New Horizons in Brain PET Instrumentation.

Dedicated brain PET scanners are optimized to provide high sensitivity and high spatial resolution compared with existing whole-body PET systems, and they can be much cheaper to produce and install in various clinical and research settings. Advancements in detector technology over the past few years have placed several standalone PET, PET/computed tomography, and PET/MR systems on or near the commercial market; the features and capabilities of these systems will be reviewed here.

Deep-learning-based cardiac amyloidosis classification from early acquired pet images.

The objective of the present work was to evaluate the potential of deep learning tools for characterizing the presence of cardiac amyloidosis from early acquired PET images, i.e. 15 min after [18F]-Florbetaben tracer injection. 47 subjects were included in the study: 13 patients with transthyretin-related amyloidosis cardiac amyloidosis (ATTR-CA), 15 patients with immunoglobulin light-chain amyloidosis (AL-CA), and 19 control-patients (CTRL). [18F]-Florbetaben PET/CT images were acquired in list mode and data was sorted into a sinogram, covering a time interval of 5 min starting 15 min after the injection. The resulting sinogram was reconstructed using OSEM iterative algorithm. A deep convolutional neural network (CAclassNet) was designed and implemented, consisting of five 2D convolutional layers, three fully connected layers and a final classifier returning AL, ATTR and CTRL scores. A total of 1107 2D images (375 from AL-subtype patients, 312 from ATTR-subtype, and 420 from Controls) have been considered in the study and used to train, validate and test the proposed network. CAclassNet cross-validation resulted with train error mean ± sd of 2.001% ± 0.96%, validation error of 4.5% ± 2.26%, and net accuracy of 95.49% ± 2.26%. Network test error resulted in a mean ± sd values of 10.73% ± 0.76%. Sensitivity, specificity, and accuracy evaluated on the test dataset were respectively for AL-CA sub-type: 1, 0.912, 0.936; for ATTR-CA: 0.935, 0.897, 0.972; for control subjects: 0.809, 0.971, 0.909. In conclusion, the proposed CAclassNet model seems very promising as an aid for the clinician in the diagnosis of CA from cardiac [18F]-Florbetaben PET images acquired a few minutes after the injection.

[18F]-Florbetaben PET/CT for Differential Diagnosis Among Cardiac Immunoglobulin Light Chain, Transthyretin Amyloidosis, and Mimicking Conditions.

OBJECTIVES: This study aimed to test the diagnostic value of [18F]-florbetaben positron emission tomography (PET) in patients with suspicion of CA. BACKGROUND: Diagnosis of cardiac involvement in immunoglobulin light-chain-derived amyloidosis (AL) and transthyretin-related amyloidosis (ATTR), which holds major importance in risk stratification and decision making, is frequently delayed. Furthermore, although diphosphonate radiotracers allow a noninvasive diagnosis of ATTR, demonstration of cardiac amyloidosis (CA) in AL may require endomyocardial biopsy. METHODS: Forty patients with biopsy-proven diagnoses of CA (20 ALs, 20 ATTRs) and 20 patients referred with the initial clinical suspicion and later diagnosed with non-CA pathology underwent a cardiac PET/computed tomography scan with a 60-min dynamic [18F]-florbetaben PET acquisition, and 4 10-min static scans at 5, 30, 50, and 110 min after radiotracer injection. RESULTS: Visual qualitative assessment showed intense early cardiac uptake in all subsets. Patients with AL displayed a high, persistent cardiac uptake in all the static scans, whereas patients with ATTR and those with non-CA showed an uptake decrease soon after the early scan. Semiquantitative assessment demonstrated higher mean standardized uptake value (SUVmean) in patients with AL, sustained over the whole acquisition period (early SUVmean: 5.55; interquartile range [IQR]: 4.00 to 7.43; vs. delayed SUVmean: 3.50; IQR: 2.32 to 6.10; p = NS) compared with in patients with ATTR (early SUVmean: 2.55; IQR: 1.80 to 2.97; vs. delayed SUVmean: 1.25; IQR: 0.90 to 1.60; p < 0.001) and in patients with non-CA (early SUVmean: 3.50; IQR: 1.60 to 3.37; vs. delayed SUVmean: 1.40; IQR: 1.20 to 1.60; p < 0.001). Similar results were found comparing heart-to-background ratio and molecular volume. CONCLUSIONS: Delayed [18F]-florbetaben cardiac uptake may discriminate CA due to AL from either ATTR or other mimicking conditions. [18F]-florbetaben PET/computed tomography may represent a promising noninvasive tool for the diagnosis of AL amyloidosis, which is still often challenging and delayed. (A Prospective Triple-Arm, Monocentric, Phase-II Explorative Study on Evaluation of Diagnostic Efficacy of the PET Tracer [18F]-Florbetaben [Neuraceq] in Patients With Cardiac Amyloidosis [FLORAMICAR2]; EudraCT number: 2017-001660-38).

