Rad 226a/BioE 226a

Winter 2018-2019
In Vivo MR: Spin Physics and Spectroscopy

Daniel Spielman, Ph.D., Dept. of Radiology

Lucas Center for MR Spectroscopy and Imaging
(corner of Welch Rd and Pasteur Dr)
office: Lucas Center PS-061, phone: x3-8697 email: [email protected]

1
 Limitations of Non-interacting
Classical Model
• Relaxation
– Tissue T1, T2, and T1ρ
– Anisotropic tissues
• Nuclei other than 1H
• Chemical exchange effects
• Molecules more complicated than water

Does it matter that water

has two 1H nuclei?
O
H H

2
 Image Contrast
• Clinical MRI primarily images water. Why do
different tissues exhibit different MRI contrast?
Are difference solely due to water content?
Proton Density

T1 T2 T1ρ map Post-GD T1 CEST SWI

3
 Lecture #1
Introduction
• Topics
– Administrative details
– Course Overview and Motivation
– Some interesting in vivo MR phenomena
• Handouts and Reading Assignments
– Biographies: Rabi, Purcell, Bloch

4
 Course Administration
• Lectures
– Tues, Thurs 3:00-4:20 pm, Lucas Learning Center P-069
– 3 units
• TA
– ??
• Office Hours
– To be determined, Office: Lucas Center PS061
– or by arrangement with instructor (email: [email protected])
• Web site
– http://web.stanford.edu/class/rad226a/
– Lecture notes, homework assignments, other handouts (pdf files)

5
 Course Materials
• Recommended Texts
– F. van de Ven, Multidimensional NMR in Liquids, Wiley-
VCH, New York, 1995.
– R. de Graaf, In Vivo NMR Spectroscopy, 2nd Edition, Wiley
& Sons, Chichester, UK, 2007
• Additional references (not required, but very useful!)
MRI • D. Nishimura, Principles of Magnetic Resonance Imaging, EE369b notes
Physics • M. Levitt, Spin Dynamics, Wiley, Chichester. UK, 2001
QM • D. Miller, Quantum Mechanics for Scientists and Engineers, Cambridge
Univ. Press, 2008.
Physics • C. Slichter, Principles of Magnetic Resonance, Springer, Berlin, 1996.

6
 Assignments and Grading
• Weekly problem sets (90%)
• Class participation (10%)
• No Midterm or Final

7
 Overview
• Main Themes:
– Classical vector model of MRI/MRS doesn’t fully
explain many important in vivo processes, particularly
those involving interactions among spins.
– Nuclear-nuclear interactions
– Nuclear-electron interactions
– We’ll discuss the physics and engineering principles of
these phenomena with examples from current research
topics and clinical applications.
• Prerequisites
– EE369b or familiarity with MRI (i.e. Rf pulses,
gradients, pulse sequence diagrams, k-space)
– Working knowledge of linear algebra
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 Roadmap
POF
Density
MR Physics
and Math

Matrix
Double quantum
coherence?
Quantum J-coupling?
Mechanics Polarization
Polarization
transfer?
transfer?
Bloch equations, k-space,
selective excitation, …
(EE369b)

large break
(prerequisites)
Intuition Have you tried using the
full density matrix?

Topics
1. Introduction and Review (2 weeks) 5. 1H MRS (1.5 weeks)
2. Quantum mechanics for NMR (2 week) 6. Decoupling (stealth lead-in to
relaxation theory) (1 week)
3. Density Matrix (1 week)
4. Product Operator Formulism (1.5 weeks)
9
 Spectroscopy
• In general, spectroscopy is the study of materials via interactions
with electromagnetic fields
EM
radiation Spectroscopy
NMR and Molecular Spies
1022
γ-rays While molecules are too small to observe
1020 Mössbauer directly, magnetic nuclei make ideal probes:
x-rays energy of
1018 chemical bonds
• Very sensitive to the local magnetic fields
ultraviolet 1016 electronic
• Interact extremely weakly with their
visible 14
10 environment permitting virtually
infrared vibrational thermal
1012 energy @37C perturbation-free measurements
microwave • Spatially localized
1010 rotational
108 NMR
RF Note: These differ by several orders of magnitude!
106
Hz
Energy 10
 NMR: A Short History
Discovery of NMR NMR in Condensed Matter
r1937 1945
B = B0 zˆ
µz
r
θ µ

