1. Introduction to different brain and other clinical imaging methods Oury Monchi, Ph.D. Parkinson Cognition Action & Neuroimaging (PCAN) Laboratory Centre de Recherche, Institut Universitaire de Gériatrie de Montréal & Université de Montréal Centre de Recherche, Institut Universitaire de Gériatrie de Montréal & Université de Montréalhttp://unfweb.criugm.qc.ca/oury

2. Imaging Techniques I. Magnetic Resonance Imaging (MRI) Brain anatomy techniques (volumetry, DTI) Brain function technique (fMRI) Vascular and heart imaging II. Positron Emission Tomography (PET) III. Single Photon Emission Computed Tomography (SPECT) IV. Application to Exercise Sciences

5. MRI Basic Principles Magnet: Very powerful (1 to 7T) and homogeneous and static magnetic field, it incites the hydrogen protons to align themselves. Earth magnetic field 0.00005T! Radiofrequency coils: Generates and receive transient electromagnetic field, at the frequency of resonance of hydrogen disrupting alignment of protons from low to high energy state. Energy released can be detected as they return to their base state Speed to return to base states depends of the tissue they are part of, this generate the T1 and T2 signals. Gradient coils: Gradual fields aligned in x, y, z axes Allows us to place detected signals in a 3D volume

10. Anatomical MRI (T1)

11. Morphological variations Large variability from one brain to the other Can we make inferences based on population criteria (age, sex, health) on this morphological basis? What criteria do we use?

12. Techniques Volumetry Voxel Based Morphometry (VBM) Diffusion Tensor Imaging (DTI)

13. Principles of volumetry An anatomical image allows us to separate the grey and white matter One can paint the region of interest on each subject’s scan We can study the variation of this region compared with a specific parameter (age, neuropsychological score, etc) or different groups (Parkinson’s vs healthy controls)

14. Volumetry: example Women suffering from somatoform disorders compared to control participants Significant difference in caudate nucleus volume Hakala et al. (2004)

15. Voxel Based Morphometry: principles VBM consists in comparing local grey matter density between two populations This comparison is not dependent on: any particular structure the experimenter’s subjectivity (as in volumetry, where regions are painted manually) VBM is performed on the entire brain

16. Voxel Based Morphometry: methods Normalization to a template Segmentation Spatial smoothing Statistical analysis

17. Voxel Based Morphometry: applications 22 Controls and 56 MCI (13 have evolved into dementia) are followed over 22 months Compared with stable MCIs, progressive MCIs exhibit atrophy in different regions Hamalainen et al. (2007)

18. Diffusion Tensor Imaging: principles Allows to obtain images based on properties of water molecule displacement in tissues Reflects tissue properties (position, orientation, anisotropy), especially of white matter Reflects tissue degradation (axons, myelin, cell wall) Made possible by an adequate acquisition sequence

19. Concept of Diffusion: isotropy and anisotropy Diffusion is isotropic if it is with the same amplitude in all directions Diffusion is anisotropic if it prefers one or more directions Fractional anisotropy characterizes local diffusion (1 > FA > 0)

20. Concept of Mean Diffusivity Isotropy is not enough to characterize diffusion:

21. DTI: MRI sequence One or more images at b=0 (T2 contrast) As many image acquisitions as there are directions at b ~ 1000 sec/mm 2

22. DTI: maps obtained Mean diffusivity map high signal in ventricles and sulci Fractional anisotropy map

23. DTI: FA and MD applications Influence of age on mean diffusivity in grey and white matter Correlation of both measures with age in grey matter, only in peak height in white matter Fibre reconstruction: average of 86 000km in aged participants compared with 118 000km in young Benedetti et al. (2006)

24. Study of anatomical connectivity a b c f e g DTI: Fiber tracking

25. Basic Principles of fMRI For a long time, a relationship between brain activity and deoxygenated hemoglobin (which is paramagnetic) in the blood has been known In the early 90's it was discovered that an MR pulse sequence could measure the rate of deoxygenated hemoglobin (Thulborn et al.; Ogawa et al.) This gave rise to Blood Oxygenation Level Dependent (BOLD) fMRI or T2* sequence, which provides us with an indirect measure of brain activity.

31. Preprocessing

32. Belin, et al. (2000) Nature Functional MRI: Voice recognition

33. Functional Connectivity studies

34. Physiological Studies: Spectroscopy

35. MRI of the heart

36. MR-measurement of aortic compliance Compliance of aorta is highly predictive of overall vascular health Flow velocity imaging allows measurement of pressure-wave propagation in aorta Vessel wall imaging allows measurement of distensibility

38. Flow velocity imaging of aorta

39. Vessel wall imaging of aorta

41. Brain vascular images

42. Positron Emission Tomography (PET)

43. Positron Emission Tomography principles PET depends on the injection of a radioactive isotope produced by a cyclotron From the time of their injection, these radio-isotopes decay and emit positrons, which collide with electrons. These collisions produce opposit γ-rays that are captured the coincidence detectors of the PET scanner Depending on the molecules that these isotopes bind with, we can get information on metabolism, blood flow, or the release of neurotransmitter (eg. 11C raclopride which binds to striatal D2 receptors)

45. Radioactive tracers for PET 18FDG (Fludeoxyglucose): glucose metabolism H215O : regional blood flow (cerebral or myocardial) 18FDOPA : Dopa uptake (dopamine precurser) [11C]raclopride : Dopamine D2 antagonist 18FP-TZTP : muscarinic agonist (acetylcholine) PHNO, FLB 457, WAY, ……….

46. FDG PET FDG-PET scan in a boy with left parietal-temporal epilepsy showing decreased glucose metabolism in the left parietal and temporal lobes

48. FDG-PET in the detection of tumor

49. Water PET Regional cerebral blood flow (rCBF) is related to glucose and oxygen consumption. Very sensitive to acute changes… E.g., patients with Parkinson’s disease who received DBS on STN perform a joystick task while OFF- or ON-DBS. Similar task-induced rCBF changes in the M1 in both condition, but greater changes in SMA. Normalizing effect of DBS.

50. Single Photon Emission Computed Tomography (SPECT)

51. SPECT Similar to PET, SPECT makes use of radioactive tracer. However the gamma radiation is mesured directly (not following positrons which annihilate with electrons like in PET). A PET allows for higher resolution images than SPECT be cause of the coincidence detection. But SPECT can use longer-lived, more easily-obtained radioisotopes than PET Important if no cyclotron

54. Inferior infarctus without other perfusion anomaly

55. What are the effects of physical training that can explain improvement in cognition? Direct effects on cognition: Aerobic exercise has an impact on cerebral functions Indirect effects: Aerobic exercise acts on moderators of cognitive aging

56. Effect of physical fitness training on brain structures and functions VBM: better cardiorespiratory fitness level (VO2max) was associated with a reduced loss in grey and white matter in the frontal, prefrontal and temporal regions in older adults Colcombe et al., 2003

57. Effect of physical fitness training on brain structures and functions Functional brain imaging studies (fMRI) showed that enhanced cardiovascular functions after aerobic training are associated to greater task-relevant activity in brain areas recruited in an attentional control task Flanker task Colcombe et al., 2004

59. Caffeine decreases exercise-induced hyperaemic myocardial blood flow Most prominent in coronary artery disease patients

60. Caffeine decreases myocardial perfusion reserves Most pronounced in coronary artery disease patients

61. Aknowledgements Kristina Martinu, BSc Rick Hoge, PhD Jean-Paul Soucy, MD/MSc Antonio P. Stradella, MD/PhD Louis Bherer, PhD The slides will be available on: unfweb.criugm.qc.ca/oury/downloads.html