Magnetic resonance (MR) is one of the most versatile of imaging modalities. With the right software, a single MR machine can create images that reveal a wide range of information about tissues and organs. The number and power of these software-driven techniques has increased, thanks in part to the dedication and creativity of U.Va. biomedical engineering department faculty members and their efforts, in conjunction with Siemens, one of the major manufacturers of MR equipment in world, to disseminate that technology to a broad base of potential users.
“Our goal is impact,” says BME Professor and Chair Frederick Epstein (MS ’90, PhD ’93).”We invent and develop MRI technology with great clinical value, and we work to move that technology into the world.”
A Breakthrough: MP-RAGE and SPACE
The efforts of John Mugler (MS ’80, PhD ’88) over the last twenty-five years to advance three-dimensional MR imaging is a case in point. Mugler, a professor of radiology and biomedical engineering, and James Brookeman, professor emeritus, developed MP-RAGE (which stands for magnetization-prepared rapid gradient echo), an innovative pulse sequence that dramatically reduced the time it took to produce high-quality, high-contrast 3D images.
It was a breakthrough. “It became practical to take 3D images rather than stitch together 2D slices,” Mugler says. By the mid-1990s, Siemens had made MP-RAGE a standard pulse sequence on its scanners, and the Alzheimer’s Disease Neuroimaging Initiative adopted MP-RAGE because of its usefulness in distinguishing among brain tissues and the ease of postprocessing analysis.
Mugler followed up on this innovation with SPACE (which stands for sampling perfection with application optimized contrasts using different flip angle evolution). A more complex 3D pulse sequence to implement than MP-RAGE, SPACE is now included in the application software found in MRI scanners worldwide.
Accelerating Image Acquisition
In recent years, Mugler has been collaborating with BME Professor Craig Meyer to introduce robust commercial applications of spiral MRI, an independent technique that can capture image data very rapidly. Because of its speed, spiral MRI makes it easier to capture images of objects in motion, whether it is a beating heart or a squirming baby. Meyer and Mugler’s primary approach is to accelerate established pulse sequences like SPACE or MP-RAGE by integrating them with spiral MRI.
One of the challenges of commercializing spiral MRI is that it is sensitive to minute variations among scanners. Meyer and Mugler have developed methods to characterize individual scanners, which they can then use to calibrate them for spiral MRI. Having access to different Siemens scanners and scanner types at the company’s headquarters has been crucial in developing this technique.
The first commercial implementation of 3D spiral MRI arising from this project, for lung imaging, is now part of a works-in-progress package that is being evaluated by other institutions in the Siemens network. “Lung imaging is difficult in MRI because there is little signal in a normal lung,” Meyer says. “We have developed a spin-off that uses another property of spiral MRI to detect rapidly decaying signals.”
Magnifying Usefulness—Multiplying Applications
Another example of how new MRI software can lead to new directions for clinical care is Epstein’s Cine DENSE MRI technique. DENSE, which stands for displacement encoding with stimulated echoes, produces a high-resolution map of the heart, quantifying cardiac contraction and activation. Epstein collaborated with Meyer to incorporate spiral readout methods in the software.
Working closely with Dr. Kenneth Bilchick, an associate professor of medicine and a cardiac electrophysiologist, Epstein is using Cine DENSE MRI to better identify heart failure patients who would benefit from cardiac resynchronization therapy (CRT) using a pacemaker. Only 60 percent of patients identified using the current method, an electrocardiogram, are actually helped by CRT.
From DENSE images, Epstein and Bilchick derive a cardiac activation map that can be used as a roadmap to guide optimal implementation of CRT.
Here too, a partnership with Siemens has been essential. Siemens provides some of the funding Epstein used to develop DENSE. It also gave him access to their network of research universities.
Currently, more than 30 universities around the world have requested access to Cine DENSE software, and each one is applying DENSE in a different way. To cite just a few examples, at the Children’s Hospital of Pennsylvania researchers are using DENSE to assess cardiac function in children with congenital heart disease, at the Royal Brompton Hospital in London they are using DENSE to study heart failure, and at the University of California at San Francisco, they have taken it out of the heart and are using it to measure aortic stiffness.
“Even when you develop a really useful technology, there is only so much that one lab can do with it,” Epstein says. “Through our relationship with Siemens and their research sites, we are able to magnify its usefulness and multiply its applications. It’s a powerful way of making sure we realize the full potential of our technology to make a difference for patients.”