2012.10.30.                                                                 Diagnostic neuroimaging modalities         Wat...
2012.10.30.„The forgotten molecule”               molecule”Water in biological tissues                              Kémiai...
2012.10.30.Image source: Brian Wandell, Stanford                                                 3
2012.10.30.                                                                                                         CHAPTE...
2012.10.30.                            The image contrast formation during                                               S...
2012.10.30.                                                                                          Displaying the diffus...
2012.10.30.                                                                            Image source: Brian Wandell, Stanfo...
2012.10.30.Diffusion tractography Tract = brain pathway, axonal pathways Tractography = displaying white matter pathways t...
2012.10.30.                                                                      Konnektivity (c) Jakab A.Beyond tensors… ...
2012.10.30.                                                                                                               ...
2012.10.30.White matter characterization with DTI?                                  Anizotrópia -   Anizotrópia - -   Aniz...
2012.10.30.DTI in neuro-oncology       neuro-                                                                             ...
2012.10.30.    Theodor Meynert                                    (1833-1892)                                             ...
2012.10.30.                                                                  Ohdo syndromaSmall girl, epileptic seizures  ...
2012.10.30.              Fiber tracking of a living fetus in              utero                                           ...
2012.10.30.Biological correspondence: regions                             Biological correspondence: regionsdefined by Atl...
2012.10.30.Any questions?                         17
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Week 2. Diffusion magnetic resonance imaging, tractography, mapping the brain's connectome.

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Week 2. Diffusion magnetic resonance imaging, tractography, mapping the brain's connectome.

  1. 1. 2012.10.30. Diagnostic neuroimaging modalities Water: Water : the forgotten molecule Diffusion magnetic resonance imaging CT – Computed Tomography Brain anatomy Structural MRI Fine brain anatomy and fiber tracking Stereotactic reference frame Vascular structure Dr. András Jakab, MD, PhD Multi-modal imaging Intra-operative imaging Diffusion, perfusion MRI Dr.Berényi Ervin, MD, PhD field spectrum for modalities, open MRI, low- Fine pathological information 1.Diagnostic imaging Positron Emission MR Spectroscopy 2.Research Tomography PET Brain metabolism Brain function Brain metabolism Biochemical mapping 3.Neurosurgery Electro encephalography, Functional MR imaging fMRI Multimodal Imaging in Neurosciences credit course, LORETTA, Brain function Magnetoencephalography 2012KEY LEARNING POINTS TODAY1. What is the biological diffusion in the human brain like?2. How does diffusion weighted MRI work? (DWI)3. How does diffusion tensor MRI work? (DTI)4. What is fiber tractography? CHAPTER I. – BIOLOGICAL5. What are the clinical applications of DWI? DIFFUSION6. What are the research applications of DTI and tractographies? Measuring tissue properties with MRI „The forgotten molecule” molecule” T1 relaxation T2 relaxation Structural MRI Proton density Diffusion- Tissue diff i Ti diffusion weighted imaging Water has special properties: Diffusion direction Diffusion tensor •H-bonds imaging Diffusion anisotropy • Favours polar molecules Diffusion spectral • Topologically binds to proteins? Diffusion maps imaging, HARDI • High surface friction Metabolites MR spectroscopy • High heat capacity • Soluble oxygen 1