Probabilistic Graphical Models for Dynamic PET: A Novel Approach to Direct Parametric Map Estimation and Image Reconstruction.

In the context of dynamic emission tomography, the conventional processing pipeline consists of independent image reconstruction of single-time frames, followed by the application of a suitable kinetic model to time-activity curves (TACs) at the voxel or region-of-interest level. Direct 4D positron emission tomography (PET) reconstruction, by contrast, seeks to move beyond this scheme and incorporate information from multiple time frames within the reconstruction task. Established direct methods are based on a deterministic description of voxelwise TACs, captured by the chosen kinetic model, considering the photon counting process the only source of uncertainty. In this paper, we introduce a new probabilistic modeling strategy based on the key assumption that activity time course would be subject to uncertainty even if the parameters of the underlying dynamic process are known. This leads to a hierarchical model that we formulate using the formalism of probabilistic graphical modeling. The inference is addressed using a new iterative algorithm, in which kinetic modeling results are treated as prior expectation of activity time course, rather than as a deterministic match, making it possible to control the trade-off between a data-driven and a model-driven reconstruction. The proposed method is flexible to an arbitrary choice of (linear and nonlinear) kinetic models, it enables the inclusion of arbitrary (sub)differentiable priors for parametric maps, and it is simple to implement. Computer simulations and an application to a real-patient scan show how the proposed method is able to generalize over conventional indirect and direct approaches, providing a bridge between them by properly tuning the impact of the kinetic modeling step on image reconstruction.

Negative binomial maximum likelihood expectation maximization (NB-MLEM) algorithm for reconstruction of pre-corrected PET data.

PURPOSE: Positron emission tomography (PET) image reconstruction is usually performed using maximum likelihood (ML) iterative reconstruction methods, under the assumption of Poisson distributed data. Pre-correcting raw measured counts, this assumption is no longer realistic. The goal of this work is to develop a reconstruction algorithm based on the Negative Binomial (NB) distribution, which can generalize over the Poisson distribution in case of over-dispersion of raw data, that may occur if sinogram pre-correction is used. METHODS: The mathematical derivation of a Negative Binomial Maximum Likelihood Expectation-Maximization (NB-MLEM) algorithm is presented. A simulation study to compare the performance of the proposed NB-MLEM algorithm with respect to a Poisson-based MLEM (P-MLEM) method was performed, in reconstructing PET data. The proposed NB-MLEM reconstruction was tested on a real phantom and human brain data. RESULTS: For the property of NB distribution, it is a generalization of the conventional P-MLEM: for not over dispersed data, the proposed NB-MLEM algorithm behaves like the conventional P-MLEM; for over-dispersed PET data, the additional evaluation of the dispersion parameter after each reconstruction iteration leads to a more accurate final image with respect to P-MLEM. CONCLUSIONS: A novel approach for PET image reconstruction from pre-corrected data has been developed, which exhibits a statistical behavior that deviates from the Poisson distribution. Simulation study and preliminary tests on real data showed how the NB-MLEM algorithm, being able to explain the over-dispersion of pre-corrected data, can outperform other algorithms that assume no over-dispersion of pre-corrected data, while still not accounting for the presence of negative data, such as P-MLEM.

Direct 4D PET reconstruction with discrete tissue types.

Dynamic positron emission tomography (dPET) is known for its ability to extract spatiotemporal information of a radio tracer in living tissue. In this paper, a novel direct reconstruction framework is presented, which include concurrent clustering as a potential aid in addressing high levels of noise typical of voxel-wise kinetic modeling. Core assumption is that the imaged volume is formed by a finite number of different functional regions, and that voxel-wise time courses are determined by the functional cluster they belong to. Probabilistic Graphical Modeling (PGM) theory is used to describe the problem, and to derive the inference strategy. The proposed iterative estimation scheme provides concurrent estimate of kinetic parameter maps, activity images, and segmented clusters. Simulation studies and exploratory application to real data are performed to validate the proposal.

