UCLA NS 172/272/Psych 213

Asst. Prof. In Statistics and Neurology
University of California, Los Angeles, Winter 2006 http://www.stat.ucla.edu/~dinov/ http://www.loni.ucla.edu/CCB/Training/Courses/NS172_2006.shtml
NS 172/272/Psych213, UCLA, Ivo Dinov
Slide 1

Slide 2
NS 172/272/Psych213, UCLA, Ivo Dinov

 “Foundation of Medical Imaging,” Z.H. Cho, J.P. Jones, M.
Singh, John Wiley & Sons, Inc., New York 1993, ISBN 0-
471-54573-2
 “Principles of Medical Imaging,” K.K. Shung, M.B. Smith, B.
Tsui, Academic Press, San Diego 1992, ISBN 0-12-640970-6
 “Handbook of Medical Imaging,” Vol. 1, Physics and
Psychophysics, J. Beutel, H. L. Kundel, R. L. Van Metter
(eds.), SPIE Press 2000, ISBN 0-8194-3621-6

Brain Mapping: The Methods , by Arthur W. Toga & John
Mazziotta
Slide 4
NS 172/272/Psych213, UCLA, Ivo Dinov


Goals:
 Create images of the interior of the living human body from the outside for diagnostic purposes.

Biomedical Imaging is a multi-disciplinary field involving

Physics (matter, energy, radiation, etc.)

Math (linear algebra, calculus, statistics)

Biology/Physiology

Engineering (implementation)

Computer science (image reconstruction, signal processing, visualization)
Slide 5
NS 172/272/Psych213, UCLA, Ivo Dinov

 Year discovered:
 Form of radiation: radiation

Energy / wavelength of radiation:




Imaging principle:
Imaging volume:
Resolution:
Applications:
1895 (Röntgen, NP 1905)
X-rays = electromagnetic
(photons)
0.1 – 100 keV / 10 – 0.01 nm
(ionizing)
X-rays penetrate tissue and create shadowgram of differences in density.
Whole body
Very high (sub-mm)
Slide 6
Mammography, lung diseases, orthopedics, dentistry, cardiovascular, GI, neuro
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 7
NS 172/272/Psych213, UCLA, Ivo Dinov

AM radio - 535 kilohertz to 1.7 megahertz [Frequency ~ 10 6 ]
Short wave radio - bands from 5.9 megahertz to 26.1 megahertz
Citizens band (CB) radio - 26.96 megahertz to 27.41 megahertz
Television stations - 54 to 88 megahertz for channels 2 through 6
FM radio - 88 megahertz to 108 megahertz
Television stations - 174 to 220 megahertz
Slide 8
NS 172/272/Psych213, UCLA, Ivo Dinov

 Year discovered:

Form of radiation:

Energy / wavelength of radiation:
1972 (Hounsfield, NP 1979)
X-rays
10 – 100 keV / 0.1 – 0.01 nm
(ionizing)
 Imaging principle: X-ray images are taken under many angles from which tomographic ("sliced") views are computed

Imaging volume:
 Resolution:
 Applications:
Whole body
High (mm)
Soft tissue imaging (brain, cardiovascular, GI)
Slide 9
NS 172/272/Psych213, UCLA, Ivo Dinov


Year discovered: 1953 (PET), 1963 (SPECT)

Form of radiation:

Energy / wavelength of radiation:
Gamma rays
> 100 keV / < 0.01 nm
(ionizing)
 Imaging principle: Accumulation or "washout" of radioactive isotopes in the body are imaged with x-ray cameras.
 Imaging volume:
 Resolution:

Applications:
Whole body
Medium – Low (mm - cm)
Slide 11
Functional imaging (cancer detection, metabolic processes, myocardial infarction)
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 12
NS 172/272/Psych213, UCLA, Ivo Dinov

Functional Brain Imaging - Positron Emission
Tomography (PET)
NS 172/272/Psych213, UCLA, Ivo Dinov
Slide 13

Functional Brain Imaging - Positron Emission
Tomography (PET)
NS 172/272/Psych213, UCLA, Ivo Dinov http://www.nucmed.buffalo.edu
Slide 14

Functional Brain Imaging - Positron Emission
Tomography (PET)
Isotope Energy (MeV) Range(mm) 1/2-life Appl’n
11
C
15 O
18
124
F
I
0.96
1.7
0.64
~2.0
1.1 20 min receptor studies
1.5 2 min stroke/activation
1.0 110 min neurology
1.6 4.5 days oncology
E:\Ivo.dir\LONI_Viz\LOVE_Distribution_062105\runNoArgs.bat
Load Volumes:
E:\Ivo.dir\LONI_Viz\data.dir\A1_Global.img
E:\Ivo.dir\LONI_Viz\data.dir\R12_Global.img
Subsample 2-2-2
VolumeRenderer + 2D Section + Change ColorMap
NS 172/272/Psych213, UCLA, Ivo Dinov
Slide 15



