Stefaan Vandenberghe

Iterative reconstruction algorithms in nuclear medicine

Iterative reconstruction algorithms produce accurate images without streak artifacts as in filtered backprojection. They allow improved incorporation of important corrections for image degrading effects, such as attenuation, scatter and depth-dependent resolution. Only some corrections, which are important for accurate reconstruction in positron emission tomography and single photon emission computed tomography, can be applied to the data before filtered backprojection. The main limitation for introducing iterative algorithms in nuclear medicine has been computation time, which is much longer for iterative techniques than for filtered backprojection. Modern algorithms make use of acceleration techniques to speed up the reconstruction. These acceleration techniques and the development in computer processors have introduced iterative reconstruction in daily nuclear medicine routine. We give an overview of the most important iterative techniques and discuss the different corrections that can be incorporated to improve the image quality.

Challenges and current methods for attenuation correction in PET/MR

Quantitative PET imaging requires an attenuation map to correct for attenuation. In stand-alone PET or PET/CT, the attenuation map is usually derived from a transmission scan or CT image, respectively. In PET/MR, these methods will most likely not be used. Therefore, attenuation correction has long been regarded as one of the major challenges in the development of PET/MR. In the past few years, much progress has been made in this field. In this review, the challenges faced in attenuation correction for PET/MR are discussed. Different methods have been proposed to overcome these challenges. An overview of the MR-based (template-based and voxel-based), transmission-based and emission-based methods and the results that have been obtained is provided. Although several methods show promising results, no single method fulfils all of the requirements for the ideal attenuation correction method for PET/MR. Therefore, more work is still necessary in this field. To allow implementation in routine clinical practice, extensive evaluation of the proposed methods is necessary to demonstrate robustness and automation.

Monte Carlo simulations of a scintillation camera using GATE: validation and application modelling

Geant4 application for tomographic emission (GATE) is a recently developed simulation platform based on Geant4, specifically designed for PET and SPECT studies. In this paper we present validation results of GATE based on the comparison of simulations against experimental data, acquired with a standard SPECT camera. The most important components of the scintillation camera were modelled. The photoelectric effect. Compton and Rayleigh scatter are included in the gamma transport process. Special attention was paid to the processes involved in the collimator: scatter, penetration and lead fluorescence. A LEHR and a MEGP collimator were modelled as closely as possible to their shape and dimensions. In the validation study, we compared the simulated and measured energy spectra of different isotopes: 99mTc, 22Na, 57Co and 67Ga. The sensitivity was evaluated by using sources at varying distances from the detector surface. Scatter component analysis was performed in different energy windows at different distances from the detector and for different attenuation geometries. Spatial resolution was evaluated using a 99mTc source at various distances. Overall results showed very good agreement between the acquisitions and the simulations. The clinical usefulness of GATE depends on its ability to use voxelized datasets. Therefore, a clinical extension was written so that digital patient data can be read in by the simulator as a source distribution or as an attenuating geometry. Following this validation we modelled two additional camera designs: the Beacon transmission device for attenuation correction and the Solstice scanner prototype with a rotating collimator. For the first setup a scatter analysis was performed and for the latter design. the simulated sensitivity results were compared against theoretical predictions. Both case studies demonstrated the flexibility and accuracy of GATE and exemplified its potential benefits in protocol optimization and in system design.

The effect of errors in segmented attenuation maps on PET quantification

PURPOSE Accurate attenuation correction is important for PET quantification. Often, a segmented attenuation map is used, especially in MRI-based attenuation correction. As deriving the attenuation map from MRI images is difficult, different errors can be present in the segmented attenuation map. The goal of this paper is to determine the effect of these errors on quantification. METHODS The authors simulated the digital XCAT phantom using the GATE Monte Carlo simulation framework and a model of the Philips Gemini TF. A whole body scan was simulated, spanning an axial field of view of 70 cm. A total of fifteen lesions were placed in the lung, liver, spine, colon, prostate, and femur. The acquired data were reconstructed with a reference attenuation map and with different attenuation maps that were modified to reflect common segmentation errors. The quantitative difference between reconstructed images was evaluated. RESULTS Segmentation into five tissue classes, namely cortical bone, spongeous bone, soft tissue, lung, and air yielded errors below 5%. Large errors were caused by ignoring lung tissue (up to 45%) or cortical bone (up to 17%). The interpatient variability of lung attenuation coefficients can lead to errors of 10% and more. Up to 20% tissue misclassification from bone to soft tissue yielded errors below 5%. The same applies for up to 10% misclassification from lung to air. CONCLUSIONS When using a segmented attenuation map, at least five different tissue types should be considered: cortical bone, spongeous bone, soft tissue, lung, and air. Furthermore, the interpatient variability of lung attenuation coefficients should be taken into account. Limited misclassification from bone to soft tissue and from lung to air is acceptable, as these do not lead to relevant errors.

