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Jan 14, 2013 Jason Su

Journal Club: Deoni et al. One Component? Two Components? Three? The Effect of Including a Nonexchanging ‘‘Free’’ Water Component in mcDESPOT . Jan 14, 2013 Jason Su. Motivation. mcDESPOT provides fast, whole-brain estimation of myelin water fraction

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Jan 14, 2013 Jason Su

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  1. Journal Club:Deoni et al. One Component? Two Components? Three? The Effect ofIncluding a Nonexchanging ‘‘Free’’ Water Component in mcDESPOT. Jan 14, 2013 Jason Su

  2. Motivation • mcDESPOT provides fast, whole-brain estimation of myelin water fraction • However, its accuracy near CSF may be questionable due to partial voluming • A third non-exchanging component in the tissue model may allow this to be accounted for • Lankford has recently criticized the precision of mcDESPOT with an unbiased fitting algorithm • Is this observed in practice with constrained SRC?

  3. Theory • The mcDESPOT signal equations are expanded to include a 3rd component or free water pool • This is a straightforward extension of the block diagonal matrices with some key assumptions, 10 total parameters • Adds 3 new parameters: T1, T2, and volume fraction of the free pool • 1500 < T1free <7500ms; 150ms < T2free < 1000ms; 0 < Ffree< 0.75 • The free pool is nonexchanging, avoids adding 2 possible new exchange rate parameters • Assumes that it models CSF separated by the blood-brain barrier • The IE pool is at least 5% of the volume of the voxel

  4. Concerns • Is degeneracy possible? Can myelin and IE pools be confused with each other? • In 2-pool model, this can occur if MWF is allowed to be ≥0.5 • What if here free pool is 0.2, the remaining 0.8 could be split between MWF and IE interchangeably, is this taken care of? • SRC algorithm • Ignoring some fundamental issues I’ve encountered, i.e. mean normalization and off-resonance as a cyclic dimension • Not stated whether it usually converges or ends due to hitting the iteration limit • In my simulations, it’s usually the latter

  5. Methods • Simulation • Simulated a 3-component model 50,000x each over a range of tissue parameters and fitted with 2- or 3-component models • In-vivo at 3T – protocol is the same as with 2-component, 8 SPGR and 8 SSFP, and low-res IR-SPGR for DESPOT-HIFI B1 maps • Intra-subject repeatability • 24yo male, 5 times over 5 weeks • Inter-subject variability • 10 1yo infants • Why infants? To accentuate variability?

  6. Results – Simulation

  7. Notes • Seems to be a fair amount of bias in Ffree estimate, almost 8% • Histograms in general are fairly large with a width of about 0.08-0.11 • My own simulations show similar or worse performance in two-pool models with SNR of 20-30 • Not sure how much noise was added in theirs

  8. Product mcDESPOT

  9. Modified mcDESPOT

  10. Notes • The 2-pool model tends to underestimate the MWF in regions near CSF compared to 3-pool • Makes sense, uses more of longer IE component as a surrogate • Would’ve liked to see this in MS brain with variety of lesions • Especially because there is the question of whether edema would allow exchange with 3rd pool

  11. Results – Curves

  12. Notes • BIC is a criterion that’s often used to compare fitting models • Penalizes for number of parameters, promotes a simpler model to avoid overfitting • Closely related to Mallow’s Cp for linear models • Is a heuristic, cross validation is better for evaluating predictive value of a model but may not work here • SSFP fits are kind of iffy, particularly phase 0

  13. Results – Reproducibility and Variability

  14. Notes • Shows the characteristic behavior of low MWF CoV in white matter, high CoV in gray • What registration was used for the inter-subject data? • Hard to interpret the intra-subject vs inter-subject results • Are 1yo infants supposed to have about the same amount of myelination, how variable is it in development? • Intra-subject variation is half of inter-subject, either MWF doesn’t vary much between infants or high variability in subject? Is 5 samples enough for CoV? • Algorithm reproducibility is bad near edges/CSF? • Wonder what this looks like for 2-pool

  15. MWF Variation in Infants Deoni et al. Investigating white matter development in infancy and early childhood using myelin water faction and relaxation time mapping. Neuroimage. 2012 Nov 15;63(3):1038-53.

  16. Discussion • 3% deviation in homogeneous WM and GM compared to 2-pool • Is it worth changing model depending on location in brain? • Is it possible in histology to examine if such a free pool in tissue is real? • The need for a 3rd pool arises out of need to account for partial voluming, so phantoms should study that not necessarily 3-component mixture • Examine the effects on 3rd pool as introduce more partial voluming, we could be able to precisely change the Ffree depending on voxel size?

  17. Discussion • Concerned about even more reduced precision compared to 2-pool • Variability of MWF near edges may indicate 3-pool model is hard to estimate where it counts. • CoV of Ffree map? • Surprising that there is nothing added to the acquisition • Can we really get a 3-pool fit for free from what we have already? • CRLB would say otherwise.

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