Photodynamic therapy (PDT) for skin cancer is sometimes only partially effective, due to inadequate levels of the
fluorescent drug (photosensitizer, PS) and due to heterogeneous distribution of PS within the tissue. To image the PS
distribution within skin tumors, we have developed a fluorescence tomography system (FTS) that combines a
fluorescence detection array with a high frequency ultrasound (HFUS) transducer. In this paper we describe in vitro and
in vivo validation of this new system. The target fluorophore for detection was Protoporphyrin IX (PPIX). Validation
experiments were performed in vivo using a subcutaneous tumor model in which A431 tumor-bearing mice were treated
with 5-aminolevulinic acid to induce production of PPIX. FTS reconstructions were compared with standard histology
and with data from bulk tumor slices imaged ex vivo on a fluorescence scanner. Reconstructed images obtained from the
FTS were correlated with the histology and the ex vivo scans, confirming several-fold increases in PPIX fluorescence in
the skin and in the tumor relative to the surrounding tissues. Our data demonstrate the feasibility of using the FTS for
subsurface imaging of PPIX in skin carcinoma in vivo. Future aims are to use this device for individualized treatment
planning, in order to improve overall patient responses to PDT.
A high frequency ultrasound-coupled fluorescence tomography system, primarily designed for imaging of protoporphyrin IX production in skin tumors in vivo, is demonstrated for the first time. The design couples fiber-based spectral sampling of the protoporphyrin IX fluorescence emission with high frequency ultrasound imaging, allowing thin-layer fluorescence intensities to be quantified. The system measurements are obtained by serial illumination of four linear source locations, with parallel detection at each of five interspersed detection locations, providing 20 overlapping measures of subsurface fluorescence from both superficial and deep locations in the ultrasound field. Tissue layers are defined from the segmented ultrasound images and diffusion theory used to estimate the fluorescence in these layers. The system calibration is presented with simulation and phantom validation of the system in multilayer regions. Pilot in-vivo data are also presented, showing recovery of subcutaneous tumor tissue values of protoporphyrin IX in a subcutaneous U251 tumor, which has less fluorescence than the skin.
A system is presented which has been developed for dermatological applications with the need to quantify levels of protoporphyrin IX in diagnosis or therapy. The design was to couple fluorescence sampling onto a high frequency ultrasound system and take multiple optical source-detector samples of the tissue of the fluorescence and transmission signals. The intensity values can then be used to estimate and image the PpIX levels present in tissue samples. The system design, calibration, and initial testing in tissue phantoms are demonstrated here. The component design has been modular and allows easy implementation as a kit which can be assembled from basic components. The control software is more elaborate and provides a seamless way to go from system start up through to fluorescence quantification of PpIX concentrations.
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