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Hi Matt and Andreas,

Thanks again for your very patient, helpful and informative reply.

Best,
Huadong





2011/2/13 Andreas Bartsch <[log in to unmask]>

> Hi,
>
> well - my only reason was that I felt the ratio was a more intuitive number
> in the particular scenario. In my cases, the reduction of trackability -
> i.e. of the waytotal - relative to the normal contralateral hemisphere was
> mainly due to perifocal tumor edema. I would use Matt's approach if I were
> facing a lateralization of a tract, for example. For a connection such as
> the CST that was harder to track due to edema I wanted to assume symmetry
> prior to the impact of the pathology (knowing that this may not have been
> the case and contribute to the variablility, but any other approach seemed
> similarly stipulative).
> All will depend on the particular conditions you are examining. For
> example, an extra-axial tumor (i.e. outside the parenchyma, such as a
> meningeoma) could be conceived to compress a tract reducing the waytotal
> without altering the 'true connectivity strength' (whatever that may be, as
> Saad already has pointed out).
> Cheers-
> Andreas
> ________________________________
> Von: FSL - FMRIB's Software Library [[log in to unmask]] im Auftrag von
> Matt Glasser [[log in to unmask]]
> Gesendet: Sonntag, 13. Februar 2011 20:28
> An: [log in to unmask]
> Betreff: Re: [FSL] AW: [FSL] Normalizing waytotal itself?
>
> So I also used the waytotals to calculate an asymmetry index (Waytotal Left
> – Waytotal Right) / (Waytotal Left + Waytotal Right).  I did not normalize
> the waytotal values by the total number of samples sent out.  Because in my
> case I believed that I was tracking entire fascicles, if a larger mask were
> required to track an entire fascicle, then I believed that the pathway was
> indeed larger.  I was using ROIs that were a single voxel thick and were
> orientated perpendicular to the pathway so as to cut it in cross section.
>  The only thing to be careful of is to ensure that you are not using a
> larger ROI because you are cutting the pathway obliquely.  I have groups of
> 30-35.
>
> Peace,
>
> Matt.
>
> ________________________________
> From: FSL - FMRIB's Software Library [mailto:[log in to unmask]] On Behalf
> Of hd x
> Sent: Sunday, February 13, 2011 11:58 AM
> To: [log in to unmask]
> Subject: Re: [FSL] AW: [FSL] Normalizing waytotal itself?
>
> Hi Andreas & Matt,
>
> Thank you very much for the reply. May I ask some more specific questions?
>
> To Andreas: Was there a special reason for you to calculate asymmetry index
> by useing the ratio of the waytotals from the tracking in one hemisphere
> diveded by the other? I asked because in my results regression analysis
> suggests the absolute difference between the left and right waytotal  is a
> better explanation for the individual variance on behavioural performance.
>
> To Matt:May I ask how large your group is? My idea of using waytotal to
> represent the connectivity strength was actually inspired by your replies as
> mentioned in the previous email. Since I found significant correlations
> between the the waytotal and the individual behavioural performance, the
> idea is even more convincing to me now. But since you mentioned that it's
> better to normalize pathways by the total number of samples you sent out, do
> you think I shall also normalize the waytotal by the total number of samples
> sent out?
>
> Best,
> Huadong
>
>
>
>
> On 10 February 2011 19:29, Matt Glasser <[log in to unmask]<mailto:
> [log in to unmask]>> wrote:
> I have found that normalizing by waytotal tends to underestimate pathway
> asymmetries, because the waytotal values themselves are highly correlated
> with pathway asymmetry (therefore, if you normalize by waytotal you remove
> the asymmetry you are looking for).  If you want the pathways to be about
> the same size on both hemispheres (or across subjects) normalizing by
> waytotal makes sense.  If you want to compare pathways across hemispheres
> looking for asymmetries, I think it is better to normalize by the total
> number of samples you sent out (and asymmetric pathways will tend to have
> different sized ROIs if you are defining the whole pathway, but the affect
> on asymmetry is not as strong as the waytotal).
