Funding by the Research Excellence Program (REP) of the UConn VP of Research, our group in collaboration with the group of Quing Zhu (UConn, Electrical and Computer Engineering), received seed funding: ‘Near-IR Absorbing and Emitting Porphyrinoids as Fluorescence and Photoacoustic Tissue Imaging Dyes’ (PI C. Brueckner; co-PI Quing Zhu, $50,000, 2015-2016).
Non-invasive high-resolution imaging of tissue has become increasingly important in biomedical diagnosis. Optical methods using near-infrared (NIR) wavelengths are particularly appealing since only NIR light penetrates tissue deeply – the NIR wavelengths between ~700 and 900 nm define the so-called spectroscopic window of tissue. Furthermore, low-energy NIR light is non-damaging to tissue, even under extended illumination, thus enabling longitudinal studies. Two specific emerging biomedical imaging technologies utilizing NIR-absorbing dyes are photoacoustic imaging (PAI) and fluorescence diffuse optical tomography (FDOT):
In PAI, the absorption of a light pulse by some dyes causes a photoacoustic effect. In essence, the absorption of light can be heard (in the ultrasonic regime). As a pulsed NIR beam is scanned through the tissue, the emitted ultrasonic wave profile is acquired and the data are used to construct 2D or 3D optical absorption maps. PAI combines the advantages of high optical contrast and ultrasound (sub-mm) spatial resolution.
FDOT provides depth-resolved spatial distributions of fluorescence in tissues with very high sensitivity. The fluorescence is captured by a detector array and used to construct 2D optical fluorescence maps.
The biggest challenge for clinical applications of both techniques for the imaging of deeply-seated tumors (or other lesions or organs) with high sensitivity is the development of contrast agents/tracers that absorb NIR light and that exhibit a photoacoustic effect or emit in the NIR. In general, few dyes absorb in the NIR regime, and even fewer are have strong photoacoustic or fluorescence responses.
We propose to:
- Screen a wider range of near-IR-absorbing dyes (commercial dyes as well as dyes prepared in our labs) under the highly controlled conditions of the tissue phantom experiment to begin to map structure-photophysical properties-PAI function relationships, something we are not aware of has been accomplished for any class of PAI dyes, but that is very important for the directed development of optimized PAI contrast agents.
- The dyes prepared to date are only soluble in organic solvents and are thus unsuitable for use in ex vivo tissue samples or mice. Hence, water-soluble derivatives of the known chromophores will be prepared.
Depending on the photophysical characteristics of the dyes, the water-soluble dyes will be used in in vivo PAI or FDOT imaging experiments using mouse models.