Abstract

.Evaluating the optical properties of biological tissues is needed to achieve accurate dosimetry during photodynamic therapy (PDT). Currently, accurate assessment of the photosensitizer (PS) concentration by fluorescence measurements during PDT is typically hindered by the lack of information about tissue optical properties. In the present work, a hand-held fiber-optic probe instrument monitoring fluorescence and reflectance is used for assessing blood volume, reduced scattering coefficient, and PS concentration facilitating accurate dosimetry for PDT. System validation was carried out on tissue phantoms using nonlinear least squares support machine regression analysis. It showed a high correlation coefficient () in the prediction of the PS concentration upon a large variety of phantom optical properties. In vivo measurements were conducted in a PDT chlorine e6 dose escalating trial involving 36 male Swiss mice with Ehrlich solid tumors in which fluences of 5, 15, and were delivered at two fluence rates (100 and ). Remarkably, quantitative measurement of fluorophore concentration was achieved in the in vivo experiment. Diffuse reflectance spectroscopy (DRS) system was also used to independently measure the physiological properties of the target tissues for result comparisons. Then, blood volume and scattering coefficient measured by the fiber-optic probe system were compared with the corresponding result measured by DRS and showed agreement. Additionally, tumor hemoglobin oxygen saturation was measured using the DRS system. Overall, the system is capable of assessing the implicit photodynamic dose to predict the PDT outcome.

Highlights

  • The results show that the least-squares support vector machines (LS-SVMs) model can predict the PS concentration in tissues with different optical properties

  • A fiber-optic probe instrument based on fluorescence and reflectance spectroscopy was used for the purpose of diagnostic and monitoring measurement of tissue

  • This system is a complement to Photodynamic therapy (PDT) as a mean of dosimetry

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Summary

Introduction

Advances in optical techniques have provided noninvasive diagnostics and effective means to improve clinical outcomes.[1,2,3] Fiber-optic probes have been increasingly utilized to provide a minimally invasive approach in tissue characterization for various biomedical applications, such as cancer diagnostics, surgical guidance, and treatment response monitoring.[4,5,6,7] Photodynamic therapy (PDT) in conjunction with fiber-optic probing is a promising modality to achieve optimal therapeutic efficiency for cancer treatment.[8,9,10] PDT is a viable minimally invasive treatment, involving the administration of photosensitizer (PS), incubation time to allow the adequate accumulation of the drug in the tumor, and activation by light of appropriate wavelength. This process results in the generation of highly active oxygen radicals that cause tumor necrosis, apoptosis, and autophagy.[11,12,13]

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