Microscale hydrogel fibers could enable imaging inside tiny tissue structures

WASHINGTON — Researchers have developed light-transmitting hydrogel fibers that are just hundreds of micrometers in diameter. With further development, these soft fibers could one day make it possible to use imaging techniques to detect early breast cancer hidden inside very small breast ducts.

“While traditional, relatively rigid fiber probes may cause mechanical damage when entering narrow, curved or soft tissue spaces, our fibers are very soft with mechanical properties more similar to those of human soft tissues,” said research team leader Yu Zhang from Harbin Engineering University in China. “We made these fibers using a draw-spinning method that was inspired by spider-silk spinning.”

In the Optica Publishing Group journal Optics Express, the researchers describe how they tested the new hydrogel fibers by incorporating them into an imaging system and using it to analyze standard pathology-stained breast tissue sections. The imaging system successfully reconstructed the microscopic features used by pathologists to evaluate tumors, and, when combined with artificial intelligence algorithms, distinguished tumor subtypes with an accuracy of 93.97%.

“Breast cancer diagnosis usually relies on medical imaging, needle biopsy and pathological analysis,” said Zhang. “In the future, flexible fibers might be able to acquire optical information from smaller, deeper or narrower locations, while artificial intelligence could rapidly evaluate tissue status. This may help doctors detect suspicious lesions earlier or provide auxiliary information for biopsy, surgical navigation and determining lesion boundaries.”

Tiny yet durable hydrogel fibers

Hydrogel materials are made of long polymer chains that can absorb and hold large amounts of water without dissolving. Although they are soft and biocompatible, hydrogel materials tend to easily lose water, become stiff or even crack when exposed to air, which affects long-term use. Additionally, most existing hydrogel fibers are millimeters in diameter, which is too large to enter narrow spaces such as breast ducts, which are only a few hundred micrometers wide.  

To overcome these challenges, the researchers used a spider-silk-inspired draw-spinning fabrication method that increases the proportion of bound water and allows the polymer chains to become denser and more ordered during stretching. Using this method, they were able to produce polyacrylamide (PAM) hydrogel fibers that maintained structural and imaging stability under ambient conditions and were very small, with diameters ranging from around 120 to 200 micrometers.

The researchers evaluated the hydrogel multimode fibers, showing that the fibers efficiently guided visible and near-infrared light with low optical loss, remained flexible and functional even when sharply bent and retained their optical properties over time. Cell studies also confirmed good biocompatibility, with cells readily adhering, spreading and proliferating on the hydrogel material.

Analyzing cancer tissue

To use the fibers to identify breast cancer, the researchers integrated them into an imaging system. When exposed to light, optical signals from a breast tumor will enter the fiber, forming complex speckle patterns as the light propagates in the fiber. Although these patterns look like random noise, they preserve information from the original image of the tissue.

The researchers developed deep learning algorithms that make it possible to decode the complex speckle patterns, turning them back into recognizable images. Using H&E-stained breast tumor pathological sections for a proof-of-concept study, the researchers showed that their two-stage deep learning framework could classify tissue as normal, invasive carcinoma or ductal carcinoma with an accuracy of 93.97%.

“These results show that the hydrogel multimode fiber can not only transmit image information but also has the potential to be integrated with intelligent diagnosis,” said Zhang. “In the future, similar technologies may be used not only for breast cancer, but also for minimally invasive detection of other diseases, surgical navigation, in-vivo sensing and intelligent medical imaging.”

To move the technology closer to clinical use, the researchers plan to improve image reconstruction accuracy, particularly for complex tissue structures, and train their algorithms on larger, more diverse medical datasets. They also aim to optimize the hydrogel fiber for in vivo use, conduct additional safety and animal studies, and integrate the fiber, imaging system and AI algorithms into a compact platform that can provide useful diagnostic information in practical settings.

Paper: M. Zhang, C. Liu, W. Jin, J. Gao, J. Mou, S. Li, C. Lou, X. Ji, Y. Zhang, Z. Liu, W. Y. Chong, K. S. Lim, C. Wu, “Hydrogel Multimode Fibers: Enabling Imaging and Intelligent Recognition of Breast Tumors,” Opt. Express