Journal Article

Anatomical accuracy of brain connections derived from diffusion MRI tractography is inherently limited

Leopold, David A., Ye, Frank Q., Thomas, Cibu, Pierpaoli, Carlo, Irfanoglu, M. Okan, Modi, Pooja, Saleem, Kadharbatcha S.

2014

Overview

Significance Diffusion-weighted MRI (DWI) tractography is widely used to map structural connections of the human brain in vivo and has been adopted by large-scale initiatives such as the human connectome project. Our results indicate that, even with high-quality data, DWI tractography alone is unlikely to provide an anatomically accurate map of the brain connectome. It is crucial to complement tractography results with a combination of histological or neurophysiological methods to map structural connectivity accurately. Our findings, however, do not diminish the importance of diffusion MRI as a noninvasive tool that offers important quantitative measures related to brain tissue microstructure and white matter architecture. Tractography based on diffusion-weighted MRI (DWI) is widely used for mapping the structural connections of the human brain. Its accuracy is known to be limited by technical factors affecting in vivo data acquisition, such as noise, artifacts, and data undersampling resulting from scan time constraints. It generally is assumed that improvements in data quality and implementation of sophisticated tractography methods will lead to increasingly accurate maps of human anatomical connections. However, assessing the anatomical accuracy of DWI tractography is difficult because of the lack of independent knowledge of the true anatomical connections in humans. Here we investigate the future prospects of DWI-based connectional imaging by applying advanced tractography methods to an ex vivo DWI dataset of the macaque brain. The results of different tractography methods were compared with maps of known axonal projections from previous tracer studies in the macaque. Despite the exceptional quality of the DWI data, none of the methods demonstrated high anatomical accuracy. The methods that showed the highest sensitivity showed the lowest specificity, and vice versa. Additionally, anatomical accuracy was highly dependent upon parameters of the tractography algorithm, with different optimal values for mapping different pathways. These results suggest that there is an inherent limitation in determining long-range anatomical projections based on voxel-averaged estimates of local fiber orientation obtained from DWI data that is unlikely to be overcome by improvements in data acquisition and analysis alone.

• Publisher: National Academy of Sciences,National Acad Sciences
• Subject: Accuracy / Algorithms / Anatomy / Animals / Axonal Transport / Axons - ultrastructure / Biological Sciences / Body Water / Brain / Connectivity / Connectome - methods / Contrast Media / Data acquisition / Determinism / Diffusion / Diffusion magnetic resonance imaging / Diffusion Magnetic Resonance Imaging - methods / Diffusion Magnetic Resonance Imaging - statistics & numerical data / Diffusion tensor imaging / Diffusion Tensor Imaging - methods / Diffusion Tensor Imaging - statistics & numerical data / Driving while intoxicated / Gadolinium DTPA / Gray matter / humans / Imaging / Leucine - pharmacokinetics / Macaca / Macaca mulatta - anatomy & histology / magnetic resonance imaging / Male / microstructure / Models, Neurological / Monkeys & apes / Motor Cortex - anatomy & histology / NMR / Nuclear magnetic resonance / Occipital Lobe - anatomy & histology / Proline - pharmacokinetics / Research Design / ROC Curve / Sensitivity and Specificity / Tensors / Tritium - analysis / White matter / White Matter - anatomy & histology