The study of photon propagation in highly scattering media (diffuse optics) is a powerful tool to noninvasively investigate biological tissues in depth.^1,2 For most biological media in the 600- to 1100-nm range, the scattering coefficient is much higher than the absorption coefficient, thus hindering information from the human body that in absence of scattering would appear transparent as a feebly colored glass. The attractiveness of probing the human tissues and their functions with light has fostered great efforts to cope with the challenges of “diffuse optics,” leading to a whole range of new physical concepts, theoretical models, instruments, measurement approaches, and applications. The terms near-infrared spectroscopy (NIRS) and diffuse optical imaging (DOI) are used in the scientific community to refer to the techniques used for noninvasive monitoring and imaging with diffuse light. Typically, light is injected into the medium and the signal re-emitted at some distance(s) on the surface is analyzed to retrieve information carried by photons along their paths. In the simplest case, continuous wave (CW) illumination and detection are employed.³ 4. ^{– 5} Conversely, the adoption either of a frequency-domain (FD)⁶ or of a time-domain (TD)⁷ 8. 9. ^{– 10} scheme permits to add a further dimension in the measurement, e.g., disentangling absorption from scattering contributions.

We present a CMOS imager consisting of 32×32 smart pixels, each one able to detect single photons in the 300-900 nm wavelength range and to perform both photon-counting and photon-timing operations on very fast optical events with faint intensities. In photon-counting mode, the imager provides photon-number (i.e, intensity) resolved movies of the scene under observation, up to 100 000 frames/s. In photon-timing, the imager provides photon arrival times with 312 ps resolution. The result are videos with either time-resolved (e.g., fluorescence) maps of a sample, or 3-D depth-resolved maps of a target scene. The imager is fabricated in a cost-effective 0.35-μm CMOS technology, automotive certified. Each pixel consists of a single-photon avalanche diode with 30 μm photoactive diameter, coupled to an in-pixel 10-bit time-to-digital converter with 320-ns full-scale range, an INL of 10% LSB and a DNL of 2% LSB. The chip operates in global shutter mode, with full frame times down to 10 μs and just 1-ns conversion time. The reconfigurable imager design enables a broad set of applications, like time-resolved spectroscopy, fluorescence lifetime imaging, diffusive optical tomography, molecular imaging, time-of-flight 3-D ranging and atmospheric layer sensing through LIDAR.

In recent years, diffuse optical spectroscopy (DOS) is advancing as a promising tool for noninvasive quantification of tissue constituents in pathological diagnostics.¹ 2. 3. ^{– 4} Traditionally, in vivo diffuse optical measurements have been performed, at most, in the 600- to 1100-nm window.⁵ 6. ^{– 7} This is due to high hemoglobin absorption below 600 nm and dominant water absorption combined with lack of suitable detection technology above 1100 nm. Furthermore, studies are most often performed below 900 nm, where more conventional and cheaper detectors are available. However, recent investigations emphasize the advantage of high penetration depth and enhanced constituent specificity in the short wave infrared (SWIR) 1100- to 1700-nm range.⁸ 9. ^{– 10} Importantly, the lack of systematic characterization of tissue constituents in the SWIR range prevents its widespread use for in vivo applications.

We demonstrate the feasibility of time-resolved diffuse reflectance measurements at small source-detector separations using a single-photon avalanche diode operated in time-gated mode. Photon time distributions at an interfiber distance of 2 mm were obtained on a homogeneous tissue phantom with a dynamic range of ${10}^6$ and collecting photons at arrival times up to 4 ns. Moreover, we were able to detect a local inhomogeneity deeply buried within a diffusive medium with better spatial resolution, higher signal intensity, and same contrast of a larger (20 mm) interfiber distance. Finally, the proposed approach proved valuable to detect in vivo a task-related brain activation.

In many time-domain single-photon measurements, wide dynamic range (more than 5 orders of magnitude) is required in short acquisition time (few seconds). We report on the results of a novel technique based on a time-gated Single-Photon Avalanche Diode (SPAD) able to increase the dynamic range of optical investigations. The optical signal is acquired only in well-defined time intervals. Very fast 200-ps gate-ON transition is used to avoid the undesired strong signal, which can saturate the detector, hide the fainter useful signal and reduce the dynamic range. In experimental measurements, we obtained a dynamic range approaching 8 decades in few minutes of acquisition.