Time-domain diffuse optics[1] or time-resolved functional near-infrared spectroscopy is a branch of functional near-Infrared spectroscopy which deals with light propagation in diffusive media.
There are three main approaches to diffuse optics namely continuous wave[2] (CW), frequency domain[3] (FD) and time-domain[4] (TD).
Biological tissue in the range of red to near-infrared wavelengths are transparent to light and can be used to probe deep layers of the tissue thus enabling various in vivo applications and clinical trials.
The two main phenomena affecting photon migration in diffusive media are absorption and scattering.
Scattering is caused by microscopic refractive index changes due to the structure of the media.
Since absorption and scattering have different effects on the DTOF, they can be extracted independently while using a single source-detector separation.
Moreover, the penetration depth in TD depends solely on the photon arrival times and is independent of the source-detector separation unlike in CW approach.
It has been demonstrated that radiative transfer equation under the diffusion approximation yields sufficiently accurate solutions for practical applications.
The final DTOF is a convolution of the instrument response function (IRF) of the system with the theoretical reflectance curve.
Instrumentation in time-domain diffuse optics consists of three fundamental components namely, a pulsed laser source, a single photon detector and a timing electronics.
Time-domain diffuse optical sources must have the following characteristics; emission wavelength in the optical window i.e. between 650 and 1350 nanometre (nm); a narrow full width at half maximum (FWHM), ideally a delta function; high repetition rate (>20 MHz) and finally, sufficient laser power (>1 mW) to achieve good signal to noise ratio.
In the past bulky tunable Ti:sapphire Lasers[6] were used.
In recent years, pulsed fiber lasers based on super continuum generation have emerged.
[7] They provide a wide spectral range (400 to 2000 ps), typical average power of 5 to 10 W, a FWHM of < 10ps and a repetition frequency of tens of MHz.
However, they are generally quite expensive and lack stability in super continuum generation and hence, have been limited in there use.
[8] They have a FWHM of around 100 ps and repetition frequency of up to 100 MHz and an average power of about a few milliwatts.
Even though they lack tunability, their low cost and compactness allows for multiple modules to be used in a single system.
Single photon detector used in time-domain diffuse optics require not only a high photon detection efficiency in the wavelength range of optical window, but also a large active area as well as large numerical aperture (N.A.)
They also require narrow timing response and a low noise background.
Traditionally, fiber coupled photomultiplier tubes (PMT) have been the detector of choice for diffuse optical measurements, thanks mainly due to the large active area, low dark count and excellent timing resolution.
However, they are intrinsically bulky, prone to electromagnetic disturbances and they have a quite limited spectral sensitivity.
They are low cost, compact and can be placed in contact, while needing a much lower biasing voltage.
Also, they offer a wider spectral sensitivity and they are more robust to bursts of light.
This is done by using the technique of time-correlated single photon counting[10] (TCSPC), where the individual photon arrival times are marked with respect to a start/stop signal provided by the periodic laser cycle.
Systems based on ADCs generally have a better timing resolution and linearity while being expensive and the capability of being integrated.
TDCs, on the other hand, can be integrated into a single chip and hence are better suited in multi-channel systems.
Making it a powerful diagnostic tool for long-term bedside monitoring in infants and adults alike.