List-mode Positron Emission Tomography Research Articles

Unsupervised deep learning framework for data-driven gating in positron emission tomography.

Physiological motion, such as respiratory motion, has become a limiting factor in the spatial resolution of positron emission tomography (PET) imaging as the resolution of PET detectors continue to improve. Motion-induced misregistration between PET and CT images can also cause attenuation correction artifacts. Respiratory gating can be used to freeze the motion and to reduce motion induced artifacts. In this study, we propose a robust data-driven approach using an unsupervised deep clustering network that employs an autoencoder (AE) to extract latent features for respiratory gating. We first divide list-mode PET data into short-time frames. The short-time frame images are reconstructed without attenuation, scatter, or randoms correction to avoid attenuation mismatch artifacts and to reduce image reconstruction time. The deep AE is then trained using reconstructed short-time frame images to extract latent features for respiratory gating. No additional data are required for the AE training. K-means clustering is subsequently used to perform respiratory gating based on the latent features extracted by the deep AE. The effectiveness of our proposed Deep Clustering method was evaluated using physical phantom and real patient datasets. The performance was compared against phase gating based on an external signal (External) and image based principal component analysis (PCA) with K-means clustering (Image PCA). The proposed method produced gated images with higher contrast and sharper myocardium boundaries than those obtained using the External gating method and Image PCA. Quantitatively, the gated images generated by the proposed Deep Clustering method showed larger center of mass (COM) displacement and higher lesion contrast than those obtained using the other two methods. The effectiveness of our proposed method was validated using physical phantom and real patient data. The results showed our proposed framework could provide superior gating than the conventional External method and Image PCA.

List-Mode PET Image Reconstruction Using Deep Image Prior.

List-mode positron emission tomography (PET) image reconstruction is an important tool for PET scanners with many lines-of-response and additional information such as time-of-flight and depth-of-interaction. Deep learning is one possible solution to enhance the quality of PET image reconstruction. However, the application of deep learning techniques to list-mode PET image reconstruction has not been progressed because list data is a sequence of bit codes and unsuitable for processing by convolutional neural networks (CNN). In this study, we propose a novel list-mode PET image reconstruction method using an unsupervised CNN called deep image prior (DIP) which is the first trial to integrate list-mode PET image reconstruction and CNN. The proposed list-mode DIP reconstruction (LM-DIPRecon) method alternatively iterates the regularized list-mode dynamic row action maximum likelihood algorithm (LM-DRAMA) and magnetic resonance imaging conditioned DIP (MR-DIP) using an alternating direction method of multipliers. We evaluated LM-DIPRecon using both simulation and clinical data, and it achieved sharper images and better tradeoff curves between contrast and noise than the LM-DRAMA, MR-DIP and sinogram-based DIPRecon methods. These results indicated that the LM-DIPRecon is useful for quantitative PET imaging with limited events while keeping accurate raw data information. In addition, as list data has finer temporal information than dynamic sinograms, list-mode deep image prior reconstruction is expected to be useful for 4D PET imaging and motion correction.

A back-projection-and-filtering-like (BPF-like) reconstruction method with the deep learning filtration from listmode data in TOF-PET.

The time-of-flight (TOF) information improves signal-to-noise ratio (SNR) for positron emission tomography (PET) imaging. Existing analytical algorithms for TOF PET usually follow a filtered back-projection process on reconstructing images from the sinogram data. This work aims to develop a back-projection-and-filtering-like (BPF-like) algorithm that reconstructs the TOF PET image directly from listmode data rapidly. We extended the 2D conventional non-TOF PET projection model to a TOF case, where projection data are represented as line integrals weighted by the one-dimensional TOF kernel along the projection direction. After deriving the central slice theorem and the TOF back-projection of listmode data, we designed a deep learning network with a modified U-net architecture to perform the spatial filtration (reconstruction filter). The proposed BP-Net method was validated via Monte Carlo simulations of TOF PET listmode data with three different time resolutions for two types of activity phantoms. The network was only trained on the simulated full-dose XCAT dataset and then evaluated on XCAT and Jaszczak data with different time resolutions and dose levels. Reconstructed images show that when compared with the conventional BPF algorithm and the MLEM algorithm proposed for TOF PET, the proposed BP-Net method obtains better image quality in terms of peak signal-to-noise ratio, relative mean square error, and structure similarity index; besides, the reconstruction speed of the BP-Net is 1.75 times faster than BPF and 29.05 times faster than MLEM using 15 iterations. The results also indicate that the performance of the BP-Net degrades with worse time resolutions and lower tracer doses, but degrades less than BPF or MLEM reconstructions. In this work, we developed an analytical-like reconstruction in the form of BPF with the reconstruction filtering operation performed via a deep network. The method runs even faster than the conventional BPF algorithm and provides accurate reconstructions from listmode data in TOF-PET, free of rebinning data to a sinogram.