Year discovered:
Form of radiation:

Energy / wavelength of radiation:




Imaging principle:
Imaging volume:
Resolution:
Applications:
Slide 16
1945 (Bloch & Purcell)
1973 (Lauterburg, NP 2003)
1977 (Mansfield, NP 2003)
1971 (Damadian, SUNY DMS)
Radio frequency (RF)
(non-ionizing)
10 – 100 MHz / 30 – 3 m
(~ 10 -7 eV)
Proton spin flips are induced, and the RF emitted by their response
(echo) is detected.
Whole body
High (mm)
Soft tissue, functional imaging
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 17
NS 172/272/Psych213, UCLA, Ivo Dinov

 Year discovered:

Form of radiation:
1952 (Norris, clinical: 1962)
Sound waves (non-ionizing)
 Frequency / wavelength of radiation:

Imaging principle:
1 – 10 MHz / 1 – 0.1 mm
Echoes from discontinuities in tissue density/speed of sound are registered.
 Imaging volume:
 Resolution:
 Applications:
< 20 cm
High (mm)
Slide 18
Soft tissue, blood flow (Doppler)
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 19
NS 172/272/Psych213, UCLA, Ivo Dinov


Year discovered:

Imaging principle: scattering)
1989 (Barbour)
 Form of radiation: Near-infrared light (non-ionizing)

Energy / wavelength of radiation: ~ 1 eV/ 600 – 1000 nm
Interaction (absorption, of light w/ tissue.

Imaging volume:

Resolution:
 Applications:
~ 10 cm
Low (~ cm)
Perfusion, functional imaging
Slide 20
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 21
NS 172/272/Psych213, UCLA, Ivo Dinov

Slide 22
NS 172/272/Psych213, UCLA, Ivo Dinov

Recipe for MRI
1) Put subject in big magnetic field (leave him/her there)
2) Transmit radio waves into subject [about 3 ms]
3) Turn off radio wave transmitter
4) Receive radio waves re-transmitted by subject
– Manipulate re-transmission with magnetic fields during this readout interval [10-100 ms: MRI is not a snapshot]
5) Store measured radio wave data vs. time
– Now go back to 2) to get some more data
6) Process raw data to reconstruct images
7) Allow subject to leave scanner
Example of non-homogeneity effects in MRI:
E:\Ivo.dir\LONI_Viz\LOVE_Distribution_062105\runNoArgs.bat
E:\Ivo.dir\Research\Data.dir\LianaApostolova_AD\FrontalVolumes2Groups/MRI_ToothMetal_Defect.img.gz
E:\Ivo.dir\LONI_Viz\LONI_Viz_VR_MetalToothDefect.bat
Source:
Robert Cox’s web slides Slide 23
NS 172/272/Psych213, UCLA, Ivo Dinov

History of NMR
NMR = nuclear magnetic resonance
Felix Block and Edward Purcell
1946: atomic nuclei absorb and reemit radio frequency energy
1952: Nobel prize in physics nuclear : properties of nuclei of atoms magnetic : magnetic field required resonance : interaction between magnetic field and radio frequency
NMR

MRI: Why the name change?
Bloch Purcell most likely explanation: nuclear has bad connotations less likely but more amusing explanation: subjects got nervous when fast-talking doctors suggested an NMR
Slide 24
NS 172/272/Psych213, UCLA, Ivo Dinov

History of fMRI
MRI
-1971: MRI Tumor detection (Damadian)
-1973: Lauterbur suggests NMR could be used to form images
-1977: clinical MRI scanner patented
-1977: Mansfield proposes echo-planar imaging (EPI) to acquire images faster
Ogawa fMRI
-1990: Ogawa observes BOLD effect with T2* blood vessels became more visible as blood oxygen decreased
-1991: Belliveau observes first functional images using a contrast agent
-1992: Ogawa et al. and Kwong et al. publish first functional images using BOLD signal
Slide 25
NS 172/272/Psych213, UCLA, Ivo Dinov

4T magnet
RF Coil gradient coil
(inside)
Necessary Equipment
Magnet Gradient Coil
RF Coil
Source: Joe Gati, photos
Slide 26
NS 172/272/Psych213, UCLA, Ivo Dinov

