Depth resolved pencil beam radiography using AI - a proof of principle study
Clinical radiographic imaging is seated upon the principle of differential keV photon transmission through an object. At clinical x-ray energies the scattering of photons causes signal noise and is utilized solely for transmission measurements. However, scatter - particularly Compton scatter, is characterizable. In this work we hypothesized that modern radiation sources and detectors paired with deep learning techniques can use scattered photon information constructively to resolve superimposed attenuators in planar x-ray imaging.
Traceable dosimetry for MeV ion beams
Standard dosimetry protocols exist for highly penetrating photon and particle beams used in the clinic and in research. However, these protocols cannot be directly applied to shallow penetration MeV-range ion beams. The Radiological Research Accelerator Facility has been using such beams for almost 50 years to irradiate cell monolayers, using self-developed dosimetry, based on tissue equivalent ionization chambers. To better align with the internationally accepted standards, we describe implementation of a commercial, NIST-traceable, air-filled ionization chamber for measurement of absorbed dose to water from low energy ions, using radiation quality correction factors calculated using TRS-398 recommendations. The reported dose does not depend on the ionization density in the range of 10-150 keV/μm.
A high resolution and high detection efficiency depth-encoding detector for brain positron emission tomography based on a 0.75 mm pitch scintillator array
The quantitative accuracy and precision of brain positron emission tomography (PET) studies can be considerably improved using dedicated brain PET scanners with a uniform high resolution and a high sensitivity across the brain volume. One approach to building such a system is to construct the PET scanner using depth-of-interaction (DOI) encoding detectors with finely segmented and thick crystal arrays. In this paper, the performance of a DOI PET detector based on two 16 × 16 arrays of 2 × 2 mm SiPMs coupled to both ends of a 44 × 44 array of 0.69 × 0.69 × 30 mm polished LYSO crystals was evaluated at different temperatures (-9°C, 0°C, 10°C, and 20°C) for brain PET applications. The pitch size of the LYSO array is 0.75 mm. The flood histograms show that all the crystal elements in the LYSO array can be resolved except some edge crystals, due to the limited light sharing. The average energy resolution, average DOI resolution, and average timing resolution across crystal elements are 21.1 ± 3.0%, 3.47 ± 0.17 mm, and 1.38 ± 0.09 ns, respectively, which were obtained at a bias voltage of 56.5 V and a temperature of 0°C.
Tomographic imaging with Compton PET modules: ideal case and first implementation
In our previous studies, we demonstrated that the Compton PET module, a layer structure PET detector with side readout, can provide high performance in terms of spatial/energy/timing resolution, as well as high gamma ray detection efficiency. In this study, we investigate how to translate the high performance of the detector module into good quality reconstructed tomographic images. This study is performed using GATE simulation, as well as with physical experiments. Similar detector geometry is used in the simulation and experiment: two identical 4-layer detector modules are placed with face to face distance of 56 mm. In the simulation study, each layer consists of a 1-mm-pitch pixelated crystal array. In the experimental study, each layer is a monolithic crystal, which is virtually binned into 1 mm cells to group single events according to the gamma ray interaction locations. A customized Derenzo phantom was placed between the two detector modules. By rotating the phantom using a motorized rotary stage, data along lines of response (LORs) at different angles were collected for reconstructing the tomographic image. The same reconstruction algorithm was used for both simulation and experimental studies. The results demonstrate that the simulation study could resolve 0.8 mm rods while the experimental study was able to resolve 1.0 mm rods.
