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Hi,

>fslmaths fdt_paths.nii.gz –div waytotal – thr % fdt_paths_norm –odt float
strictly spaking you would have to multiply by 100 (after -div waytotal) to use a percent threshold. Note, however, that the magnitude of peak probability in waytotal %, for example, may seem low and that you may want to retain even low probability voxels (i.e. apply a threshold much below 1%) to "clean up" your data. See Matt's previous posts.
>how could you threshold fdt_paths normalized to the total number of samples? Is it based on the absolute pathway intensities?
Same story: just replace the waytotal by the total number of samples send out (=number of samples send out from each voxels x number of voxels in yourt ROI). Again note that the waytotal is also a "total number" of samples, i.e. those which made their way from seed to target (that's why the name;).
>found much less volume in the ipsilateral hemisphere with respect to the contralateral hemisphere
Right, that is what you would expect.
>if we use waytotal based threshold, the asymmetries are not so evident and in some tracts they are changed to be symmetrical
Exactly. In a way you may think of it like atrophy studies normalize to brain size (if your skull is small your brain must be small as well but may still be "normal" for its size; the only difference here is that normally you don't measure the hemiskull - even though only half of the skull may be small;). So does the asymmetry you see >primarily< affect your tract of interest or can it be a secondary phenomenon? Hard to tell, isn't it? Then, if you have other evidence to support one or the other notion you may ask yourself if you need tractography at all to answer your particular question or if - like quite often - we end up in circulary reasoning;)
>However, sometimes it is difficult to say which one is false-positive or false negative.
...and sometimes it remains impossible. Practising bad science you will pick whatever will meet your purpose. Being serious you think of it before you analyze your data and decide for one or the other. I.e. do you have evidence for every single case (not just in general!) that the tract must exist in the particular brain / hemisphere? Then you may want to enforce "trackablility" despite the thresholding and use the waytotal. In normals, you may want to retain variability despite thresholding and be better of using the total number of samples send out. In some regards, the thresholding itself is just a way to "clean up " your results.
<book of Heidi and Tim
See Timi's post.
Cheers-
Andreas


________________________________
Von: FSL - FMRIB's Software Library [[log in to unmask]] im Auftrag von cathyliu [[log in to unmask]]
Gesendet: Montag, 30. März 2009 15:24
An: [log in to unmask]
Betreff: Re: [FSL] AW: [FSL] asymmetires

Hi,

We appreciate that Andreas would join our discussion!

Before we discuss further on the advantage of different thresholding way, I might need to know the definition and function of each method. The waytotal based threshold= fslmaths fdt_paths.nii.gz –div waytotal – thr % fdt_paths_norm –odt float; and how could you threshold fdt_paths normalized to the total number of samples? Is it based on the absolute pathway intensities?

Second, the ACROSS subjects means compare the same tract in the different samples or different cases, WITHIN subject means compare different tracts in the same brain?

Third, thanks Andres for sharing your experiences on clinical cases, and we might have the same experience. If we are interested in pathological cases, and there is evidently asymmetrical in the anatomy (T1 and T2 show asymmetrical structures between two hemispheres) , we use the same Max intensity and Min intensity for both side, we found much less volume in the ipsilateral hemisphere with respect to the contralateral hemisphere. However if we use waytotal based threshold, the asymmetries are not so evident and in some tracts they are changed to be symmetrical. However, sometimes it is difficult to say which one is false-positive or false negative. In brief, if now we are only interested in the normal population, which way of threshold would be better as your experience?

Last but not the least, we are looking forwards to the book of Heidi and Tim, could we please tell us the name and when it will sell on? Thanks.

Best Regards,

Yan





> Date: Mon, 30 Mar 2009 13:55:32 +0200
> From: [log in to unmask]
> Subject: [FSL] AW: [FSL] asymmetires
> To: [log in to unmask]
>
> Hi,
>
> please let me add a comment first:
> Matt suggested that thresholding fdt_paths normalized to the waytotal is good to get consistent trackings ACROSS subjects whereas thresholding fdt_paths normalized to the total number of samples send out is good to detect tract asymmetries WITHIN subject. Although I can see the point he is trying to make, it is - in my opinion and experience - not entirely true.
> Thresholding a tract by its waytotal percentages enforces a more uniform "trackability". The original rationale why Tim and I came up with this is that you may have other evidence that the tract exists, e.g. preserved motor function indicating some (residual) integrity of the pyramidal tract in brain-lesioned patients. Imagine a case where the pyramidal tract in one hemisphere passes through the perifocal edema of a tumor. The edema massively increases the diffusion uncertainty and much fewer samples reach the target from the seed. However, the patient has no motor deficit and the pyramidal tract is only embedded in the edema but not infiltrated or distructed. If you now compare your volumes based on thresholding the pyramidal tract by percentages of total number of samples send out you will end up with great asymmetry which is essentially a false-positive detection. This may be eliminated or is, at least, attenuated when you thresholding by waytotal percentages. Heidi and Tim have a book coming out where we present a chapter with clinical data illustrating and further explaining this.
> So my point is that thresholding tracts by their waytotal percentages attempts to enforce a more uniform "trackability" ACROSS OR WITHIN subjects based on other prior evidence that the tract must be there. Thresholding fdt_paths normalized to the total number of samples send out may, on the other hand, overestimate tract asymmetries within subjects if there is an interhemispheric "trackability" difference. Ok, brain lesions are obvious. But you need to ask yourself if you are sure that "trackability" is the same between the hemispheres of the same subjects. In epilepsy patients, for example, there may be less obvious microstructural differences. So the waytotal is good if you have easily accessible and measureable evidence that a tract exists (which is the case for the pyramidal tract or the optic radiatio, for example). It would be much harder for the arcuate fascicle, esp. in the right hemisphere. For many tracts, we have to keep in mind that there is no good and easy way to tell (aside from our tracking!) if they do in fact exist.
> Ok, now to your questions:
> >ROIs symmtrical between both sides
> When the anatomy is asymmetric, there is no point to make them symmetric in shape. However, you may be able enforce (roughly) the same size. We did so for the data presented in the upcoming book chapter mentioned above.
> >So if I don't reject any tracts, the waytotal should be the same as total number of samples?
> Yes.
> >but will it confuse our readers if we use different % of threshold in one article
> It certainly may. Preferably, you may have to explain based on another sample you've studied why you have decided for a particulat threshold for a given tract.
> Hope that helps,
> cheers-

