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

Abstract

Background: Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a recently completed Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect the expected light dose to the abscess wall and eventual PDT response. Purpose: The objective of this study was to simulate PDT treatment planning for the 13 subjects that received optical spectroscopy prior to clinical abscess PDT. Our goal was to determine the impact of these measured optical properties on our ability to achieve fluence rate targets in 95% of the abscess wall. Methods: During a Phase 1 clinical trial, 13 subjects received diffuse reflectance spectroscopy prior to PDT in order to determine the optical properties of their abscess wall. Retrospective treatment plans seeking to achieve fluence rate targets in 95% of the abscess wall were generated for all subjects for 3 conditions: (1) at the laser power delivered clinically with assumed optical properties, (2) at the laser power delivered clinically with measured optical properties, and (3) with patient-specific treatment planning using these measured optical properties. Factors modified in treatment planning included delivered laser power and intra-cavity Intralipid (scatterer) concentration. The effects of laser fiber type were also simulated. Results: Using a flat-cleaved laser fiber, the proportion of subjects that achieved 95% abscess wall coverage decreased significantly when incorporating measured optical properties for both the 4 mW/cm^2 (92% vs. 38%, p=0.01) and 20 mW/cm^2 (62% vs. 15%, p=0.04) fluence rate thresholds. However, when measured optical properties were incorporated into treatment planning, a fluence rate of 4 mW/cm^2 was achieved in 95% of the abscess wall for all cases. In treatment planning, the optimal Intralipid concentration across subjects was found to be 0.14 +/- 0.09% and the optimal laser power varied from that delivered clinically but with no clear trend (p=0.4). The required laser power to achieve 4 mW/cm^2 in 95% of the abscess wall was significantly correlated with measured absorption at the abscess wall (rho=0.7, p=0.008), but not abscess surface area (rho=0.2, p=0.53). When using spherical diffuser fibers as the illumination source, the optimal intralipid concentration decreased to 0.028 +/- 0.026% (p=0.0003), and the required laser power decreased also (p=0.021), compared to flat cleaved fibers. If the intra-cavity lipid emulsion (Intralipid) was replaced with a non-scattering fluid, all subjects could achieve the 4 mW/cm^2 fluence rate threshold in 95% of the abscess wall using a spherical diffuser, while only 69% of subjects could reach the same criterion using a flat cleaved fiber. Conclusions: The range of optical properties measured in human abscesses reduced coverage of the abscess wall at desirable fluence rates. Patient-specific treatment planning including these measured optical properties could bring the coverage back to desirable levels by altering the Intralipid concentration and delivered optical power. These results motivate a future Phase 2 clinical trial to directly compare the efficacy of patient-specific-treatment planning with fixed doses of Intralipid and light.

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

“…In prior retrospective studies, we have shown the importance of this for improving eligibility for PDT 25,26 . Further, the optical properties reported here have been used to generate retrospective treatment plans for the 13 subjects that received both PDT and spectroscopy 24 . In particular, the effects of abscess wall absorption have a pronounced effect on generated treatment plans.…”

“…This represents the first report on the optical properties of human abscess cavities, as well as the retention of MB following a 10 minute incubation. These optical property measurements set the stage for patient-specific treatment planning 24 , building on our retrospective study results 25,26 . We previously reported preliminary results for the first three subjects measured in this study 27 .…”

Application of Transfer Learning for Rapid Calibration of Spatially-resolved Diffuse Reflectance Probes for Extraction of Tissue Optical Properties

“…Substantial inter-patient variability in the abscess wall optical properties was found [5]. We have shown that patient-specific treatment planning incorporating knowledge of these optical properties greatly improves delivery of an efficacious fluence rate to the abscess wall [6,7]. Measurement of individual patient optical properties is therefore of high importance for the clinical success of PDT for this application.…”