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PICTURES OF THE FUTURE

  • Research Cooperation

I t could be modern art. It could be a wiring di- agram of a thought or a feeling, a snapshot of consciousness, or a moment of pain. No one knows for sure. What is certain is that it is an image of the brain like no other. Taken with a 3-Tesla magnetic resonance (MR) tomograph, researchers believe that the image shows the structure of the brain’s white matter. Like a printed circuit board in a computer, the white matter is the material responsible for commu- nication between gray matter regions — the central processing units of the mind. “In the brain, when subjected to a magnetic field, water molecules tend to wiggle in the direction of white matter fibers, so by measuring the direction in which these molecules wiggle, we can see the structure of the white matter,” explains Bruce R. Rosen, M.D. Ph.D, director of the A.A. Martinos Center for Biomedical Imag- ing, a joint center of the Harvard-MIT Division of Health Sciences & Technology and the Mass- achusetts General Hospital Radiology Depart- ment.

Snapshot of the brain taken with a Siemens Magnetom Allegra 3-Tesla scanner at MGH. By imaging the mobility of water molecules, this image shows nerve pathways. However, the images produced by Bruce Rosen (left), Larry Wald and Graham Wiggins (lying down) using MRI tomographs from Siemens and experimental detectors (right) still require lots of research.

Collaboration in Mind

Magnetic resonance tomography is an essential instrument in brain research. Research conducted by Siemens and the Massachusetts General Hospital in Boston is yielding insights into new MR products — and providing clues as to the physiological mechanisms associated with mental illnesses.

Although even top neurological researchers like Rosen do not know exactly what images like this show in terms of mental processes, they point out that such images can provide clues as to how and where medications influ- ence physical and mental activity.

With this in mind, researchers at the Marti- nos Center — and with Siemens as a partner

  • have spawned a “Center for Biomarkers and

Imaging,” which will explore how imaging can be used to accelerate drug development and expedite the process from new compounds to approved compounds.

Along the road to this goal, Siemens and MGH have enjoyed a prolific partnership — now in its fifth year — that has generated everything from insights into the physics of magnetic resonance to a stream of exciting new products for existing magnetic resonance machines. Here’s a look at some of the high- lights.

Toward an Atlas of the Brain. One of the most valuable fruits of the MGH-Siemens part- nership has been the development of “Au- toAlign.” Introduced as an upgrade for Siemens’ MR machines in mid 2004, AutoAlign determines — with sub-millimeter accuracy — exactly where any given MR “slice” belongs within a scan of a normal, adult brain by identi- fying anatomical features. It automatically aligns image planes, a process that has, until now, required considerable time to perform by experienced technicians. The product thus in- creases throughput and improves patient com- fort by reducing the time needed for an exam. It also improves accuracy. “If Mr. Smith comes back after two months for a follow-up exam, the new images will be cut at exactly the same angle as the old ones. That gives you a better opportunity to tell what has changed,” says Rosen. “But AutoAlign goes beyond the idea of the individual patient,” he adds. “It allows us to

map data from each patient’s brain onto a kind of atlas and therefore define the common characteristics of all brains.” Thus, as the Au- toAlign database grows, it helps researchers compare an individual’s brain to those of age- matched controls, making it easier to spot morphological differences, such as the early development of a tumor, as well as functional changes, such as response to a medication for schizophrenia.

Today, the high degree of imaging precision conferred by AutoAlign is making it possible to objectively assess whether a tumor is respond- ing to therapy. In the future, says Rosen, its growing database will be used to zero in on changes in blood flow, rates of tumor growth, and metabolic activity — all of which are im- portant parameters in assessing tumor ther- apy. “AutoAlign is a great example of collabora- tion,” says Franz Hebrank, coordinator of the Siemens / MGH-MR program. “We did proto-

type development here at MGH and tested it in a clinical setting. The resulting feedback was very valuable in terms of which features to in- clude in our platform.” Adds Lawrence L Wald, Ph.D., Director of the Core Facility at the Marti- nos Center, who is responsible for scanner facilities within the center and is an assistant professor of radiology at the Harvard Medical School, “This cycle sounds long, but it did not take much more than a year. One reason for that was the close collaboration with Siemens engineers. Their detailed knowledge of how AutoAlign would interface with Siemens’ MR machines in real time put development on a faster track than if the project had been con- ducted in a pure research setting.”

