This study investigated whether diffuse optical spectroscopy (DOS) measurements could assess clinical response to photodynamic therapy (PDT) in patients with head and neck squamous cell carcinoma (HNSCC). In addition, the correlation between parameters measured with DOS and the crosslinking of signal transducer and activator of transcription 3 (STAT3), a molecular marker for PDT-induced photoreaction, was investigated. Thirteen patients with early stage HNSCC received the photosensitizer 2-[1-hexyloxyethyl]-2-devinylpyropheophorbide-a (HPPH) and DOS measurements were performed before and after PDT in the operating room (OR). In addition, biopsies were acquired after PDT to assess the STAT3 crosslinking. Parameters measured with DOS, including blood volume fraction, blood oxygen saturation (StO2), HPPH concentration (cHPPH), HPPH fluorescence, and blood flow index (BFI), were compared to the pathologic response and the STAT3 crosslinking. The best individual predictor of pathological response was a change in cHPPH (sensitivity=60%, specificity=100%), while discrimination analysis using a two-parameter classifier (change in cHPPH and change in StO2) classified pathological response with 100% sensitivity and 100% specificity. BFI showed the best correlation with the crosslinking of STAT3. These results indicate that DOS-derived parameters can assess the clinical response in the OR, allowing for earlier reintervention if needed.
Photodynamic Therapy (PDT) has proven to be an effective treatment option for nonmelanoma skin cancers. The ability
to quantify the concentration of drug in the treated area is crucial for effective treatment planning as well as predicting
outcomes. We utilized spatial frequency domain imaging for quantifying the accurate concentration of protoporphyrin IX
(PpIX) in phantoms and in vivo. We correct fluorescence against the effects of native tissue absorption and scattering
parameters. First we quantified the absorption and scattering of the tissue non-invasively. Then, we corrected raw
fluorescence signal by compensating for optical properties to get the absolute drug concentration. After phantom
experiments, we used basal cell carcinoma (BCC) model in Gli mice to determine optical properties and drug
concentration in vivo at pre-PDT.
Diffuse reflectance spectroscopy (DRS) is a common technique for assessing tissue optical parameters (absorption,
scattering) non-invasively. However, choosing the correct model for light-tissue interaction is needed for accurate
quantification. The diffusion approximation is only valid for certain ranges of tissue optical properties and specific probe
geometries. For improved quantification with DRS over a wide range of optical properties and for a short source detector
separation, a probe-specific light transport model can provide more accurate analysis of optical parameters. We
developed and tested a probe-specific empirical model by using tissue simulating phantoms with promising results. We
will apply it for the analysis of patients from a clinical trial for head and neck cancer.
PDT has become a treatment of choice especially for the cases with multiple sites and large areas. However, the efficacy
of PDT is limited for thicker and deeper tumors. Depth and size information as well as vascularity can provide useful
information to clinicians for planning and evaluating PDT. High-resolution ultrasound and photoacoustic imaging can
provide information regarding skin structure and vascularity. We utilized combined ultrasound-photoacoustic
microscopy for imaging a basal cell carcinoma (BCC) tumor pre-PDT and the results indicate that combined ultrasound-photoacoustic
imaging can be useful tool for PDT planning by providing both structural and functional contrasts.
Photodynamic therapy (PDT) has recently emerged as a potential treatment alternative for head and neck cancer. There is
strong evidence that imprecise PDT dosimetry results in variations in clinical responses. Quantitative tools are likely to
play an essential role in bringing PDT to a full realization of its potential benefits. They can provide standardization of
site-specific individualized protocols that are used to monitor both light and photosensitizer (HPPH) dose, as well as the
tissue response for individual patients. To accomplish this, we used a custom instrument and a hand-held probe that
allowed quantification of blood flow, blood volume, blood oxygen saturation and drug concentration.
We report the tomographic imaging of a photodynamic therapy (PDT) photosensitizer, 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in vivo with time-domain fluorescence diffuse optical tomography (TD-FDOT). Simultaneous reconstruction of fluorescence yield and lifetime of HPPH was performed before and after PDT. The methodology was validated in phantom experiments, and depth-resolved in vivo imaging was achieved through simultaneous three-dimensional (3-D) mappings of fluorescence yield and lifetime contrasts. The tomographic images of a human head-and-neck xenograft in a mouse confirmed the preferential uptake and retention of HPPH by the tumor 24-h post-injection. HPPH-mediated PDT induced significant changes in fluorescence yield and lifetime. This pilot study demonstrates that TD-FDOT may be a good imaging modality for assessing photosensitizer distributions in deep tissue during PDT monitoring.
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