Performance evaluation of iterative PET reconstruction with resolution recovery incorporating Gallium-68 positron range correction.

BACKGROUND: The distance traveled by the positron before annihilation with an electron, the so-called positron range, negatively effects the positron emission tomography (PET) image quality for radionuclides emitting high-energy positrons such as Gallium-68 (68Ga). PURPOSE: In this study, the effect of a tissue-independent positron range correction for Gallium-68 (68Ga-PRC) was investigated based on phantom measurements. The effect of the 68Ga-PRC was also explored in four patients. METHODS: The positron range distribution profile of 68Ga in water was generated via Monte Carlo simulation. That profile was mapped to a spatially invariant 3D convolution kernel which was incorporated in the OSEM and Q.Clear reconstruction algorithms to perform the 68Ga-PRC. In addition, each reconstruction method included point spread function (PSF) modeling and time-of-flight information. For both Fluorine-18 (18F) and 68Ga, the NEMA IQ phantom was filled with a sphere-to-background ratio of 10:1 and scanned with the GE Discovery MI 5R PET/CT system. Standard non-positron range correction (PRC) reconstructions were performed for both radionuclides, while also PRC reconstructions were performed for 68Ga. Reconstructions parameters (OSEM: number of updates, Q.Clear: beta value) were adapted to achieve similar noise levels between the corresponding reconstructions. The effect of 68Ga-PRC was assessed for both OSEM and Q.Clear reconstructions and compared to non-PRC reconstructions for 68Ga and 18F in terms of image contrast, noise, recovery coefficient (RC), and spatial resolution. For the clinical validation, 68Ga-labeled prostate-specific membrane antigen (68Ga-PSMA) and 68Ga-DOTATOC PET scans were included of two patients each. For each PET scan, patients were injected with 1.5 MBq/kg of 68Ga-PSMA or 68Ga-DOTATOC and the contrast-to-noise ratio (CNR) was calculated and compared to the non-PRC reconstructions. RESULTS: For OSEM reconstructions, including the 68Ga-PRC improved the RC by 9.4% (3.7%-19.3%) and spatial resolution by 21.7% (4.6 mm vs. 3.6 mm) for similar noise levels. For Q.Clear reconstructions, 68Ga-PRC modeling improved the RC by 6.7% (2.8%-10.5%) and spatial resolution by 15.3% (5.9 mm vs. 5.0 mm) while obtaining similar noise levels. In the patient data, the use of 68Ga-PRC enhanced the CNR by 13.2%. CONCLUSIONS: Including 68Ga-PRC in the PET reconstruction enhanced the image quality of 68Ga PET data compared to the standard non-PRC reconstructions for similar noise levels. Limited patient results also supported this improvement.

Deep learning-based time-of-flight (ToF) image enhancement of non-ToF PET scans.

PURPOSE: To improve the quantitative accuracy and diagnostic confidence of PET images reconstructed without time-of-flight (ToF) using deep learning models trained for ToF image enhancement (DL-ToF). METHODS: A total of 273 [18F]-FDG PET scans were used, including data from 6 centres equipped with GE Discovery MI ToF scanners. PET data were reconstructed using the block-sequential-regularised-expectation-maximisation (BSREM) algorithm with and without ToF. The images were then split into training (n = 208), validation (n = 15), and testing (n = 50) sets. Three DL-ToF models were trained to transform non-ToF BSREM images to their target ToF images with different levels of DL-ToF strength (low, medium, high). The models were objectively evaluated using the testing set based on standardised uptake value (SUV) in 139 identified lesions, and in normal regions of liver and lungs. Three radiologists subjectively rated the models using testing sets based on lesion detectability, diagnostic confidence, and image noise/quality. RESULTS: The non-ToF, DL-ToF low, medium, and high methods resulted in - 28 ± 18, - 28 ± 19, - 8 ± 22, and 1.7 ± 24% differences (mean; SD) in the SUVmax for the lesions in testing set, compared to ToF-BSREM image. In background lung VOIs, the SUVmean differences were 7 ± 15, 0.6 ± 12, 1 ± 13, and 1 ± 11% respectively. In normal liver, SUVmean differences were 4 ± 5, 0.7 ± 4, 0.8 ± 4, and 0.1 ± 4%. Visual inspection showed that our DL-ToF improved feature sharpness and convergence towards ToF reconstruction. Blinded clinical readings of testing sets for diagnostic confidence (scale 0-5) showed that non-ToF, DL-ToF low, medium, and high, and ToF images scored 3.0, 3.0, 4.1, 3.8, and 3.5 respectively. For this set of images, DL-ToF medium therefore scored highest for diagnostic confidence. CONCLUSION: Deep learning-based image enhancement models may provide converged ToF-equivalent image quality without ToF reconstruction. In clinical scoring DL-ToF-enhanced non-ToF images (medium and high) on average scored as high as, or higher than, ToF images. The model is generalisable and hence, could be applied to non-ToF images from BGO-based PET/CT scanners.

