· MRI Looks at GAG to Evaluate Joint Disease
· iMRI Adds a Magnet to the OR
· 9.4T MRI Ready to Scan Human Brain
· Study to Assess CT Colonography with CAD

MRI Looks at GAG to Evaluate Joint Disease

A novel MRI technique has been shown to provide a noninvasive way to diagnose and monitor degenerative joint disease by mapping the concentration of glycosaminoglycans (GAG) in vivo, according to a recent report from Reuters Health. The method may also have useful applications in diagnosing disorders in a range of tissues, including cartilage, heart valves, and corneas.

Scientists conducted gagCEST MRI on a patellofemoral knee joint of a 30-year-old man with knee pain.

“The early monitoring of the GAG concentration will allow one to provide preventive diagnostics, as well as a tool for monitoring the efficacy of potential drug therapies,” Alexej Jerschow, PhD, at the New York University School of Medicine, told Reuters Health. “Measuring GAG concentrations in vivo will also allow us to better understand the mechanism of diseases.”

Delayed gadolinium-enhanced MRI contrast, which represents the current approach to mapping GAG, is hampered by the need for exogenous contrast material, poor reproducibility, and delayed diffusion into cartilage, Jerschow said. Long imaging time, lack of specificity, and the need for special hardware also limit other imaging technologies.

“The gagCEST method (chemical exchange dependent saturation transfer) of measuring GAG does not require the administration of exogenous contrast agent, and its only disadvantage is a somewhat reduced sensitivity compared to normal MRI images,” Jerschow said. “It is also relatively easy to implement on clinical scanners, and we therefore expect it to find widespread application.”

Cartilage was selected to demonstrate that gagCEST MRI is sensitive to GAG concentration variations “based on the labile protons residing on the GAGs.”

In one experiment, one side of a fresh bovine patella was submerged in a trypsin bath for two periods of 60 minutes, to release GAG from proteoglycan molecules. MRI images showed sequential decreases in signal correlated with depletion of GAG after each treatment, according to a report in the Proceedings of the National Academy of Sciences.

Additionally, the scientists conducted gagCEST MRI on a patellofemoral knee joint of a 30-year-old man who suffered from knee pain, which “displayed a clear demarcation of a cartilage lesion on the medial facet.”

In the future, GagCEST MRI is expected to be particularly useful for detecting intervertebral disk disease because “contrast agents do not diffuse into the nucleus of a disk,” Jerschow said. His team is planning to adapt the technique for the assessment of heart valves and corneas.

“GAGs in heart valves regulate water content, biomechanical function, and flexibility, [so] monitoring the concentration of GAG can give early warning signs of failure,” Jerschow said. “Similarly, GAG in corneas controls water content and flexibility, thereby providing favorable optical properties.”

—Elaine Sanchez

iMRI Adds a Magnet to the OR

Providing a huge advance in computer-assisted, image-guided technology, the intra-operative MRI has significantly affected the way pediatric and adult surgeries are performed for patients at select health care institutions.

Children’s Healthcare of Atlanta, for one, has picked up the unit to benefit its young patients who must undergo brain surgery. Installed in the hospital in September 2007 after 2 years of research and preparation, the iMRI provides real-time images to surgeons in the operating room, enabling them to see whether the entire tumor has been removed and whether they can remove the remaining tumor during the same surgery. As a result, the critical patient does not need to wait until the next day for a follow-up scan. Rather, surgeons can move freely from operating to visualizing tumors before, after, and during the procedure.

Children’s Healthcare of Atlanta is one of only four pediatric hospitals in the world to house an iMRI unit.

Allowing for continuous scanning of tumors, cysts, arteriovenous malformations, and other metabolic diseases, the iMRI utilizes the administration of enzyme and chemotherapeutic agent solutions. These solutions, mixed with dyes, are infused into the brain, where their distribution path is tracked in real time.

