Regine Trebossen

Impact of Image-Space Resolution Modeling for Studies with the High-Resolution Research Tomograph

Brain PET in small structures is challenged by low resolution inducing bias in the activity measurements. Improved spatial resolution may be obtained by using dedicated tomographs and more comprehensive modeling of the acquisition system during reconstruction. In this study, we assess the impact of resolution modeling (RM) during reconstruction on image quality and on the estimates of biologic parameters in a clinical study performed on a high-resolution research tomograph. Methods: An accelerated list-mode ordinary Poisson ordered-subset expectation maximization (OP-OSEM) algorithm, including sinogram-based corrections and an experimental stationary model of resolution, has been designed. Experimental phantom studies are used to assess contrast and noise characteristics of the reconstructed images. The binding potential of a selective tracer of the dopamine transporter is also assessed in anatomic volumes of interest in a 5-patient study. Results: In the phantom experiment, a slower convergence and a higher contrast recovery are observed for RM-OP-OSEM than for OP-OSEM for the same level of statistical noise. RM-OP-OSEM yields contrast recovery levels that could not be reached without RM as well as better visual recovery of the smallest spheres and better delineation of the structures in the reconstructed images. Statistical noise has lower variance at the voxel level with RM than without at matched resolution. In a uniform activity region, RM induces higher positive and lower negative correlations with neighboring voxels, leading to lower spatial variance. Clinical images reconstructed with RM demonstrate better delineation of cortical and subcortical structures in both time-averaged and parametric images. The binding potential in the striatum is also increased, a result similar to the one observed in the phantom study. Conclusion: In high-resolution PET, RM during reconstruction improves quantitative accuracy by reducing the partial-volume effects.

11C-DPA-713: a novel peripheral benzodiazepine receptor PET ligand for in vivo imaging of neuroinflammation.

The induction of neuroinflammatory processes, characterized by upregulation of the peripheral benzodiazepine receptor (PBR) expressed by microglial cells, is well correlated with neurodegenerative diseases and with acute neuronal loss. The continually increasing incidence of neurodegenerative diseases in developed countries has become a major health problem, for which the development of diagnostic and follow-up tools is required. Here we investigated a new PBR ligand suitable for PET to monitor neuroinflammatory processes as an indirect hallmark of neurodegeneration. Methods: We compared PK11195, the reference compound for PBR binding sites, with the new ligand DPA-713 (N,N-diethyl-2-[2-(4-methoxyphenyl)-5,7-dimethylpyrazolo[1,5-a]pyrimidin-3-yl]acetamide), using a small-animal dedicated PET camera in a model of neuroinflammation in rats. Seven days after intrastriatal injection of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA), a PET scan was performed using 11C-PK11195 or 11C-DPA-713. Immunohistochemistry for neuronal (NeuN), astrocyte (glial fibrillary acidic protein), and microglial (CD11) specific markers as well as 3H-PK11195 autoradiographic studies were then correlated with the imaging data. Results: Seven days after a unilateral injection of AMPA in the striatum, 11C-DPA-713 exhibits a better contrast between healthy and damaged brain parenchyma than 11C-PK11195 (2.5-fold ± 0.14 increase vs. 1.6-fold ± 0.05 increase, respectively). 11C-DPA-713 and 11C-PK11195 exhibit similar brain uptake in the ipsilateral side, whereas, in the contralateral side, 11C-DPA-713 uptake was significantly lower than 11C-PK11195. Modeling of the data using the simplified reference tissue model shows that the binding potential was significantly higher for 11C-DPA-713 than for 11C-PK11195. Conclusion: 11C-DPA-713 displays a higher signal-to-noise ratio than 11C-PK11195 because of a lower level of unspecific binding that is likely related to the lower lipophilicity of 11C-DPA-713. Although further studies in humans are required, 11C-DPA-713 represents a suitable alternative to 11C-PK11195 for PET of PBR as a tracer of neuroinflammatory processes induced by neuronal stress.

Joint estimation of dynamic PET images and temporal basis functions using fully 4D ML-EM

A fully 4D joint-estimation approach to reconstruction of temporal sequences of 3D positron emission tomography (PET) images is proposed. The method estimates both a set of temporal basis functions and the corresponding coefficient for each basis function at each spatial location within the image. The joint estimation is performed through a fully 4D version of the maximum likelihood expectation maximization (ML-EM) algorithm in conjunction with two different models of the mean of the Poisson measured data. The first model regards the coefficients of the temporal basis functions as the unknown parameters to be estimated and the second model regards the temporal basis functions themselves as the unknown parameters. The fully 4D methodology is compared to the conventional frame-by-frame independent reconstruction approach (3D ML-EM) for varying levels of both spatial and temporal post-reconstruction smoothing. It is found that using a set of temporally extensive basis functions (estimated from the data by 4D ML-EM) significantly reduces the spatial noise when compared to the independent method for a given level of image resolution. In addition to spatial image quality advantages, for smaller regions of interest (where statistical quality is often limited) the reconstructed time-activity curves show a lower level of bias and a lower level of noise compared to the independent reconstruction approach. Finally, the method is demonstrated on clinical 4D PET data.

