Imagine you were taking a photograph in a room with very dim lightning. You could still take a picture if you use a very long exposure: by keeping the shutter open for a long time, you can collect enough light to create your image. A problem with this approach is that it only works if the object we’re imaging remains completely still. If the object (or person) or the camera moves, we obtain a blurry picture.
|A blurry photograph|
A similar thing happens with MRI. Obtaining MRI images al ultra-high resolution requires very long scanning times (tens of hours), so it is inevitable that the subject being scanned moves during that period of time. For that reason, practical MRI scanning protocols are usually shorter than 10 minutes. However, if we want to build accurate, high resolution models of brain anatomy, there is a way of overcoming the restrictions imposed by subject motion: using ex vivo brains from cadavers.
The idea is as simple as this: dead brains don’t move, so we can scan them as long as we want without motion artifacts. Unfortunately, scanning ex vivo brains the same way we scan in vivo (meaning, living brains in living people) does not work. The reason is that the fixation process (immersion in formalin for preservation of the sample) changes the magnetic properties of the tissue. Moreover, the formalin and air bubbles introduce image artifacts that degrade the quality of the scan.
|An ex vivo brain scanned in formalin. The red arrows point at artifacts created by air bubbles|
What can we do to fix this? One way is to replace the formalin by a fluid that is transparent to MRI. Since MRI is based on detecting and measuring protons, we can use a proton-free fluid. Many studies use a lubricant called Fomblin. We use a cheaper (and less slippery) alternative called Fluorinert.
|Slice of a ex vivo brain scanned in Fluorinert|
Once we have fixed the problem with the artifacts, we have yet another problem. The hardware of clinical scanners like the one we have at the BCBL is not meant to acquire images at ultra-high resolution. For this reason, when we try to acquire a big 3D scan, the machine runs out of memory during the reconstruction (the process of transforming MRI measurements into images). This problem can be overcome by acquiring different parts of the image separately and then stitching them together. The strategy is normally to acquire several slabs that can subsequently be stacked to create our final scan.
|Stacking slabs to create a MRI scan|
Stacking slabs enables us to bypass the memory limitations of the scanner, but it introduces yet another artifact: the Venetian blind. This is because the sensitivity of the scanner is not uniform across each slab; instead, it is lower in the first and last couple of slices of each slab. If we acquire the whole 3D scan in one shot, this is not a problem, because the first and last slabs do not cover the brain anyway. But when we stack slabs, we get patterns that resemble a Venetian blind.
|Venetian blind artifact|
As bad as this might look, there is a bunch of image analysis algorithms you can use to correct for this artifact. Here I’ll show you the output from an algorithm that we have developed ourselves, and which also corrects for intensity inhomogeneities (more on that another day; for now, let’s just say that it’s an artifact that makes some regions brighter than others).
|Before (left) and after correction with our method (right)|
These are pretty pictures, right? Let’s look at a close-up of the hippocampus, and compare with a standard resolution in vivo scan.
|Left: standard resolution (1 mm). Right: ex vivo scan (0.25 mm)|
What will we do with these beautiful scans? That remains for a future post ;-)