Fast Energy Dependent Scatter Correction for List-Mode PET Data.

Improvements in energy resolution of modern positron emission tomography (PET) detectors have created opportunities to implement energy-based scatter correction algorithms. Here, we use the energy information of auxiliary windows to estimate the scatter component. Our method is directly implemented in an iterative reconstruction algorithm, generating a scatter-corrected image without the need for sinograms. The purpose was to implement a fast energy-based scatter correction method on list-mode PET data, when it was not possible to use an attenuation map as a practical approach for the scatter degradation. The proposed method was evaluated using Monte Carlo simulations of various digital phantoms. It accurately estimated the scatter fraction distribution, and improved the image contrast in the simulated studied cases. We conclude that the proposed scatter correction method could effectively correct the scattered events, including multiple scatters and those originated in sources outside the field of view.

A data-driven respiratory motion estimation approach for PET based on time-of-flight weighted positron emission particle tracking.

PurposeRespiratory motion of patients during positron emission tomography (PET)/computed tomography (CT) imaging affects both image quality and quantitative accuracy. Hardware‐based motion estimation, which is the current clinical standard, requires initial setup, maintenance, and calibration of the equipment, and can be associated with patient discomfort. Data‐driven techniques are an active area of research with limited exploration into lesion‐specific motion estimation. This paper introduces a time‐of‐flight (TOF)‐weighted positron emission particle tracking (PEPT) algorithm that facilitates lesion‐specific respiratory motion estimation from raw listmode PET data.MethodsThe TOF‐PEPT algorithm was implemented and investigated under different scenarios: (a) a phantom study with a point source and an Anzai band for respiratory motion tracking; (b) a phantom study with a point source only, no Anzai band; (c) two clinical studies with point sources and the Anzai band; (d) two clinical studies with point sources only, no Anzai band; and (e) two clinical studies using lesions/internal regions instead of point sources and no Anzai band. For studies with radioactive point sources, they were placed on patients during PET/CT imaging. The motion tracking was performed using a preselected region of interest (ROI), manually drawn around point sources or lesions on reconstructed images. The extracted motion signals were compared with the Anzai band when applicable. For the purposes of additional comparison, a center‐of‐mass (COM) algorithm was implemented both with and without the use of TOF information. Using the motion estimate from each method, amplitude‐based gating was applied, and gated images were reconstructed.ResultsThe TOF‐PEPT algorithm is shown to successfully determine the respiratory motion for both phantom and clinical studies. The derived motion signals correlated well with the Anzai band; correlation coefficients of 0.99 and 0.94‐0.97 were obtained for the phantom study and the clinical studies, respectively. TOF‐PEPT was found to be 13–38% better correlated with the Anzai results than the COM methods. Maximum Standardized Uptake Values (SUVs) were used to quantitatively compare the reconstructed‐gated images. In comparison with the ungated image, a 14–39% increase in the max SUV across several lesion areas and an 8.7% increase in the max SUV on the tracked lesion area were observed in the gated images based on TOF‐PEPT. The distinct presence of lesions with reduced blurring effect and generally sharper images were readily apparent in all clinical studies. In addition, max SUVs were found to be 4–10% higher in the TOF‐PEPT‐based gated images than in those based on Anzai and COM methods.ConclusionA PEPT‐ based algorithm has been presented for determining movement due to respiratory motion during PET/CT imaging. Gating based on the motion estimate is shown to quantifiably improve the image quality in both a controlled point source phantom study and in clinical data patient studies. The algorithm has the potential to facilitate true motion correction where the reconstruction algorithm can use all data available.

Ultra-low-dose PET reconstruction using generative adversarial network with feature matching and task-specific perceptual loss.

