Basic Physical Principles of MRI

DR. ARUN CHOUGULE

DEAN, PARAMEDICAL SCIENCES RUHS arunchougle@rediffmail.com

History of Nuclear Magnetic Resonance

NMR = nuclear magnetic resonance Felix Bloch 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

Bloch
NMR MRI

Purcell

History of fMRI
MRI -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 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 & Kwong publish first functional images using BOLD signal

The NMR Spectrometer

=>

Synopsis of MRI
Put subject in big magnetic field Transmit radio waves into subject [2~10 ms] Turn off radio wave transmitter Receive radio waves re-transmitted by subject0 Convert measured RF data to image

Outline
Magnets Shimming Gradient Coils Radio Frequency Coils Body Coil Assembly Data Acquisition System Array Processor Site Planning & Preparation

Some terms to know

B0 this is used to denote the main magnetic field also known as longitudinal magnetization objects placed within B0 will gradually align to this field (longitudinal relaxation) M0 this is used to denote the net magnetization of an object within B0 it is the M0 which is tipped out of alignment with B0 to create the MR image so M0 is now measured as transverse magnetization RF pulse radio frequency pulse not to be confused with resonant frequency to read M0 it must be tipped out of alignment with B0 this is achieved by sending an RF pulse at certain resonant frequencies and gradients

Many factors contribute to MR imaging

Quantum properties of nuclear spins Radio frequency (RF) excitation properties Tissue relaxation properties Magnetic field strength and gradients Timing of gradients, RF pulses, and signal detection

What kinds of nuclei can be used for NMR?

Nucleus needs to have 2 properties:
Spin charge

Nuclei are made of protons and neutrons

Both have spin Protons have charge

Pairs of spins tend to cancel, so only atoms with an odd number of protons or neutrons have spin
Good MR nuclei are 1H, 13C, 19F, 23Na, 31P

The Causes of Magnetism

Macroscopic View Current in wire Field is around wire
Depends on current

Depends on distance

0 I B 2p r

Microscopic View Moment of atom Field is about nucleus

Depends on material

B A cosq

Properties of Atomic Nuclei

Nuclei have two properties:
Spin (conceptual, not literal) Charge (property of protons)

Nuclei are made of protons and neutrons

Both have spin values of Protons have charge

Pairs of spins tend to cancel, so only atoms with an odd number of protons or neutrons have spin

A nucleus has the NMR Property if it has both angular momentum and a magnetic moment. Such nuclei have an odd number of protons or an odd number of neutrons.

Kinds of Magnetism
Ferromagnetic materials (e.g., Iron)
Both attract and repel other magnets Create own field

Paramagnetic materials (e.g., Gadolinium)

Attracted toward magnets Align with other fields

Diamagnetic materials (e.g., Water)

Repelled by magnets Anti-align with other fields

Protons align with a magnetic field

Basic Quantum Theory

Radiation is absorbed
Energy increases
Lower

Higher

Radiation is emitted
Energy decreases

Fields in General: Electricity

FE qE
When a particle rises We refer to electricity

E k r2
Q

V d

V Ed

*Actual cause is force of attraction of the charge of particle to the charge of Capacitor through the field of electricity

Hydrogen atoms are best for MRI

Biological tissues are predominantly 12C, 16O, 1H, and 14N Hydrogen atom is the only major species that is MR sensitive Hydrogen is the most abundant atom in the body The majority of hydrogen is in water (H2O) Essentially all MRI is hydrogen (proton) imaging

Nuclear Magnetic Resonance Visible Nuclei

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A Single Proton
There is electric charge on the surface of the proton, thus creating a small current loop and generating magnetic moment .

The proton also has mass which generates an angular momentum J when it is spinning.

Thus proton magnet differs from the magnetic bar in that it also possesses angular momentum caused by spinning.

Physics of protons. motion of electrically charged particles results in a magnetic force

orthogonal to the direction of motion protons (nuclear constituent of atom) have a property of angular momentum known as spin

Angular momentum (spin) of a proton.

