In New Paper, Dynamic Measure of Muscle Integrity

"Because we measure dynamically with high temporal resolution, we can see things which we were not able to see before."
Researchers at NYU’s Center for Advanced Imaging & Innovation Research (CAI2R) have developed a new way to measure changes in microstructure of muscle fiber. In a paper just published in NMR in Biomedicine online, CAI2R’s Steven Baete describes a new Magnetic Resonance Imaging (MRI) method that shows how muscle responds to exertion. The method, called Single Line Multiple Echo Diffusion Tensor Acquisition Technique (SL-MEDITATE) could help diagnose muscle weakness before it becomes apparent, potentially leading to earlier and more reliable diagnosis of hard-to-detect autoimmune muscle diseases such as dermatomyositis, a rare disorder associated with serious complications: cancer and severe lung disease.
 
Diffusion Tensor
When muscle fibers work, their shape and environment undergo quick and dramatic changes. To detect these changes, NYU researchers follow the most prevalent molecules in the human body, H2O, which move throughout tissues in a manner called diffusion. As muscles flex, rate and direction of diffusion change, but most of the water tracks the direction of muscle fibers, the way most car traffic in Manhattan moves along lanes painted on the roads. But if roads bristled with obstacles or lost their boundaries, fewer cars would travel in the same direction—as would water in damaged muscle tissue. If scientists were able to see the diffusion pattern, they might be able to distinguish between healthy and anomalous fibers.
 
However, seeing the motion of H2O particles inside a muscle is not as easy as looking out the window; Scientists describe such motion with a mathematical object called diffusion tensor, which has six elements; To calculate it, researchers therefore need at least six measurements, or encodings. Conventional methods capture diffusion encodings through consecutive scans, each of which excites hydrogen a little differently in a process loosely analogous to taking successive camera shots from different angles.
 
Although the method works for tissue at rest, it fails when applied to muscle undergoing rapid change. The snag lies in encoding speed—exertion dynamically alters muscle microstructure, and with one encoding per scan, conditions inside muscle fiber at the time of the final measurement differ from those at the time of the initial one. The lag “blurs the data,” according to Eric Sigmund, senior author of the paper.
 
With new method, four-second scans suffice to measure all diffusion directions simultaneously, revealing rapid changes in muscle tissue.
Multiple Echo
Dr. Baete and Dr. Sigmund came up with a new approach that, in essence, enables them to take shots from multiple angles simultaneously with every single scan, instead of doing so consecutively. “We collect all critical signals in a single block,” said Dr. Sigmund in an interview. By sending several pulses during each scan, scientists focus multiple “echoes” which in turn “suffice to calculate the diffusion tensor.” With this approach, researchers acquire diffusion data “every four seconds”—instead of every few minutes—and "in all directions at once," delivering dynamic, frame-by-frame description of changes in muscle microstructure.
 
Single Line
Increased temporal resolution, however, comes at the cost of lowered spatial coverage. Instead of producing a complete image, the new method targets a very small area called a line—a number of adjacent voxels (3D pixels). “If you take the whole image” using the conventional method, “the values are wrong,” said Dr. Baete. “But if you do it per line, you get the right dynamic. But you don’t get the whole image.”
 
The scheme has significant advantage in that it shows changes in not only the rate but also the direction of the flow of water molecules—variations indistinguishable by conventional diffusion imaging. Dr. Baete explained that “because we measure dynamically with high temporal resolution, we can see things which we were not able to see before.” Indeed, obtained data indicate that water diffuses less along the muscle fibers and more away from them immediately following exercise; And returns to initial state sometime later. Researchers are careful about interpreting these findings in physiological terms, but say that the variation may indicate temporal dilation of muscle tissue or change in transverse structure of muscle fiber, and “might in some contexts suggest anomaly,” according to Dr. Sigmund.
 
Potential
According to Dr. Andrew Franks, who has led the Autoimmune Connective Tissue Disease Center at NYU Langone Medical Center for nearly thirty years and cared for patients with dermatomyositis, timely detection is extremely challenging, because initial symptoms are consistent with more common, more benign ailments. “Many of these patients are diagnosed with allergic eczemas and non-specific sun sensitivity or even psoriasis prior to the correct diagnosis,” said Dr. Franks in an e-mail interview.
 
Often by the time a key symptom—muscle weakness—occurs, the disease has moved to a relatively advanced stage. Moreover, “about 20% of dermatomyositis patients do not have muscle weakness,” further hindering accurate timely diagnosis and suitable treatment, said Dr. Franks, adding “we have no markers to establish active disease versus damaged muscle that are reliable.”
 
CAI2R scientists hope that SL-MEDITATE brings them closer to developing markers, or quantifiable metrics, that may just do the trick.
 
—Pawel A. Slabiak

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05/23/2017 - 14:55
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We gratefully acknowledge generous support for radiology research at NYU Langone Medical Center from:
 
• The Big George Foundation
• Raymond and Beverly Sackler
• Bernard and Irene Schwartz

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