AutoAlign is just one of dozens of examples of collaboration between Siemens and the Martinos Center. Fully outfitted with the most

advanced Siemens MR equipment available, the Center has some 200 specialists conduct- ing research in areas such as how the brain processes visual information, how memory is affected by schizophrenia, and how depression affects feelings of reward. “For the psychiatric community this work is a chance to bring a de- tailed physiological and neuroscience perspec- tive to diseases whose functional characteris- tics could, until now, only be guessed at. This work is changing the very way in which we think of diseases such as schizophrenia and de- pression,” says Rosen.

Getting deeper, more detailed pictures of processes in the brain is the goal of a number of Siemens-MGH-lines of study. Here, the gold standard for improving image signal-to-noise ratio, and thus raising resolution, is the 7-Tesla magnet (see p. 86). Such devices have a mag-

HOW MAGNETIC RESONANCE MEASURES BRAIN ACTIVITY

Magnetic resonance tomography, also known as MR tomography, makes it possi- ble to look into the interior of the body without the need for surgery or harmful radiation. It is founded on the fact that hydrogen nuclei (protons) act like tiny magnets when they are placed in a strong magnetic field. Their intrinsic angular momentum — “spin” to physicists — aligns itself either parallel or antiparallel to the magnetic field. The protons can be deflected from their orientation by a high-frequency, alternating electromagnetic field. They then begin moving like tops and induce a radio signal in receiver coils. The characteristics of this signal contain the desired imaging informa- tion about surrounding tissues. The locations in the body from which the signals originate can be determined using “gradient fields” — additional magnetic fields that slightly distort the homogenous static field of the MR tomograph, and thus modify the signal. The stronger the static field, the stronger the signal radiated by the protons compared to interfering noise. At seven Tesla, this signal-to-noise ratio is 2.3 times higher than at three Tesla and 4.7 times as high as at 1.5 Tesla. This means that with seven Tesla, signals can be detected from much smaller areas of the brain than with 1.5 or three Tesla. What’s more, “functional” MR tomography can be used to determine which areas of the brain are active when. All of the processes in the brain — wiggling a finger, remembering a phone number or solving a problem — consume oxygen. In order to cover this need for oxygen, blood circulation to these areas increases — normally a few seconds later. Blood also contains hemoglobin, which in turn contains i r o n . T h e l a t t e r w h e n i t i s t r a n s p o r t i n g o x y g e n m o d i f i e s t h e s i g n a l i n t h e m a g - u e netic field. In this way it is possible to actually measure brain activity.

netic field that is 140,000 times as powerful as that of the Earth. “That kind of power allows you to see things such as functional brain ac- tivity on a molecular level,” says Wald. But in- terpretation of the resulting images is a signifi- cant hurdle. With a view to harvesting clinically valuable information from such images, the Martinos Center has become a lead site for the Biomedical Informatics Research Network (BIRN) run by the U.S. National Institutes of Health. Together with Siemens engineers, spe- cialists at MGH are developing intelligent tools designed to bridge the gap between imaging information and clinical data in areas such as schizophrenia and depression.

Another way of vastly improving resolution in neurological MR images is to increase the number of radio-frequency (RF) channels — also known as detectors — placed around the

head. “Each channel provides a separate image of the brain, with the closest areas having the highest resolution,” explains Wald. Building on Siemens’ Total imaging matrix (Tim®) technol- ogy, which uses 32 RF channels, Wald and en- gineers from Siemens have been exploring how to take this technology even further. To- gether, they recently assembled three groups of 32 channels to produce an extraordinarily powerful 96-channel system. When combined with a 7-Tesla field, the new device can pro- duce images with a resolution of 100 microns — enough, according to Rosen, “to see changes in very small nests of cells. This re- search,” he adds, “is an opportunity to address basic questions that join theory and practice that had never been explored before. It’s also an example of collaboration between industry and academia that is very rare. In fact, we c o u l d n t i m a g i n e h a v i n g a b e t t e r p a r t n e r . A r t h u r F . P e a s e

Pictures of the Future | Fall 2005

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