Heroes in Proving the Value of Imaging: Part 3

Gretchen Birbeck, MD Heroes in Proving the Value of Imaging is an occasional series about advocates for the profession who are working to enhance radiology through research, governmental affairs, humanitarian efforts, and more. In Part 3, ImagingBiz speaks with Gretchen Birbeck, MD, on using MRI to study malaria in Malawi. The list of breakthrough medical insights made possible, in part, through the use of donated imaging technology is gratifyingly long—and growing—thanks to the continuing generosity of the heroes of radiology: those with a passion for philanthropy. A prime example comes from the southern African nation of Malawi, where the Blantyre Malaria Project is underway. Researchers involved in that program have, over the past two decades, greatly enhanced science’s understanding of the malarial mechanisms responsible for killing 4 million people per year, worldwide, and leaving millions more in varying states of debilitation.

"MRI is opening up for us whole new avenues for investigating the mechanisms of injury that lead a child from being acutely ill to waking up and doing really well, versus waking up but not doing well neurologically, versus dying. MRI is transforming the questions that we can ask and increasing the speed at which we can answer them."
-Gretchen Birbeck, MD

Among that project’s most intriguing findings of late are those made by Gretchen Birbeck, MD, MPH, DTMH, associate professor and director of the International Neurologic and Psychiatric Epidemiology Program at Michigan State University (MSU) in East Lansing. “I’m currently involved in a study of Malawian children who are cerebral-malaria survivors, and imaging technology figures prominently in that effort,” she says. Nearly one-third of the study’s children have a degree of long-term neurological impairment resulting from cerebral malaria. “Some of the young survivors exhibit severe developmental delay, deficits consistent with cerebral palsy that include motor-delay problems, loss of language function, and coordination and gait issues. In addition, there is a very high rate of behavioral problems, chiefly an attention-deficit/hyperactivity-disorder syndrome that occurs three to five months after recovery from cerebral malaria,” Birbeck reports. These and other discoveries have led Birbeck to conclude that the next step should be to explore whether children being treated for malaria might benefit from concurrent treatment with neuroprotective agents. She says, “The question that needs to be answered is this: Are there existing drugs, now being used for other neurologic conditions, that could be put into play during the treatment for malaria itself in order to protect the brain from injury?” Lost Without It The answer, if there is one, is more than likely to be uncovered with help from the Ovation MRI scanner that GE Healthcare donated to the Blantyre Malaria Project through the auspices of MSU. Birbeck has been using the 0.35T unit regularly since its installation about a year ago at Queen Elizabeth Central Hospital in Blantyre, Malawi, where she works for six months of each year. This gift has proven pivotal to Birbeck’s research. “Without it, I (and others studying cerebral malaria among Malawian children) would know much less about the impact of the disease on survivors than currently is the case,” she says. “Moreover, we would be at very high risk of going down false routes of investigation. Our MRI scanner is giving us a great deal of guidance in terms of comorbid conditions being encountered. It’s enabling us to step back and make sure that the deficits we’re seeing in survivors are indeed attributable to cerebral malaria, and not actually the result of some prior injury or previous insult.” Birbeck continues, “MRI is also opening up for us whole new avenues for investigating the mechanisms of injury that lead a child from being acutely ill to waking up and doing really well, versus waking up but not doing well neurologically, versus dying. MRI is transforming the questions that we can ask and increasing the speed at which we can answer them.” Related Study Birbeck’s study cohort consists of 128 pediatric cerebral-malaria survivors plus 313 children who have never contracted the disease. The male–female ratio is about evenly split, and at the time of enrollment in the study, participants ranged in age from 9 months to 11 years. They are slated to be followed by Birbeck until February 2010. MRI scans are also being performed for young patients in a separate (but related) inquiry focused on cerebral malaria during its acute stage. Birbeck is involved with this study as well, but not as principal investigator (that role belongs to MSU’s Terrie Taylor, DO, founder and director of the Blantyre Malaria Project). Unfortunately, some of the children with acute-stage cerebral malaria die before researchers can finish making observations. “If the parents consent, autopsy studies are then performed,” Birbeck says. “It’s hoped that we’ll be able to correlate our MRI data with those from the clinical pathologic autopsies, as well as with the acute and chronic neurologic outcomes in survivors.” Wish Fulfilled Prior to the arrival of the MRI scanner, the Blantyre Malaria Project relied heavily on autopsy studies of this very sort to illuminate cerebral malaria’s effects on the brain. By the mid-2000s, though, “We began to appreciate the limitations of what we could learn