First in human measurements of abscess cavity optical properties and methylene blue uptake prior to photodynamic therapy byin vivodiffuse reflectance spectroscopy

Abstract

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(0.03-0.36 cm−1) and 10.74±15.81 cm−1(0.08-49.3 cm−1) post-MB. Reduced scattering coefficients at 665 nm were 8.45±2.37 cm−1(4.8-13.2 cm−1) and 5.6±2.26 cm−1(1.6-9.9 cm−1) for pre-MB and post-MB, respectively. Oxygen saturations were found to be 58.83±35.78% (5.6-100%) pre-MB and 36.29±25.1% (0.0001-76.4%) post-MB. Determined MB concentrations were 71.83±108.22 µM (0-311 µM).ConclusionsWe observed substantial inter-subject variation in both native wall optical properties and methylene blue uptake. This underscores the importance of making these measurements for patient-specific treatment planning.

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

“…Similarly, the MB concentration used clinically was likely too high, as evidenced by the large values of absorption at 665 nm. Further justification for use of lower MB concentrations is discussed in detail by Hannan et al 23 .…”

“…These components, as well as the Monte Carlo lookup table approach for optical property recovery, were previously described by Bridger et al 24 . A full description of the clinical measurement protocol is provided elsewhere 22,23 . This pre-MB measurement represents the native optical properties of the abscess wall.…”

“…Full details on abscess wall optical properties and MB uptake are described elsewhere by Hannan et al 22,23 . Here, we focus on the effects of these extracted optical properties on patient- specific treatment planning to optimize light delivery to individual abscess cavities.…”

“…Whereas prior abscess treatment planning studies utilized assumed optical properties 20,21 , we have now measured the optical properties of 13 human abscesses immediately prior to PDT using a spatially-resolved diffuse reflectance spectroscopy system 22,23 . These measurements were performed before and after methylene blue administration, in order to capture bulk abscess wall optical properties and MB uptake.…”

Treatment planning for photodynamic therapy of abscess cavities using patient-specific optical properties measured prior to illumination

“…Full details on abscess wall optical properties and MB uptake are described elsewhere by Hannan et al (2023aHannan et al ( , 2023b. Here, we focus on the effects of these extracted optical properties on patient-specific treatment planning to optimize light delivery to individual abscess cavities.…”