Development and testing of SPECT/CT lung phantoms made from expanding polyurethane foam.

PURPOSE: Currently, single-photon emission computed tomography (SPECT)/computed tomography (CT) lung phantoms are commonly constructed using polystyrene beads and interstitial radioactive water. However, this approach often results in a phantom with a density (typically -640 HU) that is considerably higher than that of healthy lung (-750 to -850 HU) or diseased lung (-900 to -950 HU). Furthermore, the polystyrene and water phantoms are often quite heterogeneous in both density and activity concentration, especially when reused. This work is devoted to examining methods for creating a more realistic lung phantom for quantitative SPECT/CT using 99m Tc-laced expanding polyurethane foam (EPF). METHODS: Numerous aspects of EPF utilization were studied, including stoichiometric mixing to control final foam density and the effect of water during growth. We also tested several ways of molding the foam lung phantoms. The most successful method utilized a three-part silicone mold that allowed for creation of a two-lobe phantom, with a different density and activity concentration in each lobe. RESULTS: The final phantom design allows for a more anatomically accurate geometry as well as customizable density and activity concentration in the different lobes of the lung. We demonstrated final lung phantom densities between -760 and -690 HU in the "healthy" phantom and -930 to -890 HU in the "unhealthy" phantom tissue. On average, we achieved 15% activity concentration nonuniformity and 12% density nonuniformity within a given lobe. CONCLUSIONS: Final EPF lung phantoms closely matched the densities of both health and diseased lung tissue and had sufficient uniformities in both density and activity concentration for most nuclear medicine applications. Management of component moisture content is critical for phantom reproducibility.

A CMOS Front-End Interface ASIC for SiPM-based Positron Emission Tomography Imaging Systems.

A current-mode interface chip for Silicon Photomultiplier (SiPM) array based positron emission tomography (PET) imaging front-ends is described. The circuit uses a high-speed current amplifier with a low input impedance, to minimize signal loss at the SiPM amplifier interface. To reduce the impact of dark noise, a novel high-speed threshold detection/comparator circuit is used to remove unwanted noise events. A prototype chip interfaces an array of SiPMs to the digital backend of a Positron Emission Tomography (PET) system using 64 readout channels, each of which contain a current amplifier and a threshold detection component. To reduce the number of backend channels, a row-column pulse positioning architecture (RCA) has been implemented. The ASIC occupies an area of 14.04 mm2 in 130nm STMicroelectronics HCMOS9GP process. The measured input impedance of the current amplifier is 20 ohms at 10 MHz, while the threshold detection circuit's propagation delay is 0.3-2ns.

A study of SPECT/CT camera stability for quantitative imaging.

BACKGROUND: The purpose of this study was twofold: to evaluate the quantitative stability of a SPECT/CT gamma camera over time and to determine if daily flood acquisitions can reliably serve as calibration factors for quantitative SPECT. Using a cylindrical water phantom filled with measured amounts of (99m)Tc, factors were calculated to convert counts/cc to activity/cps. Measurements were made over an 18-month period. System sensitivity data calculated from (57)Co daily quality assurance (DQA) flood acquisitions were then compared to the (99m)Tc calibration factors to determine the relationship of the factors. RESULTS: The coefficient of variation is 2.7 % for the (99m)Tc cylinder conversion factors and 2.6 % for the (57)Co DQA flood data. The greatest difference between the cylinder conversion factors and the flood data is less than 3 %. CONCLUSIONS: Based on the results, the camera was stable within 3 % over an 18-month time period. The daily flood source acquisitions can be a reliable source for tracking camera stability and may provide information on updating the calibration factor for quantitative imaging.

Light-Sharing Interface for dMiCE Detectors Using Sub-Surface Laser Engraving.

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

A Virtual Clinical Trial of FDG-PET Imaging of Breast Cancer: Effect of Variability on Response Assessment.

