Working to solve problems like irritable bowel syndrome and gastroparesis, Sameer Dhalla and the team at the Johns Hopkins Center for Neurogastroenterology are venturing into the uncharted cartography of the enteric nervous system.

By modifying their endoscopic biopsy and sample staining techniques, the center’s physicians and researchers are producing three-dimensional images of the nerve networks in patients’ GI systems.

“Standard techniques used in GI histology can’t show us the nerves that we think hold the clues to some of these idiopathic conditions,” says Dhalla. “Sliced sections in 2-D under a standard microscope are great for identifying cancer or overt inflammation. But information about nerves is lost in this process.

“Nerves in the GI tract don’t reside in a plane. They’re interconnected and have depth. To begin to understand their role in health and disease, we had to find a way to see these nerves in three dimensions.”

Dhalla’s mentor, neurogastroenterolgy director Jay Pasricha, along with Johns Hopkins GI postdoctoral fellow Ya-Yuan Fu, had previously developed specialized sectioning and staining techniques to highlight nerves in 3-D from large surgically removed samples of the intestines. “My hunch was that these same techniques might work when applied to the superficial biopsies we routinely obtain during endoscopy, and thus could be more readily incorporated into clinical practice in the future.”

Three-dimensional imaging of the superficial enteric nervous system is in its early stages, but Dhalla believes he and his colleagues are onto something.

Dhalla, Pasricha and Fu performed a pilot study that provided a clue to the mysteries of idiopathic gastroparesis. “We looked at nerves in normal stomachs and compared them to nerves in the gastroparetic stomach,” says Dhalla, “and we found that there were some significant differences in nerve density.” These findings were presented at the recent Digestive Disease Week 2015 conference in Washington, D.C.

“We see patients with debilitating symptoms who’ve often been told the problems are ‘in their head’ when all their tests come back negative,” Dhalla says. “More likely to me is that our current diagnostic tests are limited when it comes to the nerves in the gut … but we aim to change that paradigm.”

Dhalla hopes that the 3-D imaging will lead to a better understanding of the unexplained conditions seen in the Johns Hopkins neurogastroenterology clinic in order to help tailor treatment decisions for patients. “It will take time,” he says. “But we’re beginning to draw an atlas of the complicated networks of nerves that drive digestion.”