Faculty of Science and Technology
Biomedical Photonic Imaging
P.O. Box 217
7500 AE Enschede
Telephone: +31 53 489 3112
Fax: +31 53 489 1105
Investigations on contrast agents for photoacoustic imaging.
- Design, and characterize the contrast agents (gold nanoparticles) for photoacoustic imaging.
- Study the possible non-linear phenomena which may occur when the nanoparticles are irradiated with pulsed laser light.
- Study in vitro and in vivo efficiency of these contrast agents.
- Investigate the possibility of using these contrast agents (gold nanorods) to kill cancerous cells: direct (hyperthermia) or indirect (local drug delivery).
Survival rates for cancer are improved when the disease is detected at an early stage. Molecular changes are expressed early during cancer progression. To detect these changes at the molecular level, very sensitive detection techniques are needed. To help detection, contrast agents are often used. These are substances which have specificity to some molecular signatures of cancer. By direct detection of these contrast agents, the indirect detection of the target molecules is realized. Photoacoustic imaging is a new, noninvasive imaging technique which combines the advantageous of light and ultrasound to deliver images of tissue with high resolution. In photoacoustic imaging, a pulsed laser is used to irradiate an optical absorbing structure. This structure undergoes thermal expansion and emits an ultrasound wave with the amplitude and frequency depending on the properties of this object. By detecting this ultrasound wave with an appropriate ultrasound detector, it is possible to reconstruct spatially the position and the geometry of the absorbing structure inside the tissue. Cancers have endogenous contrast for this technique due to their high angiogenesis driven absorption. However this contrast may not be sufficient and may be manifested at late stages. Gold nanoparticles and in particular gold nanorods due to their tunable optical absorption properties and biocompatibility fulfill the requirements to be used as contrast agents in photoacoustic imaging. Gold nanorods with a specific size and aspect ratio absorb light very strongly. By conjugating gold nanorods with proteins with highly specificity for a cancerous cell it is possible to accumulate a these nanoparticles at a tumor site increasing the amplitude of the photoaocustic signal generated by them.
Another advantage of these nanoparticles is that they can be used to kill cells. During laser irradiation process, the temperature of these nanoparticles can be high enough to induce apoptosis in surrounding cells. Furthermore, if the laser has a proper pulse duration and energy, a thin layer of tissue, mainly water can be vaporized leading to a bubble which can also destroy locally the surrounding tissue trough the cavitation effect.
This research is focused on finding answers to questions like: what is the optimum shape and size of these gold nanoparticles to be used as contrast agents in photoacoustic imaging?, how large is the photoacoustic signal generated by them?, what is happening with these particles under the influence of continuous and pulsed light?, what other substances can be used as contrast agents for photoacoustic imaging?.
Figure left: Shape and extinction spectra for with gold nanorods.
Figure right: Photoacoustic image of a capillary filed the gold nanorods.