Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms.

Mikael Marois,Jaime Bravo,Stephen Chad Kanick,Scott C Davis

doi:10.1117/1.jbo.21.3.035003

Mikael Marois, Jaime Bravo + Show 2 more

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https://doi.org/10.1117/1.jbo.21.3.035003

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Abstract

.Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation. Optical measurements showed a linear proportionality () between fluorescence intensity and PpIX concentration (0.1 to ) over a range of Intralipid (1 to 2%) and whole blood (0.5 to 3%) for phantoms containing low surfactant (), with fluorescence intensities and scattering and absorption properties stable for 5 h after mixing. The role of surfactant in PpIX phantoms was found to be complex, as aggregation was evident in aqueous nonturbid phantoms with no surfactant (0% Tween), and avoided in phantoms containing Intralipid as the scattering source with no additional or low amounts of added surfactant ( Tween). Conversely, phantoms containing higher surfactant content ( Tween) and whole blood showed interactions that distorted the fluorescence emissions.

Highlights

Protoporphyrin IX (PpIX) is a photosensitizer and fluorophore of interest both for experimental photo-based therapies and for diagnostic assessment of suspicious tissue during surgery.[1]
Missouri) solubilized in dimethyl sulfoxide (DMSO) to yield concentrations of (0.1, 1, 10) μg∕mL, Tween 20 (SigmaAldrich) in volume fractions (TVF) of (0, 0.1, 0.5, 1, 5)%, and the balance completed with phosphate-buffered saline (PBS)
The data presented in this study are used to identify a recipe for tissue-simulating optical phantoms that yield proportional and stable PpIX fluorescence emissions

Summary

Introduction

Protoporphyrin IX (PpIX) is a photosensitizer and fluorophore of interest both for experimental photo-based therapies and for diagnostic assessment of suspicious tissue during surgery.[1] While PpIX occurs naturally in the body, temporary enhancement can be induced by administration of aminolevulinic acid (ALA), a nonfluorescent prodrug that serves to bypass the negative feedback controls of the heme-biosynthesis pathway and results in a selective retention of PpIX in tissue with altered metabolic activity.[2,3] In the field of dermatology, topical application of ALA induces PpIX in precancerous and cancerous skin lesions, where PpIX serves as a photosensitizer for photodynamic therapy.[4,5] Dosimetry studies have shown that optical measurements of PpIX fluorescence may provide insight into patient-specific responses to therapy.[6,7,8] In the field of neurosurgery, oral administration of ALA is used to induce PpIX accumulation in malignant tumors in the brain.[2] Multiple clinical investigations are considering the use of optical measurements of PpIX fluorescence to increase contrast between tumor and surrounding normal cortex.[9,10,11,12,13,14] Research in these clinical specialties has led to the development of a variety of approaches to optically sample PpIX fluorescence emissions from tissue.[1,15] Basic imaging approaches sample raw PpIX fluorescence

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