Near-Infrared Optical Tomography with Single-Photon Avalanche Diode Image Sensors

In the past decades different methods based on magnetic resonance imaging (MRI) and positron emission tomography (PET) have been developed to image a variety of hemodynamic parameters in tissue. However, simultaneous high resolution imaging of oxy- and deoxyhemoglobin is not yet possible in clinical practices with millimeter accuracy. Near-infrared Spectroscopy (NIRS) is a well established technique that has been widely utilized in research and clinical practice to monitor the concentration of different chromophores in blood. It is capable of measuring a variety of parameters such as oxygenation levels in tissue, hematocrit, and cytochrome c oxidase levels among others. By increasing the amount and complexity of the light sources and detectors integrated in NIRS systems, in the last years researchers have been able to acquire tomographic images of such chromophores. This new imaging modality is known by different names: near-infrared optical tomography (NIROT), optical tomography (OT), diffuse optical tomography (DOT), or diffuse optical imaging (DOI). One of the main factors that limited the quality of the tomographic images obtained with NIROT has been the low number of sources and detectors employed in NIROT systems. The integration of the first single-photon avalanche diode (SPAD) together with time-to-digital converters (TDCs) in CMOS enabled a whole new range of possibilities in the field of single-photon detection. In this thesis the application of a SPAD-TDC image sensor in NIROT is presented for the first time. The main objective was to develop a new system that could perform acquisitions nearly in real time and that was capable of delivering tomographic images in a short period of time for medical evaluation. A new optical setup was conceived based on this detector to take advantage of the large amount of information delivered by the SPADs. By employing line-shaped illumination sources instead of point like sources, the target is more homogeneously illuminated and consequently a reduced number of sources is necessary. It was experimentally demonstrated that a resolution of 5 mm is possible with this new NIROT system. New algorithms that reduced the ill-posed nature of the image reconstruction problem were developed thanks to the wide-field time-resolved measurements delivered by the SPAD image sensors. The large datasets obtained with our NIROT system and its time-resolved capabilities enabled the development of fast methods capable of reconstructing an image with millimeter resolution in a few seconds with a laptop computer. We also analyze the effect of microlenses on the light sensitivity of the image sensor, showing that it is possible to increase it by a factor of 10 under certain conditions. A new image sensor with 4x400 pixels implemented in a 3D CMOS technology for NIROT applications is also presented. To our knowledge, this is the first backside illuminated SPAD array that incorporates in-pixel TDCs. A novel TDC architecture was introduced that reduces the energy consumed per conversion, consequently allowing a high number of TDCs working in parallel. The study of how NIROT can benefit from SPAD image sensors is presented in this thesis. Despite their current limitations, they enable the implementation of systems with thousands of detectors capable of millimeter resolution. Further developments in SPAD array architectures and TDCs will continue improving the performance of time-resolved NIROT systems.