Fractional laser ablation as physical enhancement

of skin optical clearing

Elina A. Genina1,2*, Alexey N. Bashkatov1,2, Leonid E. Dolotov1, Ekaterina A. Kolesnikova1, Georgy S. Terentyuk1,

and Valery V. Tuchin1,2,3

1Remote Controlled Theranostic System Lab, Saratov State University, Saratov, Russia,

2Tomsk State University, Tomsk, Russia3Institute of Precise Mechanics and Control of RAS, Saratov, Russia

*eagenina@yandex.ru

Saratov Fall Meeting 2015International Symposium Optics and Biophotonics – IIIConference on Internet Biophotonics – VIIISeptember 22-25, 2015, Saratov, Russia

SaratovState

University

Outline

o Motivationo Transcutaneous Delivery of Optical

Clearing Agento Objectiveso Methods and Materialso Resultso Conclusiono Acknowledgements

Motivation

During the last 25 years the interest to the development and application of optical methods in clinical functional imaging of physiological conditions, diagnostics and therapy of cancer, and other diseases is permanently growing•

•T. Vo-Dinh (Ed.), Biomedical Photonics Handbook, CRC Press, Boca Raton, FL, USA (2003); second edition (2014).•D. Zhu, et al, Laser & Photonics Reviews 7(5), 732-757 (2013).•Tuchin V.V. Journal of Biomedical Photonics & Engineering, 1(1), 3-21 (2015).

One of simple and efficient methods of solving the problem of increasing the depth and quality of intratissular structure imaging, as well as of increasing the precision of spectroscopic information from the deep tissue layers and the blood, is the temporary reduction of the tissue light scattering•

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various sources Web of Science PubMed

According to Web of Science, PubMed and other sources, the interest to the optical clearing methods is permanently growing, which is caused by the progress of optical and laser technologies for application in biology and medicine•

• E.A. Genina, et al, Journal of Biomedical Photonics & Engineering, 1(1), 22-58 (2015).

The main advantages of transcutaneous administration of optical clearing agent (OCA) are:

o minimal invasiveness or even noninvasivenesso improved pharmacokineticso targeted delivery

Transcutaneous Delivery of Optical Clearing Agent

Follicular transport

Intercellular transport(hydrophilic OCAs)

Transcellular transport(lipophilic OCAs)

Stratumcorneum

DermisFollicle

Livingepidermis

10

- 2

0 μ

m7

5 -

15

0 μ

m

The stratum corneum and underlying living epidermis represent a barrier separating body from the environment and makes penetration of OCA deep into the skin a rather difficult problem

Skin Barrier

The basic options for improving transdermal delivery:

o skin barrier elimination

o stratum corneum/epidermis perforation

o stratum corneum penetration

Fractional laser microablation (FLMA) can be one of the prospective method for targeted OCA delivery into the skin

Microablation modeMicroperforation mode

ablation zone

E=0.8J

Objectives

Development of method of transcutaneous delivery of OCAs

The study of agent penetration with different modes of the laser fractional ablation of skin

Methods and Materials

o Four rats in vivoo Polyethylene glycol with molecular weight 300 Dalton

(PEG-300) and refractive index 1.457 (930 nm)o The Palomar Lux2940 erbium laser (Palomar Medical

Products Ltd., USA) with two modes:Mode I - ablation of skin upper layer with pulse energy 0.8 J and pulse duration 5 msMode II – microperforation with pulse energy 1 J and pulse duration 5 ms

o OCT monitoring (OCP930SR, Thorlabs, USA), ~930 nm

oFLMA

o Application of PEG-300

oOCT-monitoring during 60-70 min

Design of the experiment

In accordance with the single-scattering model (SSM) the measured signal in OCT system is defined as

i(z) is the OCT signal, µt is the total attenuation coefficient µt=µa+µs, z is the probing depth of tissueIn the SSM, the reflected power is proportional to exp(–μtz), i.e.

A is the coefficient of proportionality equal to P0α(z), P0 is the optical power launched into the tissue, and B is the background signal

The attenuation coefficient has been obtained by the minimizationof the target function

Rexp is OCT signal measured on the depth z and Ni is the number of measured points in the depth of the tissue (on the z-axis)

2 2t0

( ) exp( 2μ )i z i z

t( ) exp( μ )R z A z B

2exp0 t max 0 t max

1

,μ , exp μtN

i ii

f R R R R z R

Model

Typical B-scan of skin with marked selection regions (51 A-scans for averaging) and region of interest (a) and plot of the averaged A-scan

and the fitted curve using the single-scattering model (b)

For this case A = 1230.4, B = 79.7, and μt = 90.3 cm-1

Results

Mode I Mode II

ablation of skinupper layer

area of damage is 66 mm2 depth of damage is ~100 μm

area of damage is 88 mm2 64 vertical micro-channels

depth of damage in a channel is <150 μm

Channels0.

3 m

m

0.3

mm

0 20 40 60 800.8

1.0

1.2

1.4

1.6

t, min

t nor

m Mode I (surface ablation) Mode II (perforation) in channels Mode II (perforation) in between channels

Kinetics of attenuation coefficient normalized on the initial value (intact skin) during optical clearing

-15

-10

-5

0

5

10

15

Mode IIbetweenchannels

Mode IIin channels

Mode I

(0) (60min)

(0)

100%t t t

t

Effectiveness of dermis optical clearing:

Conclusion

o FLMA induced a swelling of damaged skin, which increased light scattering in tissue

o Laser perforation was more effective for optical clearing process than laser surface ablation because of less area of damage (less swelling)

Acknowledgements

The work was carried out under the support by Russian Federation Governmental No. 14.Z50.31.0004 designed to support scientific research projects implemented under the supervision of leading scientists at Russian institutions of higher education

and the Tomsk State University Academic D.I. Mendeleev Fund Program

Thank you for your attention!