“The technology is ideal for pediatric patients as it eliminates the need to put children through multiple brain surgeries to remove a tumor when it can now be done in a single surgery,” said Carol Totten, an MRI technologist at the facility, which is now one of four pediatric hospitals in the world to house the unit. “Follow-up MRI in the department can be very intimidating for a child and often requires sedation, which has risks involved. These risks can be eliminated by doing the iMRI follow-up during surgery.”

Explaining the distinctions between MRI and iMRI, Totten noted that the latter is a mobile 1.5 Tesla unit that is mounted on a ceiling track that moves the magnet over the stationary patient. The table can be maneuvered up, down, or tilted so as to ensure that the patient remains the isocenter in the magnet, which is controlled by remote control. After 20 to 30 minutes, once the scan is complete, the magnet is moved back into a docking bay between the OR rooms.

Totten also described an extensive checklist of numerous additional steps the iMRI requires in comparison to a routine brain surgery. Not only must patients be adequately screened for metal, but also the operating room itself. “Most equipment in the OR is ferrous and not compatible with the magnet,” Totten said. “As a result, a full instrument count has to be done prior to the start of the surgery and again prior to any MR scanning.” Furthermore, certain equipment must be powered down and placed behind the 5 gauss line. Lights and other equipment must be powered down as well, with the exception of an anesthesiology monitor.

For 2 years, service coordinator and safety nurse Robin Guthrie and lead MR tech Trista Raymer visited sites and wrote various policies, procedures, and checklists in preparation for the implementation of the iMRI, which costs more than $5 million. Totten said all OR and ancillary staff were required to complete training and perform mock cases.

Their hard work paid off on November 2, 2007, when 7-year-old Zachary Link underwent surgery to resect a right occipital tumor. Executed by Roger Hudgins, MD, the hospital’s chief medical officer of neurosciences, the total resection was made possible by an initial iMRI scan that showed residual tumor. Since this first case, 26 surgeries have already been performed, with many more scheduled.

“I definitely think iMRI will become more widely used in the future,” Totten said. “It will improve on the accuracy of brain surgeries and as a result improve on the prognosis for patients that have been afflicted by brain tumors. Its uses may also extend into other general surgeries that would normally require MRI follow-up scans.”

—E. Sanchez

9.4T MRI Ready to Scan Human Brain

The University of Illinois at Chicago (UIC) currently plays host to the world’s most powerful medical MR device, a 9.4T system that recently completed safety trials with favorable results. The study, which clears the device for research use, was published in the November Journal of Magnetic Resonance Imaging.

“Published results from ultra-high field animal studies and human studies at 8T suggest that exposure to a 9.4T magnetic field does not pose a risk to human health,” said Ian Atkinson, PhD, assistant professor in the Center for MR Research at UIC. “Based on these data, we did not expect any significant health risks due to exposure to the 9.4T MR scanner to be uncovered.”

The safety trial involved 25 healthy volunteers who were exposed to the 9.4T scanner and a mock scanner with no magnetic field. No significant changes in heart rate, blood pressure, or respiratory rate were shown; the most frequently reported discomfort was light-headedness or vertigo. “No significant changes to vital signs or cognitive performance were found, and the data collected during human exposure to the 9.4T scanner were similar to those collected during human exposure to a mock MR scanner with no magnetic field,” Atkinson said.

Conventional MR scanners—currently FDA approved up to 8T—visualize water molecules to track biochemical processes. But the 9.4T system enables visualization of the sodium ions involved in those processes, allowing researchers to measure one of the brain’s key cellular functions.

“Clinically relevant research with the 9.4T MR scanner is currently focused on quantitative measurement of tissue sodium concentration and oxygen consumption,” Atkinson explained. “Ultimately, these data may be useful in diagnosing and monitoring a variety of brain diseases.”