INTRODUCTION: There is growing interest in using positron emission tomography (PET) standardized uptake values (SUVs) to assess tumor response to therapy. However, many error sources compromise the ability to detect SUV changes. We explore relationships between these errors and overall SUV variability. METHODS: We used simulations in a virtual clinical trial framework to study impacts of error sources from scanning and analysis effects on assessment of SUV changes. We varied tumor diameter, scan duration, pretherapy SUV, magnitude of change in SUV, image reconstruction filter, and SUV metric. Poisson noise was added to the raw data before image reconstruction. Variance from global sources of error, e.g., scanner calibration, was incorporated. Two thousand independent noisy sinograms per scenario were generated and reconstructed. We used SUVs to create receiver operating characteristic (ROC) curves to quantify ability to assess response. Integrating area under the ROC curve summarized ability to detect SUV changes. RESULTS: Scan duration and image reconstruction method had relatively little impact on ability to measure response. SUVMAX is nearly as effective as SUVMEAN, especially with increased image smoothing and despite size-matched region of interest placement. For an effective variability of 15%, we found the Positron Emission Tomography Response Criteria in Solid Tumors criteria for measuring response (±30%) similar to the European Organization for Research and Treatment of Cancer criteria (±25%). CONCLUSIONS: For typical PET variance levels, tumor response must be 30% to 40% to be reliably determined using SUVs. PET scan duration and image reconstruction method had relatively little effect.

Performance Evaluation of Small Animal PET Scanners With Different System Designs.

This study evaluated the image quality metrics of small animal PET scanners based upon measured single detector module positioning performance. A semi-analytical approach was developed to study PET scanner performance in the scenario of multiple realizations. Positron range blurring, scanner system response function (SRF) and statistical noise were included in the modeling procedure. The scanner sensitivity map was included in the system matrix during maximum likelihood expectation maximization (MLEM) reconstruction. Several image quality metrics were evaluated for octagonal ring PET scanners consisting of continuous miniature crystal element (cMiCE) detector modules with varying designs. These designs included 8 mm and 15 mm thick crystal detectors using conventional readout with the photosensors on the exit surface of the crystal and a 15 mm thick crystal detector using our proposed sensor-on-the-entrance (SES) design. For the conventional readout design, the results showed that there was a tradeoff between bias and variance with crystal thickness. The 15 mm crystal detector had better detection task performance, while quantitation task performance was degraded. On the other hand, our SES detector had similar detection efficiency as the conventional design using a 15 mm thick crystal and had similar intrinsic spatial resolution as the conventional design using an 8 mm thick crystal. The end result was that by using the SES design, one could improve scanner quantitation task performance without sacrificing detection task performance.

SCOUT: a fast Monte-Carlo modeling tool of scintillation camera output.

We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout of a scintillation camera. In this work, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools.

Light-Sharing Interface for dMiCE Detectors using Sub-Surface Laser Engraving.

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of this crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for a crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mmˆ3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Geiger-Müller avalanche photodiodes from Hamamatsu. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions events. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

Highly-Integrated CMOS Interface Circuits for SiPM-Based PET Imaging Systems.

Recent developments in the area of Positron Emission Tomography (PET) detectors using Silicon Photomultipliers (SiPMs) have demonstrated the feasibility of higher resolution PET scanners due to a significant reduction in the detector form factor. The increased detector density requires a proportionally larger number of channels to interface the SiPM array with the backend digital signal processing necessary for eventual image reconstruction. This work presents a CMOS ASIC design for signal reducing readout electronics in support of an 8×8 silicon photomultiplier array. The row/column/diagonal summation circuit significantly reduces the number of required channels, reducing the cost of subsequent digitizing electronics. Current amplifiers are used with a single input from each SiPM cathode. This approach helps to reduce the detector loading, while generating all the necessary row, column and diagonal addressing information. In addition, the single current amplifier used in our Pulse-Positioning architecture facilitates the extraction of pulse timing information. Other components under design at present include a current-mode comparator which enables threshold detection for dark noise current reduction, a transimpedance amplifier and a variable output impedance I/O driver which adapts to a wide range of loading conditions between the ASIC and lines with the off-chip Analog-to-Digital Converters (ADCs).

Impact of Analog IC Impairments in SiPM Interface Electronics.