θ = 54.7 ! , I = 2 , m = 2
1 1

1 " 3
µz = 2 γ!, µ = 2 γ!
I.I. Rabi F. Bloch E. Purcell
€
€

Nobel Prize Physics Nobel Prize Physics 1952

1944 11
 NMR: A Short History
Determining 3D structures of
FT-NMR, 2D Spectroscopy
biological macromolecules
1966-1970s
1980s

1D Spectrum 2D Spectrum 3D Spectrum

R. Ernst K. Wüthrich

Nobel Prize Chemistry Nobel Prize Chemistry 12

1991 2002
NMR in the Chemistry Laboratory
• Types of NMR spectroscopy experiments
most relevant for
– High resolution studies of liquids in vivo studies

– Solid state NMR (e.g. magic angle spinning)

– Studies of substances (or nuclei) with broad resonance lines

• Types of Questions
– What is it?
– What is the structure?
bonding connectivity
spatial connectivity
molecular conformation

– What are the dynamics?

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 In Vivo MRS/MRI

pure liquid tissue crystalline solid

• Complex mixture of stuff – P. Lauterbur P. Mansfield

water, lipids, metabolites, etc

• Physiological processes

• Types of Questions
Nobel Prize: Medicine 2003
– Where is it?
– How much?
– What are the dynamics?
relaxation times
chemical processes
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 MRI
• Standard analysis based on a water signal made up of
many independent (non-interacting) nuclei +
phenomenological T1 and T2 relaxation times.
• Leads to very powerful approaches (e.g. k-space) that
adequately explain the bulk of MRI techniques and
applications.

15
 Limitations of Non-interacting
Classical Model
• Relaxation
– Tissue T1, T2, and T1ρ
– Anisotropic tissues
• Nuclei other than 1H
• Chemical exchange effects
• Molecules more complicated than water

Does it matter that water

has two 1H nuclei?
O
H H

16
 Example: Temperature effects
Hydrogen NMR Spectrum
bonds

Liquid water
peak
water
T1 effects?
ppm

Which is the correct model for the effect of temperature?

“Chemical shift “Two-pools model”
“T2 model”
model”
T= 37º C T = 38º C T = 39º C
T= 39º C T= 39º C Protons w/o
T = 38º C hydrogen
bonds
T = 38º C
T = 37º C Protons w/
T = 37º C hydrogen
bonds

ppm ppm ppm ppm ppm 17

 Example: Water, water, water
• Consider a mixture with 5% D2O and 95% H2O (D = 2H)
O O O O
1H 1H 1H 1H
1H 1H 1H 1H
O O
1H 1H
O O 2H 1H
1H 1H O
2H 1H
O O O
1H 1H 1H 1H O 1H 2H
1H 1H 2H 2H

Why is T1, D << T1, H? What about T2, D vs T2, H?

What if the solution in injected in vivo?

• Consider a mixture with 5% H217O and 95% H216O

17O 16O 16O 16O
16O 16O
H H 16O H H 16O
H HH H 17O H H H 16O
H
H H H H H H H H

Why is the proton T2 for this mixture < T2 for a pure H216O sample?
What about T1? 18
 Example: Tendon Imaging
• T2 of tendons is strongly dependent on the angular
orientation with respect to B0: magic angle = 54.7o
Tendon parallel to B0 Tendon angle = 55o

B0 B0

acute Achilles tendon rupture: 3D GRE, TR/TE=21/7 ms

What about T1?

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 Example: Fast Spin Echo
T2

• Why is fat bright on FSE images?

Conventional Spin Echo Fast Spin Echo

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TR/TE=2500/80 ms TR/TE=2500/80 ms, ETL = 8
 Example: γ-aminobutyric acid (GABA)

x 300

GABA How?
• Why? 1H Brain Spectrum
(with suppression of everything
GABA/glutamate are the major except GABA)
excitatory/inhibitory GABA
neurotransmitters in the human
brain, and are of particular interest
for conditions such as autism, for ? ?
?
which an excitatory/inhibitory x 3000
imbalance is hypothesized.
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 Example: Brain tumors
52 y.o male: MRI #1 - rule out stroke, MRI #2 - tumor?