A bar magnet in a magnetic field

magnetic field

N S S N

Solenoid for producing a strong magnetic field by passing a large current through a set of coils

In field free space Inside magnetic field Protons aligning within a magnetic field
Applied Magnetic Field (B0)

randomly oriented

oriented with or against B0 M = net magnetization

when placed in a magnetic field (B0; e.g., our MRI machines) protons will either align with the magnetic field or orthogonal to it (process of reaching magnetic equilibrium)

there is a small difference (10:1 million) in the number of protons in the low and high energy states with more in the low state leading to a net magnetization (M)
Source: Robert Coxs web slides Source: Jody Culhams web slides

Source: Mark Cohens web slides

Protons in no magnetic field

In the absence of a strong magnetic field, the spins are oriented randomly.

Thus, there is no net magnetization (M).

Precession the spinning top analogy.

What is actually aligned with the B0 is the axis around which the proton precesses the decay of precession (i.e., it is the rate of precession out of alignment with B0 together with the proton density of the tissue concerned that is crucial in MRI)

Source: Cohen and Bookheimer article

The magnetic moment and angular momentum are vectors lying along the spin axis

=gJ g is the gyromagnetic ratio g is a constant for a given nucleus

How do protons interact with a magnetic field?

Moving (spinning) charged particle generates its own little magnetic field
Such particles will tend to line up with external magnetic field lines (think of iron filings around a magnet)

Spinning particles with mass have angular momentum

Angular momentum resists attempts to change the spin orientation (think of a gyroscope)

The energy difference between the two alignment states depends on the nucleus

E = 2 z Bo E hn
n g/2p Bo known as Larmor frequency g/2p = 42.57 MHz / Tesla for proton

Resonance frequencies of common nuclei

Note: Resonance at 1.5T = Larmor frequency X 1.5

Electromagnetic Radiation Energy

X-Ray, CT

MRI

 NMR measures the net magnetization of atomic nuclei in the presence of magnetic fields Magnetization can be manipulated by changing the magnetic field environment (static, gradient, and RF fields) Static magnetic fields dont change (< 0.1 ppm / hr): The main field is static and (nearly) homogeneous RF (radio frequency) fields are electromagnetic fields that oscillate at radio frequencies (tens of millions of times per second) Gradient magnetic fields change gradually over space and can change quickly over time (thousands of times per second)

MRI uses a combination of Magnetic and Electromagnetic Fields

Radio Frequency Fields

RF electromagnetic fields are used to manipulate the magnetization of specific types of atoms This is because some atomic nuclei are sensitive to magnetic fields and their magnetic properties are tuned to particular RF frequencies Externally applied RF waves can be transmitted into a subject to perturb those nuclei Perturbed nuclei will generate RF signals at the same frequency these can be detected coming out of the subject

Basic Quantum Mechanics Theory of MR

The Effect of Irradiation to the Spin System

Lower Higher

Basic Quantum Mechanics Theory of MR

Spin System After Irradiation

Net magnetization is the macroscopic measure of many spins

Bo

Bo M c T

Net magnetization
Small B0 produces small net magnetization M Larger B0 produces larger net magnetization M, lined up with B0 Thermal motions try to randomize alignment of proton magnets At room temperature, the population ratio of antiparallel versus parallel protons is roughly 100,000 to 100,006 per Tesla of B0

MRI Block Diagram

Operator Console Array Processor

Receiver
Amplifier ADC

Magnetic Disk Archive Media

Computer Magnet
RF Amplifier

Shim Coils Gradient Coils RF Coil

Gradient Amplifiers: X, Y, Z

Magnets
The static magnetic field (Bo) can be created by:
Electromagnets
Superconducting electromagnets Resistive electromagnets

Permanent magnets

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Magnets
An electromagnet can consist of an electrically conducting wire wound around a cylinder (a solenoid). The magnetic field is strong and uniform inside the cylinder and weaker outside the cylinder. Higher electrical current produces a stronger magnet. Vendors are now producing magnets that have shorter cylinders (short bore magnets) to reduce claustrophobia.
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Bore

