Method for measuring cerebral blood flow in premature infants at the bedside

Researchers have discovered a new, noninvasive way to measure blood flow in the brains of newborns at the bedside — a method that could improve diagnosis and treatment across medicine, a Michigan Medicine study shows.

As the fetus develops, the baby’s lungs fill with fluid, and oxygen comes directly from the placenta. It is oxygen blood bypasses the lungs to reach the rest of the body through a vessel called the ductus arteriosus.

After birth, babies breathe easily, and the ductus arteriosus usually closes within a few days. But in almost 65% of premature newborns, the vessel does not close. This condition, called patent ductus arteriosus, or PDA, is shifting bleeding into an abnormal pathway that can strain the heart, clog the lungs, and steal blood and oxygen from the newborn’s brain and other organs.

Physicians must decide whether to attempt to close the PDA with medication or an implantable device, both of which have risks. Accurate measurement of blood flow in the newborn’s organs can help with this important decision. But there’s a problem: There’s no real blood flow measurement that works practically for clinical use, said Jonathan Rubin, MD, PhD, professor emeritus of radiology at the University of Michigan Medical School.

“This decision of whether to close a patent ductus arteriosus has been a problem in neonatology for at least 30 years,” Rubin said. “The debate really hinges on how blood flow has changed, complicated by a history of unreliable data, which is why measuring blood flow is so important.”

To solve this problem, Rubin and a team of researchers at Michigan Medicine developed a real-time ultrasound color flow technique that relies on a 3D sample to measure blood flow. They tested this method on 10 healthy full-term infants, obtaining measurements of total cerebral blood flow that closely matched those using more invasive or technically challenging methods. The results are published in Ultrasound in Medicine and Biology.

“With our method, we can scan babies in their parents’ arms without pain or danger, which no one has done before,” said Rubin, lead author of the paper.

“There are several other methods of measuring blood flow, but they are cumbersome and often require intravenous contrast agents, sedated or restrained children in the scanner. But premature babies are in incubators; they are fragile and these methods can be dangerous. This method of ultrasound can be used routinely in neonatal intensive care unitswhich can significantly affect outcomes for premature babies with this condition.”

How it works

There are many surrogate methods used in place of actual bleeding, such as bleeding velocity. But for real blood flow, it is necessary to know the speed of blood depending on the area it covers.

Like traffic, Rubin says, it doesn’t help to know how fast cars are going if you don’t know how many cars are on the road.

The technique, developed by Rubin and his colleagues, measures actual blood flow by calculating the flow of blood across a surface using ultrasound beams. The color image is shot in 3D.

“This method does not require contrast agents, measurements can be made in real time, and can be repeated as needed because the method is completely benign,” Rubin said.

Apps that change the game

Using a non-invasive, real-time measurement of blood flow, researchers say the technique could be used to address problems with blood flow to organs, including the brain, liver and kidneys, in many diseases, including congestive heart failuresepsis and shock.

“In the neonatal intensive care unit, we must make assumptions every day based on indirect measurements to determine how our treatments affect blood flow to the organs of critically ill newborns,” said Gary Weiner, MD, clinical assistant professor of pediatrics at the School of Medicine. UM and medical director of the Brandon Neonatal Intensive Care Unit at UM Health CS Mott Children’s Hospital.

“Having a safe, fast and accurate bedside tool that allows us to measure true blood flow could be a game changer.”

But it doesn’t stop at children. Rubin says the technique can be applied almost anywhere that ultrasound can detect, and is used for anything from assessing the need for organ transplants to detecting problems during surgical procedures.

“Clinicians perform all sorts of maneuvers to alter blood flow measurements, and the assessments are always semi-quantitative or make unwarranted assumptions about the nature of the blood flow,” he said. “They can use Doppler ultrasound to determine the velocity, but then just palpate the vessel to feel if there is flow. There is great potential for this application in diagnostic medicine because flow everywhere. We have already used this method to measure flows in the fetal umbilical cord before birth and in the adult liver. The method is being evaluated by several companies for inclusion in standard clinical ultrasound scanners.”