>
> Across large groups of subjects I get very reasonable asymmetry values just
> using the waytotal value for each pathway (e.g. in comparison with what
> others have reported in the literature).  There is certainly variation in
> the waytotal values across subjects as Andreas notes, but it good quality
> data that doesn't have pathologies this shouldn't be too bad and reasonable
> trends are apparent.  Waytotal certainly isn't a proper measure of
> strength,
> but it is correlated, particularly across a large group.  This work was a
> part of a side project that hasn't made it into a publication yet, so
> unfortunately I can't give you a reference to cite.
>
> Peace,
>
> Matt.
>
> -----Original Message-----
> From: FSL - FMRIB's Software Library [mailto:[log in to unmask]<mailto:
> [log in to unmask]>] On Behalf
> Of Andreas Bartsch
> Sent: Thursday, February 10, 2011 4:59 AM
> To: [log in to unmask]<mailto:[log in to unmask]>
> Subject: [FSL] AW: [FSL] Normalizing waytotal itself?
>
> Hi,
>
> my figure so I give it a shot:
> In that figure the waytotals were NOT used directly. Instead I used the
> ratio of the waytotals from the tracking in one hemisphere diveded by the
> other (see the legend). Because masks were equally sized in both
> hemispheres
> (p. 433 in the book), there was no need to 'normalize' further. So this
> would be an easy way to to it. Still I agree with Saad: anatomicofunctional
> correspondence should rule over mask sizes - size does not matter!
> Also note that I've excluded two outliers. Overall, in my experience the
> waytotals can easily differ by a factor of 5 between hemispheres of the
> same
> subject and that must not have any biological meaning even if you have
> high-quality scans. Still, as the figures shows normalizing to the
> contralateral hemisphere may be useful.
> Note that my measure was neurological, behavioural scores may show weaker
> or
> no correlations.
> Hth-
> Andreas
> ________________________________
> Von: FSL - FMRIB's Software Library [[log in to unmask]<mailto:
> [log in to unmask]>] im Auftrag von hd x
> [[log in to unmask]<mailto:[log in to unmask]>]
> Gesendet: Donnerstag, 10. Februar 2011 11:17
> An: [log in to unmask]<mailto:[log in to unmask]>
> Betreff: Re: [FSL] Normalizing waytotal itself?
>
> Dear Saad,
>
> Thanks a lot for your detailed reply. However, I didn't want to use the
> normalized fdt_faths to represent the connectivity strength, but use the
> waytotal directly as suggested by "Tractography for surgical targeting in
> Heidi's & Tim's book. Figure 19.12". This is also suggested by Matt in one
> of his replies to this maillinglist: "What is it that you are trying to
> show?  That subjects with a stronger/weaker pathway have some difference in
> behavioral scores? Honestly, I might correlate the waytotal values
> themselves (if you are using at least one waypoint mask) with the
> behavioral
> score."
>
> Thus my question was if I shall normalize Waytotal itself by the sum of the
> seed and target sizes. But not how to normalizde fdt_path by waytotal. I'm
> sorry I didn't made this very clear in my first email in the background of
> so many discussion about the latter in this maillinglist.
>
> I really hope I can get some comments on that since I didn't see much
> discussion about it yet.
>
> Best,
> Huadong
>
>
> On 9 February 2011 12:18, Saad Jbabdi
> <[log in to unmask]<mailto:[log in to unmask]><mailto:
> [log in to unmask]<mailto:[log in to unmask]>>> wrote:
> Dear Huadong,
>
> 1) Waytotal normalisation
> When you run probtrackx, you are effectively building up a distribution
> using sampling, in the same way you may build a histogram by counting
> samples that fall into categories (bins).
> So for example, the fdt_paths file gives you the histogram for the spatial
> distribution of connections, and waytotal counts the number of samples that
> satisfy certain conditions (waypoint/exclusion criteria). When you divide
> the fdt_paths results by waytotal, you are acknowledging the fact that
> fewer
> samples have been used to build up the spatial histogram than the maximum
> possible number (i.e. #seed voxelsX#samples per voxel). You need to do that
> in order for your histograms to be comparable across subjects/hemispheres.
