## 3 Instrumentation/Technology for Broadband TD-DOS  
The key technical challenges for time domain diffuse optical spectrometry reside in the need to cover a wide spectral range with high sensitivity, down to the single-photon level, and with picosecond temporal resolution. Two different approaches can be envisaged to perform spectroscopy, which is either a sequential scheme, where the laser emitting wavelength within a relatively narrow (\(<\)10 nm) band is scanned progressively over the entire spectral range, or a parallel scheme, where the whole spectral range is acquired simultaneously. On the source side, a laser covering a wide spectral range is needed together with--for sequential wavelength scanning--a proper mechanism for filtering the desired wavelength out of a broad emission or alternatively a pulsed tunable laser. Furthermore, when the application involves biological media, a reasonably short total measurement time is also a must. Different realizations have been proposed in the course of the last decades, based on technical advancements mainly in the generation of supercontinuum laser sources and of time-correlated single-photon counting (TCSPC) detection [57]. The very first demonstration of broadband TD-DOS was realized by exploiting the white light generated from a water cell by a focused 10 Hz amplified laser pulse and a streak-camera for detection [58]. This setup was used to acquire the first in vivo absorption and reduced scattering spectra of the female breast in the 650-820 nm range [59]. In the first realization, a table-top amplified Ti:Sapphire laser was used as an injection source based on a 76 MHz femtosecond self-locking oscillator operated at 790 nm, followed by a pulse stretcher, a first-stage amplifier with intra-cavity dumping for reduction of the repetition rate to 10 Hz, a second stage multi-pass amplifier, and finally a pulse compressor. The outcome was a 10 Hz train of 200 fs pulses with 450 mJ energy, which were then focused onto a water cuvette to produce a white light pulsed emission, representing a considerable achievement at that time. In a more recent realization (Figure 4) [60], the supercontinuum was generated into a 100 cm long photonic crystal fiber starting from a self-locked Ti:Sapphire laser. Light was injected into and collected from the sample under study using a couple of fibers for reflectance measurements or a free beam cell for transmittance measurements. Detection was achieved using an imaging spectrometer for spectral dispersion (Chromex, Model 250 IS) followed by a streak camera for temporal dispersion (Hamamatsu, Model C5680), resulting in 2D (wavelength-time) images projected onto a camera sensor. The key advantages of such an approach were the parallel spectral acquisition and the high temporal  
Figure 3: Monte Carlo simulations on a homogeneous semi-infinite medium in reflectance geometry. The source and detector separation is 1.5 cm. Effect of **(a)** absorption, with the arrow showing the increase in the slope of the distribution of the photon time-of-flight (DTOF) curves with increasing absorption and **(b)** scattering, with the arrow showing the shift in the peak position of DTOF with increasing scattering. resolution (ps) offered by the streak-camera. Also, the almost continuous acquisition over time and wavelength permitted adjustable optimization by slicing temporal and spectral photon distributions at post-processing. As limitations, we can quote the far-from-single-photon sensitivity of the detection, the non-linearity of both the temporal and spectral axes, the limited spectral range imposed by the poor quantum efficiency of the S1 photocathode in the streak-camera under use, and in general the cost/complexity of the workstation. A different concept was based on mode-locked lasers, which were sequentially tuned and permitted the use of single-channel TCSPC detection [57], as shown in Figure 5[22].