Photoacoustic imaging (PAI) has highly desirable features but has struggled with clinical translation. Photothermal therapy (PTT) is a new minimally invasive treatment that facilitates thermal tumor destruction using NIR lasers and thin optical fibers placed into the tumor. Here we show that bulk tissue temperature imaging for PTT guidance is achievable at centimeters of depth when a task-specific instrument is designed and built. Furthermore, we highlight a PTT guidance platform prototype including PAI thermometry and MRI-compatible diffuse optical treatment response probe, which when combined with tumor localizing nanoparticles (Porphysomes) provide the 3 main features required for clinical translation of PTT, i.e., tumor localization, tissue temperature, and treatment response. Visualization of pure temperature contrast in tissue mimicking coagulating phantoms and ex-vivo tissues is shown, as well as clinical in-patient optical monitoring of PTT for prostate cancer.
We present ongoing work to develop and verify a measurement technology using diffuse reflectance spectroscopy and fluorescence spectroscopy to measure in-vivo concentrations of intact and dissociated porphysomes. Porphysomes (PS) are multifunctional liposome-like nanoparticles composed of porphyrin-lipid subunits that exhibit structure-dependent optical quenching. They are attractive as agents for photothermal and photodynamic therapy but methods are required for measuring their concentration in the intact and dissociated states for treatment dosimetry and guidance. Diffuse reflectance spectroscopy is used here to measure concentrations of intact and dissociated (unquenched) PS using their unique absorption spectra, and also to correct the fluorescence signal for the optical properties of the tissue. The latter is then used to quantify the fluorescence (QF) signal from dissociated PS, providing a more direct measure of photodynamic activity. Two experiments were performed for proof-of-concept. First, a liquid phantom was used to verify measurements taken with a combined reflectance-fluorescence probe. This demonstrated that the reflectance signal was sensitive to the relative proportion of intact and dissociated PS and that the QF signal contained information about the PS unquenching. Second, a mouse model was used to demonstrate that the drop in the reflectance signal at the PS absorption peak wavelength and the fluorescence signal are consistent with Positron Emission Tomography (PET) measurements of copper-64 labeled PS.
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