> In the same way, if you have a histogram of counts where you've used 100
> samples, you cannot compare the values to a histogram that used only 50
> samples, you can compare the odds but not the raw values.
>
>
> 2) Mask size and other concerns
> Although many people think that the mask size bias is a big worry, I
> personally think there are other more fundamental issues.
> When you calculate the probability of a connection from a seed to a target,
> then if the target is appropriately matched across subjects/hemispheres
> (e.g. it is the same anatomo-functional entity), then you are comparing
> like
> with like, so you shouldn't worry about mask size. However, it is true that
> the probabilities may be higher for bigger target masks, which is a problem
> that comes from the very nature of the probabilities that you calculate.
> In probtrackx, you are _not_ calculating tract "strength" (whatever that
> is), but instead you are calculating the level of confidence that you have
> on the trajectory from the seed to the target (of course through the high
> diffusion directions, goes without saying!). So you would expect your
> confidence to be higher if, for example, your target area is bigger (other
> things may also increase or decrease your confidence). If that is not
> satisfactory when it comes to regressing against behavioural data, it is
> not
> because of the size bias, but because of the quantity that you are
> calculating, ie your confidence on the connection.
>
> So even if you manage to somehow take into account the size of the mask in
> the probability (eg if you had a model for the conditional probability on
> mask size), you are still faced with the problem that a higher confidence
> on
> a connection does not necessarily imply a stronger functional connection
> between two areas. You may need to consider other quantities (e.g.
> microstructural or functional models), that you may calculate using the
> tract distribution, and disambiguate low confidence on tract from low
> functional connectivity etc.
>
> Cheers,
> Saad.
>
>
>
> On 9 Feb 2011, at 10:44, hd x wrote:
>
> Dear list,
>
> From previous discussions, I got the impression that it's good to use
> waytotal as the connectivity index when you want to correlate pathway
> strength with individual behavoural performances and when you are using at
> least one waypoint mask. (See
>
> http://mail.google.com/mail/?shva=1#search/label%3Afsl+interpretation+waytot
> al/125995c081e68cd7
>
> http://mail.google.com/mail/?shva=1#search/label%3Afsl+threshold+pathway/12a
> 2b2c25aec6d52)
>
> I'm now working on a study which investigates the correlation between
> pathway laterality and individual behavioural performances. I have a seed
> mask, a waypoint mask and a target mask (which is the same brain area as
> the
> waypoint mask covers) in each of the hemispheres. The right masks are
> homologous areas to the left masks. Then with the left masks I traced my
> left pathway and the right masks the right pathway.  I used the waytotal of
> the pathway to represent the pathway strength and calculated the pathway
> laterality accordingly by taking the absolute difference between the left
> and right waytotal.
>
> However, I got another concern. The masks I used for the left hemisphere
> are
> not of the same size of the right ones, although all subjects used the same
> set of left and right masks. In this case, I'm wondering if I should
> normalize the waytotal based on the mask size before I calculate the
> lateralization index. If I should, what would be the right way to do it?
> Would it be good to divide the waytotal by the sum of the size of seed and
> target masks?
>
> Your inputs will be highly appreciated.
>
> Best,
> Huadong
>
>
>
>
>
> --
> Saad Jbabdi
> University of Oxford, FMRIB Centre
>
> JR Hospital, Headington, OX3 9DU, UK
> (+44)1865-222466  (fax 717)
> www.fmrib.ox.ac.uk/~saad<http://www.fmrib.ox.ac.uk/~saad><
> http://www.fmrib.ox.ac.uk/~saad>
>
>
>
> --
> ------------------------------------------------------------
> H Xiang               PhD Candidate
> Donders Institute for Brain, Cognition and Behaviour
> NIJMEGEN, The Netherlands
> http://www.ru.nl/neuroimaging
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> Founding Webmaster
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>