A miniaturized fiber-coupled terahertz endoscope system

In this study, we have designed, fabricated, and characterized a miniaturized optical fiber-coupled terahertz (THz) endoscope system. The endoscopic system utilized a photoconductive generator and detector driven by a mode-locked Ti:sapphire laser. In reflection mode, the endoscope showed a high signal-to-noise ratio and a wide frequency spectrum similar to the conventional THz time-domain spectroscopic system. The cross section of the endoscope including generator and detector head is (2 × 4 mm) × 6 mm, which is small enough to be inserted into a human body. For a feasibility test, the endoscopic system was used to measure reflective THz signals from the side wall of the mouth, tongue, and palm skin as well as from water for comparison. The absorption and refractive index of the side wall of the mouth and tongue were similar to those of water but those of the palm skin were less than water. ©2009 Optical Society of America OCIS codes: (040.2235) Far infrared or terahertz; (300.6495) Spectroscopy, terahertz; (060.2390) Fiber optics, infrared; (170.2150) Endoscopic imaging; References and links 1. R. M. Woodward, V. P. Wallace, R. J. Pye, B. E. Cole, D. D. Arnone, E. H. Linfield, and M. Pepper, “Terahertz pulse imaging of ex vivo basal cell carcinoma,” J. Invest. Dermatol. 120(1), 72–78 (2003). 2. A. J. Fitzgerald, V. P. Wallace, M. Jimenez-Linan, L. Bobrow, R. J. Pye, A. D. Purushotham, and D. D. Arnone, “Terahertz pulsed imaging of human breast tumors,” Radiology 239(2), 533–540 (2006). 3. J.-H. Son, “Terahertz electromagnetic interactions with biological matter and their applications,” J. Appl. Phys. 105(10), 102033 (2009). 4. K. Wang, and D. M. Mittleman, “Metal wires for terahertz wave guiding,” Nature 432(7015), 376–379 (2004). 5. T.-I. Jeon, and D. Grischkowsky, “Direct optoelectronic generation and detection of subps electrical pulses on sub-mm coaxial transmission lines,” Appl. Phys. Lett. 85(25), 6092–6094 (2004). 6. T.-I. Jeon, J. Zhang, and D. Grischkowsky, “THz Sommerfeld wave propagation on a single metal wire,” Appl. Phys. Lett. 86(16), 161904 (2005). 7. J. V. Rudd, and D. M. Mittleman, “Influence of substrate-lens design in terahertz time-domain spectroscopy,” J. Opt. Soc. Am. B 19(2), 319–329 (2002). 8. S. A. Crooker, “Fiber-coupled antennas for ultrafast coherent terahertz spectroscopy in low temperatures and high magnetic fields,” Rev. Sci. Instrum. 73(9), 3258–3264 (2002). 9. C. Jördens, N. Krumbholz, T. Hasek, N. Vieweg, B. Scherger, L. Bahr, M. Mikulics, and M. Koch, “Fibrecoupled terahertz transceiver head,” Electron. Lett. 44(25), 1473–1475 (2008). 10. S. J. Oh, J. Kang, I. Maeng, J.-S. Suh, Y.-M. Huh, S. Haam, and J.-H. Son, “Nanoparticle-enabled terahertz imaging for cancer diagnosis,” Opt. Express 17(5), 3469–3475 (2009). 11. D. E. Spence, P. N. Kean, and W. Sibbett, “60-fsec pulse generation from a self-mode-locked Ti:sapphire laser,” Opt. Lett. 16(1), 42–44 (1991). 12. J.-H. Son, J. V. Rudd, and J. F. Whitaker, “Noise characterization of a self-mode-locked Ti:sapphire laser,” Opt. Lett. 17(10), 733–735 (1992). 13. M. T. Reiten, and R. A. Cheville, “Effect of spherical aberration and surface waves on propagation of lenscoupled terahertz pulses,” Opt. Lett. 30(6), 673–675 (2005). 14. M. V. Exter, and D. Grischkowsky, “Optical and electronic properties of doped silicon from 0.1 to 2 THz,” Appl. Phys. Lett. 56(17), 1694–1696 (1990). 15. C. Winnewisser, F. Lewen, and H. Helm, “Transmission characteristics of dichroic filters measured by THz time-domain spectroscopy,” Appl. Phys., A Mater. Sci. Process. 66(6), 593–598 (1998). 16. S. A. Maier, S. R. Andrews, L. Martín-Moreno, and F. J. García-Vidal, “Terahertz surface plasmon-polariton propagation and focusing on periodically corrugated metal wires,” Phys. Rev. Lett. 97(17), 176805 (2006). #113732 $15.00 USD Received 2 Jul 2009; revised 13 Aug 2009; accepted 2 Sep 2009; published 10 Sep 2009 (C) 2009 OSA 14 September 2009 / Vol. 17, No. 19 / OPTICS EXPRESS 17082 17. E. Pickwell, and V. P. Wallace, “Biomedical applications of terahertz technology,” J. Phys. D Appl. Phys. 39(17), 301–310 (2006). 18. V. P. Wallace, A. J. Fitzgerald, E. Pickwell, R. J. Pye, P. F. Taday, N. Flanagan, and T. Ha, “Terahertz pulsed spectroscopy of human Basal cell carcinoma,” Appl. Spectrosc. 60(10), 1127–1133 (2006). 19. T.-I. Jeon, and D. Grischkowsky, “Characterization of optically dense, doped semiconductors by reflection THz time domain spectroscopy,” Appl. Phys. Lett. 72(23), 3032–3034 (1998).


