Ask an Expert: What do I do when the Photoacoustic imaging signal from my gold nanoparticles is too weak?
To troubleshoot low photoacoustic signal strength, let us take a closer look at the science behind the modality. In photoacoustic (optoacoustic) imaging, the received signal from a single point in the imaging plane can be described as:
The Grüneisen parameter is tissue-dependent and has little variation in water-based tissues at constant temperature, so as such it is often assumed to be constant.
Amount of light delivered & net optical absorption
If we assume that the photoacoustic system (transducer, receive electronics, laser, etc.) is operating correctly, then the amount of light delivered and the net optical absorption must be increased to get a stronger photoacoustic signal.
First, an appropriate laser wavelength should be selected that is within the near-infrared optical window of tissue (650 – 1350 nm). In this window the absorption by biological tissues is at a minimum, allowing more light to reach the nanoparticles. Second, select a nanoparticle with a maximum absorption wavelength that closely matches your source laser wavelength.
Nanoparticle-related factors
In addition to wavelength, the photoacoustic signal is dependent on the nanoparticle concentration within an imaging voxel. Other factors include:
- Monodispersity (low variation in nanoparticle size and shape) is also another important factor, because fewer monodisperse nanoparticles are required to produce the same photoacoustic signal as polydisperse nanoparticles.
- Silica coating: Modifying the surface of nanoparticles with a silica‑coating has been shown to increase the photoacoustic signal by as much as 3x, compared to nanoparticles without silica coatings. Silica-coating also increases the thermal stability of the nanorods, allowing the nanorods to withstand higher laser fluences and more laser pulses, resulting is higher photoacoustic contrast.
- More nanoparticles: The photoacoustic signal is dependent on the total number absorbers in the imaging voxel; simply, more absorbers equals more signal. A larger injection volume or nanoparticle concentration can lead to increased nanoparticle accumulation in the tissue of interest.
- Targeting: If using a systemic injection, PEGylation can increase blood circulation time to improve accumulation at tumor sites. Targeting via antibody conjugation can also provide increased accumulation at desired sites and increase specificity, allowing for molecular imaging to be performed.
Troubleshooting tips: What to do when the signal strength is low
- Make sure your rods are highly monodisperse and absorb at the appropriate wavelength of excitation. Verify with UV-Vis spectroscopy.
- Check if you are working in an optimized optical window where absorption from oxyhemoglobin and deoxyhemoglobin is minimal.
- Perform injections into tissue-mimicking phantoms to test signal at varying concentrations and depths.
- Improve circulation time and biodistribution by using PEGylated nanorods or conjugated nanoparticles.
- Use silica coated nanorods to maintain thermal stability at high fluences (Y-S chen et al, Enhanced thermal stability of silica-coated gold nanorods for photoacoustic imaging and image-guided therapy)
- Increase concentration of injection.
- Verify targeting strategy with other methods. E.g. By using gold nanoparticles conjugated with fluorescent secondary antibody.
Need additional help with troubleshooting?
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