Fringe field

Air core solenoid

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Magnets
Superconducting electromagnets TiNb wire has essentially no electrical resistance at 4 K (liquid Helium) Current in the superconducting wire is hundreds of amps at 1.5T Early magnets used liquid helium and liquid nitrogen without refrigeration Modern magnets use liquid helium with refrigeration

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Cryostat

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Delivery of 1.5T Superconducting Magnet

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Magnets
Resistive electromagnets Essentially the same as a superconducting system except: -conductors are resistive and produce heat -lower electrical current -lower magnet strength -less stable over time -Requires an electrical power supply and a cooling system

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Magnets
Permanent - soft iron permanent magnets or ceramic magnets Can be assembled from component pieces Patient is imaged in an air gap Iron yoke may be used to contain the flux lines Has essentially zero fringe magnetic field Requires no power (energy) Disadvantage -Heavy
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Magnets
Open MRI magnets are mostly resistive. Superconducting open MRI magnets with higher field strengths (0.7 T-4.0T) are now available.
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0.2 T Open MRI with permanent magnet (11 tons)

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0.7 T Open MRI with superconducting magnet

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Magnets
For optimum MR imaging the static magnetic field (Bo) should be very uniform (homogeneous) and very stable over time.

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Homogeneity values
Magnetic homogeneity can be*
< 0.1 ppm
< 4 ppm

10 cm sphere
50 cm sphere

0.0015 Gauss out of 15,000 Gauss 0.06 Gauss out of 15,000 Gauss

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Magnetic field Stability

< .1ppm/hour*
<0.0015 Gauss/hour at 1.5T

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Magnets
Fringe magnetic fields:
Fringe magnetic fields can extend great distances from an unshielded superconducting MRI magnet 5 Gauss @ 60 feet from magnet isocenter at 1.5 T
The 5 Gauss zone is the safety zone that persons wearing pacemakers should not enter.

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Magnets
Fringe magnetic fields can be reduced in extent by massive steel shielding around the outside of the magnet, or by steel shielding in the walls, floor and ceiling of the exam room. The exam room for the first 1.5 T magnet at MCG is a steel box comprised of 74 tons of steel (up to 3 thick) These passive shielding solutions are no longer popular (weight!)
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Magnets
Fringe magnetic fields can be reduced by active shielding. An additional set of superconducting coils is added outside of the main magnet coils. Current in the active shielding coils is reversed relative to the main coils. The geometry of the two magnetic fields produced by the two solenoids leads to significant cancellation of fringe magnetic fields.
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Fringe Diagram of Active Shield 1.5 T*

26 4

5 Gauss

16 6

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Magnets
Refrigeration systems

The boil off of liquid helium can nearly be eliminated by using a cold head and a recondenser to liquify helium gas. In a modern magnet, cryogens have to be replenished every few years.
The refrigeration system causes a persistent chirp that is audible in the exam room.
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Magnets
Mobile magnets: Conventional superconducting magnets for mobile systems are designed to be ramped up or down quickly (1 hour) and efficiently (small He loss).
Modern mobile units use actively shielded magnets which do not have to be ramped up/down for relocation.
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Shimming
Because the magnet itself is not adequately homogeneous, it is necessary to improve or shim the homogeneity of the static magnetic field (Bo).

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Shimming
Shimming (or adjustment of the static magnetic field homogeneity) is accomplished by two methods: (1) Passive shimming (2) Active shimming The static magnetic field is passively shimmed by the placement of iron plates in the bore of the magnet. The iron plates offset the effects of external ferromagnetic objects, and other sources of

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Shimming

Passive Shimming
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Shimming
Active shimming requires passage of electric current through coils with unique geometric configurations. The shim coils are designed to correct inhomogeneities of specific geometries. The shim coils are typically named X, Y, XY, XZ, ZY, X2Y2, Z2X, Z2Y, Z0, Z1, Z2, Z3, Z4 Shim coils may be placed inside of the cryostat superconducting shims or inside the bore of the magnet resistive shims. Resistive shims are typically watercooled. Modern magnets use 63 superconducting shims.

