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.

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.

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.

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.

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.

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.

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.

Image Reconstruction for a Partially Collimated Whole Body PET Scanner.

Partially collimated PET systems have less collimation than conventional 2-D systems and have been shown to offer count rate improvements over 2-D and 3-D systems. Despite this potential, previous efforts have not established image-based improvements with partial collimation and have not customized the reconstruction method for partially collimated data. This work presents an image reconstruction method tailored for partially collimated data. Simulated and measured sensitivity patterns are presented and provide a basis for modification of a fully 3-D reconstruction technique. The proposed method uses a measured normalization correction term to account for the unique sensitivity to true events. This work also proposes a modified scatter correction based on simulated data. Measured image quality data supports the use of the normalization correction term for true events, and suggests that the modified scatter correction is unnecessary.

Optimization of noise equivalent count rate performance for a partially collimated PET scanner by varying the number of septa.

We present a simulation study of the global count-rate performance of a positron emission tomography (PET) scanner with different levels of partial collimation to maximize the noise equivalent count rate for whole-body PET imaging. We achieve partial collimation by removing different numbers of septal rings from the standard 2-D septa set for the GE Advance PET scanner. System behavior is studied with a photon tracking simulation package, which we modify to enable the production of random coincidences. The simulations are validated with measured data taken in 2-D and fully 3-D acquisition mode on a GE Advance system using the National Electrical Manufacturers Association NU-2 count-rate phantom with two sets of annular sleeves to expand the diameter to 27 and 35 cm. For all diameters and in 2-D and fully 3-D mode, there is good agreement between measurements and simulations. All studies use the three phantom diameters to evaluate the effect of patient thickness for each amount of collimation. Optimized system parameters, such as maximum ring difference for single slice rebinning, are determined for the five partially collimated systems considered. The resulting global count rates for true, scattered, and random coincidences, the noise equivalent count (NEC) rates, and the scatter fractions for different levels of collimation are compared along with the results from the conventional 2-D and fully 3-D modes. Improved statistical data quality relative to both 2-D and fully 3-D data is found with the partially collimated systems, particularly when one-half or two-thirds of the septal rings are removed. An increase in NEC rates of as much as 50% is found for clinically relevant activities between 5-10 mCi (184-370 MBq). Scatter fractions for the partially collimated systems are intermediate between the 2-D and fully 3-D numbers. Many factors that affect image quality have not been considered in this paper. However, the significant increase in statistical data quality warrants further investigation of the impact of partial collimation on clinical whole-body PET imaging.

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.

Modeling and incorporation of system response functions in 3-D whole body PET.

Appropriate application of spatially variant system models can correct for degraded resolution response and mispositioning errors. This paper explores the detector blurring component of the system model for a whole body positron emission tomography (PET) system and extends this factor into a more general system response function to account for other system effects including the influence of Fourier rebinning (FORE). We model the system response function as a three-dimensional (3-D) function that blurs in the radial and axial dimension and is spatially variant in radial location. This function is derived from Monte Carlo simulations and incorporates inter-crystal scatter, crystal penetration, and the blurring due to the FORE algorithm. The improved system model is applied in a modified ordered subsets expectation maximization (OSEM) algorithm to reconstruct images from rebinned, fully 3-D PET data. The proposed method effectively removes the spatial variance in the resolution response, as shown in simulations of point sources. Furthermore, simulation and measured studies show the proposed method improves quantitative accuracy with a reduction in tumor bias compared to conventional OSEM on the order of 10%-30% depending on tumor size and smoothing parameter.

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.

2-[(18)F]Fluoro-2-deoxyglucose and glucose uptake in malignant gliomas before and after radiotherapy: correlation with outcome.

PURPOSE: To examine whether quantitative 1-[(11)C]glucose- or 2-[(18)F]fluoro-2-deoxyglucose (FDG)-positron emission tomography performed before and/or after radiotherapy (RT) of malignant gliomas correlates with treatment outcome. Changes in metabolism between the start and finish of RT, and immediate post-RT studies have received little attention. EXPERIMENTAL DESIGN: Adults with malignant gliomas were imaged within 2 weeks before and/or 2 weeks after RT. Four patients were imaged only before RT, 12 only after RT, and 14 both before and after RT. Each 1-[(11)C]glucose and FDG study included arterial plasma sampling. Kinetic parameters, glucose metabolic rate (MRGlc), and FDG metabolic rate (MRFDG) were estimated by an optimization program based on a three compartment, four rate constant model. Changes in MRGlc or MRFDG from pre-RT to post-RT were calculated for the 14 patients studied at both times. Overall survival was examined, and survival was computed relative to historical controls in matched prognostic classes. RESULTS: Low pre-RT MRGlc (P < 0.02) or MRFDG (P < 0.03), or an increase from pre- to post-RT in MRGlc (P < 0.004) or MRFDG (P < 0.006) are correlating with longer survival (4 patients still alive). Strikingly, the post-RT studies (n = 26) showed no correlation between MRGlc or MRFDG and survival (P = 0.73 and P = 0.46 respectively). CONCLUSIONS: Low MRGlc or MRFDG before RT probably indicates less aggressive disease. An increase in MRGlc or MRFDG from pre- to post-RT in the tumors of patients with longer survival could be because of one or more of the following or other reasons: (a) apoptosis of tumor cells in response to RT requires energy; (b) decreased tumor cell density by the RT leaving normal cells with higher metabolism; or (c) inflammatory cells infiltrate and take up glucose or FDG where tumor cells are dying. Quantitative 1-[(11)C]glucose or FDG uptake in the early weeks post-RT correlates poorly with survival.

