Biopsy Breakthrough

St. Jude researchers develop non-invasive alternative to liver biopsies

By Michael Waddell

Patients at St. Jude Children’s Research Hospital no longer have to experience painful needle liver biopsies thanks to a new procedure developed by the hospital’s researchers with the help of a former University of Memphis student.

The 12-year research effort has been led by Dr. Claudia Hillenbrand at St. Jude and has involved the hospital’s multidisciplinary team along with former student and now Dr. Aaryani Sajja.

“We’re happy that we don’t have to do (needle) biopsies anymore at St. Jude just for the sake of determining a liver iron value,” Hillenbrand said. “We have replaced an invasive and painful clinical test with a non-invasive imaging test. And because it’s non-invasive, it can be repeated often.”

St. Jude treats children with catastrophic diseases, including cancer and sickle cell disease.

Dr. Aaryani Sajja, left, a postdoctoral research associate in the Department of Diagnostic Imaging at St. Jude Children’s Research Hospital, and Dr. Claudia Hillenbrand, an associate member of the department, developed a non-invasive test to reduce the number of liver biopsies patients need. (Daily News/Houston Cofield)

“Many of these children had a stroke in the early part of their life, and it’s a very devastating outcome after a stroke,” Hillenbrand said. “For a long time, hematologists treated at-risk sickle cell patients with monthly blood transfusions to alleviate the anemia with oxygen-rich blood to prevent strokes.”

But the body has no way of getting rid of additional iron put into their systems through the transfusions. Much of the iron goes into the liver, and eventually will destroy liver tissue through fibrosis, cirrhosis or cancer. In the past, the gold standard for measuring iron levels in the body was by taking a liver biopsy with a needle.

“It’s invasive, it hurts, and it has other risks, and patients really did not want to do it,” Hillenbrand said.

St. Jude began doing iron overload research back in 2005 by taking liver biopsies of patients with chronic transfusions as well as taking MRI images of the liver.

“If you have a lot of iron, the liver becomes darker and darker,” Hillenbrand said. “If you have no iron, it will appear like other muscles in your back. The contrast changes depending on the amount of iron in your liver.”

Over the next several years, researchers, clinicians and statisticians came up with a way to quantify the contrast and then correlated it with the liver biopsy outcomes. The departments that collaborated on the development of the MRI method included Hematology (led by clinical principal investigator Dr. Jane Hankins, who was also heavily involved in the research), Diagnostic Imaging, Biostatistics, and Pathology.

Those early tests worked for many patients, but not for those who were dramatically overloaded with iron, so St. Jude applied for an National Institutes of Health grant to complete further research in that area.

Sajja, who was a student at the U of M in the mid- to late 2000s, came on board at that point thanks to funding from the grant. Her master’s degree thesis was centered around all aspects of making the process of iron quantification and analysis more accurate, as well as improving work flow.

Inside the diagnostic imaging lab used to engineer equipment for liver research at St. Jude Children’s Research Hospital. (Daily News/Houston Cofield)

Students from the U of M and UT Memphis have the opportunity to work with faculty at St. Jude on projects related to their interests.

“Aaryani is a very special student,” said Dr. Eugene Eckstein, U of M professor, chairman of the Department of Biomedical Engineering and research adviser. “The long-term effort and current clinical study for this measurement to see how to calibrate it with various MRI machines pushes the whole method of biopsies forward.”

Eckstein stresses the fact that students get to participate in a team effort, allowing them to handle a piece of the overall team project.

“With the earlier MRI sequence we are using, they work best in breath-hold conditions because there will be no motion artifacts that can impact the MRI images (with blurriness),” Sajja said. “If patients are sedated or unable to hold their breath, we get motion artifacts. This new technique is less sensitive to motion.

“I did a study comparing iron measurements, both techniques, and showed that the new technique can also be used for pediatric patients who cannot hold their breath, so now with that sequence the patients need not hold their breath.”

Right now, there are 41 patients at St. Jude with biopsy and MRI measurements, and researchers are doing the final analysis of the NIH-funded study. The breakthrough will eventually be used on adults as well as children.

“This new technique can be applied to any patient who requires iron overload analysis; it’s not restricted to pediatrics,” said Sajja, who went on to complete her doctorate work at St. Jude and graduated in August. She is now finishing up several projects for her post-doctoral phase.

The human component was an important part of the breakthrough, according to Hillenbrand: “The unique combination of scientists we have here at St. Jude, the collaboration with the hematologists and radiologists, and the amazing commitment of the patients who were willing to enroll in the study.”