Prior to 2007
Bioengineering Institute Consortium for Comparative Neuroimaging (BEI - CCNI)
For the past several years, the faculty and graduate students in the ECE and ME departments at WPI, and research scientist at UMMC have collaborated on a joint venture to improve the resolution of images generated using Magnetic Resonance Imaging (MRI) techniques, and to develop methods, instruments and software needed to apply the advanced imaging capabilities to appropriate scientific studies of fully conscious animals.
High Field Superconducting Magnets
Two state-of-the-art, ultra high-field spectrometers located in a separate building near the UMMC campus are the critical elements to this innovative research. Standard human clinical MRI systems operate at 1.5-3.0 Tesla, a unit of magnetic field strength measurement where 1T is equal to 10,000 Gauss. For comparison, the Earth's magnetic field is about 0.5 Gauss. The primary CCNI superconducting magnet generates a field of 4.7 Tesla and is used for imaging large rodents and Rhesus monkeys. In conjunction with custom gradient and RF coil designs from ECE, this CCNI system produces images at least three times shaper than standard human MRI machines. For small rodents such as mice the Center even operates a 9.4 T MR spectrometer.
Faculty researchers involved in the CCNI include Dr. Reinhold Ludwig, WPI Professor of Electrical and Computer Engineering (RF electronics, coil technology), Dr. John Sullivan, WPI Professor of Mechanical Engineering (numerical methods, imaging algorithms), Dr. Jean King, UMMC Associate Professor of Psychiatry (quantitative neuroanatomy, brain metabolism) and Dr. Craig Ferris, UMMC Professor of Psychiatry (psychopharmocology, drug action, synaptic brain activity).
Superior magnetic field strength is not the only aspect of the CCNI research that makes the CCNI high resolution imaging results so remarkable. Working side-by-side, Ludwig and Sullivan have devised restraining devices that allow MR images to be generated on alert rodents. Prior to this development, MRI experiments required that an animal be sedated so that it would remain immobilized during the generation of an image. The sedation drug created problems, however, since one of the primary research interests of CCNI scientists Drs. King and Ferris is brain activities and metabolism studies - which can easily be compromised by inducing undesired drug-related responses. With the new restrainer and the integrated coil technology, unsedated animals can be scanned in real time (also known as functional MRI, or simply fMRI). Besides being humanitarian, this enables the study of fully alert animals.
Integrated Coil Design
While the superconducting magnetic coil assemblies were obtained from commercial sources, all of the advanced magnetic gradient and excitation/sensing coils used by the CCNI researchers have been designed by Dr. Reinhold Ludwig and his graduate students in ECE at WPI. An example of these designs is the dual radio-frequency (RF) coil system developed by Ludwig. Created by using a RF transmitter coil and an RF receiver coil, Ludwig's design is specifically used for the CCNI research magnets. The dual coil system can be quickly activated and deactivated during the slice scanning process. A special electronic switch circuit provides active tuning and detuning of each coil. The RF transmitter coil plays the role of exciting the nuclei while the RF receiver coil records the RF signal emitted when the excitation coil is de-tuned. These coils can be mechanically designed so that they adapt to specific organs or parts of the body, thereby creating more accurate images of that area.
These advanced coils and magnets are only part of the process used to generate the MR images. Once the data has been collected, Dr. Sullivan and his students have developed specialized software to analyze and manipulate the images for studies. As the CCNI's Director of data and analysis, Sullivan utilizes programs that were three years in the making. His software manipulates the date collected to create a surface topology, with hundreds of thousands of tetrahydrons, enabling the image to be rotated, swiveled and sliced at any angle. For example, one 3-D images of a brain has over 1,300 itemized regions, allowing the activity in those regions to be studied.
One of the more exciting applications of the enhanced real-time MRI technology developed by Ludwig and Sullivan is a study of the effects of cocaine addiction on mice. Because a mouse's tiny brain will very quickly show the sort of abuse that it would take a human brain years to accumulate, Drs. Ferris and King administer mice doses of cocaine while at the same time a cue is given, such as a flashing yellow room light. The cocaine administration is then halted, but the cues continued. fMRI scans show that after the cue is given, brain activity can be linked to the craving behind cocaine addiction. These brain activity studies have translational value when dealing with human drug and substance abuse.