Direct Parametric Maps Estimation from Dynamic PET Data: An Iterated Conditional Modes Approach.

We propose and test a novel approach for direct parametric image reconstruction of dynamic PET data. We present a theoretical description of the problem of PET direct parametric maps estimation as an inference problem, from a probabilistic point of view, and we derive a simple iterative algorithm, based on the Iterated Conditional Mode (ICM) framework, which exploits the simplicity of a two-step optimization and the efficiency of an analytic method for estimating kinetic parameters from a nonlinear compartmental model. The resulting method is general enough to be flexible to an arbitrary choice of the kinetic model, and unlike many other solutions, it is capable to deal with nonlinear compartmental models without the need for linearization. We tested its performance on a two-tissue compartment model, including an analytical solution to the kinetic parameters evaluation, based on an auxiliary parameter set, with the aim of reducing computation errors and approximations. The new method is tested on simulated and clinical data. Simulation analysis led to the conclusion that the proposed algorithm gives a good estimation of the kinetic parameters in any noise condition. Furthermore, the application of the proposed method to clinical data gave promising results for further studies.

Accelerated PET kinetic maps estimation by analytic fitting method.

In this work, we propose and test a new approach for non-linear kinetic parameters' estimation from dynamic PET data. A technique is discussed, to derive an analytical closed-form expression of the compartmental model used for kinetic parameters' evaluation, using an auxiliary parameter set, with the aim of reducing the computational burden and speeding up the fitting of these complex mathematical expressions to noisy TACs. Two alternative algorithms based on numeric calculations are considered and compared to the new proposal. We perform a simulation study aimed at (i) assessing agreement between the proposed method and other conventional ways of implementing compartmental model fitting, and (ii) quantifying the reduction in computational time required for convergence. It results in a speed-up factor of ∼120 when compared to a fully numeric version, or ∼38, with respect to a more conventional implementation, while converging to very similar values for the estimated model parameters. The proposed method is also tested on dynamic 3D PET clinical data of four control subjects. The results obtained supported those of the simulation study, and provided input and promising perspectives for the application of the proposed technique in clinical practice.

Comparison of the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo).

PURPOSE: To compare the clinical performance of upper abdominal PET/DCE-MRI with and without concurrent respiratory motion correction (MoCo). METHODS: MoCo PET/DCE-MRI of the upper abdomen was acquired in 44 consecutive oncologic patients and compared with non-MoCo PET/MRI. SUVmax and MTV of FDG-avid upper abdominal malignant lesions were assessed on MoCo and non-MoCo PET images. Image quality was compared between MoCo DCE-MRI and non-MoCo CE-MRI, and between fused MoCo PET/MRI and fused non-MoCo PET/MRI images. RESULTS: MoCo PET resulted in higher SUVmax (10.8 ± 5.45) than non-MoCo PET (9.62 ± 5.42) and lower MTV (35.55 ± 141.95 cm3) than non-MoCo PET (38.11 ± 198.14 cm3; p < 0.005 for both). The quality of MoCo DCE-MRI images (4.73 ± 0.5) was higher than that of non-MoCo CE-MRI images (4.53±0.71; p = 0.037). The quality of fused MoCo-PET/MRI images (4.96 ± 0.16) was higher than that of fused non-MoCo PET/MRI images (4.39 ± 0.66; p < 0.005). CONCLUSION: MoCo PET/MRI provided qualitatively better images than non-MoCo PET/MRI, and upper abdominal malignant lesions demonstrated higher SUVmax and lower MTV on MoCo PET/MRI.

Concurrent Respiratory Motion Correction of Abdominal PET and Dynamic Contrast-Enhanced-MRI Using a Compressed Sensing Approach.