Because the 9.4T system enables early visualization of cellular health, it may be possible to detect disease earlier, when treatment has the greatest level of benefit. One potential application is oncology—the device allows clinicians to see whether cells within a tumor are dying long before the tumor actually begins to shrink, eliminating the wait to see whether a tumor is shrinking in response to therapy.

The system also enables higher-quality imaging in a shorter span of time, Atkinson notes. “The increased field strength enables imaging of low-concentration metabolites to be performed with acquisition times that are acceptable for human subjects,” he said. “For example, a high-quality sodium image of the human brain can be acquired in less than 6 minutes using the 9.4T MR scanner. The same image would take several times longer at 1.5T or 3T. Longer acquisition times lead to problems with subject comfort, which leads to head movement and, ultimately, image artifacts.”

Atkinson and his team are now ready to take the 9.4T unit for a spin and see what it can do, with several studies currently in progress or under review. “We’re doing additional safety testing for both healthy and patient populations,” Atkinson said. “Other studies include imaging of oxygen consumption and noninvasive monitoring of brain tumor treatment with early recurrence detection.”

—Cat Vasko

Study to Assess CT Colonography with CAD

The American College of Radiology (ACR) Image Metrix recently announced a new multireader clinical study to determine whether the addition of colon CAD from iCAD Inc, Nashua, NH, enables radiologists interpreting CT colonography images to detect more cancers than they would without the use of the iCAD system.

“We’re going to use iCAD’s CT colonography CAD as though it were a second reader,” said Bruce Hillman, MD, ACR Image Metrix director of scientific affairs. “We’ll randomize the cases to remove recall bias, and we’ll have a sizable number of readers interpreting a sizable number of cases.”

ACR Image Metrix will work with iCAD to develop and execute a clinical study as part of the FDA approval process for the company’s colon CAD software. The timing couldn’t be better: the results of the ACR Imaging Network’s National CT Colonography Trial recently indicated that CT colonography is a viable alternative to more invasive optical colonoscopy, the current clinical standard.

Additionally, Rep Barbara Cubin (R-Wyo) recently introduced a bill calling for mandatory Medicare reimbursement to providers of CT colonography. The Virtual Screening for Cancer Act would also require that CT colonography be included in the “Welcome to Medicare” program, which waives the fees associated with mammography and colonoscopy screenings for Medicare beneficiaries completed within the first 6 months of enrollment.

“Only around 35% of people follow the screening recommendations for colon cancer,” Hillman said. “There are a number of reasons why that’s true. The one that’s the most prepossessing is the combination of the preparation and the lost time for work. Our hope is that CT colonography, particularly with CAD, may offer an alternative that would increase screening compliance.” Although the preparation for CT colonography remains the same, patients undergoing the new procedure don’t require sedation, and thus lose less time. Optical colonoscopy generally requires a full day off work.

Currently, Hillman says, the study is still in the nascent stage: “We’re in the process of finishing up the protocol and working with the FDA to get their agreement that this is a suitable design,” he said. “We’ll be looking for readers next. We’re looking for general radiologists who have some experience in CT colonography and who do it in their practices.”

Though the study isn’t intended to measure the efficacy of CAD for CT colonography in general, Hillman still anticipates that the results will be of interest to the radiology community. “Of course we’re interested generally in whether CAD improves sensitivity, but in this specific case this obviously has to do with registration of the product with the FDA,” he said. “It’s not a general test of CAD, but it will provide valuable information.”

Hillman has been working with the study’s principal investigator, Abraham Dachman, MD, professor of radiology at the University of Chicago Medical Center, and Nancy Obuchowski, PhD, of the Cleveland Clinic, to develop the protocol. Now all that remains is finding a suitable number of radiologists to interpret the studies.

“We’re very excited to work with iCAD,” Hillman noted. “This is a company that clearly has a very good vision of what CAD can potentially do for a radiology practice. We’re a relatively new company, founded a little over a year ago, so this is a great opportunity for us.”

—C. Vasko