The propagation of light through turbid media, such as biological tissue, is largely governed by absorption and scattering. At the deep red wavelengths relevant to PDT, absorption in tissue is mainly due to hemoglobin, which has an oxygen-dependent absorption spectrum. Determination of tissue absorption and scattering can therefore provide information on tissue status, and inform models of light delivery. While there have been many efforts to extract these absorptive and scattering properties of tissue from surface measurements, we have focused on the interstitial measurement of optical properties deep in tissue. This has involved the creation of novel optical probes, and the algorithms necessary to determine absorption and scattering from measurements.
Many of the photosensitizers used in PDT are naturally fluorescent, meaning that information about photosensitizer localization and concentration can be determined from fluorescence measurements. This measured fluorescence is corrupted by tissue absorption and scattering, so techniques have been developed to determine quantitative fluorescence in the presence of a turbid background medium. As with the determination of absorption and scattering, we have focused on interstitial measurements of fluorescence using novel probe geometries.
Our current focus is on the development of optical spectroscopy technology for measurement of patient-specific optical properties in deep tissue abscesses, as part of our Phase 1 PDT clinical trial. This NIH-funded project (R01 EB029921) involves the development and validation of an optical spectroscopy system, measurements in patients, and generation of individual treatment plans.
T.M. Baran, J.D. Wilson, S. Mitra, J.L. Yao, E.M. Messing, D.L. Waldman and T.H. Foster. Optical property measurements establish the feasibility of photodynamic therapy as a minimally invasive intervention for tumors of the kidney. Journal of Biomedical Optics 17, 098002 (2012).
T.M. Baran and T.H. Foster. Recovery of intrinsic fluorescence from single-point interstitial measurements for quantification of doxorubicin concentration. Lasers in Surgery and Medicine 45, 542-550 (2013).
T.M. Baran, M.C. Fenn and T.H. Foster. Determination of optical properties by interstitial white light spectroscopy using a custom fiber optic probe. Journal of Biomedical Optics 18, 107007 (2013).
T.M. Baran. Cylindrical diffuser axial detection profile is dependent on fiber design. Journal of Biomedical Optics 20, 040502 (2015).
T.M. Baran. Recovery of optical properties using interstitial cylindrical diffusers as source and detector fibers. Journal of Biomedical Optics 21, 077001 (2016).
N. Hu, L. Antoury, T.M. Baran, S. Mitra, C.F. Bennett, F. Rigo, T.H. Foster, and T.M. Wheeler. Non-invasive monitoring of alternative splicing outcomes to identify candidate therapies for myotonic dystrophy type 1. Nature Communications 9, 5227 (2018).