choline
choline NAA
creatine creatine
NAA

TE = 144 ms TE = 144 ms
post-contrast T1

9 y.o male: non-enhancing lesion in left hippocampus

NAA
choline choline
creatine creatine
NAA

TE = 144 ms TE = 144 ms

post-contrast T1 22
 Next lecture:
Review of Classical MR

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Biography: Isidor Isaac Rabi
(born July 29, 1898, Rymanów, Austria-Hungary [now in Poland]—died Jan. 11, l988,
New York, N.Y., U.S.) American physicist who was awarded the Nobel Prize for Physics
in 1944 for his invention (in 1937) of the atomic and molecular beam magnetic resonance
method of observing atomic spectra. Rabi's parents settled in New York City in 1899.
After earning a bachelor's degree in chemistry at Cornell University in 1919, Rabi
switched to physics and received his Ph.D. from Columbia University in 1927. He did
postgraduate work in Europe and then joined the faculty of Columbia University in 1929,
becoming professor of physics in 1937. From 1940 to 1945 Rabi was a leader of the
group of scientists at the Massachusetts Institute of Technology, Cambridge, who helped
in the development of radar. He was a member of the General Advisory Committee of the
Atomic Energy Commission from 1946 to 1956 and succeeded J. Robert Oppenheimer as
its chairman from 1952 to 1956. He originated the concept of the CERN international
laboratory for high-energy physics in Geneva, Switz., and he was one of the founders of
the Brookhaven National Laboratory, Upton, N.Y. He also built up one of the world's
finest physics departments at Columbia University, one which was to produce several
Nobel Prize–winning physicists. Rabi's most important scientific work was his
development (in the 1930s) of a method for measuring the magnetic properties of atoms,
atomic nuclei, and molecules. The method is based on measuring the spin of the protons
in the atom's core, a phenomenon known as nuclear magnetic moments. With the
application of his magnetic resonance method, several mechanical and magnetic
properties, as well as the shape, of an atomic nucleus can be deduced. The precise
measurements yielded by this method made possible such subsequent applications as the
atomic clock, the maser, and the laser, as well as the nuclear magnetic resonance imaging
used in diagnostic medicine. Rabi's method provided the central technique for virtually all
molecular and atomic beam experimentation. 24
Biography: Felix Bloch
(born Oct. 23, 1905, Zürich, Switz.—died Sept. 10, 1983, Zürich) Swiss-born
American physicist who shared (with E.M. Purcell) the Nobel Prize for
Physics in 1952 for developing the nuclear magnetic resonance method of
measuring the magnetic field of atomic nuclei. Bloch's doctoral dissertation
(University of Leipzig, 1928) promulgated a quantum theory of solids that
provided the basis for understanding electrical conduction. Bloch taught at the
University of Leipzig until 1933; when Adolf Hitler came to power he
emigrated to the United States and was naturalized in 1939. After joining the
faculty of Stanford University, Palo Alto, Calif., in 1934, he proposed a
method for splitting a beam of neutrons into two components that
corresponded to the two possible orientations of a neutron in a magnetic field.
In 1939, using this method, he and Luis Alvarez (winner of the Nobel Prize for
Physics in 1968) measured the magnetic moment of the neutron (a property of
its magnetic field). Bloch worked on atomic energy at Los Alamos, N.M., and
radar countermeasures at Harvard University during World War II. Bloch
returned to Stanford in 1945 to develop, with physicists W.W. Hansen and
M.E. Packard, the principle of nuclear magnetic resonance, which helped
establish the relationship between nuclear magnetic fields and the crystalline
and magnetic properties of various materials. It later became useful in
determining the composition and structure of molecules. Nuclear magnetic
resonance techniques have become increasingly important in diagnostic
medicine. Bloch was the first director general of the European Organization
for Nuclear Research (1954–55; CERN).

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Biography: Edward Mills Purcell
(born Aug. 30, 1912, Taylorville, Ill., U.S.—died March 7, 1997,
Cambridge, Mass.) American physicist who shared, with Felix
Bloch of the United States, the Nobel Prize for Physics in 1952 for
his independent discovery (1946) of nuclear magnetic resonance in
liquids and in solids. Nuclear magnetic resonance (NMR) has
become widely used to study the molecular structure of pure
materials and the composition of mixtures.During World War II
Purcell headed a group studying radar problems at the Radiation
Laboratory of the Massachusetts Institute of Technology,
Cambridge. In 1946 he developed his NMR detection method,
which was extremely accurate and a major improvement over the
atomic-beam method devised by the American physicist Isidor I.
Rabi.Purcell became professor of physics at Harvard University in
1949 and in 1952 detected the 21-centimetre-wavelength radiation
emitted by neutral atomic hydrogen in interstellar space. Such radio
waves had been predicted by the Dutch astronomer H.C. van de
Hulst in 1944, and their study enabled astronomers to determine the
distribution and location of hydrogen clouds in galaxies and to
measure the rotation of the Milky Way. In 1960 Purcell became
Gerhard Gade professor at Harvard, and in 1980 he became
professor emeritus. The same year he received the National Medal
of Science.

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