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(in collaboration with the HIV/AIDS Malignancy Branch, NCI, NIH)
Kaposi's sarcoma (KS) is a common AIDS-related vascular tumor. Angiogenesis can play an important role in the development and progression of KS. No non-invasive standard technique is available for qualitatively or quantitatively evaluating the effect of anti-angiogenesis based therapy on blood flow in KS tissue. In this study, we are investigating the usefulness of several non-invasive techniques to assess the response of anti-angiogenetic drugs for treatment of KS patients. These techniques include infrared imaging, laser Doppler imaging (LDI) and near-infrared multi-spectral imaging.
Thermography and LDI images of a representative KS lesion were recorded in 16 patients and compared to normal skin either adjacent to the lesion or on the contralateral side. Eleven of the 16 patients had greater than 0.5 oC increased temperature and 12 of 16 patients had increased flux (measured by LDI) as compared to normal skin. There was a strong correlation between these two parameters (R = 0.81, p < 0.001). In ten patients, measurements were obtained prior to therapy and after receiving a regimen of liposomal doxorubicin and interleukin-12. After 18 weeks of therapy, temperature and blood flow of the lesions were significantly reduced from the baseline (p = 0.004 and 0.002 respectively). These techniques hold promise to assess physiologic parameters in KS lesions and their changes with therapy.
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Near-infrared spectroscopy is a non-contact and noninvasive method of monitoring changes in concentrations of blood volume and oxygenated- and deoxygenated-hemoglobin. Assessing these analytes is complicated by other pigments in the skin, i.e. melanin and hemosiderin. However, it is possible to correct for such pigments, and NIR spectroscopy has the potential to aid in assessing the pathogenesis of the status and changes of KS lesions during therapy.
Near-infrared spectroscopy is most closely related to visual assessment. With S. Demos at the Lawrence Livermore National Laboratory, a spectral imaging system was designed that captures images with a high-resolution CCD portable camera at six near-infrared wavelengths (700, 750, 800, 850, 900, and 1000 nm) was designed. A white light held approximately 15 cm from tissue illuminates the tissue uniformly. Using optical filters, images are obtained at the six wavelengths and the intensity images are used in a mathematical optical model of skin with epidermis and much thicker, highly scattering dermis. Each layer contains major chromophores that determine absorption in the corresponding layer and the layers together determine the total reflectance of the skin. Local variations in melanin, oxygenated hemoglobin (HbO2) and blood volume can be reconstructed through a multivariate analysis.
For the mathematical optical skin model, the effect of the thin epidermis layer on the intensity of the diffusely reflected light was determined by the effective attenuation of light. The epidermis absorption coefficient was determined by the percentage of melanin, the absorption coefficient of melanin and the absorption coefficient of normal tissue. The influence of the much thicker, highly scattering dermis layer on the skin reflectance should be estimated by a stochastic model of photon migration, e.g., random walk theory. Fitting the known random walk expression for diffuse reflectivity of the turbid slab yields a formula that depends on the reduced scattering coefficient and dermis absorption coefficient. The dermis absorption coefficient is based on the volume of blood in the tissue and hemoglobin oxygenation, i.e. relative fractions of HbO2 and deoxygenated hemoglobin (Hb). At wavelengths greater than 850 nm, the contribution of water and lipids should be taken into account. The absorption coefficient of blood was calculated by the volume fraction of HbO2 times the absorption coefficient of HbO2 plus the volume fraction of Hb times the absorption coefficient of Hb. In the dermis, large cylindrical collagen fibers are responsible for Mie scattering, while smaller scale collagen fibers and other micro-structures are responsible for Rayleigh scattering. A best-fit procedure was used to reconstruct for the melanin volume, HbO2 fraction, and blood volume fraction.
A thermal image from our Kaposi's sarcoma research appears on the cover of a new book entitled Medical Infrared Imaging.
Hassan M., R. Little, A. Vogel, K. Aleman, K. Wyvill, R. Yarchoan, and A. Gandjbakhche. Quantitative assessment of tumor vasculature and response to therapy in kaposi's sarcoma using functional noninvasive imaging. Technol. Cancer Res. Treat. 3(5), 451-7 (Oct 2004).
Hattery, D., M. Hassan, S. Demos and A. Gandjbakhche. Hyperspectral Imaging of Kaposis Sarcoma for Disease Assessement and Treatment Monitoring. Applied Imagery Pattern Recognition 124-132 (2002).
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