Review Article
The Utility of Diffusion Tensor Imaging in Neuromodulation: Moving Beyond Conventional Magnetic Resonance Imaging

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Objectives

Conventional targeting methods for neuromodulation therapies are insufficient for visualizing targets along white matter pathways and localizing targets in patient-specific space. Diffusion tensor imaging (DTI) holds promise for enhancing neuromodulation targeting by allowing detailed visualization of white matter tracts and their connections on an individual level.

Material and Methods

We review the literature on DTI and neuromodulation, focusing on clinical studies that have utilized DTI tractography for surgical neuromodulation planning. This primarily includes the growing number of studies on tractography-guided targeting in deep brain stimulation as well as magnetic resonance-guided focused ultrasound.

Results

In this review, we discuss three main topics: 1) an overview of the basic principles of DTI, its metrics, and tractography, 2) the evolution and utility of DTI to better guide neuromodulation targets, and 3) the ability of DTI to investigate structural connectivity and brain networks, and how such a network perspective may be an integral part of identifying new or optimal neuromodulation targets.

Conclusion

There is increasing evidence that DTI is superior to conventional targeting methods with respect to improving brain stimulation therapies. DTI has the ability to better define anatomical targets by allowing detailed visualization of white matter tracts and localizing targets based on individual anatomy. Network analyses can lead to the identification of new or optimal stimulation targets based on understanding how target regions are connected. The integration of DTI as part of routine MRI and surgical planning offers a more personalized approach to therapy and may be an important path for the future of neuromodulation.

Section snippets

INTRODUCTION

Neuromodulation is an emerging therapy for a vast number of medically refractory neurological and psychiatric disorders. This treatment modality has been guided primarily by advances in imaging and neurophysiology, which have led to new strategies for better targeting, identification of optimal stimulation sites, and understanding of its therapeutic mechanisms. Among the brain stimulation therapies, deep brain stimulation (DBS) is a well-established treatment that involves surgically implanting

DTI

DTI is a neuroimaging technique that measures the three-dimensional movement of water molecules in biological tissue to characterize white matter microstructure (28). The diffusion of water in three dimensions is calculated by fitting a tensor to every voxel in the brain of a diffusion-weighted MR scan. This tensor may be represented as an ellipsoid shaped mathematical model, defined by three orthogonal eigenvectors and corresponding eigenvalues (λ1, λ2, λ3). The shape of the tensor depends on

BETTER GUIDING NEUROMODULATION TARGETS BASED ON DTI

DTI has the potential to enhance surgical targeting by allowing detailed visualization of white matter tracts and their connections, given that precision and accuracy are one of the main goals of neuromodulation targeting. This approach is especially important when the putative target location cannot be reliably seen by conventional targeting methods. Along with the success of DBS for movement disorders, tractography-guided neuromodulation targeting has primarily been explored for DBS in

FINDING NEW OR OPTIMAL NEUROMODULATION TARGETS BASED ON DTI

Beyond enhancing brain stimulation targeting, DTI can also be used to find new or optimal targets. The advent of the human connectome project has enabled the opportunity to explore the full landscape of structural and functional connections of the human brain in a large-scale manner (75). Using diffusion MRI tractography, an approach for mapping the white matter connections of the entire human brain and its resulting network has been proposed (43). Connectivity and network analyses can be used

TRACTOGRAPHY-BASED TARGETING IN MRgFUS

The benefits of tractography for enhanced target identification may also be extended to noninvasive neuromodulation technologies such as MRgFUS. This method allows deep brain regions to be targeted through an intact skull. In ablative therapies, acoustic energy from an array of ultrasound transducers is concentrated to generate thermal lesions on a desired focal point (Fig. 5). Clinically, the most common application of MRgFUS is thalamotomy for ET. Using the tractography-based VIM targeting

LIMITATIONS

With any tractography method, there is the inherent drawback of the estimated white matter pathways not being wholly representative of actual tissue microstructure or anatomical connectivity. For one, the diameter of individual axons is much smaller (~1.0 μm) than a typical DTI voxel (resolutions in the range of 1–3 mm). In addition, many areas of the brain contain multiple population(s) of fibers or fibers that cross each other. The single-tensor model is particularly susceptible to the

CONCLUSIONS

In conclusion, there is increasing evidence that DTI is superior to the historically used CT and MRI scans with respect to improving brain stimulation therapies. In an era of precision medicine, it is time we move beyond conventional MRI and embrace the integration of these advanced neuroimaging modalities in neuromodulation targeting platforms. In particular, DTI has the ability to better define anatomical targets by allowing detailed visualization of white matter tracts and localizing targets

Acknowledgements

S. Tohyama is a recipient of a Canadian Institutes of Health Research Doctoral Research Award.

Authorship Statements

Sarasa Tohyama and Mojgan Hodaie conceived of the manuscript. Sarasa Tohyama, Matthew Walker, and Mojgan Hodaie prepared the manuscript draft with important intellectual input from all authors. All authors approved the final manuscript.

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    • Source(s) of financial support: Sarasa Tohyama is a recipient of a Canadian Institutes of Health Research Doctoral Research Award.

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