Assessment of 11C-PE2I Binding to the Neuronal Dopamine Transporter in Humans with the High-Spatial-Resolution PET Scanner HRRT

The high-resolution research tomograph (HRRT), dedicated to brain imaging, may offer new perspectives for identifying small brain nuclei that remain neglected by the spatial resolution of conventional scanners. However, the use of HRRT for neuroimaging applications still needs to be fully assessed. The present study aimed at evaluating the HRRT for measurement of the dopamine transporter (DAT) binding to validate its quantification and explore the gain induced by the increased spatial resolution in comparison with conventional PET scanners. Methods: Fifteen and 11 healthy subjects were examined using the selective DAT radioligand 11C-PE2I with HRRT and HR+ scanners, respectively. Quantification of the DAT binding was assessed by the calculation of binding potential (BP) values using the simplified reference tissue model in anatomic regions of interest (ROIs) defined on the dorsal striatum and in a standardized ROI defined on the midbrain. Results: Quantification of 11C-PE2I binding to the DAT measured in the midbrain and striatum with both scanners at the same spatial resolution (smoothed HRRT images) exhibited similar BP values and intersubject variability, thus validating the quantification of DAT binding on the HRRT. For age-paired comparison, BP values of subjects examined with HRRT were significantly higher than those of the subjects examined with HR+. The increase ranged from 29% in the caudate and 35% in the putamen to 92% in the midbrain. The decline in DAT binding with age in the striatum was in good agreement between both scanners and literature, whereas no significant decrease in DAT binding with age was observed in the midbrain with either HRRT or HR+. Conclusion: HRRT allows quantitative measurements of neurotransmission processes in small brain nuclei and allows recovering higher values as compared with coarser spatial resolution PET scanners. High-spatial-resolution PET appears promising for a more accurate detection of neurobiologic modifications and also for the exploration of subtle modifications in small and complex brain structures largely affected by the partial-volume effect.

Fully 4D image reconstruction by estimation of an input function and spectral coefficients

A new dynamic image reconstruction method for PET is proposed. First, a set of exponential temporal basis functions is predefined, covering the entire range of kinetics (from static through to a delta function). Just as in spectral analysis, such a selection is designed to be able to handle all possible tissue responses for multi-compartmental tissue models. Second, an initial estimate of an input function is defined. The time-dependent PET radiotracer concentration is then modeled (through the system matrix in the reconstruction algorithm) as a superposition of the exponential temporal basis functions, convolved with the input function. The reconstruction method uses an expectation maximization (EM) algorithm to operate directly on the measured PET data in order to i. estimate the coefficients of the exponential functions, and ii. improve the estimate of the input function. The coefficients and the input function are estimated only as a means of regularizing the model of the time-dependent image: the final reconstruction is used with conventional post-reconstruction kinetic analysis, with a different input function if need be (as the estimated input function may not correspond to the true input function). Results from tests on simulated data reveal a simultaneous benefit of noise reduction and improved kinetic parameter estimates when compared to conventional methodology. The method is also demonstrated on measured HRRT PET data for an FDG study.

Estimation of the β+ Dose to the Embryo Resulting from 18F-FDG Administration During Early Pregnancy

Although 18F-FDG examinations are widely used, data are lacking on the dose to human embryo tissues in cases of exposure in early pregnancy. Although the photon component can easily be estimated from available data on the pharmacokinetics of 18F-FDG in female organs and from phantom measurements (considering the uterus as the target organ), the intensity of embryo tissue uptake, which is essential for deriving the β+ dose, is not known. We report the case of a patient who underwent 18F-FDG PET/CT for tumor surveillance and who was later found to have been pregnant at the time of the examination (embryo age, 8 wk). Methods: The patient received 320 MBq of 18F-FDG. Imaging started with an unenhanced CT scan 1 h after the injection, followed by PET acquisition. PET images were used to compute the total number of β+ emissions in embryo tissues per unit of injected activity, from standardized uptake value (SUV) measurements corrected for partial-volume effects. A Monte Carlo track structure code was then used to derive the β+ self-dose and the β+ cross-dose from amniotic fluid. The photon and CT doses were added to obtain the final dose received by the embryo. Results: The mean SUV in embryo tissues was 2.7, after correction for the partial-volume effect. The mean corrected SUV of amniotic fluid was 1.1. Monte Carlo simulation showed that the β+ dose to the embryo (self-dose plus cross-dose from amniotic fluid) was 1.8E−2 mGy per MBq of injected 18F-FDG. Based on MIRD data for the photon dose to the uterus, the estimated photon dose to the embryo was 1.5E−2 mGy/MBq. Thus, the specific 18F-FDG dose to the embryo was 3.3E−2 mGy/MBq (10.6 mGy in this patient). The CT scan added a further 8.3 mGy. Conclusion: The dose to the embryo is 3.3E−2 mGy/MBq of 18F-FDG. The β+ dose contributes 55% of the total dose. This value is higher than previous estimates in late nonhuman-primate pregnancies.

