People with multiple sclerosis (MS) lose myelin in the gray matter of their brains and the loss is closely correlated with the severity of the disease, according to a new magnetic resonance imaging (MRI) study. Researchers said the findings could have important applications in clinical trials and treatment monitoring. The study appears online in the journal Radiology.
Loss of myelin, the fatty protective sheath around nerve fibers, is a characteristic of MS, an inflammatory disease of the central nervous system that can lead to a variety of serious neurological symptoms and disability.
The scheme demonstrating how an MPF map is computed from source MR images. Imaging protocol includes three gradient-echo images with variable flip angles, a gradient-echo image with off-resonance radiofrequency saturation enabling the magnetization transfer effect (MT-weighted image), and a reference image that is a similar gradient-echo image obtained without saturation. Additionally, an MR imager produces maps of the main magnetic field (B0) and radiofrequency field (B1), which are used to correct errors caused by imperfectness of imager's hardware. MPF maps are computed voxel-by-voxel in two steps, (A) and (B), using special software developed by the authors. During the first step (A), a map of the longitudinal relaxation rate (R1) is generated as described in the literature. This map along with an MT-weighted image and a reference image are used to compute an MPF map in the second step (B) based on an iterative algorithm recently described by the authors.
Credit: Radiological Society of North America
MS is typically considered a disease of the brain's signal-conducting white matter, where myelin is most abundant, but myelin is also present in smaller amounts in gray matter, the brain's information processing center that is made up primarily of nerve cell bodies.
Though the myelin content in gray matter is small, it is still extremely important to proper function, as it enables protection of thin nerve fibers connecting neighboring areas of the brain cortex, according to Vasily L. Yarnykh, Ph.D., associate professor in the Department of Radiology at University of Washington in Seattle.
"The fact that MS patients lose myelin not only in white but also in gray matter has been proven by earlier post-mortem pathological studies," he said. "However, the clinical significance of the myelin loss, or demyelination, in gray matter has not been established because of the absence of appropriate imaging methods."
To learn more about associations between MS and demyelination in both white and gray matter, Dr. Yarnykh and colleagues used a refined MRI technique that provides information on the content of biological macromolecules – molecules present in tissues and composed of a large number of atoms, such as proteins, lipids and carbohydrates. The new method, known as macromolecular proton fraction (MPF) mapping, has been hampered in the past because of the length of time required for data collection, but improvements now allow much faster generation of whole-brain maps that reflect the macromolecular content in tissues.
"The method utilizes a standard MRI scanner and doesn't require any special hardware—only some software modifications," Dr. Yarnykh said. "MPF mapping allows quantitative assessment of microscopic demyelination in brain tissues that look normal on clinical images, and is the only existing method able to evaluate the myelin content in gray matter."
The researchers looked at 30 MS patients, including 18 with relapsing-remitting MS (RRMS), the most common type of MS initially diagnosed, and 12 with the more advanced type of disease known as secondary progressive MS (SPMS). Fourteen healthy control participants were also included in the study. Each participant underwent MRI on a 3-Tesla imager, and the researchers reconstructed 3-D whole-brain MPF maps to look at normal-appearing white matter, gray matter and MS lesions. The researchers further compared the results of their imaging technique with clinical tests characterizing neurological dysfunction in MS patients.
The results showed that MPF was significantly lower in both white and gray matter in RRMS patients compared with healthy controls, and was also significantly reduced in both normal-appearing brain tissues and lesions of SPMS patients compared to RRMS patients with the largest relative decrease in gray matter. MPF in brain tissues of MS patients significantly correlated with clinical disability and the strongest associations were found for gray matter.
"The major finding of the study is that the loss of myelin in gray matter caused by MS in its relative amount is comparable to or even larger than that in white matter," said Dr. Yarnykh. "Furthermore, gray matter demyelination is much more advanced in patients with secondary-progressive MS, and it is very strongly related to patients' disability. As such, we believe that information about gray matter myelin damage in MS is of primary clinical relevance."
The improved technique has potentially important applications for MS treatments targeted to protect and restore myelin.
"First, this method may provide an objective measure of the disease progression and treatment success in clinical trials," Dr. Yarnykh said. "And second, assessment of both gray and white matter damage with this method may become an individual patient management tool in the future."
Dr. Yarnykh and colleagues are currently conducting additional research on the new method with the support of the National Multiple Sclerosis Society and the National Institutes of Health.
"This study was done on the participants at a single point in time," he said. "Now we want to compare MS patients with control participants to see how myelin content will evolve over time. We further plan to extend our method to the spinal cord imaging and test whether the combined assessment of demyelination in the brain and spinal cord could better explain disability progression as compared to brain demyelination alone."
"Fast Whole-Brain Three-dimensional Macromolecular Proton Fraction Mapping in Multiple Sclerosis." Collaborating with Dr. Yarnykh were James D. Bowen, M.D., Alexey Samsonov, Ph.D., Pavle Repovic, M.D., Angeli Mayadev, M.D., Peiqing Qian, M.D., Beena Gangadharan, Ph.D., Bart P. Keogh, M.D., Ph.D., Kenneth R. Maravilla, M.D., and Lily K. Jung Henson, M.D.
Radiology is edited by Herbert Y. Kressel, M.D., Harvard Medical School, Boston, Mass., and owned and published by the Radiological Society of North America, Inc. (http://radiology.rsna.org/)
RSNA is an association of more than 53,000 radiologists, radiation oncologists, medical physicists and related scientists promoting excellence in patient care and health care delivery through education, research and technologic innovation. The Society is based in Oak Brook, Ill. (RSNA.org)
For patient-friendly information on MRI of the brain, visit RadiologyInfo.org
Linda Brooks | Eurek Alert!
A first look at interstitial fluid flow in the brain
05.07.2018 | American Institute of Physics
A sentinel to watch over ocular pressure
04.07.2018 | Fraunhofer Institute for Microelectronic Circuits and Systems
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
13.07.2018 | Event News
13.07.2018 | Materials Sciences
13.07.2018 | Life Sciences