),” Int. J. Hyperthermia, vol. 23,
no. 2, pp. 105–120, 2007.
and C. K. Holland, “Ultrasound-enhanced thrombolysis using definity as
a cavitation nucleation agent,” Ultrasound Med. Biol., vol. 34, no. 9,
pp. 1421–1433, 2008.
 T. G. Leighton, F. Fedele, A. J. Coleman, C. McCarthy, S. Ryves, A. M.
Hurrell, A. De Stefano, and P. R. White, “A passive acoustic device for
real-time monitoring of the efficacy of shockwave lithotripsy treatment,”
Ultrasound Med. Biol., vol. 34, no. 10, pp. 1651–1665, 2008.
 S. Robinson, R. Preston, M. Smith, and C. Millar, “PVDF reference hy-
drophone development in the UK—From fabrication and lamination to
use as secondary standards,” IEEE Trans. Ultrason., Ferroelectr., Freq.
Control, vol. 47, no. 6, pp. 1336–1344, Nov. 2000.
 F. S. Foster, K. A. Harasiewicz, and M. D. Sherar, “A history of medical
and biological imaging with polyvinylidene fluoride (PVDF) tranducers,”
1371, Nov. 2000.
 G. M. Sessler, “Piezoelectricity in polyvinylidenefluoride,” J. Acoust.
Soc. Amer., vol. 70, no. 6, pp. 1596–1608, 1981.
 P. Lewin, “Miniature piezoelectric polymer ultrasonic hydrophone
probes,” Ultrasonics, vol. 19, no. 5, pp. 1420–1424, 1981.
 D. R. Bacon, “Characteristics of a PVDF membrane hydrophone for use
in the range 1–100 MHz,” IEEE Trans. Sonics Ultrason., vol. SU-29,
no. 1, pp. 18–25, Jan. 1982.
 M. Platte, “A polyvinyldene fluoride needle hydrophone for ultrasonic
applications,” Ultrasonics, vol. 23, no. 3, pp. 113–118, 1985.
 M. Schaefer, J. Gessert, and W. Moore, “Development of a high intensity
focused ultrasound (HIFU) hydrophone system,” in Proc. IEEE Ultrason.
Symp., 2005, vol. 3, pp. 1739–1742, Art. No. 1603202.
 B. Zeqiri, P. N. G´ elat, M. Hodnett, and N. D. Lee, “A novel sensor for
monitoring acoustic cavitation. Part I: Concept, theory, and prototype
development,” IEEE Trans. Ultrason. Ferroelectr., Freq. Control, vol. 50,
no. 10, pp. 1342–1350, Oct. 2003.
 S. J. Norton and I. J. Won, “Time exposure acoustics,” IEEE Trans.
Geosci. Remote Sens. E, vol. 38, no. 3, pp. 1337–1343, May 2000.
 V. A. Salgaonkar, S. Datta, C. K. Holland, and D. T. Mast, “Passive
no. 6, pp. 3071–3038, 2009.
 M. Gy¨ ongy and C. C. Coussios, “Passive spatial mapping of inertial cavi-
tation during HIFU exposure,” IEEE Trans. Biomed. Eng., vol. 57, no. 1,
pp. 48–56, Jan. 2010.
itoring of transcranial therapy,” in Proc. 9th Int. Symp. Ther. Ultrasound,
AIP Conf., 2009, vol. 1215, pp. 212–215.
 A. R. Harland, J. N. Petzing, J. R. Tyrer, C. J. Bickley, S. P. Robinson, and
R. C. Preston, “Application and assessment of laser Doppler velocimetry
for underwater acoustic measurements,” J. Sound Vibration, vol. 265,
pp. 627–645, 2003.
 L. J. Ziomek, Fundamentals of Acoustic Field Theory and Space-Time
Signal Processing.Boca Raton, FL: CRC Press, 1995, pp. 465–480.
 M. Crocco, M. Palmese, C. Sciallero, and A. Trucco, “A comparative
analysis of multi-pulse techniques in contrast-enhanced ultrasound medi-
cal imaging,” Ultrasonics, vol. 49, pp. 120–125, 2009.
compatible system for focused ultrasound experiments in small animal
models,” Med. Phys., vol. 36, no. 5, pp. 1867–1874, 2009.
 K. Hynynen, “Ultrasound heating technology,” in Thermo-Radiotherapy
and Thermo-Chemotherapy, vol. 1, Biology, Physiology, and Physics, M.
H. Seegenschmiedt, P. Fessenden, and C. C. Vernon, Eds.
Springer-Verlag, 1995, pp. 255–256.
 K. Hynynen, “Acoustic power calibrations of cylindrical intracavitary
 E. A. Neppiras, “Acoustic cavitation,” Phys. Rep., vol. 61, no. 3, pp. 159–
 T. G. Leighton, The Acoustic Bubble.
 B. Fay, G. Ludwig, C. Lankjaer, and P. A. Lewin, “Frequency response of
PVDF needle-tytpe hydrophones,” Ultrasound Med. Biol., vol. 20, no. 4,
pp. 361–366, 1994.
 P. A. Lewin, G. Lypacewicz, R. Bautista, and V. Devaraju, “Sensitivity
of ultrasonic hydrophone probes below 1 MHz,” Ultrasonics, vol. 38,
pp. 135–139, 2000.
 F. J. Fry and J. E. Barger, “Acoustical properties of the human skull,” J.
Acoust. Soc. Amer., vol. 63, no. 5, pp. 1576–1590, 1978.
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.