PET-MRI: a review of challenges and solutions in the development of integrated multimodality imaging

The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) has been an ongoing research topic for the last 20 years. This paper gives an overview of the different developments and the technical problems associated with combining PET and MRI in one system. After explaining the different detector concepts for integrating PET-MRI and minimising interference the limitations and advantages of different solutions for the detector and system are described for preclinical and clinical imaging systems. The different integrated PET-MRI systems are described in detail. Besides detector concepts and system integration the challenges and proposed solutions for attenuation correction and the potential for motion correction and resolution recovery are also discussed in this topical review.

Functional brain connectivity from EEG in epilepsy: Seizure prediction and epileptogenic focus localization

Today, neuroimaging techniques are frequently used to investigate the integration of functionally specialized brain regions in a network. Functional connectivity, which quantifies the statistical dependencies among the dynamics of simultaneously recorded signals, allows to infer the dynamical interactions of segregated brain regions. In this review we discuss how the functional connectivity patterns obtained from intracranial and scalp electroencephalographic (EEG) recordings reveal information about the dynamics of the epileptic brain and can be used to predict upcoming seizures and to localize the seizure onset zone. The added value of extracting information that is not visibly identifiable in the EEG data using functional connectivity analysis is stressed. Despite the fact that many studies have showed promising results, we must conclude that functional connectivity analysis has not made its way into clinical practice yet.

Development and evaluation of an improved quantitative 90Y bremsstrahlung SPECT method

PURPOSE Yttrium-90 ((90)Y) is one of the most commonly used radionuclides in targeted radionuclide therapy (TRT). Since it decays with essentially no gamma photon emissions, surrogate radionuclides (e.g., (111)In) or imaging agents (e.g., (99m)Tc MAA) are typically used for treatment planning. It would, however, be useful to image (90)Y directly in order to confirm that the distributions measured with these other radionuclides or agents are the same as for the (90)Y labeled agents. As a result, there has been a great deal of interest in quantitative imaging of (90)Y bremsstrahlung photons using single photon emission computed tomography (SPECT) imaging. The continuous and broad energy distribution of bremsstrahlung photons, however, imposes substantial challenges on accurate quantification of the activity distribution. The aim of this work was to develop and evaluate an improved quantitative (90)Y bremsstrahlung SPECT reconstruction method appropriate for these imaging applications. METHODS Accurate modeling of image degrading factors such as object attenuation and scatter and the collimator-detector response is essential to obtain quantitatively accurate images. All of the image degrading factors are energy dependent. Thus, the authors separated the modeling of the bremsstrahlung photons into multiple categories and energy ranges. To improve the accuracy, the authors used a bremsstrahlung energy spectrum previously estimated from experimental measurements and incorporated a model of the distance between (90)Y decay location and bremsstrahlung emission location into the SIMIND code used to generate the response functions and kernels used in the model. This improved Monte Carlo bremsstrahlung simulation was validated by comparison to experimentally measured projection data of a (90)Y line source. The authors validated the accuracy of the forward projection model for photons in the various categories and energy ranges using the validated Monte Carlo (MC) simulation method. The forward projection model was incorporated into an iterative ordered subsets-expectation maximization (OS-EM) reconstruction code to allow for quantitative SPECT reconstruction. The resulting code was validated using both a physical phantom experiment with spherical objects in a warm background and a realistic anatomical phantom simulation. In the physical phantom study, the authors evaluated the method in terms of quantitative accuracy of activity estimates in the spheres; in the simulation study, the authors evaluated the accuracy and precision of activity estimates from various organs and compared them to results from a previously proposed method. RESULTS The authors demonstrated excellent agreement between the experimental measurement and Monte Carlo simulation. In the XCAT phantom simulation, the proposed method achieved much better accuracy in the modeling (error in photon counts was -1.1 %) compared to a previously proposed method (errors were more than 20  %); the quantitative accuracy of activity estimates was excellent for all organs (errors were from -1.6 % to 11.9 %) and comparable to previously published results for (131)I using the same collimator. CONCLUSIONS The proposed (90)Y bremsstrahlung SPECT reconstruction method provided very accurate estimates of organ activities, with accuracies approaching those previously observed for (131)I. The method may be useful in verifying organ doses for targeted radionuclide therapy using (90)Y.

