Radiology

The 11 hospitals in the consortium conduct clinical trials for anticancer drugs; the Neuroimaging Center ensures that neuroimaging studies and related quality-assurance and data analysis are standard among all the institutions. The NIC also enables the consortium to incorporate imaging endpoints and to develop correlative imaging research plans related to the novel therapeutic interventions under study.

Poussaint directs a multi-disciplinary team of radiologists, computer scientists, physicists, data engineers, and other researchers, who extensively analyze the images generated in the clinical trials (typically through MRI and PET). They generate data from the imaging sequences to identify possible markers of therapeutic response and to assess whether a given treatment is working. Poussaint also works with the neuroradiologists at each of the participating institutions as well as representatives of the Clinical Research Program at Children's. "These non-invasive techniques can help us to understand the mechanisms by which the tumors respond to treatment."

The Neuroimaging Center is funded by a grant from NIH. Poussaint is associate professor of radiology, coordinator of Neurooncologic Imaging and Director of the Pediatric Neuroradiology Fellowship.

The Neuroimaging Center Team: Richard Robertson, M.D., Robert V. Mulkern, Ph.D., Sridhar Vajapeyam, Ph.D., Frederic Fahey, Ph.D., S. Ted Treves, M.D., and Thinzar Nyun, M.D., all of the Children's Hospital Boston radiology department; Stavroula Osganian, M.D., Sc.D., M.P.H., Director, clinical research program, Children's Hospital Boston .
Information Technology: John Speziale and Mukesh Rana both of Children's Hospital Boston .
Research Coordinator: Maureen Clark, MS, Clinical Research Program, Children's Hospital Boston.

Voss is developing an animal model for neuroblastoma, creating and testing targeted contrast agents that can be readily imaged with a small animal nuclear medicine camera or a small bore animal magnet. His goal is to discover tissuespecific contrast agents that will make the imaging of neuroblastoma much more specific and precise. Neuroblastoma is a perfect model system for this work, said Voss, noting that knowledge gained through his research should be applicable to other types of tumors in children. He is also collaborating with the pediatric oncologists at Children's and the Dana-Farber Cancer Institute to develop a framework within which diagnostic and follow-up imaging can be systemically evaluated so that the best strategies are used.

"What we would like to do is be more formal in our approach and in our data collection, so that in the end, instead of having to go through mountains of old films, we can go to our database and readily review the studies from the last 50 patients," said Voss, an assistant professor of radiology.

"This will be particularly important as we introduce newer technologies, such as PET scanning, into routine clinical practice," he noted. "We have a unique opportunity, and an obligation, to determine how these technologies should be utilized to provide the best patient care."

"As I look 5 to 10 years into the future," said Voss, "my goal is to be involved in integrating the discoveries made at the bench with our clinical efforts. This will require establishing an infrastructure that links basic research and development with the clinical implementation of novel imaging agents for pediatric radiology."

Mentors for Voss's KO8 Grant: George A. Taylor, M.D., Alan B. Packard, Ph.D., and Robert V. Mulkern, Ph.D., all of CHB.

Soy formula contains large amounts of isoflavones, which act as estrogens in the laboratory. The National Institute of Environmental Health Sciences (NIEHS), which is funding the study with a $575,000 grant, theorizes that a diet of soy formula might prolong the effect of maternal hormones or interfere with hormonal homeostasis in the newborn.

Working closely with experts in the Clinical Research Center at Children's, Estroff and her colleagues are using ultrasonography to measure the size and growth of estrogensensitive organs in 156 healthy, full-term infants (96 girls and 60 boys) recruited from the well-newborn nursery at Brigham and Women's Hospital (BWH) and from clinical areas at Children's. Because these organs (breasts, thyroid, thymus, uterus, ovaries, prostate, and testicles) are not typically imaged in full-term infants, Estroff's research will establish a protocol for a later and larger study to evaluate the biological response of infants to soy formula prepared with and without isoflavones. In the pilot study at Children's, the babies are divided into three groups based on their diet (breast milk, cow's milk formula, or soy formula). They'll undergo as many as four ultrasound exams at various points between birth and their first birthday. Concurrent pilot studies at Children's Hospital of Philadelphia will utilize physical exams to measure organ size and development, along with biochemical tests to assess hormone levels.