Our goal was to use a generative adversarial network (GAN) with feature matching and task-specific perceptual loss to synthesize standard-dose amyloid Positron emission tomography (PET) images of high quality and including accurate pathological features from ultra-low-dose PET images only. Forty PET datasets from 39 participants were acquired with a simultaneous PET/MRI scanner following injection of 330±30MBq of the amyloid radiotracer 18F-florbetaben. The raw list-mode PET data were reconstructed as the standard-dose ground truth and were randomly undersampled by a factor of 100 to reconstruct 1% low-dose PET scans. A 2D encoder-decoder network was implemented as the generator to synthesize a standard-dose image and a discriminator was used to evaluate them. The two networks contested with each other to achieve high-visual quality PET from the ultra-low-dose PET. Multi-slice inputs were used to reduce noise by providing the network with 2.5D information. Feature matching was applied to reduce hallucinated structures. Task-specific perceptual loss was designed to maintain the correct pathological features. The image quality was evaluated by peak signal-to-noise ratio (PSNR), structural similarity (SSIM), and root mean square error (RMSE) metrics with and without each of these modules. Two expert radiologists were asked to score image quality on a 5-point scale and identified the amyloid status (positive or negative). With only low-dose PET as input, the proposed method significantly outperformed Chen et al.'s method (Chen et al. Radiology. 2018;290:649-656) (which shows the best performance in this task) with the same input (PET-only model) by 1.87dB in PSNR, 2.04% in SSIM, and 24.75% in RMSE. It also achieved comparable results to Chen et al.'s method which used additional magnetic resonance imaging (MRI) inputs (PET-MR model). Experts' reading results showed that the proposed method could achieve better overall image quality and maintain better pathological features indicating amyloid status than both PET-only and PET-MR models proposed by Chen et al. CONCLUSION: Standard-dose amyloid PET images can be synthesized from ultra-low-dose images using GAN. Applying adversarial learning, feature matching, and task-specific perceptual loss are essential to ensure image quality and the preservation of pathological features.

GABAA Receptors in the Mongolian Gerbil: a PET Study Using [18F]Flumazenil to Determine Receptor Binding in Young and Old Animals.

Plastic changes in the central auditory system involving the GABAergic system accompany age-related hearing loss. Such processes can be investigated with positron emission tomography (PET) imaging using [18F]flumazenil ([18F]FMZ). Here, [18F]FMZ PET-based modeling approaches allow a simple and reliable quantification of GABAA receptor binding capacity revealing regional differences and age-related changes. Sixty-minute list-mode PET acquisitions were performed in 9 young (range 5-6months) and 11 old (range 39-42months) gerbils, starting simultaneously with the injection of [18F]FMZ via femoral vein. Non-displaceable binding potentials (BPnd) with pons as reference region were calculated for auditory cortex (AC), inferior colliculus (IC), medial geniculate body (MGB), somatosensory cortex (SC), and cerebellum (CB) using (i) a two-tissue compartment model (2TCM), (ii) the Logan plot with image-derived blood-input (Logan (BI)), (iii) a simplified reference tissue model (SRTM), and (iv) the Logan reference model (Logan (RT)). Statistical parametric mapping analysis (SPM) comparing young and old gerbils was performed using 3D parametric images for BPnd based on SRTM. Results were verified with in vitro autoradiography from five additional young gerbils. Model assessment included the Akaike information criterion (AIC). Hearing was evaluated using auditory brainstem responses. BPnd differed significantly between models (p < 0.0005), showing the smallest mean difference between 2TCM as reference and SRTM as simplified procedure. SRTM revealed the lowest AIC values. Both volume of distribution (r2 = 0.8793, p = 0.018) and BPnd (r2 = 0.8216, p = 0.034) correlated with in vitro autoradiography data. A significant age-related decrease of receptor binding was observed in auditory (AC, IC, MGB) and other brain regions (SC and CB) (p < 0.0001, unpaired t test) being confirmed by SPM using pons as reference (p < 0.0001, uncorrected). Imaging of GABAA receptor binding capacity in gerbils using [18F]FMZ PET revealed SRTM as a simple and robust quantification method of GABAA receptors. Comparison of BPnd in young and old gerbils demonstrated an age-related decrease of GABAA receptor binding.

Data-driven gating in PET: Influence of respiratory signal noise on motion resolution.

