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This can be seen from the technical papers that describe the fiber
orientation and tractography method, particularly Behrens et al 2003 and
Behrens et al 2007.

On 1/19/14 6:31 AM, "Meoded, Avner (NIH/NINDS) [E]" <[log in to unmask]>
wrote:

>P.s
>
>You mentioned that FA does not have direct influence on tractography, can
>you give a reference for that?
>
>Thank you
>
>Avner
>
>
>On 1/18/14 6:51 PM, "Matt Glasser" <[log in to unmask]> wrote:
>
>Hi Paul,
>
>That was a potential explanation for what might seem like
>counter-intuitive results I just thought up on a Saturday morning (there
>might be plenty of others!).  I suppose someone could test if this effect
>is real by looking at the HCP data and comparing a group with the
>smallest brains to a group of the largest brains.  One important variable
>would be whether the data were seeded from standard space (in which case
>the number of streamlines sent out would be constant across subjects) or
>native space (where the number of streamlines sent out would vary and
>potentially counteract the effect because a bigger brain would have more
>seeded streamlines).
>
>Peace,
>
>Matt.
>
>From: Chou Paul <[log in to unmask]>
>Reply-To: FSL - FMRIB's Software Library <[log in to unmask]>
>Date: Saturday, January 18, 2014 5:36 PM
>To: <[log in to unmask]>
>Subject: Re: [FSL] Values in matrix1 after probtrackx
>
>Dear Matt
>
>According to your last point of the reply, are there any references or
>approaches about how to adjust for the "smaller brain" issue in such
>tractography research ? I am focus on neurodegenerative disease and this
>problem seems very important to this field. Would you provide me some
>advices on this issue ?
>
>Thank you
>
>Best
>
>Paul
>
>> Date: Sat, 18 Jan 2014 12:39:51 -0600
>> From: [log in to unmask]
>> Subject: Re: [FSL] Values in matrix1 after probtrackx
>> To: [log in to unmask]
>>
>> I've certainly found both Mark and Tim to be extremely helpful over the
>> years and have learned an enormous amount from both of them.  I know it
>>is
>> greatly appreciated when support requests are directed to the public
>> e-mail list (so that others may benefit from and participate in the
>> discussion).
>>
>> The relationship between the number of streamlines sent out from an ROI
>> that reach another and the number (let alone mention functional
>>influence)
>> of axons is not yet well characterized.  It's worth keeping in mind that
>> FA (and more advanced measures like f1, f2, and f3) do not have any
>>direct
>> influence on tractography.  Tractography is based on sending out some
>> number streamlines and following samples of fiber orientation
>> distributions until some stopping criterion is reached (like a stop
>>mask,
>> exceeding a curvature threshold, looping back on a region previously
>> traveled, etc). Streamlines do not increase in number depending on the
>> number of steps (i.e. distance) the tractography algorithm needs to take
>> between seed and target.  One starts with a fixed number (that you set
>> when running probtrackx) and this represents the maximum possible value
>> you could get (if all streamlines travelled the whole distance between
>> seed and target ROIs).
>>
>> The two main applications where it has been successfully used are to
>>build
>> spatial uncertainty distributions of pathways (where the voxels with the
>> largest number of streamlines represent the higher probability of a
>> pathway being located there and the voxels with fewer numbers of
>> streamlines represent lower probability of a pathway being located
>>there.
>> The other is making comparisons between streamline counts in the same
>> individual, where many uninteresting factors that influence streamline
>> counts are controlled for.
>>
>> The use of tractography to produce grey matter to grey matter structural
>> connectomes is a relatively recent one.  Interpreting these results
>>across
>> individuals or between patients and controls relative to the various
>> potential confounds is quite challenging.  In this case, the explanation
>> could be as simple as the subjects with neurodegenerative disease have
>> smaller (atrophied) brains and therefore the distance between ROIs is
>> reduced, which would increase streamline counts because streamline
>>counts
>> decrease with increasing distance in a log-linear fashion (more steps
>> means more chances to be stopped/diverted away from the target).
>>
>> Peace,
>>
>> Matt.
>>
>> On 1/18/14 7:30 AM, "Meoded, Avner (NIH/NINDS) [E]"
>><[log in to unmask]>
>> wrote:
>>
>> >Dear Mark,
>> >
>> >I see you like to make assumptions. So let us assume that I am an high
>> >school student who does not understand a thing about DTI. Moreover I do
>> >not
>> >understand the basics of probabilistic tractography. So in order to
>> >understand more I read Diffusion MRI book (edited by Berg and Behrens)
>>and
>> >also papers that deal with different tractography methods. So now I
>> >understand a little bit of tractography but still there are unclear
>>issues
>> >that I would like to clarify with the experts in the field- that is the
>> >reason I contacted FSL community.
>> >If you see the title of my mail it is "Values in matrix1 after
>> >probtrackx";
>> >The specific question I have is what those values mean? Probabilistic
>> >tractography aim to quantify uncertainty on the PDD and build a
>> >connectivity
>> >distribution. Now if you go and check matrix obtained from network1
>>option
>> >in probrackx2 you will see that the matrix contain values in the range
>>of
>> >1-1,000,000 and beyond. You mentioned in you last e-mail that:
>> >"Uncertainty
>> >in direction at any point in the brain will enhance the uncertainty in
>>the
>> >tractography from that point onwards for any tracks that pass through
>>that
>> >point." How can we learn about this uncertainty from the matrix values?
>> >
>> >Indeed at the NIH there are many experts who are always available for
>> >discussion about all aspects of health and science. However, is
>> >FSL/Probtrakcx a NIH application???