Image enhancement of whole-body oncology [18F]-FDG PET scans using deep neural networks to reduce noise.

PURPOSE: To enhance the image quality of oncology [18F]-FDG PET scans acquired in shorter times and reconstructed by faster algorithms using deep neural networks. METHODS: List-mode data from 277 [18F]-FDG PET/CT scans, from six centres using GE Discovery PET/CT scanners, were split into ¾-, ½- and »-duration scans. Full-duration datasets were reconstructed using the convergent block sequential regularised expectation maximisation (BSREM) algorithm. Short-duration datasets were reconstructed with the faster OSEM algorithm. The 277 examinations were divided into training (n = 237), validation (n = 15) and testing (n = 25) sets. Three deep learning enhancement (DLE) models were trained to map full and partial-duration OSEM images into their target full-duration BSREM images. In addition to standardised uptake value (SUV) evaluations in lesions, liver and lungs, two experienced radiologists scored the quality of testing set images and BSREM in a blinded clinical reading (175 series). RESULTS: OSEM reconstructions demonstrated up to 22% difference in lesion SUVmax, for different scan durations, compared to full-duration BSREM. Application of the DLE models reduced this difference significantly for full-, ¾- and ½-duration scans, while simultaneously reducing the noise in the liver. The clinical reading showed that the standard DLE model with full- or ¾-duration scans provided an image quality substantially comparable to full-duration scans with BSREM reconstruction, yet in a shorter reconstruction time. CONCLUSION: Deep learning-based image enhancement models may allow a reduction in scan time (or injected activity) by up to 50%, and can decrease reconstruction time to a third, while maintaining image quality.

A Path to Qualification of PET/MRI Scanners for Multicenter Brain Imaging Studies: Evaluation of MRI-Based Attenuation Correction Methods Using a Patient Phantom.

PET/MRI scanners cannot be qualified in the manner adopted for hybrid PET/CT devices. The main hurdle with qualification in PET/MRI is that attenuation correction (AC) cannot be adequately measured in conventional PET phantoms because of the difficulty in converting the MR images of the physical structures (e.g., plastic) into electron density maps. Over the last decade, a plethora of novel MRI-based algorithms has been developed to more accurately derive the attenuation properties of the human head, including the skull. Although promising, none of these techniques has yet emerged as an optimal and universally adopted strategy for AC in PET/MRI. In this work, we propose a path for PET/MRI qualification for multicenter brain imaging studies. Specifically, our solution is to separate the head AC from the other factors that affect PET data quantification and use a patient as a phantom to assess the former. The emission data collected on the integrated PET/MRI scanner to be qualified should be reconstructed using both MRI- and CT-based AC methods, and whole-brain qualitative and quantitative (both voxelwise and regional) analyses should be performed. The MRI-based approach will be considered satisfactory if the PET quantification bias is within the acceptance criteria specified here. We have implemented this approach successfully across 2 PET/MRI scanner manufacturers at 2 sites.

Optimizing the frame duration for data-driven rigid motion estimation in brain PET imaging.

PURPOSE: Data-driven rigid motion estimation for PET brain imaging is usually performed using data frames sampled at low temporal resolution to reduce the overall computation time and to provide adequate signal-to-noise ratio in the frames. In recent work it has been demonstrated that list-mode reconstructions of ultrashort frames are sufficient for motion estimation and can be performed very quickly. In this work we take the approach of using image-based registration of reconstructions of very short frames for data-driven motion estimation, and optimize a number of reconstruction and registration parameters (frame duration, MLEM iterations, image pixel size, post-smoothing filter, reference image creation, and registration metric) to ensure accurate registrations while maximizing temporal resolution and minimizing total computation time. METHODS: Data from 18 F-fluorodeoxyglucose (FDG) and 18 F-florbetaben (FBB) tracer studies with varying count rates are analyzed, for PET/MR and PET/CT scanners. For framed reconstructions using various parameter combinations interframe motion is simulated and image-based registrations are performed to estimate that motion. RESULTS: For FDG and FBB tracers using 4 × 105 true and scattered coincidence events per frame ensures that 95% of the registrations will be accurate to within 1 mm of the ground truth. This corresponds to a frame duration of 0.5-1 sec for typical clinical PET activity levels. Using four MLEM iterations with no subsets, a transaxial pixel size of 4 mm, a post-smoothing filter with 4-6 mm full width at half maximum, and averaging two or more frames to create the reference image provides an optimal set of parameters to produce accurate registrations while keeping the reconstruction and processing time low. CONCLUSIONS: It is shown that very short frames (≤1 sec) can be used to provide accurate and quick data-driven rigid motion estimates for use in an event-by-event motion corrected reconstruction.