  2. 2. 2012.10.30.„The forgotten molecule” molecule”Water in biological tissues Kémiai Nobel –díj 2003: Peter Agre (aquaporins), Roderick MacKinnon (K-csat.) Diffusion: Diffusion: the biological basics Diffusion: Diffusion: basic physics 1827, Robert Brown 1905: „the miraculous year” Vis vitalis? Or someting “On a Heuristic Point of View on the Creation and Conversion of Light”(17 March else? 1905)(Photo-Electric Effect) Nobel prize in physics, 1921 Random motion “On the Electrodynamics of Moving Bodies” (30 „Thermal motion” F.M.Exner, 1900 June 1905) “Does the inertia of a body depend on its Albert Einstein, 1905 energy content?”(27 September 1905)(Theory of Special Relativity) E = mc² “Investigation on the Theory of the Brownian Movement: On the motion of small particles suspended in liquids at rest …”(11 May 1905) Einstein, 1905The molecular-kinetic theory oftemperature : Brownian motion =molecular diffusion 0 ? RANDOM WALK Source Karla Miller, FMRIB, University of Oxford 2
  3. 3. 2012.10.30.Image source: Brian Wandell, Stanford 3
  4. 4. 2012.10.30. CHAPTER II. – DIFFUSION MRI End of part I. - any questions? 1. Patient (water + fat = lot of spins) Diffusion- Diffusion-weighted MR imaging (DWI)THE MRI RECIPE 2. Excite (Shout at the patient with a Repeat this! This is called SEQUENCE radiofrequency coil) 3. Wait until the excited spins „relax” Le Bihan & Breton, CRASS, 1985 4. During relaxation, the spins (water + fat =patient) shout back at you, they Intravoxel incoherent motion send an ECHO Movement during imaging = 5. You listen to the echo and record it (this is the k-space acquisition) the MRI signal is affected , Human, made of ECH excitable spins 6. Decode the i l t image! 6 D d th signal, get i ! Spatially S ti ll variant magnetic gradient i t ti di t (HOproton spins) encodes the location of spins Stationary vs. Moving molecules are coded Forrás: Karla Miller, FMRIB, University of Oxford Forrás: Karla Miller, FMRIB, University of Oxford 4
  5. 5. 2012.10.30. The image contrast formation during Stejskal- Stejskal-Tanner sequence DWI Diffusion-weighting in the MRI sequence ◦ Apply a gradient for delta time (-> DTI!) If particles move during the imaging time, ◦ Apply in many directions (at least 3) the signal is attenuated If diffusion is slower, the signal is higher ( (more particles „stay in place”) p „ y p ) ◦ So what does DWI tells us? ◦ = the diffusion magnitude = diffusion coefficient So what does diffusion MRI measure? measure? 1. How fast is diffusion in tissues? 2. Is there a pathology, where diffusion is restricted (cells are dead)?Image source: Peter Barsi …. WHAT ELSE?? Why tissue diffusion is special? special? It has directional preference = anisotropic!! What types of diffusion are there? there? Free diffusion (isotropic) Restricted diffusion Hindered diffusion (barriers) Forrás: Karla Miller, FMRIB, University of Oxford 5
  6. 6. 2012.10.30. Displaying the diffusion’s direction Diffusion Imaging Biological diffusion shows various magnitudes in different directions. In an isotropic medium (inside a glass of water for example) water molecules naturally move according to Brownian motion. Herpes encephalitis forrás: emedicine.medscape.com In biological tissues however the diffusion is very often anisotropic. For example a molecule inside the axon of a neuron has a low probability to cross a myelin membrane. Apply gradient in a given direction dark regions correspond to where non Brownian motion has occured.S. Maier and M. Kubicki ACA stroke forrás: RADsounds Wiki Healthy brain Diffusion Tensors & Anisotropy Diffusion tensors (?) Examining diffusion from many directions = direction encoding DTI allows researchers to quantify the diffusion of water in brain tissue Diffusion for each image voxel is described by 3 perpendicular vectors λ1 λ1 λ2 λ2 Peter Basser (NIH) λ3 λ3 TENSORS: the key to display direction Anisotropic diffusion dependency Isotropic diffusion occurs when occurs when water there is no restriction to water movement is restricted to movement (e.g., ventricles, CSF) one primary direction (e.g., myelinated fibers) Mapping diffusion Diffusion weighted image Spatial representation of Calculating tensors for each acquisition diffusion magnitudes image point Displaying tensorial information on scalar images 6