Fast generation of 4D PET-MR data from real dynamic MR acquisitions

We have implemented and evaluated a framework for simulating simultaneous dynamic PET-MR data using the anatomic and dynamic information from real MR acquisitions. PET radiotracer distribution is simulated by assigning typical FDG uptake values to segmented MR images with manually inserted additional virtual lesions. PET projection data and images are simulated using analytic forward projections (including attenuation and Poisson statistics) implemented within the image reconstruction package STIR. PET image reconstructions are also performed with STIR. The simulation is validated with numerical simulation based on Monte Carlo (GATE) which uses more accurate physical modelling, but has 150× slower computation time compared to the analytic method for ten respiratory positions and is 7000× slower when performing multiple realizations. Results are validated in terms of region of interest mean values and coefficients of variation for 65 million coincidences including scattered events. Although some discrepancy is observed, agreement between the two different simulation methods is good given the statistical noise in the data. In particular, the percentage difference of the mean values is 3.1% for tissue, 17% for the lungs and 18% for a small lesion. The utility of the procedure is demonstrated by simulating realistic PET-MR datasets from multiple volunteers with different breathing patterns. The usefulness of the toolkit will be shown for performance investigations of the reconstruction, motion correction and attenuation correction algorithms for dynamic PET-MR data.

Ictal-onset localization through connectivity analysis of intracranial EEG signals in patients with refractory epilepsy.

Fifteen percent to 25% of patients with refractory epilepsy require invasive video–electroencephalography (EEG) monitoring (IVEM) to precisely delineate the ictal‐onset zone. This delineation based on the recorded intracranial EEG (iEEG) signals occurs visually by the epileptologist and is therefore prone to human mistakes. The purpose of this study is to investigate whether effective connectivity analysis of intracranially recorded EEG during seizures provides an objective method to localize the ictal‐onset zone.

Characterization of a time-of-flight PET scanner based on lanthanum bromide

A proto-type time-of-flight (TOF) 3D PET scanner based on lanthanum bromide detectors has been developed. The LaBr/sub 3/(5%Ce) Anger-logic detectors in this new scanner use 4/spl times/4/spl times/30 mm pixels and continuous light-guide coupled to a hexagonal array of 50-mm PMTs. The scanner consists of 24 modules with a 93-cm detector diameter and 25-cm axial field-of-view. Initial characterization of scanner performance has been performed, including energy and timing performance. We currently measure an overall system energy resolution of 7.5% and a system timing resolution is 460 ps, although we expect these results to improve eventually when the electronics are fully optimized. Since there are not yet standard tests to quantify the benefit of TOF, we designed two phantoms with hot and cold spheres in 27-cm and 35-cm diameter vessels to evaluate the TOF performance as a function of body size. The data from this scanner are reconstructed with a fully 3D list-mode iterative TOF algorithm with all data corrections incorporated into the system model. We find that TOF reconstruction reduces the noise and background variability, especially for the larger phantom representing a large patient. In addition, TOF improves detail and contrast of the spheres (lesions), especially the smallest 10-mm sphere. The TOF reconstruction reaches convergence faster than the non-TOF reconstruction, and the rate of convergence is seen to be more insensitive to object size. These results indicate that TOF will help improve image quality and potentially reduce scan time with clinical patients.