New Preclinical Technique Gives 3D Image of Gut Motility

The technique is called trans-illumination intestine projection (TIP) imaging, which the researchers described in a recent Nature Communications paper.

For the first time, this technique reveals how food moves through the gut in free-moving animals in real time.

The new method makes use of Raspberry Pi technology, the credit card-sized computer now ubiquitous in applications ranging from education to digital media to research.

“For the first time, TIP allows us to see intestinal motility in a freely moving mouse in 3D and in color,” says Xia, associate professor of biomedical engineering, a joint program between the Jacobs School of Medicine and Biomedical Sciences and UB’s School of Engineering and Applied Sciences.

“TIP has great potential to help us understand the mechanisms of motility control and discover the pathophysiology of motility disorders,” he adds.

Some of the most intractable gastrointestinal disorders, such as irritable bowel syndrome and inflammatory bowel disease, are motility disorders, where the contents of the intestines don’t proceed normally through the GI tract.

Such disorders are known to have a strong brain-microbiome connection, but preclinical research has typically been limited to in vitro studies or anesthetized animal models, neither of which provide a realistic picture of gut motility.

TIP makes possible a better understanding of psychosocial factors, such as stress and anxiety, that are known to affect intestinal motility through the brain and gut connection, Xia says.

“Patients with anxiety and depression are more likely to have functional GI problems and to exhibit motility issues, such as slower or faster intestinal movement or irregular movement,” he adds. “However, it is unclear how stress affects the GI function, and it is not easy to study in humans. Studying intestinal motility in animal models can lead to a better understanding of abnormal motility and how the gut-brain connection works.”

“Because the TIP system allows for the imaging of freely moving animals, we can better investigate how brain functioning/status affects the gut movement.”

Until now, many such studies involved studying intestinal motility in anesthetized animals, which, the UB study has revealed, results in slowing down motility.

A key advantage of TIP is that it allows for the visualization of peristalsis and segmentation, the motor activity that occurs in the intestine in awake, free-moving mice, which has never been reported before.

“This unique imaging ability facilitates the in vivo demonstration that the anesthetized mice exhibited a much slower intestinal motility rate than the awake mice, highlighting its ability to study central nervous system regulation,” Xia explains.

The idea behind TIP is similar to a barium X-ray, where the patient ingests barium, which illuminates the GI system as it is digested. Before the TIP experiment, the mouse is fed a light-absorbing material that can safely travel through the intestine without being absorbed by it.

Instead of an X-ray, the UB researchers used near-infrared light, which doesn’t contain ionizing radiation and is safe for imaging over long periods of time.

“The process is similar to how we conduct color photography,” Xia explains. “By imaging the mice with matching wavelengths, we can then form a colorful image of the intestine, showing how different contrasts are mixed and moved inside the intestine. This is different from the barium X-ray, where the contrast is only shown in black.”

TIP provides 3D imaging of the intestine. Whereas conventional cameras detect only the light intensity, allowing for a 2D image, the light field technology used in TIP allows for the acquisition of both light intensity and the light incident direction.

“Combining intensity and direction information allows us to digitally refocus the imaging plane at different depths, which offers a 3D view of intestinal motility,” Xia says.

By using the Raspberry Pi device, the TIP technique can track mouse movement, so that the fiber tip that is illuminating the intestine is always on top of the animal body. The Raspberry Pi device tracks the position of the animal body and then instructs the motor to move the fiber tip accordingly, Xia says.

He concludes: “The ability to view intestinal motility in 3D in conscious animals will make it possible to do more robust preclinical studies on how motility is affected by pharmacological agents under investigation as potential treatments for humans.”

Co-authors from the Department of Biomedical Engineering are:

• Depeng Wang, PhD
• Huijuan Zhang, a student in the doctoral program in biomedical engineering
• Tri Vu
• Ye Zhan, PhD
• Upendra Chitgupi, PhD
• Sizhe Zhang
• Jonathan F. Lovell, PhD, SUNY Empire Innovation associate professor

Additional co-authors are:

• Akash Malhotra, City University of Hong Kong
• Pei Wang, City University of Hong Kong
• Aliza Rai, City University of Hong Kong
• Lidai Wang, PhD, City University of Hong Kong
• Jan D. Huizinga, PhD, McMaster University, Ontario, Canada