We demonstrate bio-medical imaging using a Terahertz quantum cascade laser. This new optoelectronic source of coherent Terahertz radiation allows building a compact imaging system with a large dynamic range and high spatial resolution. We obtain images of a rat brain section at 3.4 THz. Distinct regions of brain tissue rich in fat, proteins, and fluid-filled cavities are resolved showing the high contrast of Terahertz radiation for biological tissue. These results suggest that continuous-wave Terahertz imaging with a carefully chosen wavelength can provide valuable data on samples of biological origin; these data appear complementary to those obtained from white-light images.
©2004 Optical Society of America
The development of Terahertz (THz) technology over the past decade triggered significant advances in the field of sensing and imaging using coherent electromagnetic waves with frequencies 0.1 – 5 THz. The feasibility of THz imaging was demonstrated with systems based on picosecond Terahertz pulses [1–3] and on continuous Terahertz waves [4–6]. While THz pulse imaging has the advantage of providing an image with broad frequency information between 0.1 and 5 THz , the advantage of continuous-wave (CW) THz imaging technique lies in a higher dynamic range due to orders of magnitude higher power spectral density. The problem remaining is the achievable frequency of the CW THz radiation in this imaging modality. The present generation scheme for CW THz radiation is based on photomixing [8–10] using photoconductive GaAs antennas. Generation of THz radiation at frequencies up to 3.8 THz was demonstrated with this type of optoelectronic devices . However, the parasitic impedance intrinsic to the device, and the impedance mismatch between the device and the radiating antenna, severely limits the output power at frequencies above 1 THz.
Another, more technical, issue is the need for two lasers, which have to be operated at a defined small wavelength difference. A small two-wavelength semiconductor NIR laser unit recently addressed this problem , but the level of the generated THz power at high frequencies did not exceed the 1 μW level.
Very recent advances in the technology and design of quantum cascade (QC) lasers have pushed them from the MIR to the THz frequency region. These single frequency sources of CW radiation have demonstrated to emit at 66 μm (4.54 THz) [12,13], 87 μm (3.45 THz) [14,15], and 100 μm (3.0 THz) . The peak THz power achieved with these lasers is at mW levels and thus QC lasers open the field for imaging with CW THz radiation to a broad range of applications.
In this paper we present the first demonstration of imaging at Terahertz frequencies using a Terahertz quantum cascade laser. In the imaging system a nearly diffraction limited resolution and a dynamic range of 1000 was obtained at a wavelength of 87 μm (3.45 THz). The capabilities of THz QC lasers based imaging system were demonstrated on a tissue sample of the brain.
2. Terahertz imaging system setup
2.1 Terahertz quantum cascade laser
The Terahertz quantum cascade laser used of the present report is a unipolar GaAs/AlGaAs hetero-structure and the lasing transition is a bound-to-continuum intersubband transition .
The device consists of 120 periods of the active region embedded between two n-doped contact regions. A surface plasmon guiding metal on top and the buried n-doped GaAs contact layer forms the waveguide. The structure was processed into a ridge laser with a 160 μm wide and about 3 mm long waveguide. The laser was mounted on the cold finger of a helium-flow cryostat with TPX (Terahertz transparent copolymer polymethylpentene with low index of refraction) windows.
The electrical and optical performance of the laser is shown in Fig. 1. The threshold current density for lasing is 0.28 kA/cm2. The laser emission is at frequency of 3.43 THz (~87 μm). At low currents the emission is single line, at larger operating current densities higher modes appear in the emission spectrum (see inset in Fig.1).
2.2 Terahertz imaging optics and detector
The Terahertz imaging system (Fig. 2) consists of reflective optics to avoid problems with standing wave pattern. An off-axis parabolic mirror PM1 located outside the cryostat collects the emission from the THz-QC laser. The laser beam divergence angle is about 30°. We used a 25 mm diameter wedged TPX windows on the cryostat and a 50 mm diameter off-axis parabolic collecting mirror with a focal length of 100 mm. Optics with large numerical aperture is essential for a good quality guiding and focusing of the Terahertz radiation. A large beam diameter is also essential to reach a diffraction-limited focus at the object.
Behind the collimating mirror PM1 the laser beam is guided through a silicon non-polarizing beam splitter to another off-axis parabolic mirror PM2 (see Fig.1). This mirror with a focal length of 50 mm focuses the THz radiation onto the object. The object is mounted on a computer controlled 2-D translational stage. In order to obtain either information related to the reflection from the object or to the transmission through the object, low or high reflective holders were used respectively.
The transmitted or reflected THz radiation is collected with a parabolic mirror PM2 and sent through the beam splitter onto the last mirror PM3. This mirror focuses the radiation onto a THz detector. For this work we have used a He cooled silicon bolometer, however more convenient detectors like Schottky diodes, pyroelectric detectors or novell quantum well intersuband detectors could be used as well. The whole imaging set-up was enclosed in a sealed box and purged with dry nitrogen to suppress the absorption induced by a water vapor.
The THz-QC laser operated at 5 K and run in the pulsed mode at repetition frequency of 400 Hz (given by a limited frequency response of the bolometer) and pulse width of 100 ns. The peak power of the generated THz pulses was about 20 mW (i.e., pulse energy ~ 2 nJ).
