1. Introduction to Functional and Anatomical Brain MRI Research Dr. Henk Cremers Dr. Sarah Keedy 1

2. Course Overview 2 o Week 1: Introduction o Week 2: Processing of FMRI data o Week 3: Statistical Analysis of fMRI data o Week 4: Planning MRI Research to address your scientific question o Week 5: Interpretation, limitations and new applications of fMRI

3. Week 1: Introduction 3 o Useful Resources o Basic physics: The M, The R, The I o Type of images (functional, structural) o Analysis Pipeline o Training Data & demonstration of software packages: SPM, FSL, AFNI

4. Resources * MRI physics * Type of Images * Analysis Pipeline * Software 4 Books Poldrack Ashby Huettel

5. Resources * MRI physics * Type of Images * Analysis Pipeline * Software 5 Online: Coursera: https://www.coursera.org/course/fmri (Martin Lindquist)https://www.coursera.org/course/fmri http://www.fmrimethods.org/index.php/Main_Page Software: http://www.fil.ion.ucl.ac.uk/spm/ http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/ http://afni.nimh.nih.gov/afni/ … many more

6. fMRI and other methods 6 Non-invasive Whole brain measurement

7. 7 M = Magnetic Resources * MRI physics * Type of Images * Analysis Pipeline * Software

8.  Your body is full of Hydrogen (protons). Protons spin in random direction  Applying a large external magnetic field will make the protons align in the same direction (or exact opposite direction) and precess (“turn”)  Ex. 3 Tesla (3T) ~ 50 000 times as strong as earth magnetic field Resources * MRI physics * Type of Images * Analysis Pipeline * Software

9. 9 This main field is called B0 BoBo Resources * MRI physics * Type of Images * Analysis Pipeline * Software

10. 10 R = Resonance Resources * MRI physics * Type of Images * Analysis Pipeline * Software

11. Induce another magnetic field (B1) to tip protons over B 0 (main field of scanner) B 1 (another very strong field) M (net magnetization) θ Resources * MRI physics * Type of Images * Analysis Pipeline * Software

13. The rate at which protons return to their baseline state can be expressed by certain parameters (T1/T2/T2*) Different tissue has different T parameters

14. I = Imaging Gradients (slightly) change the Strength, not Direction of the Magnetic Field You can “select” a location of the brain (=slice) to excite Resources * MRI physics * Type of Images * Analysis Pipeline * Software

15. I = Imaging Resources * MRI physics * Type of Images * Analysis Pipeline * Software By using clever pulse- sequences (eg EPI) one can focus on optimizing imaging of a certain tissue type (eg MRI) Image formation involve the construction of a three-dimensional space from a two dimensional space

16. Sequence of events (1): Brain area “becomes” active (neuronal activity). This process needs energy Energy is recruited by glycolysis (needs oxygen) Oxygen is transported in hemoglobin (protein in red blood cells) Difference in de- and oxyhemoglobin is what you measure in fMRI (T2* weighted image) fMRI thus measures brain activity in (1) a very indirect way! Blood Oxygenated Level Dependent (BOLD) signal – the f(unctional) Resources * MRI physics * Type of Images * Analysis Pipeline * Software

17. fMRI thus measures brain activity in (2) a very and slow way! Resources * MRI physics * Type of Images * Analysis Pipeline * Software Sequence of events (2): A combination of changes in blood flow and blood volume eventually tips the balance towards oxyhemoglobin This leads to a peak BOLD signal after about 4-6 seconds. After reaching its peak, the BOLD signal decreases to an below baseline This process can be modelled by a hemodynamic response function (HRF) Blood Oxygenated Level Dependent (BOLD) signal – the f(unctional)

18. 18 MRI: Protons align in strong magnetic field Applying another magnetic field tips the protons in orthogonal direction Protons start to return to their initial position = measurable signal With clever pulse sequences, and the selection of specific slices, we can measure the exact location (origin) of the signal F(MRI) Because deoxy and oxyhemoglobin have different magnetic properties we can measure oxygen consumption (~brain activity) MRI physics - Summary

19. With different “settings” (pulse sequences), you can obtain very different type of images: functional scans (T2* weighted) Task fMRI Resting state fMRI Structural scans (T1 weighted) Voxel Based Morphometry (VBM) Structural Tracing Surfaces measurement Diffusion Tensor Imaging (white matter tracts) Resources * MRI physics * Type of Images * Analysis Pipeline * Software

20. functional scans (T2* weighted) Resources * MRI physics * Type of Images * Analysis Pipeline * Software Task fMRI Resting State fMRI +

21. 21 Resources * MRI physics * Type of Images * Analysis Pipeline * Software Data Acquisition Experimental Design Scanning Parameters Reconstruction Slice-time Correction Motion Correction Co-registration Normalization (Tissue Classification) Smoothing Preprocessing Statistical Analysis General Linear Model Subject-level – Parameter estimation Group Level – Hypothesis testing Advanced Analysis Connectivity (Network approaches) Machine Learning