Supplement: Neurotrailblazer

Neurotrailblazer By Melinda Wenner Martha Shenton is pushing imaging boundaries in order to understand the schizophrenic brain © 2007 Jared Leeds ARTICLE EXTRAS The Etiology Molecular Mysteries Gazing Downstream Seeing Schizophrenia Pregnancy, Chromosomes, and Receptors Martha Shenton is what you might call a maverick. As the director of Brigham and Women's Hospital's Psychiatry Neuroimaging Laboratory in Boston, she is driven by one thing in particular: a desire to get inside the brain. And she's not at all shy about taking risks and marching into unchartered territory in order to get there. "I tend to gravitate towards things that are a new frontier," she says in her bright office on Boylston Street next to Fenway Park, where her laboratory has been based since 2005. Shenton's nonconformist spirit is somewhat betrayed by her conservative appearance and soft-spoken, warm demeanor. But over the past 21 years, she has applied up-and-coming--and often poorly understood--imaging technologies to the study of schizophrenia, paving the way for others to follow. Shenton, who traces her desire to study schizophrenia back to her childhood, where she grew up next door to the State (Mental) Hospital in Concord, New Hampshire, is best known for her pioneering work in magnetic resonance imaging (MRI). Her study in the New England Journal of Medicine (327:604-12, 1992) was the first to look at schizophrenia-related volume changes across the entire brain, and her review paper on MRI findings in schizophrenia, published in Schizophrenia Research (49:1-52, 2001) is the tenth most highly cited schizophrenia paper this decade. Shenton "is well-known and very well-respected in the field," writes Godfrey Pearlson, a psychiatrist at the Yale University School of Medicine, in an E-mail. Recently, however, her lab has ventured past structural and functional MRI--though the lab still regularly uses them--and into the realm of diffusion tensor imaging (DTI), a new form of MRI that reveals the organization of white matter tracts within the brain. Historically, scientists have focused on how schizophrenia affects discrete brain regions, such as the prefrontal cortex and the superior temporal gyrus. But researchers now realize that a complete understanding of the disorder requires knowledge of how it affects brain circuits, or multiple brain regions and the connections between them. By comparing how white matter tracts are organized in schizophrenic brains as opposed to healthy brains, scientists can learn about schizophrenia's effects on brain circuitry and communication. "I tend to gravitate towards things that are a new frontier." DTI is still in its early stages, but that doesn't deter Shenton. "There are no guideposts or standards as yet," she says, so she's rounding up the best team she can to build them. Her lab consists not only of four full-time neuroscience researchers, but also four full-time computer scientists and a biomedical engineer, who are not only experts on computer imaging, but are also extremely well versed in both neuroscience and schizophrenia--the evidence for which was clear after hearing them give a Powerpoint presentation on the scope of lab's research. All of the scientists, therefore, speak the same language, which allows them to work together--often at computers right next to each other--to collect and analyze data and find new ways to visualize them. "If you're looking to come up with a new paradigm or a new way of looking at things, you have to be at the intersection of different fields," Shenton explains. Her team also works closely with Brigham and Women's Hospital's Surgical Planning Laboratory (SPL), led by radiologist Ron Kikinis. Over the course of their 19 years of collaborations, they have worked together on 3D Slicer, an open-source national software platform developed by the surgical lab that, among other things, allows Shenton's lab to combine data from different imaging modalities--such as from structural MRI, fMRI, and DTI--enabling them to create more comprehensive images of patient brains than has ever before been possible. "You're taking into account the white matter tracts, the gray matter, and the functional [aspects], at the same time," she says. Shenton is also beginning to combine imaging with genetic studies in order to understand how they correlate with functional and anatomical brain differences. "[In] the same way I started to grow computer science in this lab, I want to grow genetics," she says. In addition, she is studying subjects at different stages of disease progression in order to identify potential phenotypic disease markers and predictors, understand how the disease progresses over time, and tie together results from various clinical and molecular tests to abnormalities in neural circuitry. Ultimately, Shenton hopes that her work will pave the way towards the development of treatments and interventions that prevent vulnerable individuals from ever developing schizophrenia in the first place. And in order to get there, she says, we must choose the path less traveled by embracing new technologies. "Just over the last 15 years, we've found out more about schizophrenia in the brain than was done in the last 100 years, and that really has to do with the technology," Shenton says. "That's really, really, really the critically important thing."

Supplement: Neurotrailblazer

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