SignificanceEfficacious photodynamic therapy (PDT) of abscess cavities requires personalized treatment planning. This relies on knowledge of abscess wall optical properties, which we report for the first time in human subjects.AimThe objective was to extract optical properties and photosensitizer concentration from spatially resolved diffuse reflectance measurements of abscess cavities prior to methylene blue (MB) PDT, as part of a phase 1 clinical trial.ApproachDiffuse reflectance spectra were collected at the abscess wall of 13 human subjects using a custom fiber-optic probe and optical spectroscopy system, before and after MB administration. A Monte Carlo lookup table was used to extract optical properties.ResultsPre-MB abscess wall absorption coefficients at 665 nm were 0.15±0.1 cm−1 (0.03 to 0.36 cm−1) and 10.74±15.81 cm−1 (0.08 to 49.3 cm−1) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm−1 (4.8 to 13.2 cm−1) and 5.6±2.26 cm−1 (1.6 to 9.9 cm−1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83%±35.78% (5.6% to 100%) pre-MB and 36.29%±25.1% (0.0001% to 76.4%) post-MB. Determined MB concentrations were 71.83±108.22 μM (0 to 311 μM).ConclusionsWe observed substantial inter-subject variation in both native wall optical properties and MB uptake. This underscores the importance of making these measurements for patient-specific treatment planning.
As part of our ongoing Phase 1 clinical trial to establish the safety and feasibility of methylene blue photodynamic therapy (MB-PDT) for human deep tissue abscess cavities, we have shown that determination of abscess wall optical properties is vital for the design of personalized treatment plans aiming to optimize light dose. To that end, we have developed and validated an optical spectroscopy system for the assessment of optical properties at the cavity wall, including a compact fiber-optic probe that can be inserted through the catheter used for the standard of care abscess drainage. Here we report preliminary findings from the first three human subjects to receive these optical spectroscopy measurements. We observed wide variability in concentrations of oxy- and deoxy-hemoglobin prior to MB administration, ranging from 7.3-213 μM and 0.1-47.2 μM, respectively. Reduced scattering coefficients also showed inter-patient variability, but recovered values were more similar between subjects (5.5-10.9 cm-1 at 665 nm). Further, methylene blue uptake was found to vary between subjects, and was associated with a reduction in oxygen saturation. These measured optical properties, along with preprocedure computed tomography (CT) images, will be used with our previously developed Monte Carlo simulation framework to generate personalized treatment plans for individual patients, which could significantly improve the efficacy of MB-PDT while ensuring safety.
KEYWORDS: Monte Carlo methods, Photodynamic therapy, Tissue optics, Optical properties, Tissues, Safety, Resistance, Optical spectroscopy, In vivo imaging, Device simulation
Despite advances in image-guided percutaneous drainage, deep tissue abscesses remain a serious cause of morbidity, mortality, and hospital stay. We initiated a Phase 1 clinical trial exploring safety and feasibility of methylene blue (MB) photodynamic therapy during drainage. Five subjects have been treated, with no study-related adverse events and high technical success.
Monte Carlo simulations were used to examine effects of optical properties on delivered light dose. We found that light dose is highly dependent upon MB uptake and Intralipid concentration. These results motivated construction of an optical spectroscopy system for determination of abscess wall optical properties in vivo.
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