title: Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis.
abstract: Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of > 0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Stephen Chad
authors.initials: SC
authors.lastname: Kanick
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Davis
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114.
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
authors.affiliation: Biomedical Engineering, Cleveland Clinic, Cleveland, Ohio 44195.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Maytin
authors.affiliation: Thayer School of Engineering, Dartmouth College, Hanover, New Hampshire 03755bWellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114dDepartment of Surgery, Section of Dermatology, Dartmouth-Hitchcock Medical Center.
authors.forename: Brian W
authors.initials: BW
authors.lastname: Pogue
authors.affiliation: Department of Surgery, Section of Dermatology, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire 03766.
authors.forename: M Shane
authors.initials: MS
authors.lastname: Chapman
mesh_terms: D006801:Humans; D055623:Keratosis, Actinic / Q000628:therapy*; D019047:Phantoms, Imaging; D010778:Photochemotherapy / Q000379:methods*; D010865:Pilot Projects; D011524:Protoporphyrins / Q000032:analysis / Q000378:metabolism; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results; D013050:Spectrometry, Fluorescence / Q000379:methods*
chemical_list: D011524:Protoporphyrins; C028025:protoporphyrin IX