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.
Minimally-invasive alternatives for prostate cancer treatment are an unmet clinical need. We are currently conducting clinical trials using interstitial photothermal therapy (PTT) in focal (intermediate-risk) prostate cancer, targeting the largest (index) lesion, utilizing near-infrared (NIR) laser light that is delivered via one or more laser fibers placed interstitially to cover the target volume. This procedure is done using an interventional MRI suite where real-time MR thermometry is used to monitor treatment progression as a surrogate for tissue coagulation. We investigate here if photoacoustic imaging (PAI) could be used instead of MR thermometry to provide direct and higher specificity/sensitivity monitoring of the coagulation-front, particularly for the purpose of avoiding rectal wall damage. For this, we developed an in vivo canine PTT model and experiments were performed in 6 beagles with intact normal prostates, using similar approaches to those used in ongoing clinical trials. PTT also performed in vivo as well as in ex vivo porcine muscle. Initial results demonstrated the feasibility of both the PTT technique as well as an optimized monitoring platform. In ex vivo porcine muscle PAI demonstrated correlation with temperature (R2 = 0.66) that provided the impetus to move in vivo. However, due to noise and the relatively small changes in the PAI signal with coagulation this did not provide as much imaging depth or resolution as MR thermometry, the current gold standard. With newer PAI probes and deployment of the PAI light sources, it may be possible to increase the sensitivity of PAI for in vivo treatment monitoring. This work was supported by the Terry Fox Research Institute (Grant #1075).
We have developed an automated, wide-field optical coherence tomography (OCT)-based imaging device (OTISTM Perimeter Medical Imaging) for peri-operative, ex-vivo tissue imaging. This device features automated image acquisition, enabling rapid capture of high-resolution (15 μm) OCT images from samples up to 10 cm in diameter. We report on the iterative progression of device development from phantom and pre-clinical (tumor xenograft) models through to initial clinical results. We discuss the challenges associated with proving a novel imaging technology against the clinical “gold standard” of conventional post-operative pathology.
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