Shimming
Because the patients tissue becomes somewhat magnetized, the nice homogeneity established by shimming is perturbed when a patient is placed in the magnet. The gradient coils can be used to re-establish good homogeneity.

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Shimming
DC current can be run through the X, Y, Z gradient coils to shim for each patients tissue. When a patient is first placed in the MRI scanner, these DC currents are adjusted by the MRI scanner in a process often called auto shim. This takes only a few seconds.
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Gradient Coils
Gradient coils are used for spatial localization. For example in a transverse image, the Z gradient would be used in selecting a slice of tissue to image. The X gradient may be used for phase encoding and the Y gradient for frequency encoding.

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Gradient Coils
Gradient coils are generally pulsed on very briefly (a few msec). How long a gradient coil must be left on is affected by the strength of the gradient. Stronger gradients pulses can have shorter durations which is important in fast MRI imaging techniques. The frequent pulsing of the gradients produces the substantial noise associated with an MRI scan.
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Gradient Coils
Gradient Coils are characterized by: * Strength: 23 mT/m Slew Rate: 120 T/m/s Rise time: 192 sec Duty Cycle (100%) Eddy current compensation: Active

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 A gradient strength of 23 mT/m can create a linear change in magnetic field of 23mT (230 Gauss) over a distance of 1 meter.

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Gradient Coils
A Z gradient can be described as a Maxwell pair, two coils with countercurrent flow of electricity. The X and Y gradients can be described as saddle coils. A saddle coil is a set of four coils that are shaped around the cylinder of a solenoid.
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Gradient Coils
Z - Maxwell pair
Two loops having current flow in opposite directions

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Gradient Coils
X, Y saddle coils Although Maxwell pairs and saddle coils are useful for conceptualizing how gradient coils work, actual gradient coils may have much more elaborate configurations

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Gradient Coils
Consider the Z coil: It can be constructed as 2 solenoidal windings (wrapped in different directions) that meet near the middle of the cylindrical bore.

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Gradient Coils
When the Z gradient is switched on or off, eddy currents can be induced to flow in the metal structures of the cryostat. These eddy currents produce time varying magnetic fields that can perturb the very gradient magnetic fields that produce the eddy currents..
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Gradient Coils
A set of eddy current compensation gradients can be placed outside of the Z gradient windings. They are wound in the opposite direction in series with the Z gradients. The effect of the eddy current compensating gradients is to cancel the gradient magnetic fields outside of the cylinder and reduce eddy current formation.
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Gradient Coils
The complex configurations for the X and Y gradients are sometimes referred to as thumb prints. Eddy current compensating thumb prints (with swirls in the opposite direction) are placed outside of the gradient windings to reduce eddy current effects. Rohmer developed compensation for eddy currents and eddy current compensation coils are sometimes known as Rhomer coils.

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Gradient Coils
Active eddy current compensation
Currents supplied to gradient coils can be tailored to further compensate for eddy currents

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RF Coils
For resonance to occur, an oscillating RF magnetic field (B1) must be applied to the patient. This B1 field is applied through an RF coil. An RF coil is also used to detect the relaxation of magnetization in the patients tissues. In many instances, the same RF coil used for exciting the tissue is used to detect relaxation of magnetization.
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RF Coils
Linear: RF coils comprised of one coil. Linear
coils can measure RF magnitude but cannot resolve positive from negative phase changes.

Quadrature: Circularly Polarized

A coil that produces an RF field with circular polarization by providing RF feed points that are out of phase by 90o. When used as a transmitter coil, a factor of two power reduction over a linear coil results; as a receiver, an increase of up to a factor of 2 can be achieved.

