Human Connectome Imaging Advances Could Improve Neurological Care

Human brain imaging with advanced MRI technology is offering new insights into the pathology of neurological and psychiatric diseases. Using this technology, we aim to improve clinical outcomes in patients with those diseases.

Brain function arises from distributed brain regions that communicate through white matter connections.

Modern imaging approaches using MRI have, for the first time, allowed visualization of both the members of these networks and the white matter pathways linking them, opening new opportunities to understand how brain networks become disrupted in neurological and psychiatric illness.

The Human Connectome Project is a field-defining initiative to build new technologies and approaches to measure brain network organization in individual people at an unprecedented level of precision.

Much of the work of the Human Connectome Project has centered on the development of next-generation magnetic resonance imaging (MRI) scanners like the Massachusets General Hospital/University of Southern California (MGH/USC) Connectom scanner. The project continues a longstanding partnership between the Athinoula A. Martinos Center for Biomedical Imaging at MGH and Siemens Healthcare.

MGH researchers, together with engineers at Siemens, spent several years building hardware to increase the gradient field strength. The gradient strength, which is different from the strength of the main magnetic field of the scanner, determines our ability to detect the direction of microscopic movement of water in the brain.

This information is important, since the water molecules in the brain tend to move along the direction of bundles of axons, the nerve fibers that connect brain regions. The ability to monitor water diffusion with strong magnetic field gradients is how we determine the local direction of those fibers. The MGH/USC Connectom scanner has a magnetic gradient strength about 7-fold higher than that of conventional scanners.

The upshot is that we are now able to resolve the paths of very fine white matter fiber structures in the living human brain.

Imaging with the Connectom scanner allows estimation of the location and direction of major fiber bundles and could enable researchers to better follow fiber pathways between brain regions that are important for brain function — even where there are many bundles overlapping and crossing one another.

This is important because many diseases and disorders are the result of disconnections between brain regions: multiple sclerosis and traumatic brain injury are two examples.

We’re also starting to see more evidence of white matter disturbance in diseases such as Alzheimer’s dementia, which has primarily been viewed as a disease caused by shrinking or atrophy of gray matter. And most recently abnormal brain circuitry has been visualized in autism and related neurodevelopmental disorders.

How can better brain imaging help clinically? The hope is that connectome imaging will contribute to more accurate and earlier diagnosis of these and other diseases. This of course could lead to better outcomes for patients, especially if treatment is started earlier in the course of the disease.

We are moving ever closer to this goal. While technology development is ongoing with the Connectom scanner, we have begun scanning a lifespan sample ranging from children to older adults.

In addition, we are now ready to begin pilot studies with groups of patients in different stages of disease, to determine the technology’s clinical utility in those populations.

The Connectom scanner project has helped to convince Siemens and other MRI manufacturers of the value of higher gradient strengths, so they are now investing in boosting gradient strengths in standard clinical machines.

This will provide the advantages of higher gradient strengths without the learning curve and power requirements of our advanced technology, meaning our work could have clinical impact even sooner than we had anticipated.

Koene R.A. Van Dijk, PhD, is a radiology instructor at the Athinoula A. Martinos Center for Biomedical Imaging in the Department of Radiology at Massachusetts General Hospital and co-investigator on the MGH/USC Human Connectome Project.

References

1. Setsompop K, Kimmlingen R, Eberlein E, Witzel T et al. “Pushing the limits of in vivo diffusion MRI for the Human Connectome Project.” Neuroimage. 2013;80:220-233.
2. Fan Q, Nummenmaa A, Witzel T, Zanzonico R et al. “Investigating the Capability to Resolve Complex White Matter Structures with High b-value Diffusion MRI on the MGH-USC Connectom Scanner.” Brain Connectivity. 2014;4(9):718-726.