PET image reconstruction using physical and mathematical modelling for time of flight PET-MR scanners in the STIR library.

This work demonstrates how computational and physical modelling of the positron emission tomography (PET) image acquisition process for a state-of-the-art integrated PET and magnetic resonance imaging (PET-MR) system can produce images comparable to the manufacturer. The GE SIGNA PET/MR scanner is manufactured by General Electric and has time-of-flight (TOF) capabilities of about 390 ps. All software development took place in the Software for Tomographic Image Reconstruction (STIR: http://stir.sf.net) library, which is a widely used open source software to reconstruct data as exported from emission tomography scanners. The new software developments will be integrated into STIR, providing the opportunity for researchers worldwide to establish and expand their image reconstruction methods. Furthermore, this work is of particular significance as it provides the first validation of TOF PET image reconstruction for real scanner datasets using the STIR library. This paper presents the methodology, analysis, and critical issues encountered in implementing an independent reconstruction software package. Acquired PET data were processed via several appropriate algorithms which are necessary to produce an accurate and precise quantitative image. This included mathematical, physical and anatomical modelling of the patient and simulation of various aspects of the acquisition. These included modelling of random coincidences using 'singles' rates per crystals, detector efficiencies and geometric effects. Attenuation effects were calculated by using the STIR's attenuation correction model. Modelling all these effects within the system matrix allowed the reconstruction of PET images which demonstrates the metabolic uptake of the administered radiopharmaceutical. These implementations were validated using measured phantom and clinical datasets. The developments are tested using the ordered subset expectation maximisation (OSEM) and the more recently proposed kernelised expectation maximisation (KEM) algorithm which incorporates anatomical information from MR images into PET reconstruction.

Real-Time Gain Control of PET Detectors and Evaluation With Challenging Radionuclides.

Accurate gain control of PET detectors is a prerequisite for quantitative accuracy. A shift in the 511 keV peak position can lead to errors in scatter correction, degrading quantitation. The PET detectors in a PET/MR scanner are subject to thermal transients due to eddy currents induced during gradient-intensive MRI sequences. Since the gain of silicon photomultiplier-based detectors changes with temperature, good gain control is particularly challenging. In this paper we describe a method that utilizes information from the entire singles spectrum to create a real-time gain control method that maintains gain of PET detectors stable within approximately ±0.5% (±2.5 keV) with varying levels of scatter and in the presence of significant thermal transients. We describe the methods used to combine information about multiple peaks and how this algorithm is implemented in a way that permits real-time processing on a field-programmable gate array. Simulations demonstrate rapid response time and stability. A method ("virtual scatter filter") is also described that extracts unscattered photopeak events from phantom data and demonstrates the accuracy of the photopeak for various radionuclides that emit energies in addition to the pure 511 keV annihilation peak. Radionuclides 52 Mn, 55 Co, 64 Cu, 89 Zr, 90 Y, and 124 I are included in the study for their various forms of spectral contamination.

Ultra-Fast List-Mode Reconstruction of Short PET Frames and Example Applications.

Standard clinical reconstructions usually require several minutes to complete, and this time is mostly independent of the duration of the data being reconstructed. Applications such as data-driven motion estimation, which require many short frames over the duration of the scan, become unfeasible with such long reconstruction times. In this work, we present an infrastructure whereby ultra-fast list-mode reconstructions of very short frames (≤1 s) are performed. With this infrastructure, it is possible to have a dynamic series of frames that can be used for various applications, such as data-driven motion estimation, whole-body surveys, quick reconstructions of gated data to select the optimal gate for a given attenuation map, and, if the infrastructure runs simultaneously with the scan, real-time display of the reconstructed data during the scan and automated alerts for patient motion. Methods: A fast ray-tracing time-of-flight projector was implemented and parallelized. The reconstruction parameters were optimized to allow for fast performance: only a few iterations are performed, without point-spread-function modeling, and scatter correction is not used. The resulting reconstructions are thus not quantitative but are acceptable for motion estimation and visualization purposes. Data-driven motion can be estimated using image registration, with the resultant motion data being used in a fully motion-corrected list-mode reconstruction. Results: The infrastructure provided images that can be used for visualization and gating purposes and for motion estimation using image registration. Several case studies are presented, including data-driven motion estimation and correction for brain studies, abdominal studies in which respiratory and cardiac motion is visible, and a whole-body survey. Conclusion: The presented infrastructure provides the capability to quickly create a series of very short frames for PET data that can be used in a variety of applications.

