fMRI (functional Magnetic Resonance Imaging) and Optic Neuritis

1
fMRI (functional Magnetic Resonance Imaging) and
Optic Neuritis

• Recovery from optic neuritis is associated with a
  change in the distribution of cerebral
  response to visual stimulation a fMRI study
• Functional magnetic resonance imaging of the
  cortical response to photic stimulation in humans
  following optic neuritis recovery
• -A.J Thompson et al

2
MRI vs. fMRI
Functional MRI (fMRI) studies brain function.
MRI studies brain anatomy.
Source Jody Culhams fMRI for Dummies web site
3
fMRI Setup
Source Jody Culhams fMRI for Dummies web site
4
Hemodynamic Response Function
signal change (point baseline)/baseline usu
ally 0.5-3 initial dip -more focal and
potentially a better measure -somewhat elusive so
far, not everyone can find it
time to rise signal begins to rise soon after
stimulus begins time to peak signal peaks 4-6 sec
after stimulus begins post stimulus
undershoot signal suppressed after stimulation
ends
Source Jody Culhams fMRI for Dummies web site
5
MRI vs. fMRI
MRI
fMRI
one image
fMRI Blood Oxygenation Level Dependent (BOLD)
signal indirect measure of neural activity

many images (e.g., every 2 sec for 5 mins)
? neural activity ? ? blood oxygen ? ?
fMRI signal
Source Jody Culhams fMRI for Dummies web site
6
The papers

• Both by the same authors and has similar
  experimental setups
• The second paper is a follow up to the results
  presented in the first paper

7
Terms and Observations

• Myelin The fatty sheath coating the axons of the
  nerves it allows efficient conduction of nerve
  impulses.
• MS (Multiple Sclerosis) Demyelination of the CNS
• ON (Optic neuritis) An inflammatory disorder of
  the optic nerve that usually occurs in only one
  eye and causes visual loss and sometimes
  blindness. It is generally temporary.
• Temporary Patients usually regain visual acuity
  after a period of time.
• Visual acuity Sharpness or clearness of vision.
• Measured using Snellen charts and Ishihara
  color plates.
• Question How is visual acuity regained? Given
  that ON is a common precursor to MS. (Implying
  that the optic pathways are probably irreparably
  damaged)

8
Hypothesis and Study

• Possibility of cortical re-adaptation (functional
  reorganization)
• Use fMRI to study patients who have recovered
  from ON.
• Pick patients who had only one eye affected.
• Match with equal number of normal subjects
• Conduct additional structural scans and VEP
  (Visual Evoked Potential)
• Interpret the fMRI analysis

9
fMRI experimental setup

• 1.5 T magnet
• One volume every 4 seconds, for a duration of 8
  minutes (860/4 120)
• Each volume has a size 969610 vox (2.5 mm in
  plane 5mm thick slices)

Acitvation Red 8hz photic stimulation to one eye
12 cycles of alteration
5 volumes per state
Baseline
10
Preprocessing Head motion correction

• Reference 9 of the first paper Methods of
  Diagnosis and treatment of stimulus-correlated
  motion in generic brain activation studies using
  fMRI
• Find mean image of time series (base)
• Minimize MAD (mean absolute difference) of each
  with respect to base
• Realignment done using tricubic spline
  interpolation
• Difference between SCM (Stimulus Correlated
  Motion) between the two groups was not
  significant. (Paper does not mention the actual
  values for them! ). Hence not accounted for in
  this study

11
fMRI data analysis GBAM

• GBAM Generic Brain Activation Map. Reference
  13 Generic brain activation mapping in
  functional magnetic resonance imaging a non
  parametric approach.
• Fit a model
• Y(t) is the time course of a single voxel
  (IMP slice wise)
• w is fundamental frequency of stimulus
• 2 harmonic components
• abt represents a linear trend
• rho(t) is the residual
• rho(t) is usually a first order autoregressive
  process.
• Pseudogeneralised lest squares fitting
• Reduce each time course to a single value
  reflecting the power at fundamental frequency

12
fMRI data analysis GBAM
Time series
FPQ maps
Median FPQ maps

• To check the hypothesis that a given voxel FPQ
  value is determined by periodic experimental
  design, authors use Randomization testing
• Randomly permute the slices (of each volume with
  corresponding slice location in another volume)
  of the time series to obtain 10 random time
  courses
• Another paper asserts that the FPQ sampled this
  way is indistinguishable from a FPQ derived from
  image sequences when no stimulus is provided
• Calculate the FPQ maps for each of these time
  courses
• Generic analysis Register these maps into the
  standard space (Talairach and Tournoux)
• GBAM obtained by comparing medians

observed

randomized
Subject 1
observed
randomized
Subject 2
Model fitting and registration
13
Results
Left 3 selected slices for controls (A and B),
unaffected patient eye (C) and ON affected
patient eye (D) Bottom Comparison of VEP delay
in affected patient eye
Key observations Extra occipital response and
phase of this response
14
Results

• The identified extra occipital areas are known to
  have extensive connections with the visual
  processing system
• Unaffected eye also displayed extra cortical
  activation areas. Possibly due to clinically
  silent abnormality
• During an episode of ON VEP amplitude decreases
  and latency increases. After recovery, amplitude
  more or less returns back to normal but latency
  persists
• The result of reduced volume in the visual cortex
  correlates with previous studies
• But did not report extra occipital response (due
  to methodological differences?)
• Strengths the hypothesis of possible cortical
  reorganization

15
Results

• Since the activation in the extra occipital areas
  was almost perfectly out of phase with stimulus,
  they conducted another study varying the epoch
  duration to rule out this chance happening
• Reduced extent of response across groups to the
  longer stimulus duration. (Largest effect seen in
  affected eye)
• Rules out a fixed delay in extra occipital
  activation and implies phase dependency
• The difference in visual cortex activation volume
  was more significant with longer epoch
• Possibly reasons
• Active inhibition during baseline
• Redistribution of cortical blood supply (Stolen)
• Possible after image in patients

16
And.

• Am Done
• Qs?