Chen-Hua Wu1, Shih-Tsung Kang1, Chih-Kuang Yeh1, Wen-Shiang Chen2, and Hsu-Hsia Peng1
1Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu City, Taiwan, 2Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan
Synopsis
This study aims to real-time monitor inertial cavitation on microbubbles
(MBs) while transmitting focused ultrasound (FUS) with various duty cycle and
pulse repetitive frequency (PRF) by gradient echo MRI. For in vitro
experiments, with increasing duty cycle, more significant signal intensity (SI)
changes or prolonged SI drop duration were shown. For in vivo experiment, two SI
drop peaks were observed, reflecting the two IC events. In conclusion, FLASH
has been proved to be a useful technique for real-time monitoring of IC when
transmitting FUS pulses to MBs for in vitro and in vivo experiments.Introduction
At the present of microbubbles (MBs), focused ultrasound (FUS) can
locally induce inertial cavitation (IC) effect and cause turbulence of fluid. .
Previous studies associated BBB opening with duty cycle and pulse repetitive
frequency (PRF) [1,2]. In this study, a fast low-angle shot (FLASH) sequence
was performed for in vitro experiments to observe MR signal changes during FUS
transmission with various conditions of duty cycle and PRF. In addition, a
preliminary test of rat experiments was conducted to demonstrate the
feasibility of this technique for in vivo experiments.
Methods
A
single-element focused piezoelectric transducer (central frequency=1.85 MHz, diameter=10
cm, curvature=12.5 cm, Imasonic, Besancon, France) transmitted 1.5 and 0.8 MPa FUS
pulses to in vitro agarose phantom with chamber diameter=6 mm. The experimental
setup was shown in Fig. 1a. The MBs solutions (lipid shell with C3F8,
mean diameter=1.25 µm, diluted to 0001X) [3] were injected into the phantom.
The FLASH sequence
(TR/TE=8/3.61 ms, pixel size=1.56x1.56x3 mm3, flip angle=20°, temporal
resolution=0.8 s) was performed in a 3.0 Tesla MR scanner (Tim Trio, Siemens,
Erlangen, Germany). All images were acquired at the focal plane and were
perpendicular to the direction of ultrasound beams. The FUS transmitted pulses for continuous 94.4
s. The regions-of-interest (ROIs), approximately 12 pixels, were selected
around the focal point for evaluating signal intensity (SI) changes (Fig. 1a).
The SI within ROI was normalized to mean SI of pre-FUS: normalized SI = (SI/SI_pre-FUS)x100%.
The minimal SI (Min. SI) and the full width at half minimum (FWHM) of the duration
of reduced SI (FUS-late) were together to characterize the time course of each
exam. Images of in vivo
experiment were prescribed at central sinus of a healthy male Sprague-Dawley
rat (300g), as the dotted line in Fig. 1b. The ROI was selected on the FUS focus
(Fig. 1c). The FLASH parameters were as follows: pixel size=0.52x0.52x1.5 mm3,
flip angle=15°, NEX=2, temporal resolution=4s. 0.02 mL solution of MBs and gadolinium
contrast agent were infused into rat via carotid artery 20 s before sonication.
FUS pulses (0.8MPa, PRF=1Hz, duty cycle=1%) were transmitted for continuous 93
s.
Results
Five specific statuses during the time courses of normalized SI and
standard deviation (SD) were indicated as: (I) Pre-FUS, (II) Flow-related enhancement
(FRE) at the beginning of FUS transmission, (III) minimal SI, (IV) latter phases
of FUS transmission (FUS-late), (V) Post-FUS. In Fig. 2, at Pre- and Post-FUS,
normalized SI were approximate 100%. As turning on 1.5 MPa FUS transmission, SI
first increased to an extremely high value due to the FRE effect and then
dropped to approximate 80-85%. With PRF=1 Hz (Fig. 2a), exams with higher duty
cycle exhibited lower minimal SI: 85.7±0.6 %, 81.9±1.3 %, and 80.2±1.1 % for
2%, 5%, and 10% of duty cycle, respectively. With PRF 100 Hz (Fig. 2b), higher
duty cycles displayed larger FWHM: 7.4, 8.0±0.1, and 13.2±0.1 s for 2%, 5% and
10% of duty cycle, respectively. The corresponding calculation of SD of SI within
ROI were shown in Figs. 2(c,d). Figure 3 showed the mean normalized SI with conditions of
0.001X MBs, 0.8 MPa, PRF 1 Hz, 1% or 0.5% duty cycle. With applying such
conditions, large FWHM of 62.23±12.7% and 87.35±2.9% s as well as distinct
minimal SI of 87.54±0.3% and 87.65±2.0% were
observable in 1% and 0.5% duty cycle. Regarding in vivo experiment, Fig. 4a exhibit
two SI drop in normalized SI.
Discussions and
conclusions
In this study, we adopted fundamental experiments of using FLASH to
monitor SI changes at the present of IC effect for in vitro gel phantom and in
vivo rat experiments. Upon transmitting FUS pulses on MBs, FRE effect can be
attributed to the effect of fresh spins flowing into imaging slice and produced
increased SI. After that, IC effect induced disturbing flow and reduced SI as
well as increased SD were exhibited to reflect the effect of intravoxel
dephasing and chaotic flowing effect [4]. In Fig. 2, larger PRF led to shorter
duration of SI drop, illustrating the fast disruption of MBs while transmitting
FUS with higher PRF. Moreover, higher duty cycle resulted in more distinct SI
changes and higher SD, suggesting the more chaotic flowing effect. For in vivo
experiment, we observed two reduced SI peaks with an interval approximately equaled
to the period of systemic circulation in rats of 20 s, presenting the
recirculation of MBs and the two IC events. In conclusion, FLASH has been
proved to be a useful technique for real-time monitoring of IC when
transmitting FUS pulses to MBs for in vitro and in vivo experiments.
Acknowledgements
No acknowledgement found.References
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[3] Fan
C.H., et al. Ultrasound in Med. & Biol. 2012:38:1372-1382.
[4] Chen W.S., et al.
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