Monte Carlo and experimental evaluation of a Timepix4 compact gamma camera for coded aperture nuclear medicine imaging with depth resolution

Purpose: We designed a prototype compact gamma camera (MediPROBE4) for nuclear medicine tasks, including radio-guided surgery and sentinel lymph node imaging with a 99mTc radiotracer. We performed Monte Carlo (MC) simulations for image performance assessment, and first spectroscopic imaging tests with a 300 μm thick silicon detector. Methods: The hand-held camera (1 kg weight) is based on a Timepix4 readout circuit for photon-counting, energy-sensitive, hybrid pixel detectors (24.6 × 28.2 mm2 sensitive area, 55 μm pixel pitch), developed by the Medipix4 Collaboration. The camera design adopts a CdTe detector (1 or 2 mm thick) bump-bonded to a Timepix4 readout chip and a coded aperture collimator with 0.25 mm diameter round holes made of 3D printed 1-mm thick tungsten. Image reconstruction is performed via autocorrelation deconvolution. Results: Geant4 MC simulations showed that, for a 99mTc source in air, at 50 mm source-collimator distance, the estimated collimator sensitivity (4 × 10-4) is 292 times larger than that of a single hole in the mask; the system sensitivity is 0.22 cps/kBq (2 mm CdTe); the lateral spatial resolution is 1.7 mm FWHM. The estimated axial longitudinal resolution is 8.2 mm FWHM at 40 mm distance. First experimental tests with a 300 μm thick Silicon pixel detector bump-bonded to a Timepix4 chip and a high-resolution coded aperture collimator showed time-over-threshold and time-of-arrival capabilities with 241Am and 133Ba gamma-ray sources. Conclusions: MC simulations and validation lab tests showed the expected performance of the MediPROBE4 compact gamma camera for gamma-ray 3D imaging

DESIGN OF A BURST MODE ULTRA HIGH-SPEED LOW-NOISE CMOS IMAGE SENSOR

Ultra-high-speed (UHS) image sensors are of interest for studying fast scientific phenomena and may also be useful in medicine. Several published studies have recently achieved frame rates of up to millions of frames per second (Mfps) using advanced processes and/or customized processes. This thesis presents a burst-mode (108 frames) UHS low-noise CMOS image sensor (CIS) based on charge-sweep transfer gates in an unmodified, standard 180 nm front-side-illuminated CIS process. By optimizing the photodiode geometry, the 52.8 μm pitch pixels with 20x20 μm^2 of active area, achieve a charge-transfer time of less than 10 ns. A proof-of-concept CIS was designed and fabricated. Through characterization, it is shown that the designed CIS has the potential to achieve 20 Mfps with an input-referred noise of 5.1 e− rms

An Optofluidic Lens Biochip and an x-ray Readable Blood Pressure Microsensor: Versatile Tools for in vitro and in vivo Diagnostics.

Three different microfabricated devices were presented for use in vivo and in vitro diagnostic biomedical applications: an optofluidic-lens biochip, a hand held digital imaging system and an x-ray readable blood pressure sensor for monitoring restenosis. An optofluidic biochip–termed the ‘Microfluidic-based Oil-Immersion Lens’ (mOIL) biochip were designed, fabricated and test for high-resolution imaging of various biological samples. The biochip consists of an array of high refractive index (n = 1.77) sapphire ball lenses sitting on top of an oil-filled microfluidic network of microchambers. The combination of the high optical quality lenses with the immersion oil results in a numerical aperture (NA) of 1.2 which is comparable to the high NA of oil immersion microscope objectives. The biochip can be used as an add-on-module to a stereoscope to improve the resolution from 10 microns down to 0.7 microns. It also has a scalable field of view (FOV) as the total FOV increases linearly with the number of lenses in the biochip (each lens has ~200 microns FOV). By combining the mOIL biochip with a CMOS sensor, a LED light source in 3D printed housing, a compact (40 grams, 4cmx4cmx4cm) high resolution (~0.4 microns) hand held imaging system was developed. The applicability of this system was demonstrated by counting red and white blood cells and imaging fluorescently labelled cells. In blood smear samples, blood cells, sickle cells, and malaria-infected cells were easily identified. To monitor restenosis, an x-ray readable implantable blood pressure sensor was developed. The sensor is based on the use of an x-ray absorbing liquid contained in a microchamber. The microchamber has a flexible membrane that is exposed to blood pressure. When the membrane deflects, the liquid moves into the microfluidic-gauge. The length of the microfluidic-gauge can be measured and consequently the applied pressure exerted on the diaphragm can be calculated. The prototype sensor has dimensions of 1x0.6x10mm and adequate resolution (19mmHg) to detect restenosis in coronary artery stents from a standard chest x-ray. Further improvements of our prototype will open up the possibility of measuring pressure drop in a coronary artery stent in a non-invasively manner.PhDMacromolecular Science and EngineeringUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/111384/1/toning_1.pd

Design of a Miniaturized Imaging System for As-built Performance

During the past two decades, many advancements in the field of optical design have occurred. Some of the more recent topics and concepts regarding optical system design are complex and require a comprehensive understanding of aberration theory, in-depth knowledge and experience with optical design software, and extensive lens design experience. This thesis focuses on the development and application of simpler methods for successful lens design for standard and miniaturized imaging systems. The impact of manufacturing tolerances of an optical system is considered, analyzed, and tested. A study of various design approaches using optical design software is presented. The design approaches introduced focus on the as-built performance of the lens, and their results are compared to determine the most effective design approach. The results of the different design approaches considered were then applied to the design of a mobile phone camera. The topics of tolerancing and miniaturized lens design are considered together during the design process for a cellphone camera. The performance, manufacturability, and design process of the cellphone camera are also presented, along with suggestions on possible improvement for future work. The as-built performance of the final design compared to the initial design resulted in a 2.5 times improvement in performance for the same percent-yield

The Quanta Image Sensor: Every Photon Counts

The Quanta Image Sensor (QIS) was conceived when contemplating shrinking pixel sizes and storage capacities, and the steady increase in digital processing power. In the single-bit QIS, the output of each field is a binary bit plane, where each bit represents the presence or absence of at least one photoelectron in a photodetector. A series of bit planes is generated through high-speed readout, and a kernel or “cubicle” of bits (x, y, t) is used to create a single output image pixel. The size of the cubicle can be adjusted post-acquisition to optimize image quality. The specialized sub-diffraction-limit photodetectors in the QIS are referred to as “jots” and a QIS may have a gigajot or more, read out at 1000 fps, for a data rate exceeding 1 Tb/s. Basically, we are trying to count photons as they arrive at the sensor. This paper reviews the QIS concept and its imaging characteristics. Recent progress towards realizing the QIS for commercial and scientific purposes is discussed. This includes implementation of a pump-gate jot device in a 65 nm CIS BSI process yielding read noise as low as 0.22 e− r.m.s. and conversion gain as high as 420 µV/e−, power efficient readout electronics, currently as low as 0.4 pJ/b in the same process, creating high dynamic range images from jot data, and understanding the imaging characteristics of single-bit and multi-bit QIS devices. The QIS represents a possible major paradigm shift in image capture