A hybrid scatter correction for 3D PET based on an estimation of the distribution of unscattered coincidences : implementation on the ECAT EXACT HR+

We implemented a hybrid scatter-correction method for 3D PET that combines two scatter-correction methods in a complementary way. The implemented scheme uses a method based on the discrimination of the energy of events (the estimation of trues method (ETM)) and an auxiliary method (the single scatter simulation method (SSS1) or the convolution–subtraction method (CONV)) in an attempt to increase the accuracy of the correction over a wider range of acquisitions. The ETM takes into account the scatter from outside the field-of-view (FOV), which is not estimated with the auxiliary method. On the other hand, the auxiliary method accounts for events that have scattered with small angles, which have an energy that cannot be discriminated from that of unscattered events using the ETM. The ETM uses the data acquired in an upper energy window above the photopeak (550–650 keV) to obtain a noisy estimate of the unscattered events in the standard window (350–650 keV). Our implementation uses the auxiliary method to correct the residual scatter in the upper window. After appropriate scaling, the upper window data are subtracted from the total coincidences acquired in the standard window, resulting in the final scatter estimate, after smoothing. In this work we compare the hybrid method with the corrections used by default in the 2D and 3D modes of the ECAT EXACT HR+ using phantom measurements. Generally, the contrast was better with the hybrid method, although the relative errors of quantification were similar. We conclude that hybrid techniques such as the one implemented in this work can provide an accurate, general-purpose and practical way to correct the scatter in 3D PET, taking into account the scatter from outside the FOV.

Iterative Kinetic Parameter Estimation within Fully 4D PET Image Reconstruction

4D PET imaging seeks to estimate kinetic parameters of physiological significance through the generation of a time series of 3D images. Conventionally the time series is reconstructed one frame at a time, and then the kinetic modeling is applied as a post-reconstruction step to estimate the desired parameters. Such a separated approach does not account for the task of kinetic parameter estimation within the reconstruction itself. This work indicates that conventional frame-by-frame maximum likelihood reconstruction in high noise situations is sub-optimal if post-reconstruction kinetic parameter estimation is to be performed. As an alternative, a simple to implement, EM-based iterative reconstruction method is proposed which uses all of the acquired data in every iteration and includes the image-space kinetic parameter estimation process within the reconstruction. The method can accommodate kinetic models of any chosen complexity with relative ease, and can deliver more accurate kinetic parameter estimates than the conventional approach for low-statistics data.

Monte Carlo simulation of the microPET FOCUS system for small rodents imaging applications

In this paper, the authors validated the microPET FOCUS modelling with GATE. The performances of this Monte Carlo platform were presented on voxelized rat brain phantom, specially for the simulation of realistic [C-11]Raclopride exam with a realistic modelling of the injected dose and acquisition time. These results are the consequence of complete installation of this Monte Carlo platform simulation on a cluster computing architecture. Finally, the authors showed a first preliminary approach to improve the quantitative analysis in rat brain dopaminergic studies with an implementation of corrections about the positron range and gamma accolinearity effects. In the future, these corrections could be included as priors in a maximum a posteriori reconstruction algorithm. Moreover, the simulation of whole body exams can be planned in order to optimize the quantitative analysis for small animal PET imaging

Comparison of clinical data sets acquired on different tomographs using 6-18F-l-dopa

Abstract.Longitudinal positron emission tomography (PET) studies of 6-18F-l-dopa uptake in the striatum are used to assess the progression of Parkinson’s disease or the survival of neuronal cells grafted in parkinsonian patients. These studies are performed over several years, and data analysis may suffer from the change from old tomographs to new machines with better sensitivity and spatial resolution. Furthermore, such studies on parkinsonian patients may be accomplished in either 2D or 3D acquisition mode. The aforementioned improvements offer great benefits for the study of neurodegenerative diseases, especially those affecting the striatum. However, direct comparison of data is not straightforward owing to variation in scanner characteristics. In this study, we assessed the feasibility of comparing the 6-18F-l-dopa striatal uptake values (Kc) measured in two groups of healthy subjects using two tomographs of different generations.We re-studied and compared acquisitions performed on 14 healthy subjects using 6-18F-l-dopa. Half of these studies had been performed in 2D acquisition mode using an ECAT 953B. The other half had been performed in 3D acquisition mode using an ECAT EXACT HR+. Different reconstruction protocols were used and the Kc values obtained were statistically compared.The results showed that lowering the transverse spatial resolution of images obtained with the scanner having the better spatial resolution, so that it more closely matched that of the other machine, allowed similar Kc values to be obtained in healthy subjects.This study shows that quantitative results of 6-18F-l-dopa scans can be matched between different scanners with different intrinsic resolutions. This can be accomplished using adequate modifications of the reconstruction parameters. Such modifications can be used to help in the longitudinal monitoring of parkinsonian patients using different tomographs.