The recent realization of Silicon Photomultiplier (SiPM) devices as solid-state detectors for Positron Emission Tomography holds the promise of improving image resolution, integrating a significant portion of the interface electronics, and potentially lowering the power consumption. Our lab has previously reported on novel board-level readout electronics for an 8×8 silicon photomultiplier (SiPM) array featuring row/column summation technique to reduce the hardware requirements for signal processing and is currently working on taking the next step by implementing a monolithic CMOS chip which is based on the row-column architecture. To date, relatively little modeling has been done to understand the impact of analog non-idealities associated with the front-end electronics, on SiPM-based PET systems. This paper focuses on various analog impairments associated with PET scanner readout electronics. Matlab was used as a simulation platform to model the noise, linearity and signal bandwidth of the frontend electronics with the measured SiPM pulses as the input.

Effects of MR surface coils on PET quantification.

PURPOSE: The goal of this work was to investigate the effects of MRI surface coils on attenuation-corrected PET emission data. The authors studied the cases where either an MRI or a CT scan would be used to provide PET attenuation correction (AC). Combined MR/PET scanners that use the MRI for PET AC (MR-AC) face the challenge of absent surface coils in MR images and thus cannot directly account for attenuation in the coils. Combining MR and PET images could be achieved by transporting the subject on a stereotactically registered table between independent MRI and PET scanners. In this case, conventional PET CT-AC methods could be used. A challenge here is that high atomic number materials within MR coils cause artifacts in CT images and CT based AC is typically not validated for coil materials. METHODS: The authors evaluated PET artifacts when MR coils were absent from AC data (MR-AC), or when coil attenuation was measured by CT scanning (CT-AC). They scanned PET phantoms with MR surface coils on a clinical PET/CT system and used CT-AC to reconstruct PET data. The authors then omitted the coil from the CT-AC image to mimic the MR-AC scenario. Images were acquired using cylinder and anthropomorphic phantoms. They evaluated and compared the following five scenarios: (1) A uniform cylinder phantom and head coil scanned and reconstructed using CT-AC; (2) similar emission data (with head coil present) were reconstructed without the head coil in the AC data; (3) the same cylinder scanned without the head coil present (reference scan); (4) a PET torso phantom with a full MR torso coil present in both PET and CT; (5) only half of the separable torso coil present in the PET/CT acquisition. The authors also performed analytic simulations of the first three scenarios. RESULTS: Streak artifacts were present in CT images containing MR surface coils due to metal components. These artifacts persisted after the CT images were converted for PET AC. The artifacts were significantly reduced when half of the separable coil was removed during the scan. CT scans tended to over-estimate the linear attenuation coefficient (micro) of the metal components when using conventional methods for converting from CT number to micro(511 keV). Artifacts were visible outside the phantom in some of the PET emission images, corresponding to the MRI coil geometry. However, only subtle artifacts were apparent in the emission images inside the phantoms. On the other hand, the PET emission image quantitative accuracy was significantly affected: the activity was underestimated by 19% when AC did not include the head coil, and overestimated by 28% when the CT-AC included the head coil. CONCLUSIONS: The presence of MR coils during PET or PET/CT scanning can cause subtle artifacts and potentially important quantification errors. Alternative CT techniques that mitigate artifacts should be used to improve AC accuracy. When possible, removing segments of an MR coil prior to the PET/CT exam is recommended. Further, MR coils could be redesigned to reduce artifacts by rearranging placement of the most attenuating materials.

DOI-based reconstruction algorithms for a compact breast PET scanner.

