Elsevier

NeuroImage

Volume 102, Part 2, 15 November 2014, Pages 875-884
NeuroImage

Voxel-based comparison of state-of-the-art reconstruction algorithms for 18F-FDG PET brain imaging using simulated and clinical data

https://doi.org/10.1016/j.neuroimage.2014.06.068Get rights and content

Highlights

  • State-of-the-art reconstruction algorithms are compared for FDG PET brain imaging.

  • First, the presence of systematic bias is investigated using normal brain images.

  • Second, it is verified whether similar results are obtained in a group analysis.

  • The analysis is performed using both simulated and measured clinical data sets.

  • The differences between the algorithms did not change the group analysis outcome.

Abstract

The resolution of a PET scanner (2.5–4.5 mm for brain imaging) is similar to the thickness of the cortex in the (human) brain (2.5 mm on average), hampering accurate activity distribution reconstruction. Many techniques to compensate for the limited resolution during or post-reconstruction have been proposed in the past and have been shown to improve the quantitative accuracy. In this study, state-of-the-art reconstruction techniques are compared on a voxel-basis for quantification accuracy and group analysis using both simulated and measured data of healthy volunteers and patients with epilepsy.

Methods

Maximum a posteriori (MAP) reconstructions using either a segmentation-based or a segmentation-less anatomical prior were compared to maximum likelihood expectation maximization (MLEM) reconstruction with resolution recovery. As anatomical information, a spatially aligned 3D T1-weighted magnetic resonance image was used. Firstly, the algorithms were compared using normal brain images to detect systematic bias with respect to the true activity distribution, as well as systematic differences between two methods. Secondly, it was verified whether the algorithms yielded similar results in a group comparison study.

Results

Significant differences were observed between the reconstructed and the true activity, with the largest errors when using (post-smoothed) MLEM. Only 5–10% underestimation in cortical gray matter voxel activity was found for both MAP reconstructions. Higher errors were observed at GM edges. MAP with the segmentation-based prior also resulted in a significant bias in the subcortical regions due to segmentation inaccuracies, while MAP with the anatomical prior which does not need segmentation did not. Significant differences in reconstructed activity were also found between the algorithms at similar locations (mainly in gray matter edge voxels and in cerebrospinal fluid voxels) in the simulated as well as in the clinical data sets. Nevertheless, when comparing two groups, very similar regions of significant hypometabolism were detected by all algorithms.

Conclusion

Including anatomical a priori information during reconstruction in combination with resolution modeling yielded accurate gray matter activity estimates, and a significant improvement in quantification accuracy was found when compared to post-smoothed MLEM reconstruction with resolution modeling. AsymBowsher provided the most accurate subcortical GM activity estimates. It is also reassuring that the differences found between the algorithms did not hamper the detection of hypometabolic regions in the gray matter when performing a voxel-based group comparison. Nevertheless, the size of the detected clusters differed. More elaborated and application-specific studies are required to decide which algorithm is best for a group analysis.

Introduction

Fluorine-18 fluoro-2-deoxyglucose (18F-FDG) positron emission tomography (PET) imaging of the brain is a well-established way to detect changes in neuronal activity induced by a variety of diseases through the alteration in glucose consumption (Varrone et al., 2009). Both filtered backprojection and iterative reconstruction algorithms are currently being used in clinical practice. However, the limited spatial resolution of PET (2.5–4.5 mm for brain imaging (Adam et al., 1997, Wienhard et al., 2002)) in combination with the small cortical thickness (average thickness of 2.5 mm (Fischl and Dale, 2000)) compromises accurate quantification of the tracer uptake in the brain (Hoffman et al., 1979).

