Overview. Fundamentals of functional MRI. Task related versus resting state functional imaging for sensorimotor mapping

Transcription

1 Functional MRI and the Sensorimotor System in MS Nancy Sicotte, MD, FAAN Professor and Vice Chair Director, Multiple Sclerosis Program Director, Neurology Residency Program Cedars-Sinai Medical Center Overview Fundamentals of functional MRI Task related versus resting state functional imaging for sensorimotor mapping Use of diffusion tensor imaging (DTI) and diffusion tensor tracking (DTT)

2 How does an MRI scanner make an image? Standard MRI scans are pictures of water (protons) Magnet lines up protons Radiofrequency (rf) energy disrupts aligned spins Return to aligned spins causes energy to be released which is used to reconstruct an image Response to rf energy is different for different tissues - this provides tissue contrast Magnetic field aligns protons Applied RF energy moves spins to higher energy state, return to baseline state causes release of energy

3 The Basics of MRI Standard MRI MS Disease monitoring FLAIR = fluid-attenuated inversion-recovery.

4 Which Patient Is More Disabled? Patient A: Age 47 T2 vol = 37.8 ml EDSS = 1.5 Patient B: Age 29 T2 vol = 38.4 ml EDSS = 2 EDSS = Expanded Disability Status Scale. Disability/Radiological Paradox Disease has diffuse effects Measures of disability do not capture many disease effects Cross-sectional studies have limited sensitivity Hidden Pathology - beyond the lesions Compensation may limit clinically apparent disability

5 Functional MRI Uses contrast of oxygenated hemoglobin level to localize active brain areas Repeated measures possible Heavily used in cognitive science research Differences are detectable early in the course of MS with both motor and cognitive tasks The Blood Oxygen Level Determination (BOLD) Effect Department of Neurology

6 Neurovascular Coupling and BOLD Department of Neurology Activation functional MRI finger opposition

7 Sensorimotor network revealed by functional MRI Faivre et al, J Clin Neuroscience (22) 2015: Intrinsic Connectivity Networks: Detectable with functional MRI Functional MRI recordings reveal spontaneous, correlated brain activity Low frequency BOLD signal fluctuations detectable Persist during sleep, general anesthesia and occurs during non-task activities ie resting state Correlated activity occurs in functionally related, but anatomically separable regions Department of Neurology Seeley et al Neuron 62(1): 42-52, 2009

8 Structurally connected regions are functionally linked Faivre et al, J Clin Neuroscience (22) 2015: Activation versus Resting state fmri Lowe et al J of Int Neuropsychol Society (2106) 22:

9 PNAS 100(1): , 2003 Department of Neurology Multiple connective networks can be detected: Seed based Department of Neurology Raichle (14) 4: , 2010

10 Networks Degenerate Together Department of Neurology Seeley et al Neuron 62(1): 42-52, 2009 Short detour through white matter connectivity..

11 Water Diffusion - Isotropic and Anisotropic Beaulieu, C. NMR Biomed 2002;15: Diffusion along axons is anisotropic Beaulieu, C. NMR Biomed 2002;15:

12 Diffusion gradients applied in 6 directions Masutani et al. Eur J Radiology, 46(2003):53-66 Tensor Displayed as an Ellipsoid Masutani et al. Eur J Radiology, 46(2003):53-66 highest lowest ε ε ε D The DT can be diagonalised to give three eigenvalues,, and three eigenvectors,

13 DTI of Major White Matter Tracts Pajevic and Pierpaoli, Mag Res Med (1999);42: Diffusion Tract Tracing (DTT)

14 Diffusion Tensor Tracking Hagmann P et al. Radiographics 2006;26:S205-S223 Van Aart E et al. Intl J Biomed Imaging Vol 2011 Tensor Eigenvalues = λ 1, λ 2, λ 3 Axial Diffusivity (AD) = λ 1 Radial Diffusivity (RD) = (λ 2 +λ 3 )/2 Fractional Anisotropy (FA) = formula not shown Callosal Agenesis Masutani et al. Eur J Radiology, 46(2003):53-66

15 Diffusion Tensor Fiber Tracking: Corpus Callosum Huang et al. Neuroimage 26(2005): DTT Reveals Thalamocortical Connectivity Department of Neurology

16 Tract Based Spatial Statistical (TBSS) Approach to DTI analysis Smith et al (2007) identifies center of each white matter tract based on highest fa value. Alignment of tract centers using non-linear warping to allow group comparisons Tract skeletons representing the centers of major tracts are created from group data Statistics can be done on voxel-wise basis using all diffusion parameters (MD, axial and radial diffusivity, fa) Whole brain analysis, corrected for multiple comparisons FA Skeleton

17 Group differences: FA RRMS vs. Controls Correlations with Motor Function: Radial Diffusion vs. Left 9HPT

18 Correlations with Motor Function: Radial Diffusion vs. Left 9HPt Aberrant Activation Patterns in Early MS Revealed by fmri Finger opposition - Right hand

19 Is this compensation? Compensation or Disinhibition? fmri during Finger tapping task Controls (A) RRMS (B) Transcallosal hand motor Fibers (TCHM- green) Left corticospinal tract (LCST- blue) 9 hole peg test (9HPT)

20 Compensation or Disinhibition? fmri during finger movements

21 Longitudinal Assessment: Practice Effects Baseline Time 2 Difference Putting it all together: Structure, function and networks

22 Resting State fmri: Default Mode Network (DMN) Damoiseaux and Greicius Brain Struct Funct 2009, 213: Summary Structural and functional connectivity can be assessed using advanced MRI techniques Intrinsic connectivity is revealed by non-task BOLD measures Brain network degeneration is implicated in specific neurodegenerative disorders Plasticity of these networks, including sensorimotor systems, may provide useful readouts assessing neuroprotective and remyelination therapies

23 Thank you for your attention!