PURPOSE: The authors discuss the design and evaluate the performance of combined event estimation and image reconstruction algorithms designed for a proposed high-resolution rectangular breast PET scanner (PETX). The PETX scanner will be capable of measuring the depth of interaction by utilizing detector modules composed of depth-of-interaction microcrystal element (dMiCE) crystal pairs. This design allows a unique combination of event estimation and fast projection methods. METHODS: The authors implemented a Monte Carlo simulator to model the PETX system using only true coincident events. The performance of the dMiCE crystal pairs was determined experimentally over a range of depths of interaction. This distribution was used to simulate the noisy dMiCE detector signals and to estimate the line of response for each decay. Three different statistical methods were implemented to determine photon event positioning. Images were reconstructed from these line of response estimators with the exact planogram frequency distance rebinning algorithm, which is an exact analytical reconstruction algorithm for planar systems. Reconstructed images were analyzed with contrast, noise, and spatial resolution metrics. RESULTS: The authors' simulations demonstrate the ability for the PETX system to produce quantitatively accurate images from true coincident events with a contrast recovery coefficient of greater than 0.8 for 5 mm spheres at the axial center of the scanner and a spatial resolution (FWHM) of 3 mm throughout most of the imaging field of view. CONCLUSIONS: The authors' proposed positioning and reconstruction algorithms for the PETX system show the potential for creating high-quality, high-resolution, and quantitatively accurate images within a clinically feasible reconstruction time.

Resolution Properties of a Prototype Continuous Miniature Crystal Element (cMiCE) Scanner.

Continuous miniature crystal element (cMiCE) detectors are a potentially lower cost alternative for high resolution discrete crystal PET detector designs. We report on performance characteristics of a prototype PET scanner consisting of two cMiCE detector modules. Each cMiCE detector is comprised of a 50 × 50 × 8 mm3 LYSO crystal coupled to a 64 channel multi-anode PMT. The cMiCE detectors use a statistics-based positioning method based upon maximum likelihood estimation for event positioning. By this method, cMiCE detectors can also provide some depth of interaction event positioning information. For the prototype scanner, the cMiCE detectors were positioned across from one another on a horizontal gantry with a detector spacing of 10.7 cm. Full tomographic data were collected and reconstructed using single slice rebinning and filtered back projection with no smoothing. The average image resolutions in X (radial), Y (transverse) and Z (axial) were 1.05 ± 0.08 mm, 0.99 ± 0.07 mm, 1.24 ± 0.31 mm FWHM. These initial imaging results from a prototype imaging system demonstrate the outstanding image resolution performance that can be achieved using the potentially lower cost cMiCE detectors.

A CMOS ASIC Design for SiPM Arrays.

Our lab has previously reported on novel board-level readout electronics for an 8×8 silicon photomultiplier (SiPM) array featuring row/column summation technique to reduce the hardware requirements for signal processing. We are taking the next step by implementing a monolithic CMOS chip which is based on the row-column architecture. In addition, this paper explores the option of using diagonal summation as well as calibration to compensate for temperature and process variations. Further description of a timing pickoff signal which aligns all of the positioning (spatial channels) pulses in the array is described. The ASIC design is targeted to be scalable with the detector size and flexible to accommodate detectors from different vendors. This paper focuses on circuit implementation issues associated with the design of the ASIC to interface our Phase II MiCES FPGA board with a SiPM array. Moreover, a discussion is provided for strategies to eventually integrate all the analog and mixed-signal electronics with the SiPM, on either a single-silicon substrate or multi-chip module (MCM).

The challenge of detector designs for PET.

OBJECTIVE: The use of PET, especially the use of PET/CT scanners, has expanded rapidly over the past few years. Although most of the detector development efforts have been focused on scintillator-based designs, other technologies, such as wire chambers, time projection chambers, and solid-state devices, are also being pursued. CONCLUSION: Many of these new technologies have not translated into commercial systems. This article will explore some of the basic challenges of PET detector designs.

SCOUT: A Fast Monte-Carlo Modeling Tool of Scintillation Camera Output.

We have developed a Monte-Carlo photon-tracking and readout simulator called SCOUT to study the stochastic behavior of signals output from a simplified rectangular scintillation-camera design. SCOUT models the salient processes affecting signal generation, transport, and readout. Presently, we compare output signal statistics from SCOUT to experimental results for both a discrete and a monolithic camera. We also benchmark the speed of this simulation tool and compare it to existing simulation tools. We find this modeling tool to be relatively fast and predictive of experimental results. Depending on the modeled camera geometry, we found SCOUT to be 4 to 140 times faster than other modeling tools.