Data-driven gating (DDG) approaches for positron emission tomography (PET) are interesting alternatives to conventional hardware-based gating methods. In DDG, the measured PET data themselves are utilized to calculate a respiratory signal, that is, subsequently used for gating purposes. The success of gating is then highly dependent on the statistical quality of the PET data. In this study, we investigate how this quality determines signal noise and thus motion resolution in clinical PET scans using a center-of-mass-based (COM) DDG approach, specifically with regard to motion management of target structures in future radiotherapy planning applications. PET list mode datasets acquired in one bed position of 19 different radiotherapy patients undergoing pretreatment [18 F]FDG PET/CT or [18 F]FDG PET/MRI were included into this retrospective study. All scans were performed over a region with organs (myocardium, kidneys) or tumor lesions of high tracer uptake and under free breathing. Aside from the original list mode data, datasets with progressively decreasing PET statistics were generated. From these, COM DDG signals were derived for subsequent amplitude-based gating of the original list mode file. The apparent respiratory shift d from end-expiration to end-inspiration was determined from the gated images and expressed as a function of signal-to-noise ratio SNR of the determined gating signals. This relation was tested against additional 25 [18 F]FDG PET/MRI list mode datasets where high-precision MR navigator-like respiratory signals were available as reference signal for respiratory gating of PET data, and data from a dedicated thorax phantom scan. All original 19 high-quality list mode datasets demonstrated the same behavior in terms of motion resolution when reducing the amount of list mode events for DDG signal generation. Ratios and directions of respiratory shifts between end-respiratory gates and the respective nongated image were constant over all statistic levels. Motion resolution d/dmax could be modeled as d/dmax=1-e-1.52(SNR-1)0.52, with dmax as the actual respiratory shift. Determining dmax from d and SNR in the 25 test datasets and the phantom scan demonstrated no significant differences to the MR navigator-derived shift values and the predefined shift, respectively. The SNR can serve as a general metric to assess the success of COM-based DDG, even in different scanners and patients. The derived formula for motion resolution can be used to estimate the actual motion extent reasonably well in cases of limited PET raw data statistics. This may be of interest for individualized radiotherapy treatment planning procedures of target structures subjected to respiratory motion.

Self-Gating: An Adaptive Center-of-Mass Approach for Respiratory Gating in PET.

The goal is to develop an adaptive center-of-mass (COM)-based approach for device-less respiratory gating of list-mode positron emission tomography (PET) data. Our method contains two steps. The first is to automatically extract an optimized respiratory motion signal from the list-mode data during acquisition. The respiratory motion signal was calculated by tracking the location of COM within a volume of interest (VOI). The signal prominence (SP) was calculated based on Fourier analysis of the signal. The VOI was adaptively optimized to maximize SP. The second step is to automatically correct signal-flipping effects. The sign of the signal was determined based on the assumption that the average patient spends more time during expiration than inspiration. To validate our methods, thirty-one 18F-FDG patient scans were included in this paper. An external device-based signal was used as the gold standard, and the correlation coefficient of the data-driven signal with the device-based signal was measured. Our method successfully extracted respiratory signal from 30 out of 31 datasets. The failure case was due to lack of uptake in the field of view. Moreover, our sign determination method obtained correct results for all scans excluding the failure case. Quantitatively, the proposed signal extraction approach achieved a median correlation of 0.85 with the device-based signal. Gated images using optimized data-driven signal showed improved lesion contrast over static image and were comparable to those using device-based signal. We presented a new data-driven method to automatically extract respiratory motion signal from list-mode PET data by optimizing VOI for COM calculation, as well as determine motion direction from signal asymmetry. Successful application of the proposed method on most clinical datasets and comparison with device-based signal suggests its potential of serving as an alternative to external respiratory monitors.

Quantitative and Visual Assessments toward Potential Sub-mSv or Ultrafast FDG PET Using High-Sensitivity TOF PET in PET/MRI.