>> >
>> >Finally I would like to show Timothy Behrens's response to my question
>>:
>> >
>> > "if you have posted it to the FSL list then you should get an answer
>> >soon.
>> >It is a very effective community forum.  You will understand that with
>> >more
>> >than 5000 users, there is no way I can personally answer every question
>> >and
>> >hope to maintain a research career!"
>> >
>> >This is the answer from the researcher who is the first author on the
>> >NeuroImage paper from 2007 about probabilistic tractography, and also
>>the
>> >one who wrote the chapter MR diffusion tractography with Saad Jbadi in
>>the
>> >book mentioned above.
>> >
>> >
>> >
>> >
>> >Avner
>> >
>> >
>> >On 1/18/14 4:58 AM, "Mark Jenkinson" <[log in to unmask]>
>>wrote:
>> >
>> >> Hi,
>> >>
>> >> Artifact "correction" methods don't fully remove all artifacts, so
>>you
>> >>cannot
>> >> rule out the possibility that artifacts are causing the things you
>>are
>> >>seeing
>> >> just because you have run artifact correction.  Such methods remove a
>> >>lot of
>> >> the effect of artifacts but not absolutely everything.
>> >>
>> >> I'm not sure what you mean by "steps" but the samples in probtrack
>> >>refer to
>> >> individual streamlines (that are selected from the probability
>> >>distribution of
>> >> possible streamlines).  Uncertainty in direction at any point in the
>> >>brain
>> >> will enhance the uncertainty in the tractography from that point
>> >>onwards for
>> >> any tracks that pass through that point.
>> >>
>> >> You definite cannot make categorical statements such as "more samples
>> >>mean[s]
>> >> more disease".
>> >> As I said, there are a *lot* of things that can influence
>>tractography
>> >>results
>> >> and you really should discuss you particular case, with your
>>particular
>> >> subjects and you particular data acquisition, with someone who is
>> >>experienced
>> >> with tractography.  There certainly should be such people in the NIH.
>> >>
>> >> All the best,
>> >> Mark
>> >>
>> >>
>> >> On 17 Jan 2014, at 13:10, "Meoded, Avner (NIH/NINDS) [E]"
>> >> <[log in to unmask]> wrote:
>> >>
>> >>> Hi
>> >>> The raw DTI data was corrected for artifacts.
>> >>> As you mentioned less uncertainty may enhance measures of
>> >>>connectivity. But
>> >>> in my case I documented reduced FA and not increased FA, the latter
>>is
>> >>>seen
>> >>> perhaps in regions with reduced crossing fibers.
>> >>> Now my question is specific to probabilistic tractography: number of
>> >>>samples
>> >>> obtained from probtrackx between to regions mean number of "steps"
>> >>>track
>> >>> does; are those "steps" depends on the uncertainty? So at the end
>>more
>> >>> samples mean more disease?
>> >>>
>> >>> Thank you
>> >>>
>> >>> Avner
>> >>>
>> >>> On 1/17/14 7:39 AM, "Mark Jenkinson" <[log in to unmask]>
>> >>>wrote:
>> >>>
>> >>>> Hi,
>> >>>>
>> >>>> These are not simple questions and it will depend a lot on the
>>nature
>> >>>>of
>> >>>> your
>> >>>> data - SNR, artefacts, amount of movement, etc.  There are also
>>some
>> >>>> potential
>> >>>> biological possibilities, such as reduction in crossing tracts,
>>which
>> >>>>can
>> >>>> enhance measures of connectivity (since there is less uncertainty
>>in
>> >>>>the
>> >>>> crossing region) without meaning that the axonal tract is
>>biologically
>> >>>> "stronger".  You should look very critically at your data and show
>>it
>> >>>>to
>> >>>> people who are experienced with diffusion analysis.
>> >>>>
>> >>>> All the best,
>> >>>> Mark
>> >>>>
>> >>>>
>> >>>> On 16 Jan 2014, at 18:08, "Meoded, Avner (NIH/NINDS) [E]"
>> >>>> <[log in to unmask]> wrote:
>> >>>>
>> >>>>> Dear FSL users
>> >>>>>
>> >>>>> I conducted a study with network1 option and then did structural
>> >>>>>connectome
>> >>>>> analysis, in patients affected with neurodegenerative disease.
>> >>>>> I also performed TBSS and found reduced FA values in different
>>areas
>> >>>>>in
>> >>>>> patients compared to controls.
>> >>>>> The problem is that I have higher values stored in the
>>connectivity
>> >>>>> matrices
>> >>>>> in patients compared to controls, and hence after connectome
>> >>>>>analyses I
>> >>>>> obtained networks that are more connected in patients. Now I know
>> >>>>>that
>> >>>>> these
>> >>>>> values cannot represent axons, but how you can explain reduced FA
>>in
>> >>>>> patients
>> >>>>> and more streamlines evaluated in probtrackx?  Or what are the
>> >>>>>numbers
>> >>>>> stored
>> >>>>> in the matrix mean? (after running seed to seed network 1)
>> >>>>>
>> >>>>> Is this because in patients (with white matter disease, lower FA)
>> >>>>>there is
>> >>>>> more uncertainty in voxels between roi1 and roi2 and therefore we
>> >>>>>get more
>> >>>>> samples so basically tracts tend to spread more and as a results
>>more
>> >>>>> sample?
>> >>>>> so at the end more samples which represents more uncertainty
>> >>>>>(disease)
>> >>>>> Should I normalize the matrices in some way
>> >>>>>
>> >>>>>
>> >>>>> Thank you
>> >>>>>
>> >>>>> Avner