2. THESIS GOAL
‘’ To perform a feasibility study on contrast agent
loaded polymeric microbubbles and their future role in
photoacoustic imaging of tissues.’’
7. 1. The synthesis of contrast agent loaded microbubbles
USPIO (ultrasmall paramagnetic iron oxide particles)
Rhodamine-B
Aurovist (commercially available gold nanospheres)
peg-GNR-GNS (pegylated gold nanorods + gold nanospheres)
2. Comparing photoacoustic images pre and post microbubble
destruction
What is the ‘’best’’ contrast agent?
3. Repeat step 2 with ‘’best’’ contrast agent in a tomography set-up.
The feasibility test
7
EXPERIMENTAL PROCEDURE
17. 17
USPIO LOADED MBS
US treatment appears to have a positive effect on
PA signal contribution. Possibly due to 1)
increased absorbed optical energy and 2) more
PA signals being able to reach the detector.
19. 19
AUROVIST LOADED MBS
The PA images contradict the results from the
spectrophotometer, indicating the presence of
Aurovist in the MB shell.
20. 20
PEGYLATED GOLD NANORODS AND GOLD
NANOSPHERES
PA images are similai to those of empty MBs.
Results indicate that the payload was
insufficient to generate a detectable PA signal.
21. 21
PEGYLATED GOLD NANORODS AND GOLD
NANOSPHERES
The polymer is not generating detectable PA
signals at a wavelength of 780nm.
24. Contribution in PA signal after US treatment mainly attributed to:
1. Radiation forces causing a local re-distribution of the medium
2. Released microbubble payload
3. Local changes in the grunheisen parameter
4. Increased absorbance of optical energy
5. Less attentuation of PA signals generated deeper down the bead
because of MB destruction.
USPIO loaded MBs gave the ‘’best’’ PA signal pre and post US
treatment. Furthermore, USPIO has been FDA approved.
24
CONCLUSIONS
31. 31
GENERAL CONCLUSIONS AND RECOMMENDATIONS
• We were able to demonstrate an increase in the recorded PA signal
after treating contrast agent loaded MBs with destructive US pulses.
• The increase in PA signal after US treatment was mainly attributed
to 1) radiation forces causing a local re-distribution of the medium 2)
released MB payload 3) local changes in the Gruneisen parameter
and 4) increased absorbance of optical energy. 5) Less attentuation
of PA signals generated deeper down the bead.
• In general, PA imaging based on the ultrasound triggered release of
contrast agents is a viable modality, but there is room for
improvements.
• Finally, we showed that it is possible to locally release the MB
payload.
a photoacoustic image is related to the optical absorption in the tissue, as the incident photons must be absorbed to have any effect. Therefore,
a photoacoustic image IS an estimate of the destribution of acoustic pressure that arises following the absorption of a pulse of light.
Source of contrast in a photoacoustic image is related to the optical absorption in the tissue.
The image itself is an estimate of the distribution of acoustic pressure that arises following the absorption of a pulse of light.
We use the transducer to investigate how the sample interacts with transmitted ultrasound. Helps to determine whether microbubbles have been destroyed or not.
Regions at 6MHz, 9MHz, might be caused by MB explosions / eigenfrequency of microbubbles.
Acoustic Backscatter
Radiation Forces
Less attenuation of PA signals. More signals are able to reach the dectector.
Redistribution of the medium.
Less attenuation of PA signals. More singals able to reach the detector
Radiation forces on USPIO particles cause accumulation near interface layer
Radiation forces cause signal shift to bottom of the bead
Radiation forces and accumulation of Aurovist results in increased concentration of gold which gives detectable PA signals.
======NOT EVERYTHING IS KNOWN =======
=======IMPROVEMENT IMAGE MODALITY======
These improvements include, MB
payload optimisation, striving for MB monodispersity and lower MB rupture onsets.
========QUANTIFICATION=====
The quantification of the released MB payload could possibly be done by employing the principle of acousto-optics
======USE IN THERAPEUTICS!!!======
