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Hi Martin,

Thanks for your answer.

I actually compare neurospychological scores at baseline between drop-out
subjects and subjects with full time-points. If I ever find that drop-out
subjects are more severely affected than the subjects with full
time-points, then there might be a bias in the results of my LME study ?

How could I argue that significant patterns found in my LME study between
both groups are still valid accounting for this bias ? Is LME method robust
enough for compensating this kind of drop-out ?

Best,
Matthieu


Le mer. 17 oct. 2018 à 18:33, Martin Reuter <mreu...@nmr.mgh.harvard.edu> a
écrit :

> Hi Matthieu,
>
> 1) survival analysis is typically used if you want to detect if the
> time to an event is longer in one group vs the other (e.g. one group
> gets placebo the other drug and we want to know if recurrence is later
> in the drug group). Not sure this is what you need. The nice thing is,
> it can deal with drop-outs
>
> 2) No, you can directly test that (e.g. do more dieseased drop out than
> healthy, or are the dropouts on average more advanced (test-scores,
> hippo-volume etc) than the diseased at baseline... many options. you
> could also test interactions with age , gender etc. However, not
> finding an interaction may not mean there is no bias, it is just small
> enough to go undetected with your data size.
>
> 3) Survival analysis is a different analysis than LME.
>
> Best, Martin
>
> On Tue, 2018-10-16 at 16:15 +0000, Matthieu Vanhoutte wrote:
> >         External Email - Use Caution
> > Hi Martin,
> >
> > It's been a long time since this discussion but I return on this from
> > now... The problem is that I followed longitudinal images of two
> > groups where I had mainly missing time points at the end. Than you
> > suggested:
> > If you have mainly missing time points at the end, this will bias
> > your analysis to some extend, as the remaining ones may be extremely
> > healthy, as probably the more diseased ones drop out. You may want to
> > do a time-to-event (or survival-analysis) which considers early drop-
> > out.
> >
> > 1) I know the survival analysis toolbox on matlab, but now I would
> > like to know what information will this survival analysis give to me
> > ?
> > 2) Will this analysis tell me if there is a bias ?
> > 3) How to consider early drop-out with this type of analysis based on
> > mass-univariate LME analysis of longitudinal neuroimaging data ?
> >
> > Thanks in advance for helping.
> >
> > Best,
> > Matthieu
> >
> > Le mer. 14 déc. 2016 à 22:14, Martin Reuter <mreu...@nmr.mgh.harvard.
> > edu> a écrit :
> > > Hi Matthieu,
> > >
> > > 1. yes, LME needs to be done first so that values can be sampled
> > > from the fitted model for the SA.
> > >
> > > 2. yes, I was talking about gradient non-linearities etc that could
> > > be in the image from the acquisition. We currently don’t use non-
> > > linear registration across time points (only rigid).
> > >
> > > Best, Martin
> > >
> > >
> > > > On Nov 22, 2016, at 9:31 PM, Matthieu Vanhoutte <matthieuvanhoutt
> > > > e...@gmail.com> wrote:
> > > >
> > > > Hi Martin,
> > > >
> > > > Please see inline below:
> > > >
> > > > > Le 22 nov. 2016 à 17:04, Martin Reuter <mreu...@nmr.mgh.harvard
> > > > > .edu> a écrit :
> > > > >
> > > > > Hi Matthieu,
> > > > > (also inline)
> > > > >
> > > > > > On Nov 21, 2016, at 10:28 PM, Matthieu Vanhoutte <matthieuvan
> > > > > > hou...@gmail.com> wrote:
> > > > > >
> > > > > > Hi Martin,
> > > > > >
> > > > > > Thanks for replying. Please see inline below:
> > > > > >
> > > > > > > Le 21 nov. 2016 à 20:26, Martin Reuter <mreu...@nmr.mgh.har
> > > > > > > vard.edu> a écrit :
> > > > > > >
> > > > > > > Hi Matthieu,
> > > > > > >
> > > > > > > a few quick answers. Maybe Jorge knows more.
> > > > > > > Generally number of subjects / time points etc. cannot be
> > > > > > > specified generally. All depends on how noisy your data is
> > > > > > > and how large the effect is that you expect to detect. You
> > > > > > > can do a power analysis in order to figure out how many
> > > > > > > subject / time points would be needed. There are some tools
> > > > > > > for that in the LME toolbox:
> > > > > > > https://surfer.nmr.mgh.harvard.edu/fswiki/LinearMixedEffect
> > > > > > > sModels#Poweranalysis
> > > > > > >
> > > > > > > 1. see above
> > > > > > > 2. yes, also time points can miss from the middle. If you
> > > > > > > have mainly missing time points at the end, this will bias
> > > > > > > your analysis to some extend, as the remaining ones may be
> > > > > > > extremely healthy, as probably the more diseased ones drop
> > > > > > > out. You may want to do a time-to-event (or survival-