Newer high-performance time-of-flight (TOF) positron emission tomography (PET) systems have the capability to preserve diagnostic image quality with low count density, while maintaining a high raw photon detection sensitivity that would allow for a reduction in injected dose or rapid data acquisition. To assess this, we performed quantitative and visual assessments of the PET images acquired using a highly sensitive (23.3cps/kBq) large field of view (25-cm axial) silicon photomultiplier (SiPM)-based TOF PET (400-ps timing resolution) integrated with 3T-MRI in comparison to PET images acquired on non-TOF PET/x-ray computed tomography (CT) systems. Whole-body 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) PET/CT was acquired for 15 patients followed by whole body PET/magnetic resonance imaging (MRI) with an average injected dose of 325±84MBq. The PET list mode data from PET/MRI were reconstructed using full datasets (4min/bed) and reduced datasets (2, 1, 0.5, and 0.25min/bed). Qualitative assessment between PET/CT and PET/MR images were made. A Likert-type scale between 1 and 5, 1 for non-diagnostic, 3 equivalent to PET/CT, and 5 superior quality, was used. Maximum and mean standardized uptake values (SUVmax and SUVmean) of normal tissues and lesions detected were measured and compared. Mean visual assessment scores were 3.54±0.32, 3.62±0.38, and 3.69±0.35 for the brain and 3.05±0.49, 3.71±0.45, and 4.14±0.44 for the whole-body maximum intensity projections (MIPs) for 1, 2, and 4min/bed PET/MR images, respectively. The SUVmean values for normal tissues were lower and statistically significant for images acquired at 4, 2, 1, 0.5, and 0.25min/bed on the PET/MR, with values of -18±28% (p < 0.001), - 16±29% (p = 0.001), - 16±31% (p = 0.002), - 14±35% (p < 0.001), and - 13±34% (p = 0.002), respectively. SUVmax and SUVpeak values of all lesions were higher and statistically significant (p < 0.05) for 4, 2, 1, 0.50, and 0.25min/bed PET/MR datasets. High-sensitivity TOF PET showed comparable but still better visual image quality even at a much reduced activity in comparison to lower-sensitivity non-TOF PET. Our data translates to a seven times reduction in either injection dose for the same time or total scan time for the same injected dose. This "ultra-sensitivity" PET system provides a path to clinically acceptable extremely low-dose FDG PET studies (e.g., sub 1mCi injection or sub-mSv effective dose) or PET studies as short as 1min/bed (e.g., 6min of total scan time) to cover whole body without compromising diagnostic performance.

Regularization parameter selection for penalized-likelihood list-mode image reconstruction in PET

Penalized likelihood (PL) reconstruction has demonstrated potential to improve image quality of positron emission tomography (PET) over unregularized ordered-subsets expectation-maximization (OSEM) algorithm. However, selecting proper regularization parameters in PL reconstruction has been challenging due to the lack of ground truth and variation of penalty functions. Here we present a method to choose regularization parameters using a cross-validation log-likelihood (CVLL) function. This new method does not require any knowledge of the true image and is directly applicable to list-mode PET data. We performed statistical analysis of the mean and variance of the CVLL. The results show that the CVLL provides an unbiased estimate of the log-likelihood function calculated using the noise free data. The predicted variance can be used to verify the statistical significance of the difference between CVLL values. The proposed method was validated using simulation studies and also applied to real patient data. The reconstructed images using optimum parameters selected by the proposed method show good image quality visually.

P1.03-054 Quantitative Accuracy and Lesion Detectability of Low-Dose FDG-PET for Lung Cancer Screening

Low-dose computed tomography (CT) screening for high-risk patients can reduce lung cancer mortality, but false-positivity rates are high. Positron emission tomography (PET)/CT is more accurate compared to CT alone, but typically is associated with a higher radiation exposure. We investigate a low radiation dose PET/CT solution without compromising quality. Twenty lung cancer patients were scanned with PET/CT after an uptake period of 60 min, following injection of 5.9±0.14 mCi 18F-Fluorodeoxyglucose. All were scanned with 2 beds covering the lungs at 10 min each, resulting in 120±25 ×106 mean true coincident counts per bed. Reduced doses were simulated by randomly discarding events in the PET list mode according to 9 predefined true count levels, from 20 to 0.25 ×106. For each patient & simulated dose, the highest possible number of independent realizations was generated & reconstructed, up to 50. The reconstruction algorithm was OP-OSEM, using TOF and PSF, with 2 iterations, 21 subsets & 5mm smoothing, producing 400x400 image matrices with voxel size 2.04×2.04×2.03mm. At each simulated dose, lesions consistent with those of early lung cancer were identified & classified by metabolic volume, signal-to-background contrast, mean & max SUV, lesion-to-background SNR, & Hotelling observer SNR. Bias & stability of the lesion activity measurements were evaluated across all simulated dose levels, and detectability was determined by various human-trained, numerical observer models. Twelve isolated lung lesions (mean volume 2.61±2.86 cm3 on CT) were studied in detail. Analyses of bias & reproducibility in the lesion activity values showed that measurements were stable until the count levels approached extreme conditions. Bias in the lesion VOI mean & max SUV were relatively negligible until true count level was decreased to 1 million. Variance on reproducibility of lesion values showed a more dramatic trend, but standard deviation was still around 10% at 5 million counts. We show that simulated images with accurate lesion characteristics can be obtained at 1/12 of a typical radiotracer dose.