Statistical LOR estimation for a high-resolution dMiCE PET detector.

We develop a statistical line of response (LOR) estimator of the three-dimensional interaction positions of a pair of annihilation photons in a PET detector module with depth of interaction capability. The three-dimensional points of interaction of a coincidence pair of photons within the detector module are estimated by calculation of an expectation of the points of interaction conditioned on the signals measured by the photosensors. This conditional expectation is computed from estimates of the probability density function of the light collection process and a model of the kinetics of photon interactions in the detector module. Our algorithm is capable of handling coincidences where each annihilation photon interacts any number of times within the detector module before being completely absorbed or escaping. In the case of multiple interactions, our algorithm estimates the position of the first interaction for each of the coincidence photons. This LOR estimation algorithm is developed for a high-resolution PET detector capable of providing depth-of-interaction information. Depth of interaction is measured by tailoring the light shared between two adjacent detector elements. These light-sharing crystal pairs are referred to as dMiCE and are being developed in our lab. Each detector element in the prototype system has a 2 x 2 mm(2) cross section and is directly coupled to a micro-pixel avalanche photodiode (MAPD). In this set-up, the distribution of the ratio of light shared between two adjacent detector elements can be expressed as a function of the depth of interaction. Monte Carlo experiments are performed using our LOR estimation algorithm and compared with Anger logic. We show that our LOR estimation algorithm provides a significant improvement over Anger logic under a variety of parameters.

FPGA-Based Front-End Electronics for Positron Emission Tomography.

Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex discrete signal processing algorithms with clock rates above 100MHz. This combined with FPGA's low expense, ease of use, and selected dedicated hardware make them an ideal technology for a data acquisition system for positron emission tomography (PET) scanners. Our laboratory is producing a high-resolution, small-animal PET scanner that utilizes FPGAs as the core of the front-end electronics. For this next generation scanner, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilizes to add significant signal processing power to produce higher resolution images. In this paper two such processes, sub-clock rate pulse timing and event localization, will be discussed in detail. We show that timing performed in the FPGA can achieve a resolution that is suitable for small-animal scanners, and will outperform the analog version given a low enough sampling period for the ADC. We will also show that the position of events in the scanner can be determined in real time using a statistical positioning based algorithm.

Parametric Design Study of a Long Axial Field-of-View PET Scanner using a Block-Detector Tomograph Simulation of a Cylindrical Phantom.

We are conducting a two-phase study, which aims to select design parameters of a long-axis positron emission tomography (PET) scanner that are a compromise between detection performance and cost. In this first phase, we examine the effects of axial length, detector thickness and collimator geometry on the noise equivalent count rate per axial length (λNEC) and noise equivalent count rate per slice (dNEC). We use these metrics as approximate, but quickly computed, indicators of a PET-scanner's performance at a detection task. From this first phase, we select a subset of scanner designs for which we can conduct a detailed study of tumor detectability and quantitation accuracy in whole-body PET imaging.

FPGA-Based Pulse Parameter Discovery for Positron Emission Tomography.

Modern Field Programmable Gate Arrays (FPGAs) are capable of performing complex digital signal processing algorithms with clock rates well above 100MHz. This, combined with FPGA's low expense and ease of use make them an ideal technology for a data acquisition system for a positron emission tomography (PET) scanner. The University of Washington is producing a series of high-resolution, small-animal PET scanners that utilize FPGAs as the core of the front-end electronics. For these next generation scanners, functions that are typically performed in dedicated circuits, or offline, are being migrated to the FPGA. This will not only simplify the electronics, but the features of modern FPGAs can be utilizes to add significant signal processing power to produce higher resolution images. In this paper we report how we utilize the reconfigurable property of an FPGA to self-calibrate itself to determine pulse parameters necessary for some of the pulse processing steps. Specifically, we show how the FPGA can generate a reference pulse based on actual pulse data instead of a model. We also report how other properties of the photodetector pulse (baseline, pulse length, average pulse energy and event triggers) can be determined automatically by the FPGA.