> > > > > > > analysis) which considers early drop-out.
> > > > > >
> > > > > > Is there any way to do with Freesurfer this kind of analysis
> > > > > > ?
> > > > >
> > > > > https://surfer.nmr.mgh.harvard.edu/fswiki/SurvivalAnalysis
> > > > > Yes, there is also a paper where we do this. It is a
> > > > > combination of LME and Survival Analysis (as for the SA you
> > > > > need to have measurements of all subjects at all time points,
> > > > > so you estimate that from the LME model).
> > > >
> > > > Thank you for the link, I will take a look at. So if understand,
> > > > this analysis has to be done after LME statistical analysis ?
> > > > Thereafter since SA need all time points, LME model will allow me
> > > > to estimate missing time points ?
> > > >
> > > > > > > 3. see above (power analysis)
> > > > > > > 4. GIGO means garbage in, garbage out, so the less you QC,
> > > > > > > the more likely will your results be junk. The more you QC
> > > > > > > the less likely will it be junk, but could still be. The FS
> > > > > > > wiki has lots of tutorial information on checking
> > > > > > > freesurfer recons. For longitudinal, you should
> > > > > > > additionally check the surfaces in the base, the brain mask
> > > > > > > in the base, and the alignment of the time points (although
> > > > > > > there is some wiggle space for the alignment, as most
> > > > > > > things are allowed to evolve further for each time point).
> > > > > >
> > > > > > For the alignment of the time points, should I better
> > > > > > comparing brainmask or norm.mgz ?
> > > > >
> > > > > It does not really matter, I would use norm.mgz. I would load
> > > > > images on top of each other and then use the opacity slider in
> > > > > Freeview to blend between them (that way the eye can pick up
> > > > > small motions). I would not worry too much about local
> > > > > deformations which could be caused by non-linearity (gradient).
> > > > > But if you see global misalignment (rotation, translation) it
> > > > > is a cause for concern) .
> > > >
> > > > Ok thank you. The non-linearity you are talking about are well
> > > > provoked by MRI system and not non-linear registration between
> > > > time points and template base, aren’t they ?
> > > >
> > > > Best regards,
> > > > Matthieu
> > > >
> > > > > > In order to avoid bias by adding further time points in the
> > > > > > model by the -add recon all command, is this better for each
> > > > > > subject to take into account all the time points existing for
> > > > > > it or only the ones that I will include in the model (three
> > > > > > time points / subject ; if existing 6 time points for any
> > > > > > subject ?)
> > > > > >
> > > > >
> > > > > Usually it is recommended to run all time points in the model
> > > > > (so a base with 6 time points) and not use the - - add flag.
> > > > > Also, Linear Mixed Effects models deal well with missing time
> > > > > points. It is perfectly OK to have differently many time points
> > > > > per subject for that. You should still check if there is a bias
> > > > > (e.g. one group always has 3 time points the other 6) that
> > > > > would not be good. Maybe also consult with a local
> > > > > biostatistician if you are not comfortable with the stats. The
> > > > > LME tools are matlab, and so are the survival-analysis
> > > > > scripts.
> > > > >
> > > > > Best, Martin
> > > > >
> > > > >
> > > > >
> > > > > > Best regards,
> > > > > > Matthieu
> > > > > >
> > > > > > > Best, Martin
> > > > > > >
> > > > > > > > On Nov 21, 2016, at 7:07 PM, Matthieu Vanhoutte <matthieu
> > > > > > > > vanhou...@gmail.com> wrote:
> > > > > > > >
> > > > > > > > Dear Freesurfer’s experts,
> > > > > > > >
> > > > > > > > I would have some questions regarding the LME model to be
> > > > > > > > used in longitudinal stream:
> > > > > > > >
> > > > > > > > 1) Which are the ratio limits or % of missing timepoints
> > > > > > > > accepted ? (according time, I have less and less subjects
> > > > > > > > time points)
> > > > > > > >
> > > > > > > > 2) Is it possible to include patients that would miss the
> > > > > > > > first timepoint but got the others ?
> > > > > > > >
> > > > > > > > 3) Considering a group in longitudinal study, which is
> > > > > > > > the number of subjects minimal of this group accepted for
> > > > > > > > LME modeling ?
> > > > > > > >
> > > > > > > > 4) Finally, concerning quality control and among a big
> > > > > > > > number of total time points, which essential controls are
> > > > > > > > necessary ? (Control of norm.mgz of the base, alignment
> > > > > > > > of longitudinal timepoints on base,… ?)
> > > > > > > >
> > > > > > > > Best regards,
> > > > > > > > Matthieu
> > > > > > > >
> > > > > > > >
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