Rigid Motion Correction for Brain PET/MR Imaging using Optical Tracking.

A significant challenge during high-resolution PET brain imaging on PET/MR scanners is patient head motion. This challenge is particularly significant for clinical patient populations who struggle to remain motionless in the scanner for long periods of time. Head motion also affects the MR scan data. An optical motion tracking technique, which has already been demonstrated to perform MR motion correction during acquisition, is used with a list-mode PET reconstruction algorithm to correct the motion for each recorded event and produce a corrected reconstruction. The technique is demonstrated on real Alzheimer's disease patient data for the GE SIGNA PET/MR scanner.

Joint estimation of activity and attenuation for PET using pragmatic MR-based prior: application to clinical TOF PET/MR whole-body data for FDG and non-FDG tracers.

Accurate and robust attenuation correction remains challenging in hybrid PET/MR particularly for torsos because it is difficult to segment bones, lungs and internal air in MR images. Additionally, MR suffers from susceptibility artifacts when a metallic implant is present. Recently, joint estimation (JE) of activity and attenuation based on PET data, also known as maximum likelihood reconstruction of activity and attenuation, has gained considerable interest because of (1) its promise to address the challenges in MR-based attenuation correction (MRAC), and (2) recent advances in time-of-flight (TOF) technology, which is known to be the key to the success of JE. In this paper, we implement a JE algorithm using an MR-based prior and evaluate the algorithm using whole-body PET/MR patient data, for both FDG and non-FDG tracers, acquired from GE SIGNA PET/MR scanners with TOF capability. The weight of the MR-based prior is spatially modulated, based on MR signal strength, to control the balance between MRAC and JE. Large prior weights are used in strong MR signal regions such as soft tissue and fat (i.e. MR tissue classification with a high degree of certainty) and small weights are used in low MR signal regions (i.e. MR tissue classification with a low degree of certainty). The MR-based prior is pragmatic in the sense that it is convex and does not require training or population statistics while exploiting synergies between MRAC and JE. We demonstrate the JE algorithm has the potential to improve the robustness and accuracy of MRAC by recovering the attenuation of metallic implants, internal air and some bones and by better delineating lung boundaries, not only for FDG but also for more specific non-FDG tracers such as 68Ga-DOTATOC and 18F-Fluoride.

PET Imaging Stability Measurements During Simultaneous Pulsing of Aggressive MR Sequences on the SIGNA PET/MR System.

The recent introduction of simultaneous whole-body PET/MR scanners has enabled new research taking advantage of the complementary information obtainable with PET and MRI. One such application is kinetic modeling, which requires high levels of PET quantitative stability. To accomplish the required PET stability levels, the PET subsystem must be sufficiently isolated from the effects of MR activity. Performance measurements have previously been published, demonstrating sufficient PET stability in the presence of MR pulsing for typical clinical use; however, PET stability during radiofrequency (RF)-intensive and gradient-intensive sequences has not previously been evaluated for a clinical whole-body scanner. In this work, PET stability of the GE SIGNA PET/MR was examined during simultaneous scanning of aggressive MR pulse sequences. Methods: PET performance tests were acquired with MR idle and during simultaneous MR pulsing. Recent system improvements mitigating RF interference and gain variation were used. A fast recovery fast spin echo MR sequence was selected for high RF power, and an echo planar imaging sequence was selected for its high heat-inducing gradients. Measurements were performed to determine PET stability under varying MR conditions using the following metrics: sensitivity, scatter fraction, contrast recovery, uniformity, count rate performance, and image quantitation. A final PET quantitative stability assessment for simultaneous PET scanning during functional MRI studies was performed with a spiral in-and-out gradient echo sequence. Results: Quantitation stability of a 68Ge flood phantom was demonstrated within 0.34%. Normalized sensitivity was stable during simultaneous scanning within 0.3%. Scatter fraction measured with a 68Ge line source in the scatter phantom was stable within the range of 40.4%-40.6%. Contrast recovery and uniformity were comparable for PET images acquired simultaneously with multiple MR conditions. Peak noise equivalent count rate was 224 kcps at an effective activity concentration of 18.6 kBq/mL, and the count rate curves and scatter fraction curve were consistent for the alternating MR pulsing states. A final test demonstrated quantitative stability during a spiral functional MRI sequence. Conclusion: PET stability metrics demonstrated that PET quantitation was not affected during simultaneous aggressive MRI. This stability enables demanding applications such as kinetic modeling.