  7. 7. 2012.10.30. Image source: Brian Wandell, StanfordSo what is needed for diffusiontensor imaging? What can we measure with DTI? Diffusion MAGNITUDE: APPARENT DIFFUSION COEFFICIENT- Many diffusion weightingdirections during a scan The orderedness of diffusion: DIFFUSION ANISOTROPY Diffusion direction (color coded maps)-At least 6 directions Diffusion magnitudes parallel and perpendicular to fibers- Suggested: 24-64 directions- Processing of images- Special display modes CHAPTER III. – TRACTOGRAPHYEnd of part II. - any questions? 7
  8. 8. 2012.10.30.Diffusion tractography Tract = brain pathway, axonal pathways Tractography = displaying white matter pathways through post- procesisng of diffusion tensor images Brain connections? Computerized data and image processingDiffusion tractography: examples Diffusion tractography: examples Displaying the cortico-spinal tractDisplaying language pathways Right handed Left handed NeuroImage 35 (2007) 1064–1076 8
  9. 9. 2012.10.30. Konnektivity (c) Jakab A.Beyond tensors… tensors… Making the resolution of axons better Q-ball imaging, High angular diffusion imaging (HARDI) End of part III. - any questions? 9
  10. 10. 2012.10.30. Summary so far: T1, T2-weighted MRI: relaxation time of tissue water protons (i.e. in „watery” of „fatty” environment) Diffusion weighted MRI (DWI) : the magnitude of diffusion, restricted diffusion Diffusion tensor MRI (DTI): the orientation of diffusion Tractography: displaying white matter pathways CHAPTER IV. – PRACTICAL USE OF Diffusion spectrum imaging (DSI): the precise spatial DIFFUSION MRI (DWI, DTI) characteristics of diffusion with high angular resolution DWI, DTI and tractography can be combined with oter imaging modalities (CT, MRI, PET…)9.1a 9.1b 9.1c 9.1d 1. DWI in ischaemic stroke Stroke: ischaemia Cells are dying, Na/K pump disfunction, cells swell, extracellular spaces are reduced (cytotoxic edema!) Diffusion becomes restricted in 15-30 minutes Ischaemic stroke is the single best clinical application of DWIDiffusion weighted image FLAIR Image T1-wtd image Post-contrast Axial T1-wtd so far! (DWI) imageDiffusion weighted image (DWI) 9.1e 9.1f 47 year-old left handed gentleman with one day history Image source: Peter Barsi of somnolence, left facial droop and slurred speech. Q9.1. Diagnosis Please MRA Circle of Willis Post-contrast coronal T1 wtd image 2. DWI differentiates abscesses and 3. DWI differentiates epidermoid cyst tumors from arachnoid cysts Necrotic high-grade Abscess tumor Image source: SS. Jhawar et al. Image source: Peter Barsi Content of an abscess = „soup”, dense pus Content of an epidermoid tumor = dense cells Content of a necrotic tumor center = liquid Content of a arachnoid cyst = liquid 10
  11. 11. 2012.10.30.White matter characterization with DTI? Anizotrópia - Anizotrópia - - Anizotrópia - -Anizotrópia ++ Anizotrópia + Diffúzió - Diffúzió ? / n Diffúzió - - DTI applications 1. DTI in neuro-oncology neuro- Structure, anatomy of white matter • DTI can characterize brain tumors preoperatively ◦ Development, anatomy of white matter – FA is reduced: vasogenic edema or infiltration? ◦ Disrupted anatomy of white matter (i.e. for – Tumor FA: cellularity, proliferation activity neurosurgeons) – „current literature”: current literature : • Frakcionális anizotrópia: Cellularitás és proliferációs aktivitás (MIB-2) • MRS és DTI: Proliferációs aktivitás (Ki-67) Tissue integrity • • FA: Low grade vs. Anaplasticus glioma ADC hisztogramok: 1p/19q l.o.h. oligodendrogliomákban ◦ Demyelinisation (Multiple sclerosis) • • „Oligo-like” és „astro-like” komponens megjelenítése ADC hisztogram: Terápiás válasz (Bevacizumab), progressziómentes időtartam becslése ◦ Axonal damage, Wallerian degeneration – Displaying white matter tract’s relation to tumors ◦ Edemea ◦ Characterizing pathological tissues mean FA: 0.1887 mean ADC(x1k): 1.4791 11