Development of a PET/EPRI combined imaging system for assessing tumor hypoxia
Precise quantitative delineation of tumor hypoxia is essential in radiation therapy treatment planning to improve the treatment efficacy by targeting hypoxic sub-volumes. We developed a combined imaging system of positron emission tomography (PET) and electron para-magnetic resonance imaging (EPRI) of molecular oxygen to investigate the accuracy of PET imaging in assessing tumor hypoxia. The PET/EPRI combined imaging system aims to use EPRI to precisely measure the oxygen partial pressure in tissues. This will evaluate the validity of PET hypoxic tumor imaging by (near) simultaneously acquired EPRI as ground truth. The combined imaging system was constructed by integrating a small animal PET scanner (inner ring diameter 62 mm and axial field of view 25.6 mm) and an EPRI subsystem (field strength 25 mT and resonant frequency 700 MHz). The compatibility between the PET and EPRI subsystems were tested with both phantom and animal imaging. Hypoxic imaging on a tumor mouse model using F-fluoromisonidazole radio-tracer was conducted with the developed PET/EPRI system. We report the development and initial imaging results obtained from the PET/EPRI combined imaging system.
Improving timing performance of double-ended readout in TOF-PET detectors
Scintillation crystals of 20mm length or longer are needed for clinical time-of-flight positron emission tomography (TOF-PET) to ensure effective detection efficiency for gamma photons. However, the use of long crystals would deteriorate the key performance of TOF-PET detectors, time and spatial resolution, because of the variations in the travel times of the photons in crystals and the effects of parallax errors. In this work, we studied double-ended readout TOF-PET detectors based on coupling a long scintillation crystal to SiPMs at both ends for correcting the depth-dependent effects to improve the coincidence time resolution (CTR). In particular, we focused our attention to analyze timing performance using different correction methods, including trigger times of the individual photodetectors at both ends of the crystal, the simple average of the trigger times, and the weighted average based on the inverse variances of the depth-dependent corrected trigger times. For a 3 mm × 3 mm × 25mm unpolished lutetium fine silicate (LFS) crystal with double-ended readout and practical head-on irradiation, a CTR of 246ps FWHM can be achieved using depth-dependent timing-correction and weighted average time method compared to 280ps FWHM using the conventional simple average time method and 393ps FWHM using the conventional single-ended readout. The results show that the depth-dependent timing-correction and weighted average time method in double-ended readout can effectively correct for the trigger time variations in TOF-PET detector utilizing long unpolished crystals, resulting in an improvement in the CTR of as much as 37% compared to single-ended readout.
Experimental evaluation of the resolution improvement provided by a silicon PET probe
A high-resolution PET system, which incorporates a silicon detector probe into a conventional PET scanner, has been proposed to obtain increased image quality in a limited region of interest. Detailed simulation studies have previously shown that the additional probe information improves the spatial resolution of the reconstructed image and increases lesion detectability, with no cost to other image quality measures. The current study expands on the previous work by using a laboratory prototype of the silicon PET-probe system to examine the resolution improvement in an experimental setting. Two different versions of the probe prototype were assessed, both consisting of a back-to-back pair of 1-mm thick silicon pad detectors, one arranged in 32 × 16 arrays of 1.4 mm × 1.4 mm pixels and the other in 40 × 26 arrays of 1.0 mm × 1.0 mm pixels. Each detector was read out by a set of VATAGP7 ASICs and a custom-designed data acquisition board which allowed trigger and data interfacing with the PET scanner, itself consisting of BGO block detectors segmented into 8 × 6 arrays of 6 mm × 12 mm × 30 mm crystals. Limited-angle probe data was acquired from a group of Na-22 point-like sources in order to observe the maximum resolution achievable using the probe system. Data from a Derenzo-like resolution phantom was acquired, then scaled to obtain similar statistical quality as that of previous simulation studies. In this case, images were reconstructed using measurements of the PET ring alone and with the inclusion of the probe data. Images of the Na-22 source demonstrated a resolution of 1.5 mm FWHM in the probe data, the PET ring resolution being approximately 6 mm. Profiles taken through the image of the Derenzo-like phantom showed a clear increase in spatial resolution. Improvements in peak-to-valley ratios of 50% and 38%, in the 4.8 mm and 4.0 mm phantom features respectively, were observed, while previously unresolvable 3.2 mm features were brought to light by the addition of the probe. These results support the possibility of improving the image resolution of a clinical PET scanner using the silicon PET-probe.