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RF Coils
Volume coils: Have the same sensitivity in the center of the coil as near the edges: (RF coils with homogenous field distributions) body coil head coil extremity coil wrist coil
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Head Coil

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RF Coils
Surface coils - simplistic loop like coils that have high sensitivity near the coil, but decreasing sensitivity with increasing distance

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Surface Coils

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RF Coils
Tuning: Optimum performance for RF coils is obtained by matching and tuning the loaded coil (coil with patient in place) to the RF transmit / receive system. For some vendors, this is done automatically by the MRI scanner when the patient is first placed in the magnet. Other vendors use broadly matched/tuned coils.
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RF Coils
Phased array: Multiple individual RF coils, each with its own receive amplifier and receive channel (4, 8, 16 channels). Each coil simultaneously detects transverse magnetization. Phased array coils reduces the need to change coils during multi-exam studies. Body Array Spine Array
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Body Array and Head Array Coils

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Body Coil Assembly

There is a coil assembly that is comprised of several of the coils described earlier:

THE BODY COIL ASSEMBLY

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Body Coil Assembly

Body coil assembly: A cylinder having several MRI coils formed onto it. Each coil is electrically insulated from other coils Outside of Cylinder Eddy Current Compensation (Rohm Gradient Coils (X, Y, Z) Body RF Coil Inside of Cylinder
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Data Acquisition System

RF Exciter (Transmitter) RF Detector (Receiver)

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RF Exciter (transmitter)
Frequency Synthesizer to create the Larmor frequency Digital envelope for frequencies to establish the bandwidth of the RF Amplifier (15kW peak, 600W average) to apply the RF waveform to an RF coil RF Coil creates an oscillating magnetic field within the coil at the Larmor frequency Power monitor to measure or calculate energy deposited in the patient (Specific Absorption 91 Rate)

RF Detector (receiver)
Preamp (in room / one per coil) Amplifier(s) ADC 10V => 24 bits @ 500kHz receiver bandwidth*

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Array Processor*
Fast bus system 320 Mbyte/sec Dynamic memory (288 Mbyte) Word length 64 bit 256 x 256 matrix recon < 0.08 s 512 x 512 matrix recon < 0.4 s

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Site Planning & Preparation

Structural Considerations -Floor loading
Magnet weight: 1.5T => ~8000 lbs

-Structural component location (within about 20 feet of

isocenter) affects shimming of the magnetic field Steel pipes

Structural steel (I-beams)

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Site Planning & Preparation

Environmental Considerations

(continued)

Distance of large moving ferrous objects from isocenter

For a 1.5 T unshielded magnet beds and wheelchairs 20 ft. minimum automobiles 25 ft. minimum trucks and elevators 33 ft. minimum
These are reduced for an actively shielded magnet.
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Site Planning & Preparation

(continued)

RF Environment Radio Frequency energy from radio, broadcast TV, pagers, cell phones, fluorescent lights, electric motors, etc. can create artifacts in MRI images. The RF energy near the Larmor frequency is monitored during site selection. The MRI exam room is shielded to attenuate this RF energy.
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Site Planning & Preparation

(continued)

RF shielding Copper foil laminates are typically used Only one electrical ground point (single point ground) Viewing windows are usually covered with copper mesh Faraday Cage
Typical attenuation is 80-100 dB from 1MHz to 100 MHz
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RF shielded room: Faraday cage

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Precession
If M is not parallel to B, then it precesses clockwise around the direction of B. Normal (fully relaxed) situation has M parallel to B, and therefore does not precess This is like a gyroscope

Recording the MR signal

Need a receive coil tuned to the same RF frequency as the exciter coil. Measure free induction decay of net magnetization Signal oscillates at resonance frequency as net magnetization vector precesses in space Signal amplitude decays as net magnetization gradually realigns with the magnetic field Signal also decays as precessing spins lose coherence, thus reducing net magnetization

T2* decay
Spin coherence is also sensitive to the fact that the magnetic field is not completely uniform Inhomogeneities in the field cause some protons to spin at slightly different frequencies so they lose coherence faster Factors that change local magnetic field (susceptibility) can change T2* decay

