Seeing the Invisible: Our New Tool for Early Diagnosis of Fibrosis Linked Diseases

Written and compiled by Biswajoy Ghosh 

Fibrosis is a disease related to the extracellular matrix, which is like the scaffolding between cells in our bodies, and can be really tricky to catch early. By the time we notice something’s wrong, it might be too late to prevent serious damage or even cancer. That’s why finding a way to diagnose these conditions sooner rather than later is so important. 

Usually, doctors use a technique called histological staining and microscopy to get a closer look at tissues and check for problems. But here’s the catch: these methods aren’t always good at spotting subtle changes in the matrix. It’s like trying to see the details of a fine painting with foggy glasses. The dyes used in traditional staining can make things even blurrier, making it hard to see what’s really going on.

But fear not! We have devised a clever solution called MUSICAL, short for Multiple Signal Classification. It’s like a superpower for microscopes, allowing us to see things that were once invisible. But that’s not all! We’ve taken MUSICAL to the next level with a method called MUSI-tAF. With MUSI-tAF, we can zoom in on proteins like collagen in tissue samples without needing fancy equipment or years of training. This label-free super-resolution method can reveal nanostructural details and density variations across a wide area of dense tissue matrix proteins. It’s like having a microscope that can see way smaller! 

MUSI-tAF works by using low magnification objectives and taking advantage of the natural glow emitted by proteins like collagen when exposed to light. By combining this autofluorescence with our powerful algorithm, we can now resolve even the tiniest structures within the matrix. This means we can detect minute density changes between tissues undergoing fibrotic maladaptations, catching problems before they become serious. 

A brief overview of the workflow in clinical/pathology labs to achieve the desired results of MUSI-tAF

To put this technique to the test, we applied MUSI-tAF to extract pathologically relevant features in pre-cancer staging, pathological fibrosis, and post-wound scars. And the results were impressive! MUSI-tAF was able to spot subtle changes in the matrix that traditional methods might have missed, giving doctors a better chance at diagnosing and treating diseases early. 

Since several diseases are associated with tissue matrix integrity and distribution, the translation of MUSI-tAF to histopathology can add value to the arsenal of existing pathological practices for label-free molecular diagnosis. 

So, thanks to MUSI-tAF, the future of diagnosing matrix-related diseases is looking brighter than ever. With this powerful tool in our arsenal, we can catch problems sooner, giving patients a better shot at staying healthy. 

To read more here is our published article:   

Ghosh, B. et al. Molecular histopathology of matrix proteins through autofluorescence super-resolution microscopy. Sci Rep14, 10524 (2024).