Development and Characterization of a High Sensitivity Segmented Fast Neutron Spectrometer (FaNS-2)
We present the development of a segmented fast neutron spectrometer (FaNS-2) based upon plastic scintillator and He proportional counters. It was designed to measure both the flux and spectrum of fast neutrons in the energy range of few MeV to 1 GeV. FaNS-2 utilizes capture-gated spectroscopy to identify neutron events and reject backgrounds. Neutrons deposit energy in the plastic scintillator before capturing on a He nucleus in the proportional counters. Segmentation improves neutron energy reconstruction while the large volume of scintillator increases sensitivity to low neutron fluxes. A main goal of its design is to study comparatively low neutron fluxes, such as cosmogenic neutrons at the Earth's surface, in an underground environment, or from low-activity neutron sources. In this paper, we present details of its design and construction as well as its characterization with a calibrated Cf source and monoenergetic neutron fields of 2.5 MeV and 14 MeV. Detected monoenergetic neutron spectra are unfolded using a Singular Value Decomposition method, demonstrating a 5% energy resolution at 14 MeV. Finally, we discuss plans for measuring the surface and underground cosmogenic neutron spectra with FaNS-2.
A front-end readout Detector Board for the OpenPET electronics system
We present a 16-channel front-end readout board for the OpenPET electronics system. A major task in developing a nuclear medical imaging system, such as a positron emission computed tomograph (PET) or a single-photon emission computed tomograph (SPECT), is the electronics system. While there are a wide variety of detector and camera design concepts, the relatively simple nature of the acquired data allows for a common set of electronics requirements that can be met by a flexible, scalable, and high-performance OpenPET electronics system. The analog signals from the different types of detectors used in medical imaging share similar characteristics, which allows for a common analog signal processing. The OpenPET electronics processes the analog signals with Detector Boards. Here we report on the development of a 16-channel Detector Board. Each signal is digitized by a continuously sampled analog-to-digital converter (ADC), which is processed by a field programmable gate array (FPGA) to extract pulse height information. A leading edge discriminator creates a timing edge that is "time stamped" by a time-to-digital converter (TDC) implemented inside the FPGA. This digital information from each channel is sent to an FPGA that services 16 analog channels, and then information from multiple channels is processed by this FPGA to perform logic for crystal lookup, DOI calculation, calibration, etc.
CMOS Active Pixel Sensors as energy-range detectors for proton Computed Tomography
Since the first proof of concept in the early 70s, a number of technologies has been proposed to perform proton CT (pCT), as a means of mapping tissue stopping power for accurate treatment planning in proton therapy. Previous prototypes of energy-range detectors for pCT have been mainly based on the use of scintillator-based calorimeters, to measure proton residual energy after passing through the patient. However, such an approach is limited by the need for only a single proton passing through the energy-range detector in a read-out cycle. A novel approach to this problem could be the use of pixelated detectors, where the independent read-out of each pixel allows to measure simultaneously the residual energy of a number of protons in the same read-out cycle, facilitating a faster and more efficient pCT scan. This paper investigates the suitability of CMOS Active Pixel Sensors (APSs) to track individual protons as they go through a number of CMOS layers, forming an energy-range telescope. Measurements performed at the iThemba Laboratories will be presented and analysed in terms of correlation, to confirm capability of proton tracking for CMOS APSs.
Proton tracking for medical imaging and dosimetry
For many years, silicon micro-strip detectors have been successfully used as tracking detectors for particle and nuclear physics experiments. A new application of this technology is to the field of particle therapy, where radiotherapy is carried out by use of charged particles such as protons or carbon ions. Such a treatment has been shown to have advantages over standard x-ray radiotherapy and as a result of this, many new centres offering particle therapy are currently under construction - including two in the U.K.. The characteristics of a new silicon micro-strip detector based system for this application will be presented. The array uses specifically designed large area sensors in several stations in an -- co-ordinate configuration suitable for very fast proton tracking with minimal ambiguities. The sensors will form a tracker capable of giving information on the path of high energy protons entering and exiting a patient. This will allow proton computed tomography (CT) to aid the accurate delivery of treatment dose with tuned beam profile and energy. The tracker will also be capable of proton counting and position measurement at the higher fluences and full range of energies used during treatment allowing monitoring of the beam profile and total dose. Results and initial characterisation of sensors will be presented along with details of the proposed readout electronics. Radiation tests and studies with different electronics at the Clatterbridge Cancer Centre and the higher energy proton therapy facility of iThemba LABS in South Africa will also be shown.