Clinical evaluation of whole-body oncologic PET with time-of-flight and point-spread function for the hybrid PET/MR system.

PURPOSE: Hybrid positron emission tomography/magnetic resonance (PET/MR) imaging is a new multimodality imaging technology that can provide structural and functional information simultaneously. The aim of this study was to investigate the effects of the time-of-flight (TOF) and point-spread function (PSF) on small lesions observed in PET/MR images from clinical patient image sets. MATERIALS AND METHODS: This study evaluated 54 small lesions in 14 patients who had undergone 18F-fluorodeoxyglucose (FDG) PET/MR. Lesions up to 30mm in diameter were included. The PET data were reconstructed with a baseline ordered-subsets expectation-maximization (OSEM) algorithm, OSEM+PSF, OSEM+TOF and OSEM+TOF+PSF. PET image quality and small lesions were visually evaluated and scored by a 3-point scale. A quantitative analysis was then performed using the mean and maximum standardized uptake value (SUV) of the small lesions (SUVmean and SUVmax). The lesions were divided into two groups according to the long-axis diameter and the location respectively and evaluated with each reconstruction algorithm. We also evaluated the background signal by analyzing the SUVliver. RESULTS: OSEM+TOF+PSF provided the highest value and OSEM+TOF or PSF showed a higher value than OSEM for the visual assessment and quantitative analysis. The combination of TOF and PSF increased the SUVmean by 26.6% and the SUVmax by 30.0%. The SUVliverwas not influenced by PSF or TOF. For the OSEM+TOF+PSF model, the change in SUVmean and SUVmax for lesions <10mm in diameter was 31.9% and 35.8%, and 24.5% and 27.6% for lesions 10-30mm in diameter, respectively. The abdominal lesions obtained the higher SUV than those of chest on the images with TOF and/or PSF. CONCLUSION: Application of TOF and PSF significantly increased the SUV of small lesions in hybrid PET/MR images, potentially improving small lesion detectability.

Design Features and Mutual Compatibility Studies of the Time-of-Flight PET Capable GE SIGNA PET/MR System.

A recent entry into the rapidly evolving field of integrated PET/MR scanners is presented in this paper: a whole body hybrid PET/MR system (SIGNA PET/MR, GE Healthcare) capable of simultaneous acquisition of both time-of-flight (TOF) PET and high resolution MR data. The PET ring was integrated into an existing 3T MR system resulting in a (patient) bore opening of 60 cm diameter, with a 25 cm axial FOV. PET performance was evaluated both on the standalone PET ring and on the same detector integrated into the MR system, to assess the level of mutual interference between both subsystems. In both configurations we obtained detector performance data. PET detector performance was not significantly affected by integration into the MR system. The global energy resolution was within 2% (10.3% versus 10.5%), and the system coincidence time resolution showed a maximum change of < 3% (385 ps versus 394 ps) when measured outside MR and during simultaneous PET/MRI acquisitions, respectively. To evaluate PET image quality and resolution, the NEMA IQ phantom was acquired with MR idle and with MR active. Impact of PET on MR IQ was assessed by comparing SNR with PET acquisition on and off. B0 and B1 homogeneities were acquired before and after the integration of the PET ring inside the magnet. In vivo brain and whole body head-to-thighs data were acquired to demonstrate clinical image quality.

The future of SPECT in a time of PET.

As positron emission tomography (PET) imaging is becoming more prevalent in clinical practice, it is reasonable to ask if there will be a role for single photon emission computed tomography (SPECT) in the future. This article considers that question, focusing on areas where SPECT can differentiate itself from PET for fundamental reasons: breadth of available radionuclides, simultaneous imaging of multiple agents, cost-effectiveness and adaptability to specific imaging situations. The conclusion is that SPECT will continue to evolve and exist alongside PET and will grow the field of molecular imaging with improved efficiency and patient workflow.