Cheng-Tao Ho1, Chen-Hua Wu1, Shih-Tsung Kang1, Chih-Kuang Yeh1, Wen-Shiang Chen2, Hau-Li Liu3, and Hsu-Hsia Peng1
1Biomedical Engineering and Environmental Science, National Tsing Hua University, Hsinchu, Taiwan, 2Physical Medicine and Rehabilitation, National Taiwan University Hospital, Taipei, Taiwan, 3Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan
Synopsis
Gas-filled microbubbles (MBs) can be locally
cavitated by spatially focused ultrasound (FUS) to trigger stable cavitation
(SC) and inertial cavitation (IC) to induce blood–brain barrier (BBB) opening ; therefore, magnetic resonance imaging (MRI) may provide useful imaging
information to real-time monitor the process of FUS cavitation on MBs. In this study,
a HASTE (Half Fourier Acquisition Single Shot Turbo Spin Echo) sequence was
used to observe the signal changes during SC for in vitro experiments.
Experiments with different acoustic pressure, pulse repetitive frequency, and
duty cycle were performed to clarify the SC effect on MR images.Introduction
Gas-filled microbubbles (MBs) can be locally
cavitated by focused ultrasound (FUS) to trigger stable cavitation (SC) and
inertial cavitation (IC) to induce blood–brain barrier (BBB) opening [1,2]. Because
of the hemolysis caused by IC [3], SC is a more preferable effect to be
conducted to BBB opening. However, to real-time observe the SC effect by MRI is
not discussed thoroughly. In this study, we aim to real-time monitor the signal
changes of MBs at the present of SC effect in an in vitro agarose phantom by half-Fourier
acquisition single-shot turbo spin-echo (HASTE) sequence.
Methods
While SC effect occurred, the vibration of MBs
may lead to flowing effect and MR signals are unable to be refocused in HASTE images.
We assumed reduced MR signals may reflect the degree of induced flowing effect.
The diluted MBs solutions
(lipid shell with C3F8, mean diameters=1.25 µm,
concentration = (4.36±0.32)×1010 droplets/mL) [4] were injected into an agarose
phantom with two hollow chambers (diameter = 6 mm).The MBs were diluted to
0.001X. A homemade single-element focused piezoelectric transducer was used as
the source of FUS sonication. FUS pulses with different acoustic pressure
(0.1, 0.2, 0.3 MPa), pulse repetitive frequency (PRF = 1, 10 Hz), and duty
cycle (1%, 10%) were applied to observe the SC effect on MR signal changes during
FUS transmission. All experiments were conducted in a 3 Tesla MR scanner (Tim Trio,
Siemens, Erlangen, Germany). The HASTE sequence (TR/TE= 1270/49 ms, pixel size=
0.78x0.78x3 mm3, pixel bandwidth= 454 Hz/pixel, temporal resolution=1.27
s, and 126 measurements (160 s)) was performed. All images were acquired at the
focal plane and were perpendicular to the direction of ultrasound beams. To
evaluate changes of signal intensity (SI), a region-of-interesting (ROI) was
selected manually with a self-developed program at chamber of MBs (Fig. 1). The SI within ROI was
normalized to mean SI before turning-on of FUS pulses (pre-FUS): normalized SI
= (SI/SI_(pre-FUS))x100%.
Results
Figure
2a displayed typical time courses of normalized SI with PRF=1Hz and duty
cycle=1% for different acoustic pressures. Specific statuses during the time
courses were marked as: (I) Pre-FUS, (II) signal changes with fluctuation, and
(III) Post-FUS. At Pre- and Post-FUS, normalized SI is approximate 100%. During
FUS transmitting, the normalized SI changed from 100% to 99.3%, 94.4%, and 88.6%
for 0.1, 0.2, and 0.3 MPa FUS pulses, respectively, indicating SI changes increased
with increase of acoustic pressure. Figures 2b-2d compared SI changes with
various PRF and duty cycle under identical acoustic pressure. With acoustic
pressure of 0.1 or 0.2 MPa, PRF= 1 or 10 Hz showed similar time courses whereas
SI changes was higher n 1 Hz than 10 Hz if
pressure increased to 0.3 MPa. If the PRF fixed as 1 Hz, duty cycle=10%
demonstrated larger SI changes than duty cycle=1%. Table 1 summarizes SI
changes of all experiments.
Figure 3 showed SI changes of experiments with PRF=1Hz and duty cycle=1%
under acoustic pressure of 0.2, 0.3, 0.4, 0.8 MPa. The slope of SI increased
with acoustic pressure during FUS transmission, exploring that higher acoustic
pressure led to faster disruption of MBs 0.8MPa FUS pulses, the IC effect could
occur, leading to MBs diminished completely and thus the normalized SI recovered
to 100% before the end of FUS transmission.
Discussion& Conclusion
In this study, HASTE sequence was performed to
monitor the SI changes at the present of MBs SC effect. We investigated the SI
changes of experiments with various conditions of acoustic pressure, PRF, and
duty cycle. Upon the transmission of FUS pulses, the normalized SI dropped
suddenly and fluctuated till the end of transmission (Fig. 2). Under fixed acoustic
pressure and PRF, the longer duty cycle allowed more time to accumulate the
energy from FUS pulse and therefore resulted in more substantial flowing
effect, accompanying with more SI changes. Regarding to higher PRF, it could be
seen as separate the transmission into several sections, leading to less energy
accumulation and thus less SI changes, particular in higher acoustic pressure
of 0.3 MPa in Fig. 2d. In conclusion, we used HASTE sequence to real-time
monitor SI changes at the present of SC effect of MBs. Further studies shall be conducted to clarify the SC
effect on SI changes to optimize MR scanning parameters and to comprehend the
influence of various MB concentrations and FUS conditions in the future.
Acknowledgements
No acknowledgement found.References
[1]Pouliopoulos
AN, et al. Physics in medicine and biology. 2014;59(22):6941.[2]Liu
H-L, et al. Theranostics. 2014;4(4):432.
[3]Chen
W-S, et al. Ultrasound in medicine & biology. 2003;29(5):739-48.
[4]Fan C.H., et al.
Ultrasound in Med. & Biol. 2012:38:1372-1382.