High Performance Integrated Circuits for Biomedical Imaging Applications
Authors: Cheng Zeng , Peng Hao , Deen M. Jamal 
Published: February 2020

Biomedical imaging modalities, such as time-of-flight (ToF) positron emission tomography (PET) and fluorescence-lifetime imaging microscopy (FLIM) have been primarily employed for molecular and cellular imaging in medical diagnosis and the health care fields [1]. In particular, ToF-PET plays a critical role in cancer detection at an early stage due to its noninvasive, in-vivo characteristics.
To obtain high precision, high temporal resolution and high contrast medical images, state-of-the-art electronics with high sensitivity, high counting rates and fine time resolution are needed. To meet these requirements, single photon avalanche diodes (SPAD) are employed as extremely sensitive photo-detectors. SPADs have compact size and can be designed and manufactured in a standard low-cost CMOS technology [2-4]. Figure 1a shows a schematic diagram of our SPAD-based bioimaging system.
As the time intervals between two coincidence pulses from ToF-PET detectors have a direct relationship with the spatial resolution of the final reconstructed PET images, our principal work is to design a time-to-digital converter (TDC) which has sub-gate time resolution, small area and low-power consumption, and is integrated with the SPADs in the same CMOS technology. A Vernier-gated ring oscillator TDC is used. Figure 1b shows the block diagram of the proposed TDC.
The TDC proposed employs Vernier technique to achieve fine time resolution. Two delay lines are arranged in a ring format such that pulses can propagate continuously (more than once) inside the rings. The dynamic range is increased by utilizing digital counters. Using this ring configuration in Vernier mode, fine resolution and large dynamic range are easily achieved simultaneously with short delay chains, and hence requires less silicon area occupation.
The proposed TDC has its intrinsic first-order tolerance towards common mode noises, because the delay-cells are configured in the differential method. Additional common mode noise tolerance is provided by the Vernier operation behavior.
The TDC is implemented in a commercial, mainstream 0.13μm CMOS technology. With the proposed Vernier-gated ring oscillator TDC, less than 10ps time resolution is achieved. This will greatly help improve the spatial resolution of the final reconstructed images, making an early detection of cancers and/or small size cancers possible. Future work will aim to integrate the proposed TDC with SPADs for digital silicon photomultiplier (SiPM).

References:
[1] D Palubiak, MM El-Desouki, O Marinov, MJ Deen, Q Fang, "High-speed, single-photon avalanche-photodiode imager for biomedical applications", IEEE Sensors Journal, 11, 2401-2412, (2011).
[2] MM El-Desouki, D Palubiak, MJ Deen, Q Fang, O Marinov, "A Novel, High-Dynamic-Range, High-Speed, and High-Sensitivity CMOS Imager Using Time-Domain Single-Photon Counting and Avalanche Photodiodes", IEEE Sensors Journal, 11, 1078-1083 (2011)
[3] M. R. Dadkhah, M. Jamal Deen, and Shahram Shirani, “Block-Based Compressive Sensing in a CMOS Image Sensor,” IEEE Sensors Journal,
PP(91), 1-12 (2012)
[4] F. S. Campos, N. Faramarzpour, O. Marinov, M. J. Deen, J. W. Swart, “Photodetection with Gate-Controlled Lateral BJTs from Standard CMOS Technology”, IEEE Sensors Journal, 13(5), 1554-1563 (2013).
Figure 1. a) A conceptual diagram of the integrated circuits for biomedical imaging applications. b) Block diagram of the vernier gated ring oscillator TDC