Download Clinical Oral Cancer Diagnosis with Optical Coherence Tomography

Study on fractional CO2 laser-assisted drug delivery with optical
coherence tomography
Ting-Yen Tsai, Zhung-Fu Lee, Feng-Yu Chang, Yi-Cheng Lee, Meng-Tsan Tsai*
Department of Electrical Engineering, Chang Gung University, 259, Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan,
33302 Taiwan
Chih-Hsun Yang
Department of Dermatology, Chang Gung Memorial Hospital, 5 Fusing Street, Kwei-Shan, Tao-Yaun 33302,
Taiwan
[email protected]
ABSTRACT
Laser photothermal therapy is an effective method for skin resurfacing. Delivering drug into nail is essential
for the topical therapy of nail diseases, e.g. nail fungal infection. A variety of physical methods or chemical
enhancers have been tested to increase drug permeation into the intact nail plate. Therefore, in this study, we
propose to use optical coherence tomography (OCT), to investigate the effect of laser exposure on the nail with
three-dimensional imaging. Clinically it is difficult to evaluate the effect of laser exposure noninvasively since the
parameters including the penetration depth and the beam diameter cannot be obtained immediately. In our
experiments, the nails after fractional laser exposures were scanned with our SS-OCT system. The quantitative
results from OCT images including the penetration depth and ablative area are analyzed and also compared with
the histology results. In addition to observe the results after fractional laser exposures with OCT, we use OCT to
evaluate the water diffusion through laser ablative channels based on estimating speckle variance of OCT signal.
The results showed that OCT can be effective to monitor the photothermal effect induced by fractional CO2 laser
and to evaluate the water or drug diffusion from the microthermal zone to the nail bed.
Keywords: optical coherence tomography, fractional photothermolysis, drug delivery
1. INTRODUCTION
Recently, a lot of studies have been focused on the improvement of drug delivery such as focused ultrasound,
microwave, and microneedle patch. With exposure of focused ultrasound, the vascular permeability can be
enhanced, making drug delivery easy. Currently, focused ultrasound is mostly applied to brain blood barrier
opening. In addition, low-temperature microwave enables to open up pores in bacteria cells, inducing significant
improvement in drug delivery. Furthermore, microneedle patch can bypass the stratum cornium barrier to produce
the microscopic holes into the epidermis layer of skin, facilitating drug to diffuse to the dermal microcirculation.
However, the abovementioned methods only can be applied to specific applications.
In the past, laser skin resurfacing was performed by scanning the whole skin surface with laser beams. This
treatment frequently leads to delayed skin recovery because the entire epidermis was removed. Fractional
photothermolysis was developed to replace traditional full-surface skin resurfacing. Treatment with the Fractional
CO2 laser (10600 nm) laser creates microscopic ablation zones (MAZ) that extend into the dermis and are
surrounded by intact tissue, allowing for rapid healing. Because the tissue surrounding each microscopic wound is
intact, healing is rapid from residual viable epidermal and dermal cells. Beside aesthetic treatment, fractional laser
ablation has been shown to efficiently disrupt stratum corneum and facilitate transcutaneous drug and vaccine
delivery. Arrays of spatially separated microscopic wound generated by fractional laser can provide free paths for
drug delivery into the skin. Delivering drug into nail is essential for the topical therapy of nail diseases, e.g. nail
fungal infection. A variety of physical methods or chemical enhancers have been tested to increase drug
permeation into the intact nail plate. Currently, ablative fractional laser that generate many tiny microchannels in
the nail provide an effective method for drug delivery to nail.
Optical coherence Tomography (OCT) has attracted much attention for biomedical imaging because of its
noninvasive, high-speed, and 3-D imaging nature. Recently, due to the development of detection techniques,
Fourier domain OCT (FD-OCT), including spectral-domain OCT (SD-OCT) and swept-source OCT (SS-OCT)
have demonstrated superior performance of imaging speed and sensitivity over those of the time domain OCT
systems. In FD-OCT, the amplitude and echo time delay of the backscattered light are resolved through fast
Fourier transform of the collected interfered spectral data. In SD-OCT, a high-speed spectrometer is used as the
wavelength resolved detection unit, which makes the mechanical scanning component in the reference arm
unnecessary. On the other hand, SS-OCT system utilizes a frequency-swept laser source and thus eliminates the
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requirement of the spectrometer for detection purpose. Therefore, an SSOCT system has several advantages over
those of an SD-OCT system, including robust system configuration, higher imaging speed, and superior imaging
sensitivity. Previous study has demonstrated high-speed SS-OCT operation with a polygon-mirror tuning filter in
the spectral range of 1.3 m. An SS-OCT system with the swept laser source near 1 m in wavelength was also
reported. Such a system can reach a larger imaging depth, such as posterior eye, and is suitable for ophthalmic
scanning in choroid study. SS-OCT is particularly important for imaging in the wavelength ranges of 1.0 and 1.3
m where charge-coupled devices (CCDs) or detector arrays are not fully optimized. Although a swept laser source
may have the problem of intensity fluctuation in output spectrum, the use of balanced detection has suppressed the
system noise of SS-OCT significantly. In this study, to achieve deeper penetration depth, an SS-OCT system in 1.3
m is implemented for dermatology study.