Super-Resolution Reconstruction of 3D PET Images Using Two Respiratory-Phase Low-Dose CT Images

Positron emission tomography (PET) images usually suffer from incorrect quantification of the radioactive uptake of small lesions due to low spatial resolution. To improve the spatial resolution, we previously proposed super-resolution (SR) algorithms based on wobble scanning. The proposed algorithms, however, require mechanical motion of the patient bed or a system gantry for wobble scanning. In this paper, we propose a framework for SR reconstruction of 3D PET images based on the use of respiratory motion rather than wobble motion. As in the conventional protocol of PET imaging, gated list-mode PET data are acquired in a free breathing condition. In addition, we acquire two low-dose CT images in a breath-hold manner at exhale and inhale phases, without increasing the radiation burden to a patient. Using the two low-dose CT images, we estimate the 4D motion vector field (MVF) and correspondingly generate a virtual 4D CT image that are matched to the 4D PET image. The 3D CT images have much better spatial resolution than PET images and therefore the corresponding estimated 3D MVFs can be considered reliable for PET SR reconstruction. We then estimate space-variant point spread functions (PSFs) in the imaging field of view using a minimum number of PSFs obtained through Monte-Carlo simulations. Finally, SR reconstruction is performed by incorporating the estimated 3D MVFs and space-variant PSFs. In the SR reconstruction, to avoid the resolution degradation in the evenly spaced parallel-beam rebinning and to reduce the computational time on the graphics processing unit, we introduce a parallel-friendly spanned line of response reconstruction technique based on fan-beam reordering. The proposed framework is evaluated via Monte-Carlo simulations with the digital XCAT phantom and via experiments with several patient datasets including moving lung lesions. Both the simulation and experiment results show that the proposed framework provides much clearer organ boundaries as well as more accurate quantitative lesion information than the conventional methods, with a considerable reduction of computational time.

Repurposing the Microsoft Kinect for Windows v2 for external head motion tracking for brain PET

Medical imaging systems such as those used in positron emission tomography (PET) are capable of spatial resolutions that enable the imaging of small, functionally important brain structures. However, the quality of data from PET brain studies is often limited by subject motion during acquisition. This is particularly challenging for patients with neurological disorders or with dynamic research studies that can last 90 min or more. Restraining head movement during the scan does not eliminate motion entirely and can be unpleasant for the subject. Head motion can be detected and measured using a variety of techniques that either use the PET data itself or an external tracking system. Advances in computer vision arising from the video gaming industry could offer significant benefits when re-purposed for medical applications. A method for measuring rigid body type head motion using the Microsoft Kinect v2 is described with results presenting ⩽0.5 mm spatial accuracy. Motion data is measured in real-time at 30 Hz using the KinectFusion algorithm. Non-rigid motion is detected using the residual alignment energy data of the KinectFusion algorithm allowing for unreliable motion to be discarded. Motion data is aligned to PET listmode data using injected pulse sequences into the PET/CT gantry allowing for correction of rigid body motion. Pilot data from a clinical dynamic PET/CT examination is shown.

Sensitivity estimation in time-of-flight list-mode positron emission tomography.

An accurate quantification of the images in positron emission tomography (PET) requires knowing the actual sensitivity at each voxel, which represents the probability that a positron emitted in that voxel is finally detected as a coincidence of two gamma rays in a pair of detectors in the PET scanner. This sensitivity depends on the characteristics of the acquisition, as it is affected by the attenuation of the annihilation gamma rays in the body, and possible variations of the sensitivity of the scanner detectors. In this work, the authors propose a new approach to handle time-of-flight (TOF) list-mode PET data, which allows performing either or both, a self-attenuation correction, and self-normalization correction based on emission data only. The authors derive the theory using a fully Bayesian statistical model of complete data. The authors perform an initial evaluation of algorithms derived from that theory and proposed in this work using numerical 2D list-mode simulations with different TOF resolutions and total number of detected coincidences. Effects of randoms and scatter are not simulated. The authors found that proposed algorithms successfully correct for unknown attenuation and scanner normalization for simulated 2D list-mode TOF-PET data. A new method is presented that can be used for corrections for attenuation and normalization (sensitivity) using TOF list-mode data.

Automatic Cardiac Self-Gating of Small-Animal PET Data.

