Giving New Dimension to Diagnostic Imaging

October 20, 2009 — As recently as a decade ago, physicians ordering a magnetic resonance imaging (MRI) scan of a patient's brain typically reviewed results rendered in only two dimensions. Results were viewed on a series of films held up to light-boxes, with each film representing sets of half-centimeter-thick 'slices' of the brain. Important details of tumors or other maladies not adequately captured in any of these relatively thick slices could go unnoticed, and untreated.

Although they didn't yet know it, what physicians needed was the ability to review MRI results in three dimensions, representing thinner slices and viewable from any orientation. Happily, today — to borrow a common marketing phrase — 'There's an app for that.'

'Just as Apple® does with the iPhone™ and apps,' says James R. Brookeman, Ph.D., 'major MRI manufacturers like Siemens have developed software tools and research partnerships that allow groups like the University of Virginia to essentially write applications for MRI scanners.'

Brookeman and John P. Mugler III, Ph.D., professors of radiology and biomedical engineering at U.Va., have done just that. The researchers' innovative pulse sequences, which essentially serve as instructions that tell MRI machines how to operate and collect data, have been implemented in the machines of major industry MRI equipment manufacturers.

Mugler and Brookeman's leading technology in terms of commercial and societal impact thus far is a fast, 3-D pulse sequence technique referred to as MP-RAGE (Magnetization-Prepared Rapid Gradient Echo).

Prior to MP-RAGE, early 3-D MRI techniques required approximately 10 minutes to obtain enough data to render 3-D images with sufficient detail for many important applications. Consequently, these early techniques proved impractical, and 2-D acquisitions remained the norm.

'With conventional MR imaging methods, the patient has to remain still in order for the images to be clear,' Brookeman says. 'But after 10 minutes, even healthy people have to move.'

'We worked to make 3-D MRI technology faster, with higher resolution and other important improvements, making it possible to acquire 3-D images with desirable contrast on the order of five minutes,' Mugler adds. 'Suddenly, it became practical to take 3-D images.'

The researchers' improved pulse sequences yielded images that were more detailed and thus more likely than their predecessors to reveal subtle abnormalities, providing for earlier and more accurate diagnoses. And unlike 2-D acquisitions, 3-D MP-RAGE produces detailed images that can be viewed from any orientation on modern computer workstations.

Although the U.Va. Patent Foundation received an issued patent on this technology in 1993, it wasn't until some years later that companies were first willing to adopt MP-RAGE for their scanners. Back then, Brookeman says, MRI manufacturers were skeptical of the technology, fearing information overload. In contrast to the 15 or so half-centimeter-thick slices rendered by traditional 2-D techniques, MP-RAGE rendered the equivalent of 128 one-millimeter-thick slices of the brain for each of the three dimensions. Even one experienced neuro-radiologist told the researchers at the time, 'That's too many slices!'

'The field just wasn't ready for routine 3-D imaging at that time,' Brookeman explains. 'For our technology to be adopted, two things had to happen: First, computers had to develop enough to support 3-D functionality, and second, those who had grown up playing with Atari® and Nintendo® had to become doctors.'

The Patent Foundation has since licensed the patent rights to Siemens AG and Koninklijke Philips Electronics NV (Philips). As a result, MP-RAGE is now implemented in MRI scanners in hospitals and research institutions worldwide.

The widespread implementation of the MP-RAGE technique — and its use in such studies as the Alzheimer's Disease Neuroimaging Initiative, a pioneering series of trials designed to record an array of brain measurements of Alzheimer's patients — have helped to establish MP-RAGE as a very useful primary standard in 3-D magnetic resonance imaging.

In honor of their groundbreaking work in MRI techniques over the past two decades, the U.Va. Patent Foundation named Mugler and Brookeman the 2009 Edlich-Henderson Inventors of the Year. The highest honor bestowed by the Patent Foundation, the annual Edlich-Henderson Inventor of the Year award recognizes an inventor or team of inventors whose research discoveries have proven to be of notable value to society.

'Through their incredible talent and foresight, Drs. Mugler and Brookeman have made an indelible impact on the field of magnetic resonance imaging,' says Miette H. Michie, interim executive director and CEO of the U.Va. Patent Foundation. 'We are proud to recognize these dedicated researchers as the 2009 Edlich-Henderson Inventors of the Year and congratulate them on their continued success.'

In addition to MP-RAGE, Mugler, Brookeman and colleagues have developed several other innovative MRI techniques. The researchers' most recent cutting-edge work with hyperpolarized noble gases as MRI contrast agents for the lungs is currently being explored with colleagues at U.Va. and in clinical trials by a major manufacturer.

Mugler and Brookeman partly credit the University's collaborative clinician–scientist atmosphere and research capabilities, such as a research agreement with Siemens AG, for their success. 'This type of research couldn't happen everywhere,' Mugler says. 'With all successful new technologies, it's not just having the idea; it's also having the right environment in which to practice.'

Mugler and Brookeman have received research funding from the National Institutes of Health, Virginia's Commonwealth Technology Research Fund, Siemens AG and Nycomed Amersham Imaging (since acquired by General Electric Company).

Mugler and Brookeman were honored April 13 at the Patent Foundation's annual awards banquet, which also celebrated those U.Va. inventors who received U.S. patents and copyrights in 2008.