title: Optical clearing of skin using flash lamp-induced enhancement of epidermal permeability.
abstract: OBJECTIVE
  Strong light scattering in skin prevents precise targeting of optical energy in therapeutic and diagnostic applications. Optical immersion based on matching refractive index of scattering centers with that of surrounding matter through introduction of an exogenous index-matching agent can alleviate the problem. However, slow diffusion of the index-matching agent through skin barrier makes practical implementation of this approach difficult. We propose a method of accelerating penetration of the index-matching compounds by enhancing skin permeability through creating a lattice of micro-zones (islets) of limited thermal damage in the stratum corneum (SC).
  
  
  METHODS
  A flash lamp (intense pulsed light) system and an island mask with a pattern of absorbing centers (center size approximately 75-120 microm, lattice pitch approximately 450-500 microm) were used to create the lattice of islets of damage (LID). Index-matching agents, such as glucose solution, propylene glycol solution, and glycerol solution, were applied.
  
  
  RESULTS
  Experimental results of optical clearing ex vivo rat and pig skin, and ex vivo and in vivo human skin are presented. Optical transmission spectra of the skin samples with LID were measured during some 2 hours after application of index-matching chemical agents. In order to assess and compare the clearing rate under different treatment and clearing agents we calculated the quantity that we call "relative transmittance": T(rel) = I(t)(lambda)/I(0)(lambda), were I(t)(lambda) is the intensity measured at elapsed time t. The dynamics of relative transmittance of skin samples at 470 and 650 nm shows that the implementation of limited thermal damage technique leads to a 3-10-fold increase of optical clearing (rise of transmittance) rate compared to the results obtained when the samples were treated with high-intensity light pulses but without the use of island damage mask (IDM). It was observed from the plotted spectra of relative transmittance that the maximum increase of transmitted light intensity has been obtained with glucose solution as a clearing agent. Noteworthy is the difference in the trend of spectral curves: relative transmittance spectrum for glycerol reveals, on the whole, a greater slope which may be indicative of higher extent of index matching between the scattering centers and base material for this index-matching agent. Under the transillumination of the skin sample by the wide flat beam the more effective clearing (the increase of transmitted intensity) is attained within the hemoglobin absorption bands; with the narrow quasi-collimated beam the higher relative transmittance was observed over the intervals of minimum absorption.
  
  
  CONCLUSIONS
  The use of specially designed island mask combined with non-laser intensive pulse irradiation produces a lattice of islands of limited thermal damage in SC that substantially enhances the penetration rate of topically applied index-matching agents. The suggested technique gave comparable magnitudes of clearing dynamics enhancement for glucose solution, glycerol solution, and propylene glycol solution applied to mammalian skin.
authors.affiliation: Research-Educational Institute of Optics and Biophotonics, Saratov State University, Saratov, Russia. tuchin@sgu.ru
authors.forename: V V
authors.initials: VV
authors.lastname: Tuchin
authors.forename: G B
authors.initials: GB
authors.lastname: Altshuler
authors.forename: A A
authors.initials: AA
authors.lastname: Gavrilova
authors.forename: A B
authors.initials: AB
authors.lastname: Pravdin
authors.forename: D
authors.initials: D
authors.lastname: Tabatadze
authors.forename: J
authors.initials: J
authors.lastname: Childs
authors.forename: I V
authors.initials: IV
authors.lastname: Yaroslavsky
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D003451:Cryoprotective Agents / Q000008:administration & dosage; D004058:Diffusion / Q000187:drug effects / Q000528:radiation effects; D005240:Feasibility Studies; D005950:Glucose Solution, Hypertonic; D005990:Glycerol / Q000008:administration & dosage; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D008027:Light; D008297:Male; D023421:Models, Animal; D055095:Optics and Photonics; D010539:Permeability / Q000187:drug effects / Q000528:radiation effects; D019946:Propylene Glycol / Q000008:administration & dosage; D051381:Rats; D012542:Scattering, Radiation; D012867:Skin / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D012869:Skin Absorption / Q000187:drug effects / Q000528:radiation effects; D012881:Skin Temperature / Q000187:drug effects / Q000528:radiation effects; D012997:Solvents / Q000008:administration & dosage; D013053:Spectrophotometry; D013552:Swine; D013997:Time Factors
chemical_list: D003451:Cryoprotective Agents; D005950:Glucose Solution, Hypertonic; D012997:Solvents; D019946:Propylene Glycol; D005990:Glycerol