>
> ________________________________
> Von: FSL - FMRIB's Software Library [[log in to unmask]] im Auftrag von cathyliu [[log in to unmask]]
> Gesendet: Montag, 30. März 2009 11:21
> An: [log in to unmask]
> Betreff: Re: [FSL] asymmetires
>
> Thank Matt for sharing your experiences!
>
> Some other things to think about regarding this (to add what I said below): Bigger tracts will often have bigger masks, and if you are really interested in structural asymmetries, you want to be sure that you get the entire pathway for each of your subjects. If you leave something out, you could either create a false asymmetry or miss a true one. Making sure you get the whole pathway (but only the whole pathway), is more important than keeping the size of your masks exactly the same in my opinion. At the same time, if you are using the size of the ROI as a part of your thresholding or normalization scheme, you need to be sure that you don’t have “extra” voxels in your ROIs, i.e. voxels that don’t track the pathway, or don’t track anything at all. Example: You have ROI A of 100 voxels in which 50 voxels track a pathway of interest. You have ROI B of 50 voxels in which all 50 voxels track the pathway of interest. If you are generating thresholds based on the size of your ROIs, the pathway from ROI A will be more stringently thresholded than the pathway from ROI B.
>
> <<<< We put relatively bigger masks in order to get the entire pathway, and meanwhile we try to make the ROIs symmtrical between both sides. But as you know the brain structures are asymmetrica, so it is impossible to make the ROIs both sides exactly the same sizes. By the way, if we use waytotal-based thresholding, could it avoid the effect of different size of the ROIs?
>
> I personally tried both waytotal-based thresholding and thresholding based on total number of samples (# voxels in the ROI X # of samples sent out per voxel) on a study of pathway asymmetry. I found significantly better correlation between a gold standard measure of functional lateralization and tract volume asymmetries generated from thresholding based on total number of samples than on tract volume asymmetries generated from waytotal-based thresholding. I observed that waytotal-based thresholding tended to make pathway volumes more consistent across subjects and hemispheres, thus making it harder to see interhemispheric differences.
>
> <<<< I read the information from the mail list again. If I understand well: waytotal= # voxels in the ROI (fslstats -V) X # of samples sent out per voxel(5000 by default) if no tract is rejected. So if I don't reject any tracts, the waytotal should be the same as total number of samples?
>
> Regarding normalization vs thresholding, you will have to do thresholding regardless of whether you normalize. If you normalize, you can just use the same number as your threshold for all subjects, but you lose information about the absolute pathway intensities. If you don’t normalize, you will need to calculate the threshold separately for each pathway (i.e. decide on some proportion of the waytotal or total number of samples tracked, then for each pathway, multiply the proportion X the waytotal or the total number of samples tracked to get the threshold value for that pathway). I think this is more of a question of personal taste, rather than right or wrong, as both methods are equally valid for interhemispheric comparisons. If you want to compare across subjects, however, it is better to normalize (and to normalize using wayotals), as this can account for global differences between scans (e.g. more motion).
>
> <<<< If we are interested in series of tracts, some of them are across subjects, but some of them are not, should we keep the same way of thresholding? As you mentioned in last mail, we could choose different % of threshold for different tracts, but will it confuse our readers if we use different % of threshold in one article?
>
> Best Regards,
>
> Yan
>
>
>
>
>
>
>
> ________________________________
>
> From: FSL - FMRIB's Software Library [mailto:[log in to unmask]] On Behalf Of cathyliu
> Sent: Wednesday, March 25, 2009 9:28 AM
> To: [log in to unmask]
> Subject: [FSL] asymmetires
>
>
>
> Hi,
>
>
>
> We want to compare the structural asymmetries between the right and left hemisphere by probabilistic tractography. We still have some concerns: if the size of the masks will have an effect on the results? For example, a big mask will have more tracts, and in fact we couldn't make the masks exactly the same on the both sides. The second, for comparing the results, if it is necessary to do the normalization and what is the function of normalization? In one of your emails, it mentioned that:
>
>
>
> My understanding is that dividing by the waytotal is the way to normalize
> across subjects as best as you can. Then you could threshold at some
> fractional proportion of the waytotal and binarize. This should give you
> the most similar spatial distributions across subjects. However, I think
> that this method is less useful when you are making comparisons within a
> brain, for example between the same pathway in the two hemispheres, when you
> are interested in pathway asymmetries for example.
>
>
>
> So what is the best method, if we are interested in pathway asymmetries?
>
>
>
> Best Regards,
>
>
>
> Yan
>
>
>
>
>
>
>
> ________________________________
>
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> ________________________________
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