Simulation of charge transport in pixelated CdTe
The Voxel Imaging PET (VIP) Pathfinder project intends to show the advantages of using pixelated semiconductor technology for nuclear medicine applications to achieve an improved image reconstruction without efficiency loss. It proposes designs for Positron Emission Tomography (PET), Positron Emission Mammography (PEM) and Compton gamma camera detectors with a large number of signal channels (of the order of 10). The design is based on the use of a pixelated CdTe Schottky detector to have optimal energy and spatial resolution. An individual read-out channel is dedicated for each detector voxel of size 1 × 1 × 2 mm using an application-specific integrated circuit (ASIC) which the VIP project has designed, developed and is currently evaluating experimentally. The behaviour of the signal charge carriers in CdTe should be well understood because it has an impact on the performance of the readout channels. For this purpose the Finite Element Method (FEM) Multiphysics COMSOL software package has been used to simulate the behaviour of signal charge carriers in CdTe and extract values for the expected charge sharing depending on the impact point and bias voltage. The results on charge sharing obtained with COMSOL are combined with GAMOS, a Geant based particle tracking Monte Carlo software package, to get a full evaluation of the amount of charge sharing in pixelated CdTe for different gamma impact points.
Measurement of mobility and lifetime of electrons and holes in a Schottky CdTe diode
We report on the measurement of drift properties of electrons and holes in a CdTe diode grown by the travelling heating method (THM). Mobility and lifetime of both charge carriers has been measured independently at room temperature and fixed bias voltage using charge integration readout electronics. Both electrode sides of the detector have been exposed to a Am source in order to obtain events with full contributions of either electrons or holes. The drift time has been measured to obtain the mobility for each charge carrier. The Hecht equation has been employed to evaluate the lifetime. The measured values for (mobility-lifetime product) are in agreement with earlier published data.
Optimization, evaluation, and comparison of standard algorithms for image reconstruction with the VIP-PET
A novel positron emission tomography (PET) scanner design based on a room-temperature pixelated CdTe solid-state detector is being developed within the framework of the Voxel Imaging PET (VIP) Pathfinder project [1]. The simulation results show a great potential of the VIP to produce high-resolution images even in extremely challenging conditions such as the screening of a human head [2]. With unprecedented high channel density (450 channels/cm) image reconstruction is a challenge. Therefore optimization is needed to find the best algorithm in order to exploit correctly the promising detector potential. The following reconstruction algorithms are evaluated: 2-D Filtered Backprojection (FBP), Ordered Subset Expectation Maximization (OSEM), List-Mode OSEM (LM-OSEM), and the Origin Ensemble (OE) algorithm. The evaluation is based on the comparison of a true image phantom with a set of reconstructed images obtained by each algorithm. This is achieved by calculation of image quality merit parameters such as the bias, the variance and the mean square error (MSE). A systematic optimization of each algorithm is performed by varying the reconstruction parameters, such as the cutoff frequency of the noise filters and the number of iterations. The region of interest (ROI) analysis of the reconstructed phantom is also performed for each algorithm and the results are compared. Additionally, the performance of the image reconstruction methods is compared by calculating the modulation transfer function (MTF). The reconstruction time is also taken into account to choose the optimal algorithm. The analysis is based on GAMOS [3] simulation including the expected CdTe and electronic specifics.
