Brainwaves

By David Yousem of Johns Hopkins Hospital

A better understanding mental disorders and degenerative diseases such as Alzheimer’s is the basis for research at the neuroradiology department of Johns Hopkins Hospital under the guidance of David Yousem.

Medical imaging still in its infancy

“We are surrounded by brilliant people on a daily basis, and the quality of the people in the clinical realm of neurosurgery, neurology, neuroscience and psychiatry is just fantastic”
-David Yousem of Johns Hopkins Hospital

Ever since David Yousem arrived at Johns Hopkins his work has mostly involved mentoring and developing people in his division. As Director of Neuroradiology and Professor of Radiology at the hospital his division consists of 10 physicians and four PhDs specializing in neuroradiology.However the Russell H. Morgan Department of Radiology and Radiological Science also includes a number of groups including a CT group, an interventional group treating tumors and fibroids of the uterus, and members working in pediatric imaging, ultrasound, nuclear medicine, and tumor imaging. “We are surrounded by brilliant people on a daily basis, and the quality of the people in the clinical realm of neurosurgery, neurology, neuroscience, and psychiatry is just fantastic,” he says. “Johns Hopkins is a wonderful environment to work in.

He is particularly proud of his division members’ achievements and recalls how several of his faculty members have been promoted and have gone on to become full professors. “In the ten years I’ve been here, several people have become recognized as international experts in carotid plaque imaging (Bruce Wasserman), semantic processing (Mike Kraut), molecular imaging (Marty Pomper), and teaching (Nafi Aygun, Doris Lin) largely through their own work and my minimal mentorship. It’s been most gratifying to see my people come into their own and be promoted and get recognition.”

Yousem highlights how clinical work has virtually doubled in the past 10 years. The hospital has to deal with more cases and more patients are getting scanned than ever before. This is partly due to an aging population with a lot more patients being evaluated for conditions such as dementia or degenerative spine disease.“We’ve seen a lot more patients being evaluated for low back pain or neck pain as they grow older. In neuroradiology, MRI’s and CAT scans of the spine are part of the work that we do.

As the incidences of Alzheimer’s disease grow, getting to the bottom of why some are susceptible to the disease in comparison to others is a discovery Dr David Yousem would like to unearth. More than 26 million people worldwide were estimated to be living with Alzheimer’s disease in 2006, according to a study conducted by Johns Hopkins Bloomberg School of Public Health. Worryingly, the global prevalence of Alzheimer’s disease will grow to more than 106 million by 2050. Having been fascinated by everything centered around the brain and the central nervous system ever since his time as a medical student Alzheimer’s is an important aspect of his focus and of those that he mentors.

“One of my goals as a neuroradiologist is to find a test that would identify relatively early those people at highest risk for Alzheimer’s disease before they develop symptoms and before cognitive decline,” he explains. “Even before patients with Alzheimer’s disease have memory deficits, they often have deficits with their sense of smell. It turns out that sense of smell and memory are very closely collocated in the brain. I was interested in trying to determine whether there was a way of exploring patients’ sense of smell through imaging at a point where there was no clinical evidence to suggest they had a loss of cognition. I then wanted to determine whether this would predict whether or not a patient would go on to Alzheimer’s disease from a young age.”

There are a number of factors that make people more susceptible to getting the disease. Genetics is the first of these with some people just having a genetic susceptibility for it. Much work has been done on the APOE Type 4 allele, which is one of the genetic factors that may influence the onset of Alzheimer’s disease.

Head trauma has also been linked to Alzheimer’s. “When you look at a lot of the patients who have Alzheimer’s disease, they have had an event that was related to head trauma, identifies Yousem. “We know this for example in patients who were once boxers and have become ‘punch drunk’.

Lastly, the vascular risk factors for stroke are also increased in patients with Alzheimer’s disease. If you’re injuring the brain because of tiny little micro-strokes then this also seems to be a predisposing factor for development of Alzheimer’s disease.

As the baby boomer generation gets older incidences of diseases like Alzheimer’s are likely to put a lot of pressure on the healthcare system. Already a huge amount of money is being spent on assisted living for patients who can no longer take care of themselves. As people live longer their end-of-life expenses in the last two years of their life just get higher. “We don’t have a handle on prevention of Alzheimer’s disease, good treatment for Alzheimer’s disease or a lot of the other neurodegenerative disorders. There has been so much research into heart attacks and atherosclerosis, and we’ve done pretty well with stroke but on the neurodegenerative disorders, both in the brain and the spine, we really haven’t made all that much progress. This is therefore an area of potential growth.

MRI

Some of the most interesting developments that have been taking place in neuroradiology techniques include imaging the brain and mind with functional MRI being the main technique used. By using this technology it is much easier to understand where different emotions, instincts or reactions are processed in the brain. “We can actually see what part of the brain is activated given a particular challenge or task,” highlights Yousem. “The functional MRI team at Hopkins, led by Jay Pillai, can now tell you what part of the gray matter of the brain is being activated, but the areas of the brain are connected via the white matter. Over the last five years, neuroscientists have developed the techniques to look at the white matter tracts.”

