Fixel-based analysis on subject level?

1

Hi everyone,

this question is probably due to my incorrect understanding of the process or the point, but I was wondering why we can’t do individual fixel-based analysis in subject space in order to make statements about a single person’s white matter the way we can with DTI based metrics?

I have seen it mentioned in this discussion a few years ago Fixel based analysis for fibre density - #2 by rsmith, but I didn’t really understand the rationale

(“I don’t understand what you mean by “why a population based template is created instead of subject based”. The phrase “subject-based template” would only make sense in a repeated-measures experiment; and even then it would be only as an intermediate step towards a population or standard template. FBA (in the strictest definition of performing statistical inference at the per-fixel level) necessitates spatial correspondence across subjects, thus precluding calculations from being performed solely in subject space.”)

On a related note I was wondering if anyone could clarify Rob’s explanation in the same thread:

“Imagine you have a cohort of two subjects. In one subject, a typical WM voxel is filled with 20% axons and 80% extra-cellular fluid; in the other, a typical WM voxel is filled with 80% axons and 20% extra-cellular fluid. If you used subject-specific response functions rather than common ones, you’d detect no difference in “fibre density” between these two subjects.”

Why is it that we would detect no difference in density in this example? I thought I understood well how fixel-based analysis works but this makes me think I’m missing something…

I read here Fixel-based analysis in subject space that “the number and location of fixels used to derive those quantities will almost certainly vary between subjects” which seems to be an argument against a subject-level analysis, but is that not something normal/informative? Or are we assuming that differences would be driven by artifacts and not the biological reality?

Thank you in advance!

2

Hi,
Here’s how I (humbly) understand it. When you make a statement about an individual’s white matter, that’s in reference to a “norm”, and it is often in a template space (MNI etc). But there is not exactly a norm for fixels (yet?). For example, FC (fibre-bundle cross-section) is a measure of difference compared to the template space, but you can’t make a statement if you have no reference template to compare your subject to. Similarly, the fibre density is relative to a subject’s “typical” WM response function, so I think the second citation means that the fibre density may have the same value in both scans since they’re relative to what’s common in their respective scan. I don’t think there is any established “value” fixels are supposed to have since every time it is computed, it’s relative to a specific space. But I do wonder if there could not be a public large population-reference FOD template on which to register individual subjects to in the future.