Evaluation of Compton gamma camera prototype based on pixelated CdTe detectors
A proposed Compton camera prototype based on pixelated CdTe is simulated and evaluated in order to establish its feasibility and expected performance in real laboratory tests. The system is based on module units containing a 2×4 array of square CdTe detectors of 10×10 mm area and 2 mm thickness. The detectors are pixelated and stacked forming a 3D detector with voxel sizes of 2 × 1 × 2 mm. The camera performance is simulated with Geant4-based Architecture for Medicine-Oriented Simulations(GAMOS) and the Origin Ensemble(OE) algorithm is used for the image reconstruction. The simulation shows that the camera can operate with up to 10 Bq source activities with equal efficiency and is completely saturated at 10 Bq. The efficiency of the system is evaluated using a simulated point source phantom in the center of the Field-of-View (FOV) achieving an intrinsic efficiency of 0.4 counts per second per kilobecquerel. The spatial resolution measured from the point spread function (PSF) shows a FWHM of 1.5 mm along the direction perpendicular to the scatterer, making it possible to distinguish two points at 3 mm separation with a peak-to-valley ratio of 8.
Simulation and evaluation of a high resolution VIP PEM system with a dedicated LM-OSEM algorithm
Over the last two decades there have been a growing number of designs for positron emission tomography (PET) cameras optimized to image the breast. These devices, commonly known as positron emission mammography (PEM) cameras allow much more spatial resolution by putting the photon detectors directly on the breast. PEM cameras have a compact geometry with a restricted field of view (FOV) thus exhibiting higher performance and lower cost than large whole body PET scanners. Typical PEM designs are based on scintillators such as bismuth germanate (BGO), lutetium oxorthosilicate (LSO) or lutetium yttrium orthosicilate (LYSO), and characterized by large parallax error due to deficiency of the depth of interaction (DOI) information from crystals. In the case of parallel geometry PEM, large parallax error results in poor image resolution along the vertical axis. In the framework of the Voxel Imaging PET (VIP) pathfinder project, we propose a high resolution PEM scanner based on pixelated solid-state CdTe detectors. The pixel PEM device with a millimeter-size pixel pitch provides an excellent spatial resolution in all directions 8 times better than standard commercial devices with a point spread function (PSF) of 1 mm full width at half maximum (FWHM) and excellent energy resolution of down to 1.6% FWHM at 511 keV photons at room temperature. The system is capable to detect down to 1 mm diameter hot spheres in warm background.
Optical properties of quantum-dot-doped liquid scintillators
Semiconductor nanoparticles (quantum dots) were studied in the context of liquid scintillator development for upcoming neutrino experiments. The unique optical and chemical properties of quantum dots are particularly promising for the use in neutrinoless double-beta decay experiments. Liquid scintillators for large scale neutrino detectors have to meet specific requirements which are reviewed, highlighting the peculiarities of quantum-dot-doping. In this paper, we report results on laboratory-scale measurements of the attenuation length and the fluorescence properties of three commercial quantum dot samples. The results include absorbance and emission stability measurements, improvement in transparency due to filtering of the quantum dot samples, precipitation tests to isolate the quantum dots from solution and energy transfer studies with quantum dots and the fluorophore PPO.
A robust general phase retrieval method for medical applications
From medical imaging perspective the robustness of a phase retrieval method is of critical importance. In this presentation we compare the robustness of two general phase retrieval methods, namely the transport of intensity equation inversion (TIE-inversion) method and the attenuation partition based (AP-based) method. We showed that the TIE-inversion method, regardless if being assisted with the Tikhonov regularization, failed to retrieve the phase maps in two experimental studies. The failure exposes this method's weakness as being unstable against the noise. In contrast, the sample phase maps are retrieved successfully by using the AP-based method. The stark performance differences of the two methods are rooted in their different techniques dealing with the singularity problem. This comparison shows that the robust AP-based phase retrieval method will be superior to the TIE-inversion method for medical imaging applications where radiation doses are stringently limited.
