Diffusion Tensor Imaging (DTI) e Neurite Orientation Dispersion and Density Imaging (NODDI)
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1 Diffusion Tensor Imaging (DTI) e Neurite Orientation Dispersion and Density Imaging (NODDI) Claudia AM Gandini Wheeler-Kingshott, PhD Prof. of MRI Physics Overview Diffusion and microstructure NODDI theoretical background Conclusions 1
2 Diffusion and microstructure Introduction Diffusion behavior = microstructure signature Diffusion and microstructure Diffusion MRI: MR images sensitive to diffusion Random motion of water molecules Microstructure Pattern of diffusion MRI scanner Task: retrieve the microstructure that best explains the measured MR signals Diffusion-weighted MRI signal S(sequence; microstructure) 2
3 Diffusion and microstructure The diffusion MRI experiment b = 0 (no gradient) G G Study a voxel: Task: infer the microstructural properties of the tissue within which spins diffuse from the observation of a set of DW signals in each voxel. Diffusion and microstructure Diffusion Tensor Imaging ε D= ε ε T λ highest 0 λ ε 1 0 ε 2 λ 3 ε 3 lowest From the DT it is possible to calculate indices which are ROTATIONALLY INVARIANT, i.e. they do NOT depend on patient positioning in the scanner: 3
4 Diffusion and microstructure Diffusion Tensor Imaging (DTI) Fractional anisotropy: FA = 3 2 ( λ 1 D ) 2 + ( λ 3 D ) 2 + ( λ 3 D ) 2 λ 1 2 +λ 2 2 +λ 3 2 Mean Diffusivity ( ) MD = λ 1 + λ 2 + λ 3 3 Diffusion and microstructure The Diffusion Tensor model: DTI shape High anisotropy colour A P Low anisotropy L R x I-S Basser P.J, Biophys J (1994); Pierpaoli C., Radiology (1996) Alexander Leemans (Alexander@isi.uu.nl) 4
5 NODDI theoretical background Neurite orientation dispersion and density imaging Axons: transmit information Image of a neuron (by 1906 Nobel prize Santiago Ramón y Cajal) Neurites: dendrites and axon Neurite density index (NDI) amount of neurites in a voxel, ranging in [0; 1] Dendrites: receive information Cell body: contains the nucleus Orientation dispersion index (ODI) spread of neurite orientations, ranging in [0; 1] ODI = 0 ODI = 1 NODDI theoretical background The three-compartment NODDI model Physical substrate CSF, oedema, inflammation axons & dendrites, excluding myelin neuronal cell bodies, glial cells, ECM Courtesy of Prof GC DeLuca, Oxford Courtesy of Prof GC DeLuca, Oxford Geometric model and compartment Free space Isotropically dispersed sticks Anisotropically hindered space (Isotropic compartment) (Intra-neurite compartment) (Extra-neurite compartment) 5
6 Dominant Orientation DTI Fractional Anisotropy 0 1 Orientation Dispersion 0 1 NODDI Neurite Density 0 1 CSF 0 1 NODDI disentangles the key microstructural factors contributing FA Scatterplots are colored by stratified FA values Neurite Density White Matter Orientation Dispersion Grey Matter Orientation Dispersion 6
7 NODDI and Epilepsy: Focal Cortical Dysplasia (FCD) FCD : Malformation of cortical development Disrupted laminar architecture Disrupted columnar organisation Abnormal cells, including dysmorphic neurons and balloon cells 42% of patients are MRI negative NODDI Tissue Model Fitted parameters include Intracellular volume fraction (FICVF) or Neurite Density Index (NDI) Concentration parameter of Watson distribution transformed to orientation dispersion index (ODI) 7
8 Methods and Aims Six patients (5 FCD, 1 tuberous sclerosis) 3T GE Signa Excite HDx scanner Full clinical protocol + NODDI protocol Single shot EPI, mm slices, 96x96 matrix (zero filled to 128x128), FOV 24x24cm, TE 85ms, TR 13s, gradients 40mT/m Two HARDI shells (9 b=0, 24 b=700, 48 b=2000) Scan time 18 minutes Fitting with NODDI Matlab Toolbox 1 + FDT (FSL) Maps of NDI compared to clinical + DTI (FA, MD) Hypothesis: reduction in NDI will be detected in vivo 1 T1 NDI #1 8
9 T1 T2 PROPELLER #2 FA MD NDI #2 Similar findings in patients 3, 4 and 5 9
10 T1 T2 FLAIR #6 MD NDI #6 10
11 Discussion: Previous Studies Structural T1 thickened cortex/blurred grey-white boundary T2 cortical/subcortical signal hyperintensities 1 42% undergoing surgery with normal MRI have FCD 2 DTI Reduced FA/increased MD in underlying white matter Non-specific, extends beyond abnormality 3 FA affected by neuronal density, fibre orientation dispersion, axonal diameter, degree of myelination, Cannot evaluate dysplastic grey matter (low FA, CSF) 1 Barkovich J Clin Neurophysiol 1996, 2 Chapman JNNP 2005, 3 Eriksson Brain 2001 Discussion: Current Study (NODDI) Abnormality clearly identified in 6 patients Consistent localised reduction of NDI More readily identifiable than on clinical/dti scans Advantages of NODDI Disentangles contributors to FA e.g. NDI Suitable for grey and white matter Avoids CSF contamination NODDI is viable in a clinical population and may aid identification of FCD in patients with epilepsy 11
12 Conclusions NODDI in epilepsy NODDI is sensitive to microstructure NODDI is clinically feasible Reduced protocol to acquire data in 10 minutes Protocols available for Siemens Skyra and Philips Achieva (no need for research agreement!) Hypothesis: Sensitivity of NODDI in TLE lesions superior to DTI Specificity of NODDI in TLE lesions revealing microstructural abnormalities Prediction of clinical outcome after surgery Thank you for your attention! 12
NeuroImage 61 (2012) Contents lists available at SciVerse ScienceDirect. NeuroImage. journal homepage:
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