Analysis and Modeling of Noninvasive measurement of Tissue Chromophores by the Optical Pharmacokinetic System

摘要: Efficient design of anti-cancer treatments involving radiation- and photo-sensitizing therapeutics requires knowledge tissue-specific drug concentrations. This dissertation investigates the utility Optical Pharmacokinetic System (OPS), a fiber-optic based elastic-scattering spectroscopy device, to noninvasively quantitate concentrations sensitizing compounds hemoglobin within tissue in vivo. The OPS was used motexafin gadolinium (MGd), mouse tissues vivo situ. An algorithm developed quantify MGd absorbance by integration peak area, thereby relaxing requirement that extinction coefficient be known priori. Concentrations measured were well-correlated with measurements high-performance liquid chromatography (HPLC). Compartmental pharmacokinetic models from HPLC. Models predicted both rapid initial distribution slow elimination plasma, fast transport out skin, retention at long times tumor. In tumor estimated linear combination tumor, skin PK profiles. A theoretical analysis measurement conducted using Monte Carlo (MC) model light through included discrete blood vessels. Simulation results motivated extensions previous algorithm, including: (1) novel analytic functionality between mean photon path length total absorption coefficient; (2) incorporation vessel correction factor account for pigment packaging effect vessels on OPS-estimated coefficient. These improved OPS-estimates silicon phthalocyanine (Pc4) concentration xenograft following photodynamic therapy (PDT). Mathematical utilized investigate silico sensitivity chronically acutely hypoxic regions tissue. PDT-induced acute hypoxia occured via simulation reaction. Subsequent suggested may sensitive presence (an saturation &ge 57 indicated < 6 hypoxic), but have limited application detection PDT.