Zhe-Wei Wu1, Wu Chen-Hua2, Hsu Po-Hong3, Hao-Li Liu3, Yeh Chic-Kuang2, and Peng Hsu-Hsia2
1Biomedical Engineering and Environmental Sciences, Nation Tsing Hua University, Hsinchu, Taiwan, 2Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan, 3Electrical Engineering, Chang-Gung University, Taoyuan, Taiwan
Synopsis
The
aim of this study was to real-time assess flow velocity changes in the
neighboring pixels of acoustic radiation force (ARF) aggregated bubbles by
using phase-contrast MRI (PC-MRI). The flow velocity increased with the
increase of microbubbles (MBs) concentrations, which might be attributed to the
increase of aggregated bubbles size, narrowing the chamber diameter and thus
presenting higher flow velocity. In conclusion, we verified the feasibility of
using PC-MRI to assess flow velocity changes on pixels near ARF aggregated
bubbles. In the future, a systematic investigation shall be conducted to
comprehend the association between bubble size and the flow velocity. Introduction
The acoustic
radiation force (ARF) induced by microbubbles (MBs) with focused ultrasound
(FUS) was well-known as a scheme of localizing drug delivery by primary
radiation force and secondary radiation force, which can respectively propel
MBs to the side of tubes or vessels and aggregate MBs to form a large-size bubble
[1,2]. At the present of secondary ARF, the larger-size bubbles on one side of
the tube or vessel can be seen as a barrier of flow and thereby may be able to change
the local flow velocity. A previous study reported the influence of MBs
concentrations and acoustic pressure on the aggregated bubble size [3]. In this
study, we aim to adopt phase-contrast MRI (PC-MRI) to real-time evaluate the
changes of flow velocity nearby bubbles formed by secondary ARF. In the
preliminary tests, we performed experiments with different MBs concentrations
to clarify its influence on the measured velocity.
Method
All
images were acquired with PC-MRI (TR/TE= 26.9/8.42 ms, pixel size= 0.313 x 0.313
x 1 mm3, pixel bandwidth= 260 Hz/pixel, flip angle= 10,
Venc = 6 cm/s, temporal resolution = 2.2 s) in a 7 Tesla scanner (Biospec 47/40, Bruker, Ettlingen, Germany).
The experimental setup was shown in
Fig. 1. MBs were diluted to the concentration of 0.001X and 0.01X. The
solutions of MBs (lipid shell with C3F8, mean diameter=1.25
µm (Number %) were injected with a velocity of 2 cm/s into a gel phantom with
chamber diameter=6 mm. The FUS pulses were transmitted from a single-element
probe (central frequency 1.014276 MHz, 2.5 cm diameter, 2.0 cm curvature, RK300,
FUS Instruments, Toronto, Canada). Continuous FUS pulses were transmitted to
MBs solutions with acoustic pressure of 100 kPa. The imaging slices were prescribed parallel to
the chamber of phantom. We acquired 40 measurements (Pre-FUS=1-9, ARF=10-30,
Post=31-40). We analyzed the flow velocity with a self-developed program
written in Matlab. To calculate the velocity changes, we determined the region
of interest at the side of near field, as shown in Fig. 1. The pixel velocity
of forty measurements during the statuses of Pre-FUS, ARF, and Post-FUS (21
pixel/measurement) were put together in a histogram to observe the distribution
of velocity within ROI.
Result
Figure 1 displayed the
magnitude images and phase images of experiments with MBs concentrations of
0.01X and 0.001X. In the zoom-in plot of ARF in Fig. 1a, the hypointensive
region, indicated by arrow, could be attributed to the formation of aggregated
bubble. Figure 2a and 2b illustrated the time courses of velocity within the
ROIs. The light blue cycles emphasized the velocity changes upon turning-on and
turning-off FUS pulses. With 0.01X MBs, the
mean velocity increased from 0.45±0.05 cm/s to 0.65±0.05 cm/s. As ceasing FUS
pulses, the mean velocity fell back to 0.45±0.05 cm/s. While lowering the
MBs concentration to 0.001X, we observed relatively minor increased mean velocity
of 0.57±0.05cm/s.
Figures 2c and 2d presented the velocity distribution within ROI. Either with
0.01X or 0.001X MBs, the histograms tended to shift to right in ARF status,
indicating the increase of pixel velocity.
Discussion and Conclusion
In this study, we used PC-MRI to real-time evaluate the flow velocity changes
surrounding bubbles aggregated by secondary ARF. The increased flow velocity
values were observable in both MBs concentrations during transmitting FUS
pulses. The right-shifting velocity distributions in histograms further
verified the increase of velocity (Fig. 2). The higher the MBs concentration,
the more significant velocity changes could be observed. Masuda et al
previously reported that the size of MBs aggregations by ARF was related to acoustic
pressure, MBs concentration, and pulse duration time. Therefore, the more
substantial velocity changes in 0.01X MBs might be attributed to the increase
of aggregated bubbles size, narrowing the chamber diameter and thus presenting
higher flow velocity. In conclusion, we verified the feasibility of using PC-MRI
to real-time assess the flow velocity changes on pixels near ARF aggregated
bubbles. In the future, a systematic investigation of various MBs and FUS
conditions shall be conducted to comprehend the association between the
aggregated bubble size and the measured flow velocity changes.
Acknowledgements
No acknowledgement found.References
[1]Paul A. Dayton et al, “A Preliminary Evaluation Of
The Effects Of Primary And Secondary Radiation Forces On Acoustic Contrast
Agents”, IEEE, 1997
[2] Paul Dayton
et al,” Acoustic Radiation Force In Vivo: A Mechanism To Assist Targeting Of
Microbubbles”, ELSEVIER, 1999
[3] Kohji Masuda et al, “Observation Of Flow
Variation In Capillaries Of Artificial Blood Vessel By Producing Microbubble
Aggregations”, IEEE, 2012