2. SS-OCT SYSTEM
In this study, we demonstrated an SS-OCT system with a scanning probe for skin imaging, as shown in Figure
1. The central wavelength of the wavelength-sweeping laser is located at 1310 nm with a scanning range of 105 nm,
which corresponds to a theoretical longitudinal resolution of 7 m. The laser source can provide a scanning rate
and an output power 100 kHz and 20 mW, respectively. Then, the output light was connected to a Mach–Zehnder
interferometer, consisting of two circulators and two couplers. For skin scanning, a handheld probe with
three-dimensional imaging ability was fabricated, which is composed of a two-axis galvanometer and a 10
objective lens. Thus, in our system, the transverse resolution is approximately 7 m. In order to compensate the
dispersion induced by the objective lens used in the scanning probe, a dispersion compensator was inserted in the
reference arm. Finally, the interference signal combined from the sample and reference arms was detected by a
balanced detector. To resample the interference spectrum, a k-clock signal generated from the light source was
utilized as an external clock and received by a digitizer. To scan human skin, the physical area of OCT imaging
was set to be approximately 2  2  3 mm3, corresponding to 1000  500  600 voxels. With an A-scan rate of 100
kHz, the frame rate of our OCT system can achieve 100 frames/s, in which each frame consists of 1000 A-scans.
Fig. 1 Schematic diagram of OCT system. FC: fiber coupler; CIR: circulator; G: two-axis galvanometer; SMF: single-mode
fiber, DC: dispersion compensator, M: mirror, and OB: objective lens. The physical scanning area of OCT imaging was set to
be approximately 2  2 mm2.
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3. SS-OCT SCANNING RESULTS
Firstly, to understand the relationship between the ablative depth and the exposure energy, various exposure
energies of fractional CO2 laser were performed on the different nails. Then, the nails were scanned with the OCT
system. Figure 2 shows the OCT B-scan results of fingernails with fractional laser exposure. Figures 2(a)–(d)
represent B-scan results after being exposed to various exposure energies of 15 mJ, 20 mJ, 25 mJ and 30mJ,
respectively. Figures 2(e)–(t) show the en-face images of the nails’ surfaces, extracted from three-dimensional
OCT images. Figs. 2 (a)-(d) show the ablative depth becomes deeper with increasing the exposure energy.
Moreover, the en-face images also illustrate that the ablative area increases with the exposure power.
Fig. 2. Ex vivo OCT images of the fingernail after exposed to various exposure energies. (a) 15 mJ, (b) 20 mJ, (c) 25 mJ, and (d)
30mJ. En-face images of the nails’ surfaces extracted from three-dimensional OCT images after being exposed to various
exposure energies. (e) 15 mJ, (f) 20 mJ, (g) 25 mJ, and (h) 30mJ.
Fig. 3 Photos of fingernails treated with a pulse energy of 20 mJ.
4. CONCLUSIONS
This study is focused on the feasibility of fractional laser-assisted drug delivery by using OCT as a monitoring
tool. In addition to observe the results after fractional laser exposure with OCT, we use OCT to evaluate the water
diffusion through laser ablative channels based on estimation of speckle variance of OCT signal. The results
showed that OCT can be effective to monitor the photothermal effect induced by fractional CO2 laser and to
evaluate the water or drug diffusion from the microthermal zone to the nail bed.
ACKNOWLEDGEMENT
This research was supported by the National Science Council (NSC), and Chang Gung Memorial Hospital, Taiwan,
the Republic of China, under the NSC 102-2221-E-182-061-MY2, 103-2221-E-182 -039-, and CMRPD2B0032
grants.
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