The Roots of Diffusion Imaging

The roots of diffusion imaging with MRI run deep in the Martinos Center. In fact, the first demonstration of diffusion anisotropy in the human brain— anisotropy would later be one of the core principles underlying the development of the approach —was reported by Martinos graduate student Daisy Chien in 1988, in a conference paper presented to the Society for Magnetic Resonance in Medicine. A series of papers by Chien and colleagues followed (her colleagues included the Center’s Ken Kwong, who would soon introduce a means to measure brain activity entirely noninvasively), both fleshing out the methods used to track diffusion in the brain and exploring early applications of those methods.

For example, they were the first to demonstrate in humans that diffusion imaging was sensitive to changes brought on by acute stroke, as shown in a series of technically demanding and indeed heroic experiments conducted in the midst of a Boston winter with a 0.6-T scanner in a trailer parked outside Mass General.

Work progressed elsewhere in the Center as well. In the early 1990s, Center investigators Van Wedeen and Tim Davis wrote the first algorithms to produce maps of white matter fibers based on diffusion data. They described this work in 1995 in an abstract presented to the annual meeting of the Organization for Human Brain Mapping, which included the following tantalizing note about its potential: “Reconstruction of white matter tracts by vector field integration successfully indicates known large-scale white matter anatomy in prototypical cases. This technique may allow for integration in an individual of activated neural systems with their underlying connectivity.” (Emphases ours.)

Wedeen continued to pursue this work and, in 2012, reported in the journal Science a groundbreaking study showing a remarkable grid-like structure of fiber pathways in the brain, yielding new and utterly intriguing insights into how the brain is organized. After its publication in March of that year, the work was highlighted in over 3,000 news stories worldwide. The Boston Globe; national media outlets such as Science, Nature, New Scientist, Smithsonian Magazine, US News, Time, Technology Review and National Public Radio; and international publications such as der Spiegel (Germany), Science et Vie (France) and the Daily Mail (UK) all rushed to cover Wedeen’s exciting new findings.

Based on the trailblazing work Wedeen and colleagues had done over the years, the National Institutes of Health chose the Martinos Center to help build a next-generation device to enable the same kind of imaging in humans. In September 2010, the NIH awarded grants totaling $40 million for what would be known as the Human Connectome Project. The recipients of the grants were two consortia with the common goal of mapping structural connections within the human brain, one of which was led by the Martinos Center in collaboration with the Laboratory of Neuro Imaging at the University of California, Los Angeles (now at the University of Southern California).

The MGH/UCLA consortium would focus on developing the MRI technology that would enable imaging of neural pathways: the structural connections by which different areas of the brain communicate. They would achieve this with a new 3T “Connectom” MRI scanner. Designed and built collaboratively by Larry Wald and Van Wedeen and their respective teams at the Martinos Center and engineers at Siemens Healthcare, this scanner would offer unprecedented sensitivity and resolution of the human brain’s white matter connectivity: that is, its “Connectome.”

Installation of the Connectom scanner at the Martinos Center (the dropped “e” in the name was intentional) was completed in September 2011. With the powerful new tool in place, the MGH-UCLA team made steady and important progress in developing, optimizing and testing the new hardware, pulse sequences and reconstruction methods designed expressly for the unique gradient system of the scanner. The Martinos Center’s efforts focused on characterizing and optimizing its performance for human brain imaging, eventually opening the door to studies with healthy human volunteers.