The Big Magnet
Very strong
1 Tesla (T) = 10,000 Gauss
Earth’s magnetic field = 0.5 Gauss
4 Tesla = 4 x 10,000
 0.5 = 80,000 times Earth’s magnetic field
Continuously on
Main field = B
0
Robarts Research Institute 4T
B
0
Slide 27
NS 172/272/Psych213, UCLA, Ivo Dinov

Magnet Safety -
The whopping strength of the magnet makes safety essential. Things fly – Even big things!
Source: www.howstuffworks.com
Source: http://www.simplyphysics.com/ flying_objects.html
Screen subjects carefully
Make sure you and all your students & staff are aware of hazards
Develop strategies for screening yourself every time you enter the magnet
Slide 28
NS 172/272/Psych213, UCLA, Ivo Dinov

Subject Safety
Anyone going near the magnet – subjects, staff and visitors – must be thoroughly screened:
Subjects must have no metal in their bodies:
• pacemaker
• aneurysm clips
• metal implants (e.g., cochlear implants)
• interuterine devices (IUDs)
• some dental work (fillings okay)
Subjects must remove metal from their bodies
• jewellery, watch, piercings
• coins, etc.
This subject was wearing a hair band with a ~2 mm copper clamp. Left: with hair band. Right: without.
• wallet
• any metal that may distort the field (e.g., underwire bra)
Source: Jorge Jovicich
Subjects must be given ear plugs (acoustic noise can reach 120 dB)
C:\Ivo.dir\Research\Data.dir\LianaApostolova_AD\FrontalVolumes2Group s\MRI_ToothMetal_Defect.img.gz (Show-VolumeRenderer)
C:\Ivo.dir\LONI_Viz\LONI_Viz_MAP_demo\runNoArgs.bat
Slide 29
NS 172/272/Psych213, UCLA, Ivo Dinov

Protons
1
13
19
23
31
1
2
Both protons and neutrons possess spins , i.e. they revolve round their own axis, much as earth does. If the nucleus has just one proton, it would spin on its axis and would impart a net spin to the nucleus as a whole. One would imagine that two protons would double up the spin for the nucleus but it doesn’t happen that way; the spins of the two protons tend to cancel out, with the result that the nucleus has no net spin . A nucleus with three protons again has a net spin (as there is one unpaired proton) and a nucleus with four protons again would have no spin. The same is true for neutrons; an odd number of neutrons imparts a net spin to the nucleus, an even number doesn’t. So out of protons or neutrons if any one of these
(or both) are in odd number, the nucleus would have a net spin. If both are even, the nucleus would not have any net spin.
Slide 30
NS 172/272/Psych213, UCLA, Ivo Dinov

1
2
3
31
23
17
13
19
4
16
12
Slide 31
NS 172/272/Psych213, UCLA, Ivo Dinov

Outside magnetic field – random orientation
In Mag Field -
Protons align with field
randomly oriented
Inside magnetic field
M
M = 0
• spins tend to align parallel or anti-parallel to B
0
• net magnetization (M) along B
0
• spins precess with random phase
• no net magnetization in transverse plane
• only 0.0003% of protons/T align with field longitudinal axis
Longitudinal magnetization
Source: Mark Cohen’s web slides
Source:
Robert Cox’s web slides
Slide 32 transverse plane
NS 172/272/Psych213, UCLA, Ivo Dinov

As its name implies, NMR is a resonance phenomenon. This means that it will occur only if the applied RF pulse is tuned to the natural resonance frequency of the nucleus in question.
The natural resonance frequency of any given nucleus depends on the strength of the applied main magnetic field ; more strength   higher frequency.
4T fMRI Broadcasts at a frequency of 170.3 MHz!
To locate each atom within the sample make the main magnetic field graded so that it is not of uniform strength but rather increases slightly in strength from one side of the sample to the other, the resonance frequencies of different nuclei would differ.
Slide 33
NS 172/272/Psych213, UCLA, Ivo Dinov

Larmor equation
(frequency) f
=

B
0
(field strength)

= 42.58 MHz/T (constant for each Atom).
For example for Hydrogen: At 1.5T, f
= 63.76 MHz
At 4T, f
= 170.3 MHz
170.3
Resonance
Frequency for 1 H
63.8
1.5
4.0
Field Strength (Tesla)
Slide 34
NS 172/272/Psych213, UCLA, Ivo Dinov