Most of this work has been carried out at Johns Hopkins by the researcher Susumu Mori who was one of the first people to develop diffusion tensor imaging (DTI). This allows researchers to see the white matter tracts that connect gray matter areas in the brain. “Due to this process we are now able to understand much better how the brain is wired,” explains Yousem. “This has been really useful because up until now when neurosurgeons did surgery they’ve been able to avoid the gray matter areas that are important for speech, motor activity or for memory. However, they would have trepidation about cutting across the white matter tracts that connect those areas to other parts of the brain. Now they can avoid not only the gray matter areas that are critical to good life function, but also identify the white matter tracts they also have to avoid. The result is that patients who are having neurosurgery have much fewer deficits when they come out of surgery.”

Molecular imaging is something that is still in its infancy. This is the ability to image chemicals that the brain is making or cell surface markers on the surface of the cells in the brain. Yousem highlights how this is allowing researchers like Marty Pomper and Dima Hammoud to investigate the chemical environment of the brain and to identify where there is a higher concentrations of one particular protein or chemical in the brain compared to others and how this can be manipulated with medications to treat disease.

A way with words

Yousem has been credited with injecting humor and fun into the subject of neuroradiology, which is perfectly exemplified in the book Neuroradiology: The Requisites, which he co-authored with Bob Grossman of New York University Medical School. As Yousem admits, a science like neuroradiology can be a dry subject to cover; therefore writing a book on the subject that was different and catchy was the ultimate aim. As he discusses: “Our goal was to write a book that could be read cover to cover in sequential order so it was important that it contained an underlying plot. We achieved this by injecting an underlying theme of politics or art history or humor in each of the chapters so that people enjoyed the ‘story of neuroradiology.’ We also sought to use the humor, limericks, poems, alliteration as a mnemonic device for learning differential diagnoses.”

An example that illustrates this technique can be found in his chapter on brain tumors. Yousem likens each brain tumor to a different impressionist artist. For instance, for diseases that spread on the surface of the brain Yousem compares this to the dripping objects that are characteristic of the work of Salvador Dali.

Not content with keeping his mind active through mentoring, clinical care, and research, Yousem is also a keen participant in sporting pursuits and has completed two marathons, several triathlons, a half ironman and a full ironman competition. He is a keen advocate of the principles discussed in the book The Seven Habits of Highly Effective People by Stephen Covey which includes the motto ‘Live, love, learn and leave a legacy’. Yousem aims to incorporate these ideas into his own life as he explains:

“When the author speaks about live, he is referring to the physical world and the things you do for your body. Love is your emotional and spiritual world. Learn is your intellectual side, and leave a legacy is what you do for your community and your social society service.

“I try to follow these by setting goals for myself with respect to the physical world as far as competition, exercise and health. I kept pushing the bar higher from initially completing 10K runs to a half marathon, then a triathlon, a mini-ironman and then doing the ironman. This was part of my live realm. As far as the Love realm is concerned this involved me getting more into religion, meditation and Eastern philosophy. Learning is the process of research and continuing to maintain my knowledge in my field. Finally, leaving a legacy would include the volunteer work I’ve done, for example, in Mexico with Mayan tribes, but also I feel the books that I write are part of my leaving a legacy to the neuroradiology community.”

Future focus

An area that Yousem is keen for his team to focus on in future is neurodegenerative disorders or learning disorders. He notes that the incidence of conditions such as Attention Deficit Hyperactivity Disorder (ADHD) and autism seem to have dramatically increased. Yousem recalls how when he was growing up the instances of these disorders were minimal: “It is a weird phenomenon. We don’t know what is causing this increase – could it be due to the environment or things like vaccinations? We need to get to the bottom of why it is occurring more frequently, and to use either imaging by our pediatric Neuroradiology team of Thierry Huisman, Aylin Tekes, Doris Lin, and Izlem Izbudak or therapeutic interventions that we can instill in the brain to reverse these deficits in order to allow our children to reach their full potential.”

“It’s just shocking to me how many children are developmentally disabled in America. We should be able to do something more for these kids. I hope that through things like molecular imaging we will be able to identify the areas of abnormality and intervene.”

David Yousem is currently the Director of Neuroradiology and a Professor of Radiology at the Johns Hopkins Hospital. His expertise spans the full gamut of neuroradiology techniques including CT, MRI, myelography, sialography, plain films, CT guided aspirations and biopsies, functional MRI, diffusion and perfusion imaging, MR/CT angiography, and 3D reconstructions. He is a noted authority on disorders of the brain, spine, head and neck, olfaction, cranial neuropathies and neurodegeneration.