Introduction
Studies reveal that terahertz (THz) electromagnetic (EM) waves can be employed to distinguish cancerous tumors from healthy tissues [1,2] and a lot of research is being done worldwide to develop a THz cancer diagnostic system that may be used for medical imaging [3].However, because of the large EM absorption due to water molecules in the THz frequency region, such new system will be used for certain applications such as diagnosing skin and breast cancers or during surgical procedures.To extend the versatility of the THz based diagnostic system to the internal organs of the body, an endoscope should be developed.Extensive research is being done on developing efficient waveguides at THz frequencies.The propagation of THz waves has been studied on metal wires [4] and sub-mm coaxial cables [5].However, these waveguides are not practical for THz endoscopes as the small bends of a metal wire can significantly attenuate the guided signal [4,6].A realistic alternative is to generate and detect THz signals near the reflective surface of an organ through the excitation of generator and detector by an optical fiber coupled femtosecond laser.Recently fiber-coupled THz time-domain spectroscopic (TDS) system [7][8][9] was reported, but they were too big to be applied as an endoscope.Meanwhile the necessity of guiding a visible or infrared (IR) laser beam near an organ surface also comes from a newly invented THz cancer diagnosis technique.Cancer cells targeted with nanoparticle-contrast agents demonstrated a huge THz signal modulation as high as 3,000% upon differential illumination using IR laser beam [10].This scheme requires irradiation by an IR laser and can be achieved with one laser, such as the mode-locked Ti:sapphire laser [11,12], if a fiber-coupled endoscopic system is utilized to generate and detect THz.
In this paper, we have designed, fabricated, and characterized a miniaturized fiber-coupled THz endoscopic system that utilizes a photoconductive generator and detector driven by a mode-locked Ti:sapphire laser through dispersion compensated optical fibers.With the generator and detector attached parallel to each other, the endoscope head is only 8 mm × 6 mm that is small enough to be inserted into a human body.This endoscope system was tested by the measurements of reflective THz signals from the side walls of the mouth, tongue, palm skin and as well as from water for comparison.