We present an approach for concurrent reconstruction of respiratory motion-compensated abdominal dynamic contrast-enhanced (DCE)-MRI and PET data in an integrated PET/MR scanner. The MR and PET reconstructions share the same motion vector fields derived from radial MR data; the approach is robust to changes in respiratory pattern and does not increase the total acquisition time. Methods: PET and DCE-MRI data of 12 oncologic patients were simultaneously acquired for 6 min on an integrated PET/MR system after administration of 18F-FDG and gadoterate meglumine. Golden-angle radial MR data were continuously acquired simultaneously with PET data and sorted into multiple motion phases on the basis of a respiratory signal derived directly from the radial MR data. The resulting multidimensional dataset was reconstructed using a compressed sensing approach that exploits sparsity among respiratory phases. Motion vector fields obtained using the full 6-min (MC6-min) and only the last 1 min (MC1-min) of data were incorporated into the PET reconstruction to obtain motion-corrected PET images and in an MR iterative reconstruction algorithm to produce a series of motion-corrected DCE-MR images (moco_GRASP). The motion-correction methods (MC6-min and MC1-min) were evaluated by qualitative analysis of the MR images and quantitative analysis of SUVmax and SUVmean, contrast, signal-to-noise ratio (SNR), and lesion volume in the PET images. Results: Motion-corrected MC6-min PET images demonstrated 30%, 23%, 34%, and 18% increases in average SUVmax, SUVmean, contrast, and SNR and an average 40% reduction in lesion volume with respect to the non-motion-corrected PET images. The changes in these figures of merit were smaller but still substantial for the MC1-min protocol: 19%, 10%, 15%, and 9% increases in average SUVmax, SUVmean, contrast, and SNR; and a 28% reduction in lesion volume. Moco_GRASP images were deemed of acceptable or better diagnostic image quality with respect to conventional breath-hold Cartesian volumetric interpolated breath-hold examination acquisitions. Conclusion: We presented a method that allows the simultaneous acquisition of respiratory motion-corrected diagnostic quality DCE-MRI and quantitatively accurate PET data in an integrated PET/MR scanner with negligible prolongation in acquisition time compared with routine PET/DCE-MRI protocols.

New Imaging Frontiers in Cardiology: Fast and Quantitative Maps from Raw Data.

BACKGROUND: Among the novelties in the field of cardiovascular imaging, the construction of quantitative maps in a fast and efficient way is one of the most interesting aspects of the clinical research. Quantitative parametric maps are typically obtained by post processing dynamic images, that is, sets of images usually acquired in different temporal intervals, where several images with different contrasts are obtained. Magnetic resonance imaging, and emission tomography (positron emission and single photon emission) are the imaging techniques best suited for the formation of quantitative maps. METHODS: In this review article we present several methods that can be used for obtaining parametric maps, in a fast way, starting from the acquired raw data. We describe both methods commonly used in clinical research, and more innovative methods that build maps directly from the raw data, without going through the image reconstruction. RESULTS: We briefly described recently developed methods in magnetic resonance imaging that accelerate further the MR raw data generation, based on appropriate sub-sampling of k-space; then, we described recently developed methods for generating MR parametric maps. With regard to the emission tomography techniques, we gave an overview of both conventional methods, and more recently developed direct estimation algorithms for parametric image reconstruction from dynamic positron emission tomography data. CONCLUSION: We have provided an overview of the possible approaches that can be followed to realize useful parametric maps from imaging raw data. We moved from the conventional approaches to more recent and efficient methods for accelerating the raw data generation and the of parametric maps formation.

A Conway-Maxwell-Poisson (CMP) model to address data dispersion on positron emission tomography.

Positron emission tomography (PET) in medicine exploits the properties of positron-emitting unstable nuclei. The pairs of γ- rays emitted after annihilation are revealed by coincidence detectors and stored as projections in a sinogram. It is well known that radioactive decay follows a Poisson distribution; however, deviation from Poisson statistics occurs on PET projection data prior to reconstruction due to physical effects, measurement errors, correction of deadtime, scatter, and random coincidences. A model that describes the statistical behavior of measured and corrected PET data can aid in understanding the statistical nature of the data: it is a prerequisite to develop efficient reconstruction and processing methods and to reduce noise. The deviation from Poisson statistics in PET data could be described by the Conway-Maxwell-Poisson (CMP) distribution model, which is characterized by the centring parameter λ and the dispersion parameter ν, the latter quantifying the deviation from a Poisson distribution model. In particular, the parameter ν allows quantifying over-dispersion (ν<1) or under-dispersion (ν>1) of data. A simple and efficient method for λ and ν parameters estimation is introduced and assessed using Monte Carlo simulation for a wide range of activity values. The application of the method to simulated and experimental PET phantom data demonstrated that the CMP distribution parameters could detect deviation from the Poisson distribution both in raw and corrected PET data. It may be usefully implemented in image reconstruction algorithms and quantitative PET data analysis, especially in low counting emission data, as in dynamic PET data, where the method demonstrated the best accuracy.