No sponge left behind: tags for surgical equipment A simple, easy-to-implement technology could prevent the debilitating injuries that can occur when organs are damaged by surgical tools left in the body.

Items left behind in patients after surgery can have an enormous personal cost when organs and tissues are damaged. Surgical sponges are among the worst offenders – difficult to see in post-surgical X-rays and yet capable of causing holes when the intestines grow around them, for example. These rare cases, estimated around one in 3,000 surgeries that carry a risk, add up to around $1.5 billion in costs per year.

X-ray image showing scissors inside a cadaver
Marentis took about 2,800 X-ray images of the tag to train and test the software.

The current method of accounting for surgical tools involves counting them before and after surgery and performing an X-ray if there’s a mismatch. Without the metal bands inside them, the gauze sponges wouldn’t appear at all, but they are still difficult to see. A new, unmistakeable tag could change that – and its signature is so clear that computers can also detect it.

The tag, which is about the same size and shape as an acetaminophen tablet, contains four metal spheres, arranged at the points of a tetrahedron. This simple shape can be recognized by the computer no matter how it is turned. With human radiologists having a first look at the X-rays and then comparing their findings with a computer, over 98 percent of the tags can be seen. In contrast, as many as half of surgical sponges are missed in X-rays today.

The research team has formed the company Kalyspo, and they are building partnerships with surgical sponge manufacturers and hospitals in an effort to make the tag and software a standard part of surgical procedures, keeping patients safer.

Nikolaos Chronis, an associate professor of mechanical engineering at U-M, led the development of the tag. Theodore Marentis, then a radiology resident at U-M, identified the need for such a tag and worked with Chronis to develop and test it. Lubomir Hadjiyski, a professor of radiology at U-M, led the development of the software that locates the tags.

Chronis is also an associate professor of biomedical engineering and macromolecular science and engineering. Marentis is now a radiologist at the Mercy Medical Center in Mt. Shasta, CA.


Reading cancer’s chemical clues A nanoparticle-assisted optical imaging technique could one day read the chemical makeup of a tumor.


A tumor’s chemical makeup holds valuable clues about how to fight it. But today, it’s difficult or impossible to examine the chemistry inside a tumor. A nanoparticle-assisted optical imaging technique could one day enable doctors to read those clues in real time, providing a non-invasive precision medicine approach that could match treatment to individual tumors.

“Tumors vary widely from one patient to the next, so the more we know about them, the more effective our treatments become. This is especially important with chemotherapy because of its high cost and severe side effects,” said Xueding Wang, a University of Michigan professor of biomedical engineering who helped develop the technique. “This could form the basis of precision medicine treatments that offer better outcomes, fewer side effects and lower costs.”

Most of us are working in the dark with regard to tumor imaging. -Xueding Wang

Doctors already know, for example, that some treatments don’t work on acidic tumors while others are ineffective against tumors that have low oxygen levels. If they know the chemical makeup of a given tumor, they can start the right treatment immediately, then keep close tabs on its effectiveness over time.

In a recent paper, U-M researchers successfully used the process to get a three-dimensional view of the pH level inside tumors in mice, and they believe that they will also be able to use it to read a variety of other important chemical markers inside cancers. The new technology is detailed in a paper published September 7 in Nature Communication.

Images of a mouse tumor obtained with the new technique. Row A shows the presence of the nanoparticle itself, in blue. Row B shows the pH of the tumor. Image C shows oxygen saturation and image D shows hemoglobin concentration. Photo courtesy of Janggun Jo, Michigan Engineering

“Most of us are working in the dark with regard to tumor imaging. There are very few cases where we can study the chemistry of a tumor,” said Wang. ”We hope to change that with this technology, which offers a spatially detailed, real-time look at the chemistry inside a tumor, even when it’s deep inside the body.”

The technique uses a two-part system, starting with a purpose-built, injectable nanoparticle that’s absorbed only by cancerous cells. The particles were loaded with a marker dye that changes color in response to the tumor’s pH to measure acidity.

Wang and Raoul Kopelman, the Richard Smalley Distinguished University Professor of Chemistry, Physics and Applied Physics, made the nanoparticles small enough to fit through tiny cracks in the walls of cancer cells called fenestrations—imperfections that form because cancer cells grow so quickly. They then coated the particles with protein fragments, or peptides, that are attracted to cancerous cells.

“The peptides on the particle are like tugboats guiding an ocean liner,” Kopelman explained.

The particles were injected into mice, where they infiltrated the cancerous cells and the pH-sensitive dye did its work. Next, the team read the dye by flashing pulses of laser light into the tumor from outside the mouse’s body and recording the ultrasound signal that’s reflected back.

Chang Lee, Ph.D., examines the pH-sensitive dye used in the new cancer imaging technique. Photo: Akhil Kantipuly, Michigan Engineering

“Inside the body, the laser’s energy turns from light into heat, then from heat into sound, a bit like thunder,” said Wang. “We can use ultrasound to read that sound energy, then digitally convert it back to optical information. That provides a painless, non-invasive way for us to see the color change in the injected dye, even when it’s deep inside the body.”

The researchers caution that an approved treatment is several years off. But they note that the imaging technology is already under clinical trial, as are the individual components of the nanoparticle. In the meantime, they are working on similar approaches that could be used to measure markers other than pH, like potassium and oxygen levels. They envision a treatment that could measure several different aspects of a tumor’s chemistry using a single scan.

The paper is titled “In vivo quantitative imaging of tumor pH by nanosonophore assisted multi-spectral photoacoustic imaging.” The research was supported by funding from the National Institutes of Health through the National Cancer Institute (grant number R01CA186769).


Virtual biopsy

From: Kate McAlpine
Michigan Engineering

A new imaging method in development at U-M uses infrared light to recover both ultrasound images and chemical information from tissues inside the body without breaking the skin. The technique could improve traditional biopsies or, in some cases, replace them.

Most of us know about ultrasound imaging – bouncing ultrasonic sound waves off structures inside bodies to image organs, tissues or babies-in-progress. Shining infrared light into the body can cause the tissue to generate its own ultrasonic sound waves that can be used for imaging.

“It’s like a thunderstorm,” said Xueding Wang, an associate professor of biomedical engineering and radiology. “There is a flash of light, and then you hear the thunder.”

The ultrasound waves are so high-frequency that they reveal structures inside the body at a cellular level. Because the cells aren’t flattened out on a microscope slide, the technique makes abnormally shaped cells more apparent.

Meanwhile, some of the infrared light absorbed by the body is emitted again as a form of light, giving information about the chemicals present in the tissue. This can reveal important factors such as fat deposits and inflammation. The team led by Wang and Guan Xu, a research investigator in radiology, used the technique to differentiate between mice with normal livers, fatty livers, and liver fibrosis without taking a physical biopsy.

The virtual biopsy could be used alongside traditional biopsy to guide doctors to the abnormal tissue, said Wang. This would minimize the likelihood of missing a cancer diagnosis and also reduce the number of samples taken from the patient. In some cases, it could even replace biopsy, cutting costs and sparing the patient pain. Wang thinks it will be particularly helpful in monitoring chronic diseases, where repeat biopsies pose additional risks to the patient.

This study is described in the journal Scientific Reports, in a paper titled “High resolution Physio-chemical Tissue Analysis: Towards Non-invasive In Vivo Biopsy.”

This work was supported by the American Heart Association grant 14POST17840001, Michigan Institute for Clinical & Health Research UL1TR000433 and National Institute of Health under grant numbers R01AR060350 and R01CA186769.