High-performance electronics for time-of-flight PET systems
We have designed and built a high-performance readout electronics system for time-of-flight positron emission tomography (TOF PET) cameras. The electronics architecture is based on the electronics for a commercial whole-body PET camera (Siemens/CPS Cardinal electronics), modified to improve the timing performance. The fundamental contributions in the electronics that can limit the timing resolution include the constant fraction discriminator (CFD), which converts the analog electrical signal from the photo-detector to a digital signal whose leading edge is time-correlated with the input signal, and the time-to-digital converter (TDC), which provides a time stamp for the CFD output. Coincident events are identified by digitally comparing the values of the time stamps. In the Cardinal electronics, the front-end processing electronics are performed by an Analog subsection board, which has two application-specific integrated circuits (ASICs), each servicing a PET block detector module. The ASIC has a built-in CFD and TDC. We found that a significant degradation in the timing resolution comes from the ASIC's CFD and TDC. Therefore, we have designed and built an improved Analog subsection board that replaces the ASIC's CFD and TDC with a high-performance CFD (made with discrete components) and TDC (using the CERN high-performance TDC ASIC). The improved Analog subsection board is used in a custom single-ring LSO-based TOF PET camera. The electronics system achieves a timing resolution of 60 ps FWHM. Prototype TOF detector modules are read out with the electronics system and give coincidence timing resolutions of 259 ps FWHM and 156 ps FWHM for detector modules coupled to LSO and LaBr crystals respectively.
An ultra-thin Schottky diode as a transmission particle detector for biological microbeams
We fabricated ultrathin metal-semiconductor Schottky diodes for use as transmission particle detectors in the biological microbeam at Columbia University's Radiological Research Accelerator Facility (RARAF). The RARAF microbeam can deliver a precise dose of ionizing radiation in cell nuclei with sub-micron precision. To ensure an accurate delivery of charged particles, the facility currently uses a commercial charged-particle detector placed after the sample. We present here a transmission detector that will be placed between the particle accelerator and the biological specimen, allowing the irradiation of samples that would otherwise block radiation from reaching a detector behind the sample. Four detectors were fabricated with co-planar gold and aluminum electrodes thermally evaporated onto etched n-type crystalline silicon substrates, with device thicknesses ranging from 8.5 μm - 13.5 μm. We show coincident detections and pulse-height distributions of charged particles in both the transmission detector and the commercial detector above it. Detections are demonstrated at a range of operating conditions, including incoming particle type, count rate, and beam location on the detectors. The 13.5 μm detector is shown to work best to detect 2.7 MeV protons (H), and the 8.5 μm detector is shown to work best to detect 5.4 MeV alpha particles (He). The development of a transmission detector enables a range of new experiments to take place at RARAF on radiation-stopping samples such as thick tissues, targets that need immersion microscopy, and integrated microfluidic devices for handling larger quantities of cells and small organisms.
Development of broad-band high-reflectivity multilayer film for positron emission tomography system
The use of non-ideal reflective materials and low-precision manual manufacturing technologies is a fundamental technical obstacle blocking the positron emission tomography (PET) systems from achieving better performances. We propose to address that long-standing obstacle with advanced multilayer dielectric coating technologies. We designed an broad-band multilayer high-reflectivity (HR) film that can be coated directly on the surface of ultra-precision polished lutetiumyttrium oxyorthosilicate (LYSO) scintillators. The film consists of 48 layers of TiO2/SiO2/HfO2 which are deposited on LYSO scintillator crystal alternately using the electron beam evaporation method. The overall thickness of the HR film is about 3μm. The HR film combines 3 quarter wavelength reflective films, with the central wavelengths of 365 nm, 430 nm and 570 nm respectively, to match the emission spectrum of the LYSO scintillator. The optical experimental results show that the HR film achieved an excellent average reflectivity of 99.50% at 8° incident angle for incident lights with wavelengths between 360 to 620 nm. The average reflectivity at 60° incident angle is higher than 90%. The results of the hardness experiments and the adhesive strength experiments show that the HR film has an excellent mechanical strength. The HR coating technology developed in this study is very attractive because it allows to "print" high-performance reflectors on a scintillator directly with high-precision, instead of manually gluing reflective films on the scintillator. Thus, we conclude that the HR film provides a viable solution to the long standing technical bottleneck that limits the development of high-performance detectors for advanced PET imaging.