FDG-PET hypometabolism is more sensitive than MRI atrophy in Parkinson's disease: A whole-brain multimodal imaging meta-analysis

Abstract

Recently, revised diagnostic criteria for Parkinson's disease (PD) were introduced (Postuma et al., 2015). Yet, except for well-established dopaminergic imaging, validated imaging biomarkers for PD are still missing, though they could improve diagnostic accuracy. We conducted systematic meta-analyses to identify PD-specific markers in whole-brain structural magnetic resonance imaging (MRI), [18F]-fluorodeoxyglucose-positron emission tomography (FDG-PET) and diffusion tensor imaging (DTI) studies. Overall, 74 studies were identified including 2323 patients and 1767 healthy controls. Studies were first grouped according to imaging modalities (MRI 50; PET 14; DTI 10) and then into subcohorts based on clinical phenotypes. To ensure reliable results, we combined established meta-analytical algorithms - anatomical likelihood estimation and seed-based D mapping - and cross-validated them in a conjunction analysis. Glucose hypometabolism was found using FDG-PET extensively in bilateral inferior parietal cortex and left caudate nucleus with both meta-analytic methods. This hypometabolism pattern was confirmed in subcohort analyses and related to cognitive deficits (inferior parietal cortex) and motor symptoms (caudate nucleus). Structural MRI showed only small focal gray matter atrophy in the middle occipital gyrus that was not confirmed in subcohort analyses. DTI revealed fractional anisotropy reductions in the cingulate bundle near the orbital and anterior cingulate gyri in PD. Our results suggest that FDG-PET reliably identifies consistent functional brain abnormalities in PD, whereas structural MRI and DTI show only focal alterations and rather inconsistent results. In conclusion, FDG-PET hypometabolism outperforms structural MRI in PD, although both imaging methods do not offer disease-specific imaging biomarkers for PD.

Keywords: DTI; FDG-PET; MRI; Meta-analysis; Parkinson's disease.

Fig. 1

PRISMA statement flow diagram. Flow of information through different phases of the systematic literature search identifying the neural correlates of Parkinson's disease. Image modified according to the PRISMA statement (Moher et al., 2009).

Fig. 2

Hypometabolism and atrophy in Parkinson's disease (PD) patients compared to controls. Upper rows: Meta-analysis of FDG-PET (249 PD/186 controls) and MRI-VBM (1292 PD/1014 controls) studies. The SDM∩ALE conjunction highlights brain regions consistently found in both analyses. Anatomical regions are highlighted only for these consistent results. Bottom row: The contrast analysis shows significant regions for the contrast FDG-PET > MRI-VBM. Images shown in neurological convention in MNI space. Abbreviations: ALE Anatomical Likelihood Estimation, CdN caudate nucleus, FDG-PET [18F]-fluorodeoxyglucose-positron emission tomography, FWE Family-Wise Error rate, IPC inferior parietal cortex, mOC middle occipital cortex, MRI-VBM voxel-based morphometry analysis of magnetic resonance imaging, PD-All cohort of all PD patients, SDM Seed-based D mapping.

Fig. 3

Hypometabolism and atrophy across Parkinson's disease (PD) clinical subgroups and white matter changes comparing PD to controls. The SDM∩ALE conjunction highlights brain regions consistently found in both analysis algorithms. Anatomical regions are highlighted only for these consistent results. Images shown in neurological convention in the MNI space. Abbreviations: ALE Anatomical Likelihood Estimation, CdN projections surrounding caudate nucleus, DTI diffusion tensor imaging, FDG-PET [18F]-fluorodeoxyglucose-positron emission tomography, FWE Family-Wise Error rate, GP projections surrounding globus pallidus, IPC inferior parietal cortex, MRI-VBM voxel-based morphometry analysis of magnetic resonance imaging, OFC orbitofrontal cortex, PD-Cog PD with cognitive impairment, PD-Inc gray matter increases in PD, PD-Motor idiopathic PD with only motor symptoms, PU putamen/projections surrounding putamen, SDM Seed-based D mapping.