Different tissues have different relaxation times. These relaxation time differences can be used to generate image contrast.
T1 - Gray/White matter T2 - Tissue/CSF T2* - Susceptibility (functional MRI)

USC Trio Siemens 3T MRI

MRI DEVICE

RF Coil
RF Coils are used to excite the spins and to receive the signal A typical coil is a tuned LC circuit and may be considered a near field antenna

Magnetic Resonance Imaging (MRI)

NMR and MRI Use Similar Instruments Powerful magnets

An NMR spectrometer

An MRI instrument

Protons in no magnetic field

In the absence of a strong magnetic field, the spins are oriented randomly.

Thus, there is no net magnetization (M).

Transverse Magnetization
Bo
Bo Longitudinal Axis (z direction)

B is used for magnetic fields.

B0 is the scanners main field.

Transverse Plane (xy plane)

Static Contrast Images

Examples from the Siemens 3T
T1 and T2 Weighted Images
T1 Weighted Image (T1WI)
(Gray Matter White Matter)

T2 Weighted Image (T2WI)

(Gray Matter CSF Contrast)

add a gradient to the main magnetic field excite only frequencies corresponding to slice plane
Freq

Spatial Coding
Gradient magnetic field = applied in the slice plane (i.e., the x direction) thus Gx

Field Strength (T) ~ z position

Gradient coil

Magnetic fields are powerful!

Shimmingrf coil

rf gradient coil

main magnet

main magnet

Transmit

Receive

Control Computer

Image Noise and SNR

Low Signal-to-Noise Ratio High Signal-to-Noise Ratio

Cartilage Imaging: Knee Anatomy

Patella

Patellar Cartilage

Femur

Synovial Fluid
Femur

Femoral Cartilage

Tibia

Axial Image
(T2-weighted with Fat Suppression)

Sagittal Image
(T1-weighted)

MRI Contrast Agent

3.0

MRI + Contrast Agent

Kidney
2.4

1.8 Bladder

1.2
0.6

Tumor

Int

Image Intensity enhanced by: 1) Contrast Agent concentration 2) Hypoxic/Ischemic regions

Oxygen Mapping with OMRI

Rat, respiratory model 1.5 mmol/kg

100

mm Hg

0 Time (min.) % Oxygen in breathing air 0:45 21% 6:20 9.5% 12:00 17:30 9.5% 23:20 21%

21%

Oxygen Maps from OMRI Correspond with Changes in Tissue Oxygenation Dynamic changes in pO2 can be monitored

Air

140 120 100 80 60 40 20 0

(Oxygen, mm Hg)

Carbogen

140 120 100 80 60 40 20 0

(Oxygen, mm Hg)

Metabolic fates of pyruvate

Pyruvate
Transamination Reduction

Carboxylation Oxaloacetate

Oxidative decarboxylation
Acetyl-CoA

With converted hyperpolarized molecules, Pyruvate is suitableinto lactate, alanine, oxaloacetate or Acetyl-CoA depending on the it is possible to distinguish breakdown needs of the tissues. products based on their chemical shifts by 13C MRI.

In vivo metabolic mapping using 13C-pyruvate

3D surface rendering

MR Spectroscopy
Candidates for MRS include: 1H, 31P, 13C, 23Na, 7Li, 19F, 14N, 15N, 17O, 39K The most commonly studied nuclei are 1H and 31P This lecture is focused on Proton (1H) Spectroscopy
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Nuclear Magnetic Resonance Spectroscopy

1H

NMRSpin-Spin Splitting

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MR Spectroscopy
Magnetic Resonance Spectroscopy (MRS) provides a non-invasive method of studying metabolism in vivo. The tissues chemical environment determines the frequency of a metabolite peak in an MRS spectrum.