Future plans for the CCNI include expanding the work to include cancer-related screening. Since cancer research begins with non-invasive ultra high-field MR imaging and spectroscopy, the Center provides the tools for progressive research. Its facilities offer unprecedented and unrivaled anatomical and spectral resolution which can be utilized to localize and characterize tumors.
Currently, both Ludwig and Sullivan are working to develop alternative breast cancer screening methodologies. Utilizing a strategy known as adaptive dual-mesh development, Sullivan is creating image and data processing algorithms to extract relevant physical tissue properties. These properties are then used to restructure the mestopology and resolution. Proven to work effectively with multiple material regions of arbitrary shape, this technique is the basis in model-based image reconstruction.
Ludwig, working on the hardware side of MRI, is developing a custom designed RF coil for non-invasive, non-discomforting high resolution breast imaging core. In the US alone, breast cancer is the 2nd leading cause of female cancer mortality. Each year breast cancer strikes more than 200,000 US women and results in the deaths of approximately 40,000. WPI's goal is to develop an anatomically correct dual-mode cup-shaped coil configuration.
Research and Education
CCNI faculty are partially funded by the National Institutes of Health. The consortium is used as a learning lab for WPI students studying bioengineering, computer engineering, electrical engineering and mechanical engineering, and for UMMS M.D./Ph.D. candidates in psychiatry, neurology, pediatrics and oncology. Professors Ludwig and Sullivan have developed a new curriculum to train students in the engineering aspects of MRI. "For example," they say, "we will develop new radio frequency coil technology for sending and receiving the electromagnetic signals used in collecting the data that produce the images. Students can generate realistic computer simulations of the magnetic field lines interacting with the animal's brain. These numerical models allow us to predict and optimize the performance of the coil on a computer. With the theoretical models as a template, students are able to construct high-performance coils, or antennas, whose actual performance as a tool for brain imaging can immediately be evaluated in the magnets at CCNI. This practical lab experience will be of tremendous value to future generations of engineering students with interests in high-field magnetic resonance imaging."
Students interested in ECE graduate studies and research opportunities should contact Dr. Reinhold Ludwig directly at firstname.lastname@example.org.
Article research and draft provided by Valery Sheridan (ECE '06). Portions of this article have been excerpted from WPI ECE Transmissions - Spring 2002.
To learn more about the CCNI's current research and the people behind the innovations, visit the CCNI Web site.
There are a number of excellent references to MR Imaging on the web. Interested readers are directed to the following sites as a starting point.
The WPI Bioengineering Institute (BEI) is a WPI organization dedicated to creating life science based products by commercializing the results of academic research. The commercialization process is founded on academic, industry and government partnerships that blend the intellect of academia, the market needs of industry and the public policy needs of government. Through this effort BEI creates innovative solutions to healthcare problems and in so doing stimulates new manufacturing, creates jobs and promotes overall economic development in Central Massachusetts. For more information, visit the BEI Web site.
Humans are mostly composed of water and fat, each molecule of which is composed of many hydrogen atoms with their own tiny magnetic fields. At the most basic level, the technology behind an MRI scanner is based on causing hydrogen nuclei in a magnetic field (the M in MRI) to transition between a low and high energy state by exciting the nuclei with the correct resonant frequency (the R in MRI) RF signal. Subsequently, the density of hydrogen nuclei is inferred by removing the RF excitation signal and measuring the resulting signal strength as the hydrogen nuclei transition back to the lower energy state.
Images (the I in MRI) are formed by designing a system that creates a strong static magnetic field with a superimposed dynamic gradient magnetic field. In conjunction with a high frequency magnetic field tuned to the MRI system's unique resonant frequency, thin 2D slices, or tomograms can be obtained. Location sampling is established by changing the frequency of the RF exciter to select a specific slice location according to its resonant frequency. Once a thin 2D slice is imaged, the gradient field is indexed to identify the next slice and the imaging process is repeated. When the object volume has been fully sampled, the data is processed into a 3D image representing a density distribution of the hydrogen nuclei.
April 1, 2004