The FDG lumped constant in normal human brain.

UNLABELLED: The lumped constant (LC) is a correction factor used to infer glucose metabolic rate (MR(glc)) from FDG metabolic rate (MR(FDG)). METHODS: LC was determined in normal brain in 10 subjects (4 male, 6 female) by measuring regional MR(glc) and MR(FDG) independently using 1-(11)C-glucose and (18)F-FDG with dynamic positron tomographic imaging, arterial blood sampling, and region-of-interest time-activity curve analysis with appropriate compartmental models. RESULTS: The mean LC (+/-SD) for normal brain was found to be 0.89 +/- 0.08. The value for cerebellum was slightly lower, 0.78 +/- 0.11 (P = 0.006; 2-tailed paired t test). CONCLUSION: The LC values determined in this study are considerably higher than older values in the literature, probably because of methodologic differences, but agree with a recent study by Hasselbalch.

18F-FDG PET of gliomas at delayed intervals: improved distinction between tumor and normal gray matter.

UNLABELLED: We hypothesized that delineation of gliomas from gray matter with 18F-FDG PET could be improved by extending the interval between 18F-FDG administration and PET data acquisition. The purposes of this study were, first, to analyze standard and delayed 18F-FDG PET images visually and quantitatively to determine whether definition of tumor improved at later imaging times and, second, to investigate the dynamics of model-derived kinetic rate constants, particularly k4. METHODS: Nineteen adult patients with supratentorial gliomas were imaged from 0 to 90 min and once or twice later at 180-480 min after injection. In 15 patients, arterial sampling provided the early input function. Venous sampling provided the remaining curve to the end of the imaging sequence. Standardized uptake value (SUV) was calculated as tissue concentration of tracer per injected tracer dose per body weight. Ratios of tumor SUV relative to the SUV of gray matter, brain (including gray and white matter), or white matter were calculated at each imaging time point. Dynamic image data from tumor, gray matter, brain, or white matter were analyzed using a 2-compartment, 4-parameter model applied for the entire duration of imaging, in which delay, K1, distribution volume, k3, and k4 were optimized using a nonlinear optimization method. Parameter estimation for each region included both an early subset of data from a conventional dynamic imaging period (0-60 min) and the full, extended dataset for each region. RESULTS: In 12 of the 19 patients, visual analysis showed that the delayed images better distinguished the high uptake in tumors relative to uptake in gray matter. SUV comparisons also showed greater uptake in the tumors than in gray matter, brain, or white matter at the delayed times. The estimated k4 values for tumors were not significantly different from those for gray matter in early imaging analysis but were lower (P < 0.01) using the extended-time data. CONCLUSION: The kinetic parameter results confirm the visual and SUV interpretation that tumor enhancement is greater than enhancement of surrounding brain regions at later imaging times, consistent with a greater effect of FDG-6-phosphate degradation on normal brain relative to glioma.

PET-CT image registration in the chest using free-form deformations.

We have implemented and validated an algorithm for three-dimensional positron emission tomography transmission-to-computed tomography registration in the chest, using mutual information as a similarity criterion. Inherent differences in the two imaging protocols produce significant nonrigid motion between the two acquisitions. A rigid body deformation combined with localized cubic B-splines is used to capture this motion. The deformation is defined on a regular grid and is parameterized by potentially several thousand coefficients. Together with a spline-based continuous representation of images and Parzen histogram estimates, our deformation model allows closed-form expressions for the criterion and its gradient. A limited-memory quasi-Newton optimization algorithm is used in a hierarchical multiresolution framework to automatically align the images. To characterize the performance of the method, 27 scans from patients involved in routine lung cancer staging were used in a validation study. The registrations were assessed visually by two expert observers in specific anatomic locations using a split window validation technique. The visually reported errors are in the 0- to 6-mm range and the average computation time is 100 min on a moderate-performance workstation.

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.

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.