THz endoscope system
The experimental setup for the THz endoscopic system with fiber-coupled generator and detector is schematically represented in Fig. 1(a).Laser pulses from the Ti:sapphire modelocked laser have approximately 70 fs duration at a repetition rate of 83 MHz.To compensate for the group velocity dispersion occurring in the optical fibers, the laser pulses are dispersion-compensated using a grating pair before being injected into the 2 m long singlemode optical fiber.The average laser beam power at the output of the optical fiber is 12 mW to the generator and 6.8 mW to the detector.As shown in Fig. 1(b), the length of generator or detector modules is 26 mm including fiber ferrule which is 2.46 mm diameter and 10.46 mm long.With an outside diameter of 6 mm, the modules are cut on both side surfaces to reduce the width to 4 mm as shown in Fig. 1(c).When the generator and detector are attached at a parallel, their cross section is (2 × 4 mm) × 6 mm.Each module consists of fiber ferrule, silicon lens, optical lenses, a generator chip (1.8 mm x 1.9 mm) and a detector chip (2 mm x 2.8 mm).The optical lenses are composed of a 3 mm diameter drum lens and a plano-convex lens in order to focus laser beams on the generator and detector chips.The radius and the diameter (plano-surface) of the silicon lens are 2.5 mm and 4 mm respectively.While the height of the silicon lens used for the generator and detector are 3.03 mm and 3.16 mm respectively.Because of the silicon lens design, the emitted THz beam concentrates most at the center of the beam radiation [13].All electrical and optical parts are fixed by epoxy in the limited volume of the module.The simple coplanar transmission lines structure of the generator chip consists of two 10 µm wide metal lines separated by 200 µm fabricated on high resistivity GaAs.The guided laser beam from the optical fiber is focused on the metal-GaAs interface with + 90 V peak ac bias with 500 Hz frequency.The THz radiation detector used a low temperature grown GaAs chip with dipole antenna geometry.The 10 µm wide dipole antenna structure with a 5 µm gap is embedded in a coplanar transmission line consisting of two parallel 10 µm wide lines separated from each other by 20 µm.The THz beam directed towards the receiving antenna by the silicon lens.The amplitude of the peak transient voltage induced across the receiving antenna is obtained by measuring the collected charge which represents current [14].The generator ac bias lines and detector signal lines extend from out of the middle of the modules to connect to the ac power source and current amplifier, respectively.The bias and signal lines use a 1.1 mm diameter coaxial cable.Since the generator and detector modules are very compact, the THz system can be used as endoscope in order to measure in vivo samples.

Propagation of THz beams
The inserted graph in Fig. 2 (a) shows the THz pulse when the generator and detector are separated by 2 cm for face-to-face measurement.The THz pulse is obtained by a single measurement without any filtering process.Because the silicon lens is not precisely aligned, there is a bump near 14 psec.The generator and detector chips are attached to the silicon lens using an optical microscope without any THz chip alignments.Therefore, the THz antennas may not have been perfectly positioned at the center of the silicon lens.However the amplitude of the bump is only 3.2% compared to the main THz pulse, which has 6.2 nA peakto-peak amplitude.Since the generator and detector are closely located, the offset of the THz pulse is 520 pA.Although all optical and electrical parts are fixed into the tiny module, the amplitude of the THz signal is very high.The full width half maximum of the measured THz pulse is found to be 0.5 psec.As shown in Fig. 2(b), the corresponding amplitude spectrum using a numerical Fourier transform extended to beyond 2 THz.The peak of the amplitude spectrum is 0.43 THz.Low and high cutoff frequencies which are defined by exp(−1) are 0.16 THz and 0.97 THz respectively.
The generator module is moved by ±20 degrees from the center line, maintaining 2 cm separation in order to determine any divergence in THz radiation.The measured 3-dimensional THz pulses are shown in Fig. 2(a).The amplitude is dramatically reduced upon increasing the angle, which depends on the 3-dimensional THz spectra of each pulse as shown in Fig. 2(b).The spectrum amplitude and bandwidth are also dramatically reduced upon increasing the angle.Because of the silicon lens design, most of the THz energy concentrates at the center.Figure 2(c) shows the peak-to-peak pulse amplitude with different distances between the generator and detector.The dots represent the experimental data and the solid curves represent the Lorentzian fits.When the measurement is normalized, the exp (−1) exists at ± 8.1 degrees at 2 cm separation.When the detector module is moved back, the distance between the generator and detector is increased from 8 cm to 12 cm to 20 and the peak-topeak pulse amplitudes are reduced to 2 nA, 1.3 nA, and 0.7 nA, respectively.In order to get larger THz signals, the incidence angle and distance to the target should be small so that it may be used as a THz endoscope.