  12. 12. 2012.10.30.DTI in neuro-oncology neuro- DTI: clinical examples A. Jakab, M. Emri, P. Molnár, E. Berényi. Glioma grade assessment by using histogram analysis of diffusion tensor imaging- derived maps. Neuroradiology. 2010 Sep 21.What is the tumor’sgrade?Low? (WHO I-II)High? (WHO III-IV) • Forrás: Nucifora et al. (2007) Diffusion-Tensor MR Imaging and Tractography: Exploring Brain Microstructure and Connectivity. Radiology. 245, 367-384. 12
  13. 13. 2012.10.30. Theodor Meynert (1833-1892) • Role of the frontal lobe • White matter connections underlie intelligence? • Disconnection in syndromes • Forrás: Nucifora et al. (2007) Diffusion-Tensor MR Imaging and Tractography: Exploring Brain Microstructure and Connectivity. Radiology. 245, 367-384. • Forrás: Nucifora et al. (2007) Diffusion-Tensor MR Imaging and Tractography: Exploring Brain Microstructure and Connectivity. Radiology. 245, 367-384. Cerebral palsy in a 20-month-old girl with spastic hemiplegia.• Forrás: Nucifora et al. (2007) Diffusion-Tensor MR Imaging and Tractography: Exploring Brain • Forrás: Lee et al. Diffusion-Tensor MR Imaging and Fiber Tractography: A New Method of Microstructure and Connectivity. Radiology. 245, 367-384. Describing Aberrant Fiber Connections in Developmental CNS Anomalies 13
  14. 14. 2012.10.30. Ohdo syndromaSmall girl, epileptic seizures • Source: Berényi E, Jakab A DTI and neuroscience research Understanding brain development in utero 14
  15. 15. 2012.10.30. Fiber tracking of a living fetus in utero Language pathways Left side Right side Displaying the arcuate fasciculus Normal anatomy vs. Aphasia! Right dominance! Jakab A, Béres M, Spisák T, Kis SA, Emri M, Berényi E, Handedness and interhemispheric differences in the Image credits: Gregor Kasprian, University of anatomical connectivity of perisylvian language areas: a network-based approach, Magn. Reson. Mat. Phys. Vienna Biol. Med. 24 (S1):276, 2011. Malformations • The anatomy of the arcuate in severe brain developmental diseases in children • Schizencephaly, polymicrogyria, lissencephaly, … • Jakab A, M Paldino – Harvard Medical A M.Paldino School, Children’s Hospital 1 Parcellating grey matter from connectivity Segmenting the thalamus • Visualizing the connections from subcortex to cortex • Thalamus • Specific cortical connectionsBehrens et al. Non-invasive mapping of connections between human thalamus and cortex New type of image contrastusing diffusion imaging Nature Neuroscience 6, 750 - 757 (2003) 15
  16. 16. 2012.10.30.Biological correspondence: regions Biological correspondence: regionsdefined by Atlas vs. connectivity defined by Atlas vs. connectivityBiological correspondence: regions Cortico-thalamic connections depicted using probabilisticdefined by Atlas vs. connectivity tractography. Points represent the center-of-gravities of each connectivity map. Axial (top) view, isometric 3d display. Connections of the precentral and Applications: neurosurgical planning postcentral gyrus and the spatial relationship between connectivity- (thalamotomies) based landmarks and the MNI152- transformed Morel Atlas data (VLpv, Kincses ZT et al. (2012) VPLa, VPLp nuclei). Points represent Target Identification for the center-of-gravities of each Stereotactic Thalamotomy connectivity map. Using Diffusion Superior view, isometric 3d display. Tractography- PloS One. 7(1): e29969. doi:10.1371/ journal.pone.0029969 Jakab A et al. (2012) Generation of Individualized Thalamus Target Maps by Using Statistical Shape Models and Thalamocortical Tractography. AJNR American Journal of Neuroradiology. doi: 10.3174/ajnr.A3140 16
  17. 17. 2012.10.30.Any questions? 17

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