Scattered Light

Researchers at Duke University in Durham, North Carolina, USA, have developed a light-scattering technique to screen for Alzheimer’s disease. The technique – angle-resolved low coherence interferometry (a/LCI) – combines imaging modalities to measure both the thickness and the texture of various layers of the retina. Studies have shown that Alzheimer’s disease can cause structural changes to the retina. Notably, thinning of the inner retinal layers can indicate a decrease in the amount of neural tissue, suggesting Alzheimer’s is present. However, other diseases – namely, glaucoma and Parkinson’s – can cause similar thinning. The researchers hopes this new measurement could be a more easily accessible biomarker for Alzheimer’s and are are now incorporating the technology into a low-cost clinical OCT scanner (currently awaiting FDA clearance). Built with 3D-printed parts, the scanner is portable and lightweight at just four pounds. We speak to Adam Wax, Professor of Biomedical Engineering and Physics at Duke and the technique’s creator, to find out more. 

What is the advantage of combining imaging modalities? Is there a reason why this hasn't been done before?

Several efforts have used OCT to look for signs of Alzheimer’s.  While OCT has great resolution in the depth direction, it is difficult to get good resolution in the lateral direction. This is here our light scattering technique, a/LCI comes in. a/LCI stands for angle-resolved low coherence interferometry (LCI) which looks at the angular scattering pattern from tissue to determine the scattering structures while using the depth resolution from LCI that OCT uses.  This lets you see structures that can’t be easily visualized in OCT. For example, we have used a/LCI for early cancer detection by measuring the size of cell nuclei in epithelial tissues.  We have conducted in vivo trials in esophagus and cervix and obtained great results.

Other folks have tried multimodal approaches but there have only been a handful of studies to use light scattering in the retina. Since we’ve been developing this approach for years, we were the first to combine it with OCT.

At what point could the test be used to identify Alzheimer's?

The goal would be to have a screening test that could be performed when one went for an eyecare checkup or even at the general physician’s office.  I would expect that it wouldn’t be needed for younger patients but maybe to begin for patients in their 40’s or 50’s.  As our ability to detect Alzheimer’s improves, it opens the door for greater preventative measures. With a diagnostic test that is easy to use, there is a chance to monitor disease progression much as we may check blood pressure or cholesterol now.

Is it possible to differentiate between thinning of the retina for glaucoma or Parkinson's and Alzheimer's?

Our technique measured retinal thinning with OCT but added further information by measuring the texture of the retina through light scattering.  Our next research goal is to test this in humans with AD. At first, we will avoid scanning patients with glaucoma or Parkinson’s to avoid any confounding effects but then we will seek to more clearly distinguish between these diseases. So, while OCT can detect thinning which can be AD or other causes, the hope is that light scattering can provide complimentary information that can help separate them.

Can you tell us more about your custom machine; how long did it take to bring this idea to fruition? Have you had any experience with 3D printing parts before?

The low-cost OCT system started back in 2014 and we developed it for several years before we got it right.  I’m proud to say that Lumedica has brought low cost OCT to the research market since 2017 and we are now working to gain FDA clearance of our clinical OCT scanner.  This will be a great platform for incorporating an AD scan since the low cost will make it more accessible.  However, the use of 3D printed parts also makes it very lightweight (just 4 pounds) and portable.

My lab started using 3D printing several years ago.  It was a curiosity at first but then we found all sorts of roles for the technology.  It really serves to create an agile mechanical design process where you can create an object, then change it to better meet your needs, just within a few hours.  At this point, it is an indispensable tool for my lab.  We have four different 3D printers which have different capabilities such as build speed, resolution and material.