Functional Magnetic Resonance Imaging (fmri)

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1 Functional Magnetic Resonance Imaging (fmri) Beth Meyerand, PhD Department of Medical Physics University of Wisconsin-Medical School Madison, Wisconsin

2 Outline: Introduction to fmri physics ( BOLD ) Overview of post-processing / analysis Review of fmri paradigms and procedures Clinical applications

3 Blood Oxygen Level Dependent (BOLD) Imaging * Requires a difference in oxygenation states ACTIVE (increased oxyhemoglobin) compared to RESTING (decrease oxyhemoglobin) fmri measures a blood flow ( hemodynamic ) effect, therefore it is only an INDIRECT measure of neuronal activity

4 How Are MR Images Affected By Oxygen Changes? Hemoglobin: its magnetic properties depend on its oxygenation state. Oxygenated Hemoglobindiamagnetic, like water and cellular tissue. Deoxygenated Hemoglobin- more paramagnetic than tissue, produces a stronger MR effect. If an appropriate imaging sequence is selected, these differences in oxygen levels may be large enough to affect MR image intensity (T2*, or susceptibility).

5 Blood Oxygen Level Dependent (BOLD) Imaging Cortical activation Increase in cerebral metabolism Increase CBF and CBV Oxygen delivery exceeds oxygen demand Oxygenation of venous pool increases Concentration of dhb decreases fmri signal increase (< 5% at 1.5T)

6 BOLD signal time course Signal (%) 3 delay start stop Time (seconds) Task, or stimulus timing

7 Echo Planar Imaging Imaging the whole brain involves acquiring ~20 slices that are 6-7 mm thick spaced apart by 1 mm. The trade-off for fast scanning is low spatial resolution. To study brain function (changes in oxygen levels) we acquire over 100 whole brain images collected over a time span of a few minutes.

8 fmri Data Acquisition signal n slices x 100 repetitions = time 100 time points If 100 whole brain images are acquired in a scan, each voxel will be represented by a time series of 100 time points.

9 Overview of typical fmri analysis procedures - Motion correction - Spatial smoothing pre-processing steps - Image co-registration - Generation of statistical maps of BOLD response - Selective interpretation of results

10 fmri pre-processing uncorrected time courses

11 fmri pre-processing motion corrected time courses

12 fmri pre-processing motion corrected & spatially smoothed time courses

13 Spatial smoothing - Increases SNR fmri post-processing - Some fmri analysis software requires spatial smoothing as part of the analysis Before After

14 fmri post-processing Motion correction - choose a time point in the middle of your time series - register all images in time series to that time point Before After

15 Motion correction fmri post-processing

16 Motion correction fmri post-processing effects on the time course Before After

17 fmri post-processing EPI co-registration with high resolution anatomicals - register (align in 3D space) EPI data to anatomicals - sometimes very challenging due to susceptibility effects - automatic or manual

18 Image registration fmri post-processing Left - Right

19 Image registration fmri post-processing Inferior - superior

20 Image registration fmri post-processing Roll

21 Image registration fmri post-processing Pitch

22 fmri pre-processing EPI co- registration with high resolution anatomicals

23 How Do You Determine the Active Voxels? The time series must be analyzed to determine the areas of activation during the task. Signal Intensity After masking out the voxels outside the brain, we are left with ~15,000 voxel time series. Task Performed: task Time rest

24 Which voxels best fit this model? Reference Function of task performed: Signal Intensity Task Timing: task rest Time

25 Determining Activation Areas in fmri At every voxel, a test statistic is computed. A color intensity value is given corresponding to the value of this statistic. Functional Maps

26 Statistical Analysis Paired t-test - used when 2 groups of data are correlated; the same subject is scanned during activation (ON) and rest (OFF) periods. X X t = 1 2 S N Difference between the means of two groups divided by the standard error of the mean

27 Determining Activation Areas in fmri The statistically significant voxels are determined according to the sampling distribution. Functional maps after applying threshold

28 Determining Activation Areas in fmri The statistically significant voxels are determined according to the sampling distribution. Functional maps after applying threshold and then overlaid on coregistered anatomical images