RF Excitation
Excite Radio Frequency (RF) field
• transmission coil : apply magnetic field along B1 (
^ to B
0
) for ~3 ms
• oscillating field at Larmor frequency
• frequencies in range of radio transmissions
• B
1 is small: ~1/10,000 T
• tips M to transverse plane – spirals down
• analogies: guitar string, swing
• final angle between B
0 and B
1 is the flip angle Transverse magnetization
B
0
B
1
Slide 35
Source: Robert Cox’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

Relaxation and Receiving
Receive Radio Frequency Field
• receiving coil : measure net magnetization (M)
• readout interval (~10-100 ms)
• relaxation : after RF field turned on and off, magnetization returns to normal longitudinal magnetization
 
T1 signal recovers transverse magnetization
 
T2 signal decays
Slide 37
Source: Robert Cox’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

T1 and TR
T1 = recovery of longitudinal (B
0
) magnetization
• used in anatomical images
• ~500-1000 msec (longer with bigger B
0
)
TR ( repetition time ) = time to wait after excitation before sampling T1
Slide 38
Source: Mark Cohen’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

Spatial Coding: Gradients
Add a gradient to the excite only frequencies corresponding to slice plane main magnetic field
How can we encode spatial position?
• Example: axial slice
Use other tricks to get other two dimensions
• left-right: frequency encode
• top-bottom: phase encode
Field Strength (T) ~ z position
Gradient switching – that’s what makes all the beeping & buzzing noises during imaging!
Gradient coil
Slide 39
NS 172/272/Psych213, UCLA, Ivo Dinov

How many fields are involved after all?
In MRI there are 3 kinds of magnetic fields:
1. B0 – the main magnetic field
2. B1 – an RF field that excites the spins
3. Gx, Gy, Gz – the gradient fields that provide localization
Slide 40
NS 172/272/Psych213, UCLA, Ivo Dinov

Precession In and Out of Phase
• Protons precess at slightly different frequencies because of
(1) random fluctuations in local field at the molecular level affect both T2 and T2*;
(2) larger scale variations in the magnetic field (such as the presence of deoxyhemoglobin!) that affect T2* only.
• Over time, the frequency differences lead to different phases between the molecules (think of a bunch of clocks running at different rates – at first they are synchronized, but over time, they get more out of sync until they are random)
• As the protons get out of phase, the transverse magnetization decays
• This decay occurs at different rates in different tissues
Source: Mark Cohen’s web slides
Slide 41
NS 172/272/Psych213, UCLA, Ivo Dinov

T2 and TE
T1 = recovery of longitudinal (B
0
) magnetization
TR ( repetition time ) = time to wait after excitation before sampling T1
T2 = decay of transverse magnetization
TE (time to echo) = time to wait to measure T2 or T2* (after refocussing with spin echo or gradient echo)
Slide 42
Source: Mark Cohen’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

Pulse sequence: series of excitations, gradient triggers and readouts t = TE/2
A gradient reversal (shown) or
180 pulse (not shown) at this point will lead to a recovery of transverse magnetization
Gradient echo pulse sequence
Echos – refocussing of signal
Spin echo – use a 180 degree pulse to “mirror image” the spins in the transverse plane when “fast” regions get ahead in phase, make them go to the back and catch up
measure T2
ideally TE = average T2
Gradient echo – flip the gradient from negative to positive make “fast” regions become “slow” and viceversa
measure T2*
ideally TE ~ average T2*
TE = Time to Echo – wait to measure refocussed spins
Slide 43
Source: Mark Cohen’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

T1 vs. T2
Repetition
Time:
Time to Echo
Slide 44
Source: Mark Cohen’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

T1 vs. T2 – contrast and noise
Slide 45
Source: Mark Cohen’s web slides
NS 172/272/Psych213, UCLA, Ivo Dinov

Tissue
Grey Matter (GM)
White Matter (WM)
Muscle
Cerebrospinal Fluid (CSF)
Fat
Blood
T1 (ms) T2 (ms)
950
600
100
80
900 50
4500 2200
250 60
1200 100-200
Slide 46
NS 172/272/Psych213, UCLA, Ivo Dinov

T1 Contrast
T
E
T
R
= 14 ms
= 400 ms
T2 Contrast
T
E
T
R
= 100 ms
= 1500 ms
Slide 47
Proton Density
T
E
T
R
= 14 ms
= 1500 ms
NS 172/272/Psych213, UCLA, Ivo Dinov

T1 Contrast
T
E
T
R
= 14 ms
= 400 ms
T2 Contrast
T
E
T
R
= 100 ms
= 1500 ms
Slide 48
Proton Density
T
E
T
R
= 14 ms
= 1500 ms
NS 172/272/Psych213, UCLA, Ivo Dinov

