Calcium Imaging In Electrically Stimulated Flat-Mounted Retinas.

Retinal dystrophies are a leading cause of blindness worldwide. Extensive efforts are underway to develop advanced retinal prostheses that can bypass the impaired light-sensing photoreceptor cells in the degenerated retina, aiming to partially restore vision by inducing visual percepts. One common avenue of investigation involves the design and production of implantable devices with a flexible physical structure, housing a high number of electrodes. This enables the efficient and precise generation of visual percepts. However, with each technological advancement, there arises a need for a reliable and manageable ex vivo method to verify the functionality of the device before progressing to in vivo experiments, where factors beyond the device's performance come into play. This article presents a comprehensive protocol for studying calcium activity in the retinal ganglion cell layer (GCL) following electrical stimulation. Specifically, the following steps are outlined: (1) fluorescently labeling the rat retina using genetically encoded calcium indicators, (2) capturing the fluorescence signal using an inverted fluorescence microscope while applying distinct patterns of electrical stimulation, and (3) extracting and analyzing the calcium traces from individual cells within the GCL. By following this procedure, researchers can efficiently test new stimulation protocols prior to conducting in vivo experiments.

First results of a highly granulated 3D CdTe detector module for PET.

We present the performance of a highly granulated 3D detector module for PET, consisting of a stack of pixelated CdTe detectors. Each detector module has 2 cm × 2 cm × 2 cm of CdTe material, subdivided into 4000 voxels, where each voxel has size 1 mm × 1 mm × 2 mm and is connected to its own read-out electronics via a BiSn solder ball. Each read-out channel consists of a preamp, a discriminator, a shaper, a peak-and-hold circuit and a 10 bits SAR ADC. The preamp has variable gain where at the maximum gain the ADC resolution is equivalent to 0.7 keV. Each ASIC chip reads 100 CdTe pixel channels and has one TDC to measure the time stamp of the triggered events, with a time resolution of less than 1 ns. With the bias voltage set at -250 V mm-1 and for 17838 working channels out of a total of 20 000, we have obtained an average energy resolution of 2.2% FWHM for 511 keV photons. For 511 keV photons that have undergone Compton scattering, we measured an energy resolution of 3.2% FWHM. A timing resolution for PET coincidence events of 60 ns FWHM was found.

A 2D 4×4 Channel Readout ASIC for Pixelated CdTe Detectors for Medical Imaging Applications.

We present a 16-channel readout integrated circuit (ROIC) with nanosecond-resolution time to digital converter (TDC) for pixelated Cadmium Telluride (CdTe) gamma-ray detectors. The 4 × 4 pixel array ROIC is the proof of concept of the 10 × 10 pixel array readout ASIC for positron-emission tomography (PET) scanner, positron-emission mammography (PEM) scanner, and Compton gamma camera. The electronics of each individual pixel integrates an analog front-end with switchable gain, an analog to digital converter (ADC), configuration registers, and a 4-state digital controller. For every detected photon, the pixel electronics provides the energy deposited in the detector with 10-bit resolution, and a fast trigger signal for time stamp. The ASIC contains the 16-pixel matrix electronics, a digital controller, five global voltage references, a TDC, a temperature sensor, and a band-gap based current reference. The ASIC has been fabricated with TSMC 0.25 µm mixed-signal CMOS technology and occupies an area of 5.3 mm × 6.8 mm. The TDC shows a resolution of 95.5 ps, a precision of 600 ps at full width half maximum (FWHM), and a power consumption of 130 µW. In acquisition mode, the total power consumption of every pixel is 200 µW. An equivalent noise charge (ENC) of 160 e-RMS at maximum gain and negative polarity conditions has been measured at room temperature.

Simulation of the expected performance of a seamless scanner for brain PET based on highly pixelated CdTe detectors.

The aim of this work is the evaluation of the design for a nonconventional PET scanner, the voxel imaging PET (VIP), based on pixelated room-temperature CdTe detectors yielding a true 3-D impact point with a density of 450 channels/cm(3), for a total 6 336 000 channels in a seamless ring shaped volume. The system is simulated and evaluated following the prescriptions of the NEMA NU 2-2001 and the NEMA NU 4-2008 standards. Results show that the excellent energy resolution of the CdTe detectors (1.6% for 511 keV photons), together with the small voxel pitch (1 × 1 × 2 mm(3)), and the crack-free ring geometry, give the design the potential to overcome the current limitations of PET scanners and to approach the intrinsic image resolution limits set by physics. The VIP is expected to reach a competitive sensitivity and a superior signal purity with respect to values commonly quoted for state-of-the-art scintillating crystal PETs. The system can provide 14 cps/kBq with a scatter fraction of 3.95% and 21 cps/kBq with a scatter fraction of 0.73% according to NEMA NU 2-2001 and NEMA NU 4-2008, respectively. The calculated NEC curve has a peak value of 122 kcps at 5.3 kBq/mL for NEMA NU 2-2001 and 908 kcps at 1.6 MBq/mL for NEMA NU 4-2008. The proposed scanner can achieve an image resolution of ~ 1 mm full-width at half-maximum in all directions. The virtually noise-free data sample leads to direct positive impact on the quality of the reconstructed images. As a consequence, high-quality high-resolution images can be obtained with significantly lower number of events compared to conventional scanners. Overall, simulation results suggest the VIP scanner can be operated either at normal dose for fast scanning and high patient throughput, or at low dose to decrease the patient radioactivity exposure. The design evaluation presented in this work is driving the development and the optimization of a fully operative prototype to prove the feasibility of the VIP concept.

Toward VIP-PIX: A Low Noise Readout ASIC for Pixelated CdTe Gamma-Ray Detectors for Use in the Next Generation of PET Scanners.

VIP-PIX will be a low noise and low power pixel readout electronics with digital output for pixelated Cadmium Telluride (CdTe) detectors. The proposed pixel will be part of a 2D pixel-array detector for various types of nuclear medicine imaging devices such as positron-emission tomography (PET) scanners, Compton gamma cameras, and positron-emission mammography (PEM) scanners. Each pixel will include a SAR ADC that provides the energy deposited with 10-bit resolution. Simultaneously, the self-triggered pixel which will be connected to a global time-to-digital converter (TDC) with 1 ns resolution will provide the event's time stamp. The analog part of the readout chain and the ADC have been fabricated with TSMC 0.25 µm mixed-signal CMOS technology and characterized with an external test pulse. The power consumption of these parts is 200 µW from a 2.5 V supply. It offers 4 switchable gains from ±10 mV/fC to ±40 mV/fC and an input charge dynamic range of up to ±70 fC for the minimum gain for both polarities. Based on noise measurements, the expected equivalent noise charge (ENC) is 65 e- RMS at room temperature.