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

http://unfweb.criugm.qc.ca/oury

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

MRI Basic PrinciplesMagnet:

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

Anatomical MRI (T1)

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?

Techniques

Volumetry

Voxel Based Morphometry (VBM)

Diffusion Tensor Imaging (DTI)

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)

Volumetry: exampleWomen suffering from somatoform disorders compared

to control participants

Significant difference in caudate nucleus volume

Hakala et al. (2004)

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

Voxel Based Morphometry:methods

Normalization to a template

Segmentation

Spatial smoothing

Statistical analysis

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)

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

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)

Concept of Mean Diffusivity

Isotropy is not enough to characterize diffusion:

DTI: MRI sequenceOne or more images at b=0 (T2 contrast)

As many image acquisitions as there are directions at b ~ 1000 sec/mm2

DTI: maps obtainedMean diffusivity map

high signal in ventricles and sulci

Fractional anisotropy map

DTI: FA and MD applicationsInfluence 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)

Study of anatomical connectivity

a

b

c f

e

g

DTI: Fiber tracking

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.

Preprocessing

Belin, et al. (2000) Nature

Functional MRI: Voice recognition

Functional Connectivity studies

Physiological Studies: Spectroscopy

MRI of the heart

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

Flow velocity imaging of aorta

Vessel wall imaging of aorta

Brain vascular images

Positron Emission Tomography (PET)

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)

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, ……….

FDG PET

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

FDG-PET in the detection of tumor

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.

Single Photon Emission Computed Tomography

(SPECT)

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

Inferior infarctus without other perfusion anomaly

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

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

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

Caffeine decreases exercise-induced hyperaemic myocardial blood flow

Most prominent in coronary artery disease patients

Caffeine decreases myocardial perfusion reserves

Most pronounced in coronary artery disease patients

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