•Echo Time (TE)
•Slice Thickness
•Slice Order
•Averaging
•Bandwidth
•Imaging Matrix
•Patient Motion
•Surface Coils
•Repetition Time(TR)
•Interslice Gap
•Field of View
•Number of Echos
•Motion Comp
•Window Level
•Photography
•Equipment Performance
Mark Cohen
Field of View
Slide 49
NS 172/272/Psych213, UCLA, Ivo Dinov

Sampling in the Fourier domain leads to replicatio n in the image domain.
Spacing of the replicated image/obje ct is (1/
 k
X
,1/
 k
Y sample spacing in the k
X
& k
Y directions is
), where Fourier domain
:
 k
X
&
 k
Y
.
The replicated images will not overlap the original image if the highest spatial position in X is X max

1
2
 k
X and the highest spatial position in Y is Y max

1
2
 k
Y
.
If this is not satisfied, then ther e will be spatial overlap in the images (or aliasing).
The field of view of an acquisitio n is typically defined as one over the
K will space not sample occur if spacing
X max
: FOV
X

½ FOV
X

 k and
1
X
Y and max
FOV
Y

1
 k
Y

½ FOV
Y
.
and aliasing
Slide 50
NS 172/272/Psych213, UCLA, Ivo Dinov

Source: Traveler’s Guide to K-space (C.A. Mistretta) http://www.cis.rit.edu/htbooks/mri/ Slide 51
NS 172/272/Psych213, UCLA, Ivo Dinov

A Walk Through (sampling from ) K-space single shot two shot
Kspace can be sampled in many “shots”
(or even in a spiral)
Note: The above is k-space, not slices
2 shot or 4 shot
• less time between samples of slices
• allows temporal interpolation vs.
both halves of k-space in 1 sec
1 st half of k-space in 0.5 sec
2 nd half of k-space 1 st in 0.5 sec half of k-space in 0.5 sec
2 nd half of k-space in 0.5 sec
1st volume in 1 sec
Slide 52 interpolated 2nd volume in 1 sec image
NS 172/272/Psych213, UCLA, Ivo Dinov

T
2
* relaxation Sequences without a spin echo will be T
2
* weighted rather than T
2
-weighted. The longer the echo time
(TE) the greater the T
2 contrast.
- dephasing of transverse magnetization due to both:
- microscopic molecular interactions (T
2
)
- spatial variations of the external main field

B
(tissue/air, tissue/bone interfaces)
• exponential decay (T
2
*

30 - 100 ms, shorter for higher B o
)
M xy
M o sin 
T
2
T
2
* time
Slide 53
Source: Jorge Jovicich
NS 172/272/Psych213, UCLA, Ivo Dinov

Susceptibility
Adding a nonuniform object (like a person) to B
0 magnetic field nonuniform will make the total
This is due to susceptibility : generation of extra magnetic fields in materials that are immersed in an external field
For large scale (10+ cm) inhomogeneities, scanner-supplied nonuniform magnetic fields can be adjusted to “even out” the ripples in B — this is called shimming sinuses ear canals
Susceptibility Artifact
-occurs near junctions between air and tissue
• sinuses, ear canals
-spins become dephased so quickly (quick
T2*), no signal can be measured
Susceptibility variations may be seen around blood vessels where deoxyhemoglobin affects T2* in nearby tissue
Source: Robert Cox’s web slides
Slide 54
NS 172/272/Psych213, UCLA, Ivo Dinov

Signal-to-Noise Ratio (SNR)
Pick a region of interest (ROI) outside the brain free from artifacts (no ghosts, susceptibility artifacts). Find mean (

) and standard deviation (SD).
e.g.,

=4, SD=2.1
Pick an ROI inside the brain in the area you care about. Find
 and SD.
SNR =
 brain
/
 outside
= 200/4 = 50 e.g.,

= 200
Alternatively SNR =
 brain
/ SD outside
= 200/2.1 = 95
(should be 1/1.91 of above because

/SD ~ 1.91)
When citing SNR, state which denominator you used.
Head coil should have SNR > 50:1
Surface coil should have SNR > 100:1
Slide 55
NS 172/272/Psych213, UCLA, Ivo Dinov

Motion Correction raw data
SPM output
Gradual motions are usually well-corrected
Abrupt motions are more of a problem (esp. if related to paradigm linear trend removal motion corrected in SPM
Caveat: Motion correction can cause artifacts where there were none!!!
Slide 56
NS 172/272/Psych213, UCLA, Ivo Dinov