through autopsies, since they told us nothing about the children who survived or about their structural anatomy,” Birbeck says. Something more was needed, and that was MRI. Accordingly, Taylor approached the chair of MSU’s radiology department, E. James Potchen, MD, to request a scanner. Potchen, in turn, asked GE if the company might be willing to contribute the desired equipment—a plea made easier by the longstanding collaborative relationship between the vendor and MSU. For its part, GE was quick to recognize the worthiness of the research conducted by the Blantyre Malaria Project and agreed to fulfill the research team’s wish. GE decided to enlarge its gift by also handling, at no cost, the installation and startup of the donated scanner. MSU’s radiology department made several important contributions of its own in support of the new MRI, including ongoing IT services for transmission and archiving of acquired images from Malawi, Birbeck indicates. Growing Archive The images are produced by Malawian personnel who received training from MSU radiologic technologists in basic scanning techniques and in ensuring patient safety. “Unfortunately, our Malawian technologists are not yet skilled enough to be able to add new sequences or make changes to the programming that’s involved, so we’re addressing this with further training,” Birbeck says. Following acquisition, images are reviewed on-site by project researchers and Malawian clinicians for findings that might have relevance to the immediate care of the patient. Assisting in this process is MSU-trained Sam Kampondeni, MD, a radiologist in the department of radiology at the University of Malawi’s College of Medicine in Blantyre. His expertise in neuroradiology and intimate familiarity with the Ovation MRI make him an ideal interpreter of images of cerebral-malaria survivors’ brain function, Birbeck says. Approximately 300 sets of MRI images have been acquired and interpreted so far. All have been transmitted via satellite to MSU for further review (a task headed by Michael J. Potchen, MD, associate professor of radiology). Ratcheting Up Until recently, Birbeck and Taylor were virtually the only researchers at Queen Elizabeth Central Hospital making use of the donated MRI scanner. That is about to change. “A number of others are excitedly lining up to utilize this technology for their own projects,” Birbeck says. This could pose a problem, however: As more colleagues take turns with the system, Birbeck’s own share of time on it will decrease. “Access will likely be more limited; that is true,” she laments. “We anticipated this, though, which is one of the reasons why we have in place an MRI steering committee whose job it will be to prioritize researchers’ use of the magnet.” Access to the scanner is further constrained by the fact that it is not exclusively employed in scientific study. “Only about a third of the magnet’s time is dedicated to research,” Birbeck notes. “The other two-thirds of the time, it’s available for clinical care and for training.” Queen Elizabeth Central Hospital is a teaching hospital that provides care to all Malawians at no charge. “The nearest available MRI, after ours, is in South Africa, about 600 miles away,” Birbeck explains. To maximize the potential of the donated MRI, the support team at MSU is developing what Birbeck describes as “a very structured, drop-down–menu approach to systematic scoring of the MRI findings. This will allow for a much easier quantitative analysis of images than would be possible with a text-based interpretation alone. We’re also implementing protocols for acquisition of volumetric studies.” Since Birbeck has only used the MRI to image sick children, she believes that it will be crucial now to obtain normative data “so that we can better understand whether the abnormalities seen are part of the normal range of findings for these children or if, indeed, there are predisposing factors that occur in cerebral-malaria patients.” She and her research colleagues recently submitted a grant proposal to fund just such an endeavor to the US National Institutes of Health through the National Institute of Neurological Disorders and Stroke (NINDS). Birbeck’s group is also busy developing a protocol for a clinical trial of neuroprotective agents for pediatric cerebral-malaria survivors. The protocol will be described in a proposal expected to be in the hands of NINDS for consideration sometime this fall, she says. Making a Difference Noble though the efforts of the Blantyre Malaria Project may be, some critics argue that installing a single MRI scanner in an underdeveloped nation like Malawi cannot possibly make much of a difference to either clinical care or scientific research. Birbeck concedes that they might have a point, but only with regard to clinical care. “Malawi is a nation of approximately 12 million people, and even if that lone MRI operated 24/7, it would have very minimal effect clinically,” she says. “It would amount to a drop in the bucket.” On the other hand, she says, “Queen Elizabeth Central Hospital has one of southern Africa’s most powerful research infrastructures for studying tropical diseases—top-of-the-line laboratory facilities for ongoing studies into conditions that have never before been imaged. Even with one MRI scanner, it is possible in this particular setting, to learn a great deal, because the amount of scientific data that can be acquired and managed is enormous.”