A Closer Look at Microscopy

At a Glance

• Unlike in research laboratories, the optics for clinical microscopy don’t need  to be improved – but that doesn’t mean the technology isn’t evolving
  
• The inexorable march toward digitization means that labs are scrambling not to obtain the perfect image, but to store it
  
• In order to fully adopt digital pathology, hospitals need to commit to putting the necessary IT infrastructure in place
  
•  Lab medicine professionals also play a key role in adopting new technologies, and keeping up with the times requires keeping an open mind

In 1939, Adrianus Pijper described the microscope as “man’s noblest, supreme, and most far-reaching tool.” Though this opinion is now three-quarters of a century old, pathologists who use microscopes every day in their work are hard-pressed to find fault with it. But in most laboratories, the microscope that sees the most use is a simple light microscope, not so different to the ones that were state-of-the-art when Pijper made his claim. So if the microscopes themselves aren’t changing significantly, what is – and how can pathologists keep up?

A continual evolution

To understand how the science of microscopy is growing and changing, it’s important to differentiate between research and clinical settings. Research is where new applications and methods are being developed, whereas in routine clinical microscopy, the optics don’t really need much development – they’re already good enough for applications like histology. There are still improvements to be made to usability, workflow, automation and ergonomics, but the technology itself works well for clinical pathology in its current form.

But that doesn’t mean there aren’t ways for established technology to evolve. One example of innovation in a mature technology is fluorescence-lifetime imaging microscopy. FLIM was developed about 25 years ago for applications in cell biology. It works on the basis that a fluorescence signal has a lifetime, which is usually very short but when you have a modulated light source (like an LED or laser), you can analyze the phase shift between the excitation light and the emission signal to distinguish between the lifetimes of two different signals. That lets you differentiate between two fluorophores more accurately than with standard filter-based techniques. With the recent development of easy to use FLIM solutions, this technique might become interesting for routine use. For histology slides, rather than looking at fluorescence markers, you can observe autofluorescence properties that vary depending on cell type and even subcellular structures – meaning that FLIM might allow you to see certain tissue features easily and efficiently, without the need for staining. The technology isn’t quite ready for routine microscopy use yet; it’s still in the process of evolving from a complicated research setup into an easy-to-use system – but I believe it’s worth keeping an eye on.

It goes without saying, that the ergonomics of a microscope are of utmost importance to lab professionals, who spend long hours each day examining microscopy samples. To that end, a lot of innovation is taking place in this area, with new technologies aiming to make the user experience as comfortable and as practical as possible. Development is also being focused on making workflow better, reducing repetitive steps and automating the microscope in a way that the user doesn’t need to perform so many steps – for example with slide scanning systems. I think there is still some room for improvement in that respect.

Digitization is another area of development with a huge impact on the pathologist’s workflow. There’s a significant need for digital slides to aid with clinical diagnosis, consulting with colleagues, and education. The big hurdle is how we handle all the data. If a pathology department goes completely digital, every slide needs to be scanned and made digitally available. Some labs even discard the original glass slide, so the digital slides need to be stored and archived indefinitely as reference for the diagnosis. No matter how you look at it, digitization results in a lot of data and data management. Fortunately, that’s an area that seems to be improving in leaps and bounds!

Obstacles to adoption

One challenge of developing new microscopy technology is that there’s still a long way to go if you want to use it for clinical diagnosis – even if a new technique is already at the point where it delivers results at a single push of a button. Before you can use it for patient testing, there have to be clinical studies to prove that the new technique can produce a reliable diagnosis. That uses a lot of resources and time, so it can be difficult. And once it’s done, commercializing the technique isn’t easy, either. Not only does it have to be simple to use, but you also need to make sure the new method is widely applicable in order to attract a broad user base. Without market potential, it’s hard to convince a company to invest in developing your system.

But even after a technology is ready for the clinic, there are hurdles to overcome to ensure its success. With the ongoing trend toward digitizing slides, for instance, those digital images need to be integrated into the existing IT infrastructure. And again, for that, you need to be sure there’s enough storage available. Big pathology departments can deal with several hundred slides per day, all of which need to be backed up, so you can imagine how fast the data accumulates – especially when you consider that many pathologists are legally required to archive digital slides for many years. Slide scanners are well evolved by this point, but individual institutions still need to take that last step and provide the IT infrastructure for them.

Last but not least, you have to win over the people who will be using your new technology. If a microscopist has spent 20 years doing their job a certain way and someone comes along and tells them to do it differently, the transition can be difficult – and requires a compelling reason to change. I personally believe that the traditional microscope will never vanish. I hear from microscope users who tell me it’s a different story to see an image directly through the microscope than to see it on a screen, even acknowledging the potential benefits of digital imaging.

The best of both worlds

One of the most important things for pathologists to remember as technology evolves around them is to keep an open mind, and pay attention to what’s going on in the world of microscopy. While digital slide technology has its obstacles, it also presents a great opportunity for laboratory medicine professionals. Usually, you have people who are either experts in the microscopes and their applications, or experts in computing and IT. There aren’t very many people who are at home in both worlds, which means there’s a gap that people working in laboratory science are well-placed to fill. If institutions have access to people with a background in both IT and laboratory medicine, then they really have the best of both worlds.