Worldwide R&D

Ultrasound DDS using Microcapsules and Visualizationof Oxygen Saturation Levels in Microcirculations
Kohji Masuda, Norihiko Tateishi, Eizen Kimura, and Ken Ishihara
Department of Medical Informatics, Ehime University Hospital

1. Ultrasound DDS Using Microcapsules
The surfaces of microcapsules collapse when exposed toultrasound at their resonance frequency. Research on aphysical drug delivery system (DDS)1) is being conductedusing this effect on microcapsules filled with drugs, whereinultrasound is radiated from the surface of the body toadminister drugs selectively to an affected organ. This
technique is advantageous in that capsules can be broken
while simultaneously monitoring the organ and capsule
distribution in ultrasonic tomographic images.
We are using F-04E microcapsules manufactured by
Matsumoto Yushi-Seiyaku. The microcapsules have an
average particle size of 4 microns and can easily bedisintegrated by an acoustic pressure of several 10 kPa.
Microcapsules were fixed in a thin rubber balloon together
with a deaerated medium of high viscosity to serve as ahighly concentrated virtual organ. The organ is about 30 mm
in diameter with a high concentration and about a 1/106
weight ratio. Fig. 1 is a tomographic image showing
observations of the virtual organ by a sector scanning probewith a center frequency of 2.5 MHz that were taken while
exposing the organ to a pulse Doppler beam to break thecapsules.2) The Doppler beam is irradiated in the direction
indicated by the arrow in the diagram. The brightness of thebeam decreases along its trajectory, indicating that capsulesin that region are broken. Fig. 2 shows the echographic
diagnosis robot3)4) to control ultrasound probe on a bodysurface to radiate ultrasound accurately from the surface.

Fig. 2 The echographic diagnosis robot on the bodysurface to observe the organ and radiate ultrasoundimages obtained, the amount of hemoglobins in the red blood
cells and a two-dimensional image of oxygen saturation wassuccessfully generated.5)
Fig. 3 is a two-dimensional image showing the oxygen
saturation level of microvessels in rabbit mesentery. Fromthese two-dimensional images, we can see that the image on
the right has a lower oxygen level than the one with nearoxygen saturation on the left.6) The Fahraeus effect indicatinga drop in hemoglobins was observed in two-dimensional
images, confirming the effectiveness of the system.
Oxygen saturation
100（％）

20µm

500Fig. 3 2D images showing oxygen saturation in microvessels ofrabbit mesentery (left: saturated state, right: low oxygen state)

3. References
1) K. Ishihara, et al., Proc. of IEEE Micro Elec. Mech.
Sys.(MEMS), pp.176-181(1991)
2) K. Masuda, et al., Proc. of the 39th Conference for the Japan
Society for Medical and Biological Engineering, p.282 (2000)
3) K. Masuda, et al., Proc. of IEEE Eng. In Med. & Biol.
Soc.(EMBS), in press (2001)
4) K. Masuda, et al., Proc. of IEEE Intel. Robot and Sys.
(IROS), in press (2001)
5) N. Tateishi, et al., Microcirculation, Vol.4, pp.403-412 (1997)
6) N. Tateishi, et al., Proc. of the 20th Joint Conference on
Medical Informatics, pp. 556-557 (2000)

Fig. 1 Using ultrasound beams to break microcapsules ina virtual organ (circular shape)

2. Two-Dimensional Visualization of Oxygen
Saturation in Red Blood Corpuscles
Although it is important to elucidate the oxygen supply
state of the tissue, until now it has been difficult to visualize
actual gas exchange (oxygen movement) in blood vessels ofseveral microns. We used six interference filters of differing
wavelengths to elucidate the dynamic state oxygen supply.
Based on the multiple regression of the six microscopic

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