Current medical imaging often fails to see clearly through thick tissue or capture fast-moving targets like blood cells in real time. To make a diagnosis, doctors resort to removing tissues, cutting them into thin slices, and dyeing them for analysis through a microscope. It can take days to get the lab results.
Biomedical engineer Nicholas Durr and surgical resident Gregory N. McKay, Med ’24 (MD/PhD), have developed a new microscopy method to change that. Called back-illumination tomography (BIT) and detailed in the journal Optica, the technique produces real-time, high-resolution images of living tissue and flowing blood cells—opening a potential path toward faster diagnoses and fewer invasive biopsies.
Here’s how it works:
1. It uses tissue scattering rather than avoiding it.
Thick tissues scatter light, creating a murky “fog” that hides details. A standard biopsy removes tissue from the body so that it can be sliced into thin, transparent slices. The BIT system takes advantage of tissue-scattering. It projects a virtual light source deep into a tissue. Tissue-scattering creates a virtual semicoherent source that back-illuminates the more superficial structures. This light interferes with a reference wave, revealing structures that were previously hard to image.
2. It doesn’t need chemical stains.
Most cells are transparent and require chemical dyes to be viewed under a microscope. The BIT system skips the dyes by harnessing how light scatters and creates distinctive interference patterns when it hits cellular components like a nucleus or a membrane. By capturing these patterns, BIT generates sharp, 3D images of unstained tissue that reveal the same structural details as traditional biopsies but without chemical processing or tissue removal.
3. It tracks highspeed motion.
The BIT system captures moving targets far more effectively than traditional imaging. While standard microscopes are often too slow to track rapid movement, the BIT system captures full frames at high speed, making it possible to visualize fast biological processes—such as individual blood cells racing through a vessel—in real time without the motion blur common in other techniques.
4. It eliminates wait times.
With further refinements, the technology could transform disease diagnosis. By using AI to virtually “stain” the images, results that currently take days to process in a lab could be delivered instantly. The team is now combining views from different angles for more accurate 3D images, with the goal of replacing lengthy surgical biopsies with bedside diagnosis.
— CATHERINE GRAHAM