3 Experimental results
3.1 Spatial resolution of imaging system
One of the key parameters of the imaging system is the spatial resolution. We have evaluated this parameter on a object phantom which carries series of gold stripes of different width and pitch. The phantom is scanned across the THz focus and the reflected THz signal is recorded (see inset in Fig. 3). That gives the THz signal modulation with the spatial period equal to the stripes’ pitch. The modulation depth MD is evaluated then as follows:
, where Imax and Imin are the maximum and minimum signal intensities. Finally, the spatial resolution is obtained as a reciprocal value of the stripes’ pitch for which a modulation depth MD of 50% is obtained.
The fundamental mode of the laser is TEM00 and with respect to the geometry of the laser waveguide we expect an elliptical shape of the THz beam. Actually, the experimental data on the achieved resolution prove that (see Fig. 3). The spatial resolution is about 170 and 240 μm when scanning in the sample plane (X and Y directions). The polarization of the laser beam was always oriented in 45 degree with respect to the stripes. We conclude that the beam ellipticity in the focus is about 2:3. The achieved resolution is slightly larger than that given by the diffraction limit. We believe that non-optimal coupling of the laser radiation to the first off-axis parabolic mirror is the key problem of the imaging system setup and will be addressed in future work.
The dynamic range of the present imaging system setup is about 1000. We performed an analysis of the sources of the noise in our system. We found that i) a pulse-to-pulse instability of the THz-QL laser; ii) 1/f detector and electronics noise contribute to the obtained noise level and hence achieved dynamic range. Since we used a silicon composite bolometer as THz detector, which is intrinsically slow, a low modulation frequency <500 Hz had to be used during imaging. An improvement of the signal dynamic range can be achieved using novel high-speed detector  locked to the pulses driving the THz-QC laser.
3.2 Image of a rat brain histology sample
The imaging capability of the system setup with THz QC laser as a radiation source was demonstrated on a specimen of rat brain. Thin sections through the rat brain were provided by the Research Laboratory of the Dept. of Neurology at the University of Innsbruck (Austria). The sections came from a surplus pool generated during a study on embryonic neural grafts in a rat model of striatonigral degeneration . For the preparation of brain sections the animals were perfused transcardially with paraformaldehyde (4%) and the brain was cut on a cyrotome at a thickness of 32 μm. The sections were stored in ethylene and for THz imaging were mounted on a gold-coated flat glass substrate.
During alignment in the imaging system close attention was paid to the tilt of the sample holder to suppress Fabry-Perot modulation of the background in the image. Figure 4 shows white-light and THz images of the brain tissue samples. The THz images were collected in transmission mode at scanning step size of 200 μm. The field of view is about 10x15 mm. The data acquisition rate was 1 pixel per second. The figures show frontal sections through the rat brain in which the cerebral cortex, the corpus callosum, hippocampal structures, the lateral ventricles and the basal ganglia can all be identified clearly.
THz images allow clear identification of the anatomical structures of the rat brain. The dark (high absorption) structures in the image seem to correlate with white matter tissue (e.g., corpus callosum, hippocampus, capsula interna, commisura anterior) which are more or less heavily myelinated and they consist largely of lipids, i.e., fats. The differing gray values thereby seem to correspond to the differing content of fat. The gray matter of the brain (e.g., cortical cortex), which naturally has a much higher content of water and proteins, gives higher signal intensities in THz images (less absorption) than do tissues with high fat content. Since THz radiation is usually strongly absorbed by water it has to be noted that during sample preparation the brain sections were dehydrated. The brightest structures (the lowest THz absorption) in the images correspond to the ventricular system, which in-vivo contains water (in the form of cerebrospinal fluid) and in-vitro contained air.
The results presented here clearly indicate that THz images obtained with the method described above give anatomically meaningful results reflecting, for the brain section used, mainly the fat distribution of the respective tissue. Especially in brain tissue the fat distribution is correlated to the degree of myelination, which is important for several degenerative disorders. It is to be expected that loss of lipids in demyelinating disorders would be highlighted clearly in images of this type. Other pathologies which should be easily detectable on this kind of THz images include oedema, comprising local accumulations mainly of water, and tumors which generally contain little fat, often have an oedematous edge, and which may disturb the normal anatomical relationships which can be seen clearly in such images.
The bio-medically-relevant imaging at frequency of 3.4 THz is presented. For the first time a Terahertz quantum cascade laser source of coherent radiation was used. We have obtained images with spatial resolution better than 250 μm and dynamic range of about 1000. With these data THz imaging offers adequate spatial resolution and contrast for the visualization of structural details of a small mammalian brain, a structure of high complexity. The present images base largely on contrast derived from differential absorption of THz frequencies by lipid-rich and water-rich tissues.
The work was in part supported by the Austrian Science Foundation (FWF SFB ADLIS). Authors kindly acknowledge the Neurologic research laboratory (University of Innsbruck, Austria) for providing the brain sections and Dr. T. Fitzgerald (now with TeraView Ltd., U.K.) for providing the image test phantoms.
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