Objectives: We performed a systematic review to assess alterations in measures of diffusion tensor imaging (DTI) in parkinsonian syndromes, exploring the potential role of DTI in diagnosis and as a candidate biomarker.
Methods:We searched EMBASE and Medline databases for DTI studies comparing parkinsonian syndromes or related dementias with controls or another defined parkinsonian syndrome. Key details for each study regarding participants, imaging methods, and results were extracted. Estimates were pooled, where appropriate, by random-effects meta-analysis.
Results:Of 333 results, we identified 43 studies suitable for inclusion (958 patients, 764 controls). DTI measures detected alterations in all parkinsonian syndromes, with distribution varying differentially with disease type. Nine studies were included in a meta-analysis of the substantia nigra in Parkinson disease. A notable effect size was found for lowered fractional anisotropy in the substantia nigra for patients with Parkinson disease vs controls (20.639, 95% confidence interval 20.860 to 20.417, p , 0.0001).Conclusion: DTI may be a promising biomarker in parkinsonian syndromes and have a future role in differential diagnosis. Larger cohort studies are required to investigate some encouraging preliminary findings. Given the complexity of the parkinsonian syndromes, it is likely that any potential DTI biomarker would be used in combination with other relevant biomarkers. Differences in natural history and therapy options make early and accurate diagnosis of parkinsonian syndromes important. 1 Emission tomography (SPECT or PET) has a role but it can be expensive, with limited availability, and requires radioactive tracers. 2 There is particular interest in the potential of advanced structural MRI techniques to differentiate among parkinsonian syndromes and to offer candidate biomarkers, facilitating early or premanifest diagnosis and monitoring of disease progression.Diffusion tensor imaging (DTI) is an MRI technique assessing the orientation and integrity of white matter tracts in vivo by measuring the diffusion of water molecules in neural fibers 3 and it also shows promise for studying gray matter areas. It estimates both the degree of directionality using anisotropy (frequently fractional anisotropy [FA]) and the overall movement of molecules (mean diffusivity [MD]; trace; apparent diffusion coefficient [ADC]). These measurements can either be extracted locally in predefined regions using region of interest (ROI) analysis or tractography or, alternatively, globally using voxel-based analysis (VBA) or tract-based spatial statistics (TBSS). Disruptions to microstructural tissue integrity, such as those found in the neurodegeneration of parkinsonian syndromes can be associated with alterations in anisotropy and diffusivity measures. 3 We therefore performed a systematic review of the literature to assess