The cardiac gating signal (CGS) in positron emission tomography (PET) studies is usually obtained from an electrocardiography (ECG) monitor. In this work, we propose a method to obtain the CGS in small-animal PET using the acquired list-mode data without using any hardware or end-user input. The CGS was obtained from the number of coincidences over time acquired in the lines-of-response connected with the cardiac region. This region is identified in the image as its value changes with frequencies in the range of 3 to 12 Hz. The procedure was tested in a study with 29 Wistar rats and 6 mice injected with 2-deoxy-2-[(18)F]fluoro-D-glucose, which underwent a 45-min single-bed list-mode PET scan of the heart syncronized with an ECG. The estimated signals and the reconstructed images using eight-gated frames were compared with the ones obtained using the ECG signal from the monitor. The differences of the PET-based CGS with respect to the ECG relative to the duration of the heartbeats were 5.6 % in rats and 11.0 % in mice. The reconstructed gated images obtained from the proposed method do not differ qualitatively with respect to the ones obtained with the ECG. The quantitative analysis of both set of images were performed measuring the volume of the left ventricle (LV) of the rats in the end-of-systole and end-of-diastole phase. The differences found in these parameters between both methods were below 12.1 % in the ESV and 9.3 % in the EDV with a 95 % confidence interval, which are comparable to the accuracy (7 %) of the method used for segmenting the LV. The proposed method is able to provide a valid and accurate CGS in small-animal PET list-mode data.

Single-cell tracking with PET using a novel trajectory reconstruction algorithm.

Virtually all biomedical applications of positron emission tomography (PET) use images to represent the distribution of a radiotracer. However, PET is increasingly used in cell tracking applications, for which the "imaging" paradigm may not be optimal. Here, we investigate an alternative approach, which consists in reconstructing the time-varying position of individual radiolabeled cells directly from PET measurements. As a proof of concept, we formulate a new algorithm for reconstructing the trajectory of one single moving cell directly from list-mode PET data. We model the trajectory as a 3-D B-spline function of the temporal variable and use nonlinear optimization to minimize the mean-square distance between the trajectory and the recorded list-mode coincidence events. Using Monte Carlo simulations (GATE), we show that this new algorithm can track a single source moving within a small-animal PET system with 3 mm accuracy provided that the activity of the cell [Bq] is greater than four times its velocity [mm/s]. The algorithm outperforms conventional ML-EM as well as the "minimum distance" method used for positron emission particle tracking (PEPT). The new method was also successfully validated using experimentally acquired PET data. In conclusion, we demonstrated the feasibility of a new method for tracking a single moving cell directly from PET list-mode data, at the whole-body level, for physiologically relevant activities and velocities.

MR‐based motion correction for PET imaging using wired active MR microcoils in simultaneous PET‐MR: Phantom study

Artifacts caused by head motion present a major challenge in brain positron emission tomography (PET) imaging. The authors investigated the feasibility of using wired active MR microcoils to track head motion and incorporate the measured rigid motion fields into iterative PET reconstruction. Several wired active MR microcoils and a dedicated MR coil-tracking sequence were developed. The microcoils were attached to the outer surface of an anthropomorphic(18)F-filled Hoffman phantom to mimic a brain PET scan. Complex rotation/translation motion of the phantom was induced by a balloon, which was connected to a ventilator. PET list-mode and MR tracking data were acquired simultaneously on a PET-MR scanner. The acquired dynamic PET data were reconstructed iteratively with and without motion correction. Additionally, static phantom data were acquired and used as the gold standard. Motion artifacts in PET images were effectively removed by wired active MR microcoil based motion correction. Motion correction yielded an activity concentration bias ranging from -0.6% to 3.4% as compared to a bias ranging from -25.0% to 16.6% if no motion correction was applied. The contrast recovery values were improved by 37%-156% with motion correction as compared to no motion correction. The image correlation (mean ± standard deviation) between the motion corrected (uncorrected) images of 20 independent noise realizations and static reference was R(2) = 0.978 ± 0.007 (0.588 ± 0.010, respectively). Wired active MR microcoil based motion correction significantly improves brain PET quantitative accuracy and image contrast.

Electrocardiographically gated 11C-hydroxyephedrine PET for the simultaneous assessment of cardiac sympathetic and contractile functions

