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

Abstract

Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm−2 (92% versus 38%, p = 0.01) and 20 mW cm−2 (62% versus 15%, p = 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm−2 target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm−2 target was significantly correlated with measured abscess wall absorption (ρ = 0.7, p = 0.008), but not abscess surface area (ρ = 0.2, p = 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p = 0.0005) and required laser power (p = 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm−2 target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as ‘Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,’ with ClinicalTrials.gov identifier NCT02240498).