Estroff said she hopes to participate when NIEHS undertakes a full clinical trial. She is a clinical associate professor of radiology at Harvard Medical School and co-director of fetal imaging in the radiology department. "Participating in a multi-institutional, multi-centered trial has been fascinating, from getting through six institutional review boards to screening six or seven adorable babies each week," Estroff said. "Conducting clinical research is an exceptional privilege."

Co-Investigators: Jane Share, M.D., CHB; Richard B. Parad, M.D., M.P.H., Carol Benson, M.D., Lise Johnson, M.D., and Kathleen Howard, R.N., all of BWH. Julie Hart, R.N., CHB.

"You need a technique that's quick and relatively non-invasive," Paltiel explained, noting that a delayed or incorrect diagnosis of testicular torsion can result in the loss of the testicle and subsequent subfertility. "My hope is to improve our discrimination between normal and compromised blood flow."

Working with rabbits, Paltiel and her colleagues are using a balloon catheter to progressively constrict the flow of blood from the spermatic cord to the testicle. Then they image flow with conventional color Doppler ultrasound methods, followed by pulse-inversion ultrasound with IV infusion of a microbubble contrast agent (encapsulated bubbles of gas smaller than red blood cells). Once a steady-state infusion has been achieved, a high-energy ultrasound pulse is delivered into the scrotum to destroy the bubbles within the testes. The researchers then perform low-energy scanning of the scrotum while the intratesticular microbubbles are refreshed. Next, they correlate the accuracy of flow determination from the ultrasound images, both quantitatively and qualitatively, to that of radio-labeled microspheres, an experimental gold standard. Paltiel, an associate professor of radiology, said her experimental techniques could help assess blood flow in other organs. "There are many potential applications," she said, "for example, in assessing perfusion after kidney or liver transplants, in the brain of premature infants, and in suspected ovarian torsion."

Co-Principal Investigators: Anthony Atala, M.D., and George A. Taylor, M.D., both of CHB. Co-Investigators: Carol E. Barnewolt, M.D., and David Zurakowski, Ph.D., both of CHB. Consultants: Barry Goldberg, M.D., and Patrick O'Kane, M.D., both of Thomas Jefferson University, Philadelphia; and Ferdinand Frauscher, M.D., of Universitaetsklinik fuer Radiologie II in Innsbruck, Austria.

"MRI depicts more fetal anatomy, and it can be very helpful when ultrasound doesn't provide enough information," said Ward, an instructor in radiology who has enrolled 30 of the desired 50 pregnant women in her study. She expects to find that MRI will provide additional information about fetal chest masses, which can impair normal lung development and pose life-threatening complications. Ward and her colleagues will evaluate the impact of prenatal MRI on diagnostic accuracy, clinical decision-making, performance of therapeutic fetal interventions, the timing or method of birth, and any medical or surgical intervention at delivery. Shtern, the department's director of research, was instrumental in helping to assemble a team of mentors and co-investigators from a variety of disciplines, Ward said.

The GERRAF fellowship, which is sponsored by GE Medical Systems and the Association of University Radiologists, is awarded annually to three or four junior faculty members nationwide. It is designed to "strengthen the research interest of radiologist-investigators by broadening their opportunities for continuing scholarship" and to foster original "clinical and health-services research in technology assessment, health and economic outcome methods, and decision analysis," according to GE Medical Systems. Recipients are selected based on the "strength of their commitment to research careers; the quality, creativity, and vision of their proposed research projects; and the continuing support provided by their institutions."

To fulfill the educational component of her fellowship, Ward is taking epidemiology and biostatistics courses toward a Master of Public Health degree from the Harvard School of Public Health.

Co-Investigators in Radiology: Carol E. Barnewolt, M.D., and Judy A. Estroff, M.D., both of CHB; Deborah Levine, M.D., and Tejas Mehta, M.D., both of BIDMC. Neonatology: Richard Parad, M.D., BWH, and Lawrence Rhein, M.D., CHB. Fetal Surgery: Russell Jennings, M.D., and Luanne Nemes, R.N., M.S., P.N.P., both of CHB. Health Services and Technology Assessment: G. Scott Gazelle, M.D., M.P.H., Ph.D., MGH Institute for Technology Assessment; Donald A. Goldmann, M.D., CHB; Benjamin Littenberg, M.D., University of Vermont; and Bruce Hillman, M.D., University of Virginia. Perinatology: Jodi Abbott, M.D., BIDMC; Susan Ponkey, M.D., BWH; and Lucy Bayer-Zwirello, M.D., Bay State Medical Center. Genetics: Mira Irons, M.D., CHB.