Applications of endoscopes
Because of fiber-coupled design of the generator and detector modules, application of the endoscope (reflection measurement) is possible without any optical alignments for in vivo human samples.The generator and detector are closely adjusted with 3 mm separation and 20 degree angle from each other as shown in Fig. 1(a).The electric field from 90V ac bias of the generator influences the detector chip and it increases offset to the signal.A metal plate is inserted between the generator and detector modules to reduce the offset.In order to create the same incident angle and even surface of the samples, a 3 mm thick and 15 mm diameter Teflon plate is attached to the modules as shown in the inset of Fig. 3(a).The distance from the end of the silicon lens to the Teflon plate is 1.5 cm, with which the samples are in contact.The refractive index of Teflon is 1.44 in our measured frequency range [15]. is replaced by the samples.Since metallic surface is almost a perfect conductor in THz frequency range [16], the reflected THz pulse from the Al surface is considered as reference.
Because of the refractive index of water at THz frequency range [3,17], the peak-to-peak amplitude of the reflected THz pulse is reduced at approximately 73% compared with the reference.As the human body is mostly composed of water (70%), the THz pulses reflected from the side wall of the mouth and tongue are also reduced by 76% and 73% respectively.However, the THz reflected by the skin is reduced about 83%, 10% smaller than the amplitude of water reflection, primarily because the dryness of the skin results in a refractive index that is a bit lower than that of water [17,18].Figure 3(b) shows the spectra of the samples.The reference spectrum extends up to 2.5 THz while the relative amplitude of the other samples extends to 2.0 THz because of less reflection at a high frequencies.The amplitude of the side wall of the mouth, tongue, and water are little bit different whereas that of the skin is much lower at the measured frequency range.The ratio of the skin is only 73% and 62% compared to those of the side wall of the mouth and tongue respectively at 0.5 THz.Since reflected THz signals have magnitude and phase information for the samples, the refractive index and power absorption will be measured without Kramers-Kronig (K-K) analysis [19].The real (n) and imaginary (k) part of refractive index are given by: where R and θ are magnitude ratio and phase difference between reference and output signal, respectively.n Tef is the refractive index of the Teflon.We neglect the 3-degree incident angle from the Teflon to samples.The relationship between imaginary refractive index and power absorption is α=4πfk/c, where f is a given THz frequency and c is the speed of light.The measured refractive index and power absorption are shown in Fig. 4. The solid lines indicate fitting curves for the measurements.Because the refractive index of the Teflon is very sensitive to temperature, the phase information cannot be taken precisely.Therefore, we measured it several times and marked the ensuing error bars in the figure.However, the refractive index and power absorption of water are very similar compared to the previous measurements [3,17,18].While the side wall of the mouth and tongue possess similar characteristics with that of water, the skin has much lower refractive index and power absorption.The human adipose (fat) tissue has much lower refractive index and power absorption compared to a healthy skin [17].Therefore, the skin changes in characteristics depending on its adipose contents.

Summary and conclusions
In order to realize a THz endoscopic system, we developed a millimeter size generator and detector modules ((2 × 4 mm) × 6 mm cross section) excited by an optical fiber-guided femtosecond laser.The peak-to-peak amplitude of THz signal is 6.2 nA and its spectrum extends up to 2 THz in face-to-face measurement.The modules were inserted in the mouth for the simulation of THz endoscopy and the reflections were measured from the side wall of the mouth and tongue.From the measurements, the absorption and dispersion of the samples were obtained without K-K analysis.The refractive index and power absorption of the side wall of the mouth and tongue are similar to those of water.This might be due to the moist surfaces of the side wall of the mouth and tongue.To develop commercial endoscopes, this moist problem on internal organics has to be overcome by sucking water or liquids from surface.The values obtained for the skin are lower because of the skin's adipose content.
If the surfaces of soft internal organs changed, we expect, the THz beam can detect the surface conductions, which would show the possibility of THz endoscope to detect changes in tissues with the human body.With this miniature endoscopic system, THz signal detection for the respiratory tract and stomach will be performed in the future.

Fig. 2 .
Fig. 2. THz transmission measurement with different angles for 2cm separation between generator and detector modules (The inset pulse and spectrum are for the case when generator and detector are in a straight line).(a) Time domain THz pulses.(b) Spectra; (c) Angle dependent peak-to-peak THz amplitude with different separations.

Figure 3 (
a) shows the measured reflective THz signals from the side wall of the mouth, tongue, palm skin, water, and aluminum (Al) surfaces.The pulses are numerically shifted for comparison.After the measurement of the THz reflection from the Al surface, the Al surface #113732 -$15.00USD Received 2 Jul 2009; revised 13 Aug 2009; accepted 2 Sep 2009; published 10 Sep 2009 (C) 2009 OSA

Fig. 4 .
Fig. 4. Measured absorption and dispersion of samples.(a) Refractive index of water and side wall of mouth.(b) Refractive index of tongue and skin.(c) Power absorption of water and side wall of mouth.(d) Power absorption of tongue and skin.