DTI and ALS

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					Corticospinal Degeneration in
Amyotrophic Lateral Sclerosis
            (ALS)

        Investigation with DTI
    Sarah Carrington Heidi Johansen-Berg Emma Sillery

                         FMRIB
            What is ALS?
• Progressive neuromuscular disease

• Incidence ~ 2/10,000

• Charcot & Joffroy (1869) – Involves both
  upper (UMN) and lower motor neurons
  (LMN)

• Associated with dementia in ~3.5% of
  cases
        Lower vs. upper motor neuron
                 syndromes

•    Progressive             •   Primary Lateral
    Muscular Atrophy             Sclerosis (PLS)
    (PMA)                    •   ~1% of Patients
•   ~10% of patients         •    Symptoms
•    Symptoms                    include:
    include:                 1. Hyper-reflexia
1. Muscular                  2. Babinski Sign
   weakness
                             3. Spasticity
2. Muscular wasting
3. Fasciculations
              Pathology of ALS
• Axonal degeneration, gliosis, and myelin pallor in the
  posterior limb of the internal capsule
• Loss of large pyramidal motor neurons (Betz cells) and
  cortical degeneration

• BUT ALL OF THESE SIGNS ARE
  FOUND POST MORTEM
• As yet, there is no objective and sensitive marker of
  UMN involvement.
   Aims and hypotheses: Part 1
• To assess the integrity of the corticospinal tract (CST)

• Diffusion Tensor Imaging to investigate the degree of
  anisotropic diffusion

• In white matter, the principle direction
  of diffusion corresponds well with the
  orientation of major fibres in each voxel


• If CST is degenerated in ALS patients, would expect
  less anisotropy of diffusion compared with controls
   – Ellis et al., 1999; Toosey et al., 2003
           Fractional Anisotropy
                   (FA)

• A value that reflects the extent to which diffusion
  can be accounted for by anisotropic diffusion




                  R                  L
              Methods: Part 1
• 9 patients – 7 males
  – 3 with PLS, 1 with PMA, 5 with ALS
  – Assessed on the Amyotrophic Lateral Sclerosis
    Functional Rating Scale
• 7 controls – 5 males
• DTI – 63 volumes
  – 3 without diffusion weighting
  – 60 diffusion gradients with different weightings
• Structural – T1.5 – converted into standard
  space
           Analysis: Part 1
• Registration and motion correction
• FA calculated for each voxel – FA map
• Converted into standard space
• Smoothed with 3mm kernel
• FA map for each individual was then
  merged into one file
• Used T-tests to look for areas where FA
  was significantly different between patients
  and controls
             Results:
Part 1 – Areas where patients have
  reduced FA relative to controls




            R       L
R      L
         Part 2: Tractography
• By following the direction of diffusion, it is
  possible to ‘reconstruct’ major fibre pathways




    R             L


• Probabilistic tractographic algorithm creates a
  quantitative reconstruction of these tracts
             Part 2 - tractography
•    Investigating projections from the internal
     capsule (z=2) to the primary motor cortex
•    4 main measures
    1.   The mean probability that voxels are connected to M1

    2.   Intensity – the probability that the voxel maximally connected
         to M1 reaches the target

    3.   Cross-sectional volume of the CST in the internal capsule

    4.   Cross-sectional volume of the high probability core of the CST
         in the internal capsule
•    If the CST is degenerated in patients with ALS,
     should be less able to track along it
                                         The mean probability and intensity of
                                        connection to M1 appears decreased in
                                           patients compared with controls

                                                                                       1
Mean probability of connection




                                 0.25

                                  0.2                                                0.95




                                                                         Intensity
                                 0.15                                                 0.9
           to M1




                                  0.1                                                0.85

                                 0.05                                                 0.8

                                   0                                                 0.75
                                           Controls           Patients                      Controls           Patients
                                                      Group                                            Group




                                                      Non-significant (p<0.05)
Thresholded volume of internal capsule is
    smaller in patients than controls

                           27.8
                           27.6
      Thresholded volume



                           27.4
                           27.2
                            27
                           26.8
                           26.6
                           26.4
                           26.2
                            26
                                     Controls           Patients
                                                Group




                                  Non-significant (p<0.05)
Volume of CST in the internal capsule is
    larger in patients than controls

               51

               50

               49

               48
      Volume




               47

               46

               45

               44

               43
                       Controls           Patients
                                  Group




                    Non-significant (p<0.05)
               Pending…
• Does disease severity correlate with FA
  and ability to track between internal
  capsule and Primary motor cortex?

• Does diagnosis correlate with either of
  these points?

				
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posted:10/25/2011
language:English
pages:15