Common-path optical coherence tomography guided fibre probe for spatially precise optical nerve stimulation K. Zhang, E. Katz, D.H. Kim, J.U. Kang and I.K. Ilev A simple and effective common-path optical coherence tomography guided fibre probe for optical nerve stimulation has been developed and tested. The probe is capable of real-time monitoring of the fibreto-nerve distance up to more than 1 mm at an axial resolution of approximately 3 mm, thus improving the precision and safety of stimulation laser power delivery.
Introduction: Optical nerve stimulation is based on laser power delivery through a fibre-optic probe that provides the essential advantages of noncontact operation, high spatial selectivity and is free of interfascicular crosstalk artefact compared to traditional tissue-implanted electrical stimulation [1]. From the point of view of effectiveness of optical nerve stimulation and laser safety, one critical parameter is the average optical radiant exposure (or the average laser radiation dose determined in the unit of [J/cm2]) on the target nerve tissue, which can be calculated using either the laser average power and the exposure time (for a continuous-wave laser) or the laser pulse energy (for a pulsed laser), and the laser beam spot size [2]. While the stimulation energy is easier to control and pre-calibrate, the on-site fibre-to-nerve distance, which basically determines the laser radiation spot size, is usually monitored by a side view microscope and cannot be precisely controllable. For a 1.85 mm wavelength Aculight laser nerve stimulator using a 600 mm core-diameter delivery fibre, the optimal fibre-to-nerve distance is in the range of 500– 750 mm, and the evaluated stimulation radiation dose threshold (0.4 – 0.6 J/cm2) is very close to the damage dose threshold (0.75– 0.85 J/cm2) for protein denaturation [2, 3]. In such a narrow range, a small axial displacement may cause a significant dose change owing to the diverging laser beam profile, and therefore, this will make it difficult to deliver the dose precisely. Recently, a series of single-fibre/fibre bundle common-path optical coherence tomography (CP-OCT) probes have demonstrated their ability for precise distance sensing, scan-free depth-resolved imaging and compact features for instrument integration [4, 5]. This Letter proposes a simple and effective Fourier-domain common-path optical coherence tomography (FD-CP-OCT) guided fibre probe capable of the real-time fibre-to-nerve distance perception with an axial resolution of about 3 mm.
The fibre probe design is shown in Fig. 1b. A singlemode fibre having a 5.6 mm/125 mm core/cladding diameter is attached by epoxy to a much larger multimode fibre for nerve stimulation laser power delivery. The core diameter of the multimode fibre is usually 200 – 600 mm, depending on the geometry of the target nerves. The average laser radiation dose D to the nerve tissue through the multimode fibre probe can be expressed as: D½J/cm2 ¼
Ep E½J Pa te ¼ ¼ A½cm2 p½d tan a þ r2 p½d tan a þ r2
where E is the laser energy delivered to the irradiated tissue area A. For continuous-wave and high repetition rate lasers, E is determined by the average delivered laser power Pa and the exposure time te , while for single pulse and low repetition rate pulse lasers by the delivered laser pulse energy Ep. The fibre acceptance angle a ¼ sin1 ðNA=nÞ is determined by the numerical aperture NA of the delivery fibre and the refraction index n of the media. d is the fibre-to-nerve distance and r is the core radius of the delivery fibre. For a certain value of the stimulation laser energy using a specific delivery fibre, the radiation dose is determined by the distance d. For light-nerve tissue interactions, the 800 nm band SLED light is much less absorptive than the 1.85 mm stimulation laser and it requires a much lower power of ,5 mW, which allows some possible photothermal effects caused by the OCT light to be neglected [2]. A prior investigation has determined that, at the peak wavelength of 810 nm, laser pulses of up to 200 J/cm2 did not produce neuronal activation, and did not affect the amplitudes of electrically evoked compound nerve potentials (N ¼ 36, data not shown). The stimulation spot can be considered as uniformly distributed in the near field (d r) and as Gaussian in the far field (d r) [6], therefore the optical nerve stimulation is usually operated in the near field. The OCT light spot will fall within the stimulation spot owing to the commonly used diverging beam configuration [1 – 3, 7]. Fig. 1c shows a digital microscope imaging of an integrated probe prototype, where a 200 mm core diameter multimode fibre is used as the delivery fibre. The offset between the CP-OCT fibre tip and the power delivery fibre tip is measured to be 14 mm using the digital microscope. The whole probe is mounted onto a 3-D linear stage and submerged in the saline solution of the nerve sample, pointing perpendicular to the tissue surface.
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System schematic and probe design: A principle FD-CP-OCT setup is shown in Fig. 1a. The superluminescence diode (SLED) light source is centred at 870 nm with an FWHM spectral width of 90 nm, which inputs into an 830 nm broadband fibre coupler. One arm of the fibre coupler output with a 908 cleaved bare fibre probe acts as both the sample and the reference arm, where the reference signal comes from the Fresnel reflection of the fibre tip. The reference and the signal couple back into a high speed spectrometer and then output to a computer for analysis.