Application of the electrocardiographically (ECG) gated positron emission tomography (PET) technique with (11)C-hydroxyephedrine (HED) would allow the simultaneous assessment of cardiac sympathetic and contractile functions. However, there are uncertainties regarding the diagnostic accuracy of left ventricular (LV) volume measurements using ECG-gated HED-PET. The purpose of this study was to clarify the minimal requirement of count statistics to measure LV volumes with ECG-gated HED-PET and to investigate the reliability of the measurements. Five healthy volunteers and 11 patients with heart failure underwent a 40-min list-mode PET scan after an injection of HED (197 ± 35 MBq). The list-mode data were histogrammed into multiple sets of acquisition periods at 0.5, 1.0, 2.0, 4.0, 6.0, 8.0, 12.0 Mcount/bin and reconstructed into corresponding gated images using an iterative algorithm. The LV end-diastolic volume (LVEDV), the LV end-systolic volume (LVESV), and the LV ejection fraction (LVEF) were calculated in each acquisition period. These values were compared with those obtained by cardiac magnetic resonance imaging (MRI). Possible effects of HED retention on the accuracy of the volume measurements were investigated. Collecting less than 4.0 Mcount/bin resulted in noisy cardiac images. The lower counts resulted in underestimation in the volume measurements. Reasonably accurate volume measurements required equal to or greater than 6.0 Mcount/bin. This corresponded to 7.0 ± 1.9 min (range, 4.0-10.3 min) for the acquisition period. Volumetric results using the 6.0 Mcount/bin data highly correlated with cardiac MRI (LVEDV: r = 0.85, p < 0.0001; LVESV: r = 0.89, p < 0.0001; LVEF: r = 0.77, p < 0.01). The HED retention did not affect the volumetric results compared to the MRI volumetry. The volumetric accuracy with ECG-gated HED-PET was affected by the count statistics rather than the HED retention. LV volume measurements were feasible with 10-min acquisition period for most of the patients. This technique allows the simultaneous assessment of cardiac sympathetic and contractile functions without the need for an additional injection or scanning time, thus reducing overall costs for diagnostic imaging.

Erroneous cardiac ECG-gated PET list-mode trigger events can be retrospectively identified and replaced by an offline reprocessing approach: first results in rodents

The assessment of left ventricular function, wall motion and myocardial viability using electrocardiogram (ECG)-gated [18F]-FDG positron emission tomography (PET) is widely accepted in human and in preclinical small animal studies. The nonterminal and noninvasive approach permits repeated in vivo evaluations of the same animal, facilitating the assessment of temporal changes in disease or therapy response. Although well established, gated small animal PET studies can contain erroneous gating information, which may yield to blurred images and false estimation of functional parameters. In this work, we present quantitative and visual quality control (QC) methods to evaluate the accuracy of trigger events in PET list-mode and physiological data. Left ventricular functional analysis is performed to quantify the effect of gating errors on the end-systolic and end-diastolic volumes, and on the ejection fraction (EF). We aim to recover the cardiac functional parameters by the application of the commonly established heart rate filter approach using fixed ranges based on a standardized population. In addition, we propose a fully reprocessing approach which retrospectively replaces the gating information of the PET list-mode file with appropriate list-mode decoding and encoding software. The signal of a simultaneously acquired ECG is processed using standard MATLAB vector functions, which can be individually adapted to reliably detect the R-peaks. Finally, the new trigger events are inserted into the PET list-mode file. A population of 30 mice with various health statuses was analyzed and standard cardiac parameters such as mean heart rate (119 ms ± 11.8 ms) and mean heart rate variability (1.7 ms ± 3.4 ms) derived. These standard parameter ranges were taken into account in the QC methods to select a group of nine optimal gated and a group of eight sub-optimal gated [18F]-FDG PET scans of mice from our archive. From the list-mode files of the optimal gated group, we randomly deleted various fractions (5% to 60%) of contained trigger events to generate a corrupted group. The filter approach was capable to correct the corrupted group and yield functional parameters with no significant difference to the optimal gated group. We successfully demonstrated the potential of the fully reprocessing approach by applying it to the sub-optimal group, where the functional parameters were significantly improved after reprocessing (mean EF from 41% ± 16% to 60% ± 13%). When applied to the optimal gated group the fully reprocessing approach did not alter the functional parameters significantly (mean EF from 64% ± 8% to 64 ± 7%). This work presents methods to determine and quantify erroneous gating in small animal gated [18F]-FDG PET scans. We demonstrate the importance of a quality check for cardiac triggering contained in PET list-mode data and the benefit of optionally reprocessing the fully recorded physiological information to retrospectively modify or fully replace the cardiac triggering in PET list-mode data. We aim to provide a preliminary guideline of how to proceed in the presence of errors and demonstrate that offline reprocessing by filtering erroneous trigger events and retrospective gating by ECG processing is feasible. Future work will focus on the extension by additional QC methods, which may exploit the amplitude of trigger events and ECG signal by means of pattern recognition. Furthermore, we aim to transfer the proposed QC methods and the fully reprocessing approach to human myocardial PET/CT.