29 Determining Activation Areas in fmri Functional maps at varying thresholds: t > 2 t > 4 t > 5

30 Software for fmri data processing & display MRI vendorspecific software BrainWave GE Medical Systems Advanced Neuro Siemens Medical Systems IView Phillips Medical Systems Unix-based shareware AFNI National Institutes of Health SPM Wellcome Dept. of Imaging Neuroscience Other fmrispecific software Brain Voyager Brain Innovation B.V. Med-X Sensor Systems

31 fmri acquisition set-up LCD projector Projection screen RF coil mirror Laptop headphones Stereo system Scanner control room MRI magnet

32 fmri paradigms for clinical patients Pick and choose: Motor Sensory Visual Auditory Language Cognitive memory visual organization computation

33 fmri paradigms: alternating-hand finger tapping task Right hand task cycles Left hand task cycles rest right left rest right left rest right left rest right left rest 4 cycles each of right hand, left hand, and rest 20-second task epochs

34 fmri paradigms: alternating-hand finger tapping task R L Yellow/orange = right hand Blue/cyan = left hand Comparative hemispheric responses in primary sensorimotor, thalamus, putamen, superior and inferior cerebellum

35 fmri somatotopic motor mapping A B Presurgical fmri mapping with multiple motor paradigms: A) alternating-hand finger tapping task B) foot/ankle movement task

36 Comparison between finger motor task & palm tactile stimulation Finger motor task Right hand Palm tactile stimulation Right hand L L

37 Sensory Paradigms Propofol-sedated 3 year old with right parietal mass - left hand palm stimulation

38 fmri language paradigms Antonym generation Expressive language Word generation from letters Alphabet letter generation Word generation from categories Synonyms task Receptive language Text reading / comprehension Narrated text

39 covert language generation paradigms Word generation from antonyms, letters, or categories Simple block paradigms for robust signal localization task rest Task is performed silently to minimize head motion Covert performance precludes patient monitoring, and motor vocalization response

40 Language generation paradigms Left-frontal glioma L L antonym word generation category word generation Repeated tasks increase confidence

41 fmri of language networks Text reading paradigm Text reading cycles Letter strings cycles rest text letters rest text letters rest text letters rest text letters rest 10 cycles each of descriptive text, letter strings, and blank screen fixation 8-second task epochs

42 fmri of language networks L Text reading paradigm

43 Primary visual stimulus paradigm 8Hz checkerboard fixation

44 Primary visual stimulus Left occipital lesion R fmri response absent in affected hemisphere

45 Interpretation of clinical fmri for presurgical mapping Guidelines and caveats

46 Interpretation of clinical fmri for presurgical mapping Caveats and limitations: Inspect mapping for technical adequacy Extent of BOLD response is not directly related to functional extent of cortex fmri relies on a hemodynamic effect, does not directly measure neuronal activity

47 Interpretation of clinical fmri for presurgical mapping Caveats and limitations: Some tumors have been reported to affect hemodynamic autoregulation Disturbances in cerebral blood flow and metabolism can affect BOLD fmri EPI susceptibility-related signal loss can mask regions of eloquent cortex

48 Effect of Pathology - AVM L Patient with extensive right frontal-temporal AVM Text listening paradigm, no functional response seen in right superior temporal gyrus > R Temporal signal-to-noise map of the EPI signal shows low SNR in AVM region BOLD response could be masked by hemodynamic instability

49 Effect of Pathology - Susceptibility R Activation absent Patient with reoccurring left frontal glioma, previous resection Word generation paradigm, no functional response seen in left inferior / middle frontal gyri, right hemisphere language dominance indicated

50 Effect of Pathology - Susceptibility EPI signal intensity mask shows region of susceptibilityinduced signal loss

51 Effect of Pathology - Susceptibility EPI signal intensity mask shows region of susceptibilityinduced signal loss

52 The furture is here!

53 Acknowledgements Thank you to the faculty, staff and students at Univ. Wisconsin-Medical School Chad H. Moritz fmri Research Program Manager Victor Haughton professor of Neuroradiology Howard Rowley professor of Neuroradiology Behnam Badie professor of Neurosurgery Robert Dempsey professor of Neurosurgery Bruce Hermann professor of Neurology Sterling Johnson professor of Neurology

54 Contact:

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