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Fig. 1 System schematic; probe design; integrated probe prototype a System schematic b Probe design SMF: multimode fibre MF: singlemode fibre c Integrated probe prototype.
Fig. 2 FD-CP-OCT point spread function in saline solution; A-scan of nerve tissue and determination of distance a FD-CP-OCT point spread function in saline solution b A-scan of nerve tissue and determination of distance
Resolution test and tissue edge searching: The distance-perception ability of the FD-CP-OCT probe is calibrated by submerging the
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probe into a Petri dish with the same type of saline solution used to maintain the nerve tissue (composition in mM: 10 dextrose, 136 NaCl, 5.6 KCl, 1.2 MgCl2 . 6 H2O, 2.2 CaCl2 . 2 H2O, 1.2 NaH2PO4, and 14.3 NaHCO3 , equilibrated with 95% O2 – 5% CO2 pH between 7.3 and 7.5). The probe is perpendicularly pointed to the Petri dish bottom surface, which acts as a good reflector and gives the point spread function of the system. A high-precision digital micro-actuator is used to control the z-axis of the 3-D linear stage, and a series of displacements and axial pixel numbers from the corresponding A-scan are obtained and fitted. The axial resolution is finally found to be about 3 mm, as illustrated in Fig. 2a. Then a rat sciatic nerve sample is prepared and maintained in physiological saline solution [6]. A sample A-scan is shown in Fig. 2b, where the FD-CP-OCT fibre-to-nerve distance dOCT is measured to be 85 + 2 mm, using the 1-D edge-searching algorithm [4]. Distance perception test: Next, as in the calibration part, we use the micro-actuator to make displacement steps of 50 mm and then find the dOCT obtained from the corresponding A-scan by edge-searching. As can be seen in Fig. 3a, the distance-perception results have very good linearity with the actual displacements caused by the micro-actuator. The effective distance-perception can be larger than 1 mm, which is very sufficient for near field operation.
To investigate further the accuracy of distance-perception, an identical test as shown in Fig. 3a was repeated at different positions of the nerve tissue and a total number of 51 samples were obtained. Next, we analysed the error between each displacement caused by the micro-actuator and the resulting Dd obtained from FD-CP-OCT, as shown in Fig. 3b. As can be seen, the main error values are +2 mm, which agrees well with the axial resolution of 3 mm. The error becomes larger up to 6 mm when the measurement is performed at distances beyond 1 mm where the OCT signal gets weaker owing to the fringe wash out of the spectrometer. Conclusion: We have developed and tested a simple FD-CP-OCT guided distance-perception fibre probe. The probe is capable of real-time detection of the fibre-to-nerve distance up to more than 1 mm at an axial resolution of about 3 mm, which can significantly help the stimulation probe make precise positioning and improve the accuracy and safety of optic nerve stimulation. In vivo nerve stimulation experiments will be conducted separately in future work. Disclaimer: The mention of commercial products, their sources, or their use in connection with material reported here is not to be construed as either an actual or implied endorsement of such products by the U.S. FDA.
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# The Institution of Engineering and Technology 2010 16 November 2009 doi: 10.1049/el.2010.3221 One or more of the Figures in this Letter are available in colour online.
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E. Katz, D.H. Kim and I.K. Ilev (Center for Devices and Radiological Health, U.S. Food and Drug Administration, 10903 New Hampshire Ave, Silver Spring, MD 20993, USA)
1 Wells, J., Bendett, M., Webb, J., Richter, C., Izzo, A., Jansen, E.D., and Mahadevan-Jansen, A.: ‘Frontiers in optical stimulation of neural tissues: past, present, and future’, Proc. SPIE., 2009, 6854, p. 68540B-1 2 Wells, J., Kao, C., Konrad, P., Milner, T., Kim, J., Mahadevanjansen, A., and Jansen, E.: ‘Biophysical mechanisms of transient optical stimulation of peripheral nerve’, Biophys. J., 2007, 93, pp. 2567– 2580 3 Aculight Corporation, Application Note – Rat Sciatic Nerve, 12/6/06, Revision: 01, (http://www.aculight.com/infrarednervestimulator.html) 4 Zhang, K., Wang, W., Han, J., and Kang, J.U.: ‘A surface topology and motion compensation system for microsurgery guidance and intervention based on common-path optical coherence tomography’, IEEE Trans. Biomed. Eng., 2009, 56, pp. 2318–2321 5 Han, J., Liu, X., Song, C.G., and Kang, J.U.: ‘Common path optical coherence tomography with fibre bundle probe’, Electron. Lett., 2009, 45, pp. 1110– 1112 6 Verdaasdonk, R.M., and Borst, C.: ‘Ray tracing of optically modified fibre tips. 1: Spherical probes’, Appl. Opt., 1991, 30, pp. 2159– 2171 7 Katz, E., Kim, D.H., Ilev, I.K., and Krauthamer, V.: ‘Effects of optical irradiation parameters on safe peripheral nerve stimulation with infrared light’, Proc. SPIE, 2009, 7180, p. 71800P-1
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