History Background

Just weeks after Wilhelm Conrad Roentgen discovered X-rays in 1895, the first medical imaging with this new type of radiation was taken. Since then, X-rays have become an invaluable tool in medical diagnosis. However, despite its fascinating possibilities, this technique has some counterparts and disadvantages. The most obvious is that X-rays are ionizing, and therefore harmful to living organisms, and can cause cancer, so its use for disease prevention is discarded. Furthermore, the spatial resolution of X-ray images is limited not only by the wavelength between 0.1 to 10 nanometers, but by the fundamental effect of "Rayleigh scattering". Even with today’s most modern techniques, the best achievable resolution is not more than 50 micrometer. The absorption of X-rays is proportional to the thickness and density of the tissues under study and to the cube of the atomic number of the items it contains. As a result, it is not possible to distinguish between soft tissues and organs due to low contrast.

Since these limitations are intrinsic to X-rays and can not be solved, new diagnostic techniques such as Computed Tomography (CT) were devised. These techniques, using X-Ray transmitters and receivers allow for a three-dimensional image of the body under inspection. Anyway, the information obtained is limited by the maximum power transmitters can emit while avoiding X-Rays being too harmful to the living tissues. In addition, CT has less contrast than the two-dimensional images of X-rays, having to apply external contrasts in order to enhance the images.

For a great contrast, images based on magnetic resonance imaging (MRI) must be used. These use microwave emissions that occur between the different transitions from levels of spins in order to get the picture. The transition frequency can be controlled through the use of an external magnetic field, giving rise to a separation of the spins of nuclear states. Using magnetic field gradients, achieve different spatial positions can be achieved. The signal strength depends on the longitudinal relaxation time of the microwave transitions. As they have different values for different tissues due to the difference in water content of the same, it provides a great contrast in the image. However, the spatial resolution is limited to 0.5mm by the frequency at which the transitions are produced.

Another important alternative approach is the Positron Emission Tomography (PET), which is under development and expected to soon be imposed as a routine technique for early detection of cancer. In this case, the patient is injected a glucose containing radioactive isotopes that emit positrons. The sugar molecules accumulate in regions with a high metabolic activity. There is a radiation of positrons when they find an electron in its journey inside the body, which is detected outside. This radiation has a frequency of operation whose resolution is of the order of 1 or 2 mm so that the spatial resolution of this technique is very poor.

Sonography is an imaging technique that uses longitudinal sound waves instead of transverse electromagnetic waves. In this case, you use generator that emits ultrasonic frequencies between 2 and 30 MHz is used. Due to the mismatch in different tissues of the wave when spreading within the body, an echo reflection is detected at the sender. From this echo, images of different organs or tissue sections, showing details of the analyzed organs, can be obtained. The spatial resolution and depth of penetration that are achieved depend on the frequency at which they work. While a 2 MHz frequency can penetrate several hundred cm in the tissues of the body with a resolution of about 400 micrometers, a 30 MHz frequency, achieves 25 micron resolution with a limited penetration depth of a few centimetres.

There are also other techniques based on reflection of light called optical coherence tomography (OCT). This technique is quite new and allows imaging of sections of organs by analyzing the time delay and the magnitude of the echo of light when reflected in the tissues or organs in different positions. The achieved spatial resolution is of the order of 1 to 15 microns, which is two orders of magnitude higher than ultrasonography, but the depth of penetration is limited to 2-3 mm.

All these techniques allow in vivo diagnosis thanks to its depth of penetration, but there are other techniques that require small samples of tissue from the patient. The most prominent is using the optical microscope, which has a resolution of several hundred nanometers. However, it often requires the use of substances to ensure sufficient contrast to see the images correctly. Recent advances include laser scanning microscopy and scanning microscopy of two photons; both give rise to three-dimensional images with resolutions comparable to those obtained in two dimensions with the microscope. The spatial resolution of these techniques is sufficient to discern details within cells. Less spatial resolution is obtained when the working wavelength of the diagnostic technique becomes larger. Spectroscopy based on Fourier Transform Infrared (FTIR) working between 120 and 380THz and mid-infrared 12-120THz is appropriate for information on the chemical composition of biological and medical samples with a resolution from few hundreds of microns (depending on working frequency).

The realization of THz imaging in the far infrared range from 0.3 to 10THz allows achieving resolutions of a few hundred microns, and will provide information on the chemical composition of tissue samples, provided it is not too thick, as well as incorporating the advantages of Sonography and OCT due to the coherence of the emitting source. The use of this technology in medical diagnosis will be a new source of information that allow the physician to make fewer errors in diagnosis by allowing getting more benefits in the observation of both organs and tissues in vivo. It is also a source of information on laboratory samples for DNA detection and analysis because their emissivity peaks in this frequency range. A remarkable fact of this technique is that it is NON-IONIZING radiation, so that this technique can be used to prevent diseases without harming the living. By using THz signals, due to their coherence, one can detect both intensity and phase, and do as a function of frequency. This is one of the differences of THz against X-rays, MRI, PET, etc., which only detect intensity and also provide information on the frequency. Thus, in addition to the imaging applications previously described, it is feasible to carry out spectroscopy.

Thus, by spectroscopy, THz can detect specific materials (biomolecules, drugs, etc..), because the vibrations and rotations of low frequency single molecules or between molecule bounds occur in this frequency range.

For example using spectroscopic techniques in the THz range the spectral response of different molecules ("fingerprint" of the molecule) can be studied. Thus, with THz radiation changes in biomolecules such as proteins (markers in some cancers), and DNA (denatured and hybridized) can be detected. There are also applications in the distinction between different crystalline forms, mixtures, etc., which are of great utility in the pharmaceutical industry.

Moreover, due to the high absorption of THz radiation in water, which is the main component of biological tissues, high contrast between skin, muscle, fat, veins, nerves, etc can be obtained. In particular, this high sensitivity of THz to the concentration of water provides a high contrast between tumour (high water content) and normal tissues. Thus, characterizing the refractive index and absorption of various tissues is the key to the use of THz in the Life Sciences both for spectroscopy and imaging and in the design of biochips.