Two approaches have been recommended to improve the quantitative accuracy. The first one is to correct for the partial volume effect after reconstruction, by estimating the point spread function and correcting for its effect on the reconstructed activity, given spatially aligned tissue segmentation information. Different partial volume correction methods for brain 18F-FDG PET imaging have been compared in Yang et al. (1996). The second approach is to model the spatial resolution during image reconstruction to sharpen the image (‘resolution recovery’ or ‘resolution modeling’). Even in high-resolution PET systems this can reduce the partial volume effect and improve the quantitative accuracy (Sureau et al., 2008), but it is worth noting that resolution modeling may induce some unwanted secondary effects, such as an increase in inter-voxel correlations and Gibbs artifacts. Hence, an improvement in one figure of merit does not imply an improvement of all possible figures of merit (Alessio et al., 2013). To suppress noise and Gibbs artifacts, resolution modeling is best combined with the use of anatomical prior information during, e.g., a maximum a posteriori (MAP) image reconstruction (Vunckx et al., 2012). In addition, detection accuracy of hypometabolic regions can be significantly improved in this way (Baete et al., 2004a, Goffin et al., 2010).

Unfortunately, segmentation of, e.g., structural magnetic resonance (MR) images does not yield perfect brain tissue classification. Especially subcortical structures are very hard to segment, although increasingly accurate segmentation methods are being developed (Babalola et al., 2009). Partial volume correction (PVC) techniques and anatomical priors that heavily rely on segmentations will automatically translate the segmentation errors into quantification errors and reconstruction artifacts. Therefore, segmentation-free anatomical priors have been proposed as well in the past (Bowsher et al., 2004, Nuyts, 2007, Somayajula et al., 2005).

Because noise suppression through the use of anatomical information was found to be superior with MAP reconstruction compared to with post-processed maximum likelihood reconstruction (Nuyts et al., 2005), we concentrated on the evaluation of reconstruction-based partial volume correction algorithms in this work. Furthermore, diagnosis based on 18F-FDG PET brain images is often performed by looking for locally deviating patterns or small hypometabolic regions. Therefore, we focused on voxel-based rather than region of interest-based image quality evaluation. Also in group analyses, voxel-based statistical parametric mapping techniques are typically used to highlight differences in tracer uptake.

The aim of the present study was to investigate where systematic differences are to be expected when using MLEM with resolution recovery, MAP reconstruction with a segmentation-based prior or MAP with a segmentation-free anatomical prior (three state-of-the-art reconstruction algorithms), and whether the choice of the algorithm influences the outcome of a group analysis. Through the use of a simulation study, results can also be compared to the true activity distribution. The evaluation on clinical data sets enabled us to verify whether similar results are obtained in a realistic setting.

Section snippets

MLEM with resolution modeling

Some of the resolution lost due to blur during the detection process can be recovered by modeling the resolution of the detector during iterative reconstruction. In these iterative algorithms, the currently estimated activity distribution Λold = [λ1 λJ] (with J as the number of reconstruction image voxels) is gradually improved based on a comparison between the measurement Q = [q1  qI] (with I as the number of detector pixels) and the forward projected Λold, which can be written as kcikλkold (with

Bias with respect to true activity and differences between algorithms

The results of the comparison studies are shown in Fig. 1, Fig. 2, Fig. 3, Fig. 4. The colored voxels indicate the percentage difference in reconstructed activity, but only in those voxels in which these differences were considered to be significant. For the mutual comparison of the reconstruction algorithms (Fig. 2, Fig. 3, Fig. 4), three voxel-based analyses were performed, i.e. on reconstructions of simulated normal brain data in native space, of simulated data after spatial normalization

Discussion

All reconstruction methods under investigation include resolution recovery, which makes that even MLEM yields a strong partial volume correction. Because resolution recovery requires many iterations to reach convergence, the MLEM images are too noisy to be useful in clinical practice. Therefore, its quantification accuracy was only investigated after post-smoothing, which obviously resulted in a great loss of the recovered resolution, apparent as a significant underestimation of the GM activity

Conclusion

Three state-of-the-art iterative algorithms for PET image reconstruction, i.e. (post-smoothed) MLEM with resolution recovery, and two MAP algorithms using either a segmentation-based (A-MAP) or a segmentation-less (AsymBowsher) anatomical prior, have been compared for their use in human 18F-FDG PET brain imaging using voxel-based statistical analysis techniques. In the first study, the algorithms were compared to the true activity and to each other. Significant differences were mainly found at

Acknowledgments

K. Vunckx is a postdoctoral researcher of the Research Foundation — Flanders (FWO Vlaanderen). K. Van Laere is a Senior Clinical Investigator of the Research Foundation — Flanders.

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