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MR Spectroscopy
Because we divide the signal from each voxel into a smaller number of components (chemically distinct species) the SNR of spectra is lower than that of MR images-- to obtain an acceptable level of SNR in reasonable imaging times, much larger voxels are required for MRS than MRItypically MRS uses voxel sizes of 1 to 8 cm3, whereas voxels for imaging are 1 to 5 mm3.
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Proton Spectroscopy
Recall that the Larmor equation describes the resonant precessional frequency of a nuclear magnetic moment in an applied static magnetic field.

w g Bo

Where:

w precessional frequency
= gyromagnetic ratio (MHz/Tesla) [42.58 MHz/Tesla for hydrogen nuclei]

(resonant frequency)

Bo

= magnetic field (Tesla)

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Proton Spectroscopy
If all the proton nuclei in a mixture of molecules had the same Larmor frequency, the MR spectra would be limited to a single peak. However, the magnetic B0 field seen by a nucleus is shielded by the covalent electron structure surrounding the nucleus. Electrons are negatively charged and have spin properties. Thus, when placed in an externally applied magnetic field, electrons will precess and induce a small magnetic 129 field around the nuclei.

Proton Spectroscopy
These local magnetic fields generated by the surrounding electrons can add or subtract from the applied magnetic field B0. Consequently, the nuclei experience slightly different magnetic fields based on chemical structures. Due to this small change in the local magnetic field, nuclei will resonate at slightly shifted Larmor frequencies.
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Proton Spectroscopy
Nuclei with different chemical neighbors will have slightly different resonance frequencies given by:

w g Bo(1- )

Where is a screening constant ( << 1). This small change in the resonance frequency, referred to as chemical shift, is the basis for magnetic resonance spectrosocpy.
Note that both the overall molecular structure and the proton(s) position within the molecule will determine .

Proton Spectroscopy
J coupling, also known as scalar coupling or spin-spin splittingrefers to the interaction of two nuclear spins on the same molecule by means of distortions in their electron clouds. J coupling interactions are responsible for the fine-line splitting (doublets, multiplets) seen in high resolution MRS.

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Proton Spectroscopy
For example, consider ethanol: CH3-CH2-OH There are two protons in the CH2 (methylene) group so it splits the CH3 resonance into a triplet; there are three protons in the CH3 (methyl) group so it splits the CH2 resonance into a quartet. The splittings are small, independent of the field strength B0.

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Ethanol spectrum

OH CH2

CH3
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http://www.steve.gb.com/science/spectroscopy.html

Proton Spectroscopy
Chemical shifts in ppm are independent of the strength of the applied field B0 and correspondingly, the instrument frequency Chemical shifts in Hz are field and frequency dependent

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Proton Spectroscopy
In the frequency domain, the area under a specific peak is proportional to the number of protons precessing at that frequency However, there is a problem with using a frequency axis to display MR spectra:
The axis is proportional to B0 which means that peak locations on the axis will depend on the field strength used for measurement.
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Proton Spectroscopy
A parts per million (ppm) scale is used instead:

( i - r) ______________
0 x 10 -6

is dimensionless and is measured in parts per million (ppm) . The significance of is that the chemical shift positions of nuclei with the same atomic number measured in parts per million are independent of the field 137 strength used.

Proton Spectroscopy
Local magnetic field inhomogeneities widen and distort the spectral lines. Improved magnetic field homogeneity increases SNR and narrows peak widths-thus improves both sensitivity and spectral resolution. Maximum homogeneity is accomplished by adjusting DC currents in the gradient coils and room temperature shim coilsa process known as shimming

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Proton Spectroscopy
An alternative to images: MR offers the possibility to visualize the chemical environment via spectroscopy, examining the metabolism of areas in question. How? Transmit a broadband RF pulse (which excites multiple nuclear species) and analyze the receive signal for the amplitude of different frequency components abundance of different species.
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Proton Spectroscopy
The two common approaches in MR spectroscopy are single voxel spectroscopy (SVS) and chemical shift imaging (CSI). For SVS techniques, the two main acquisition schemes are spin echo (SE), or Point-RESolved Spectroscopy (PRESS), and stimulated echo acquisition method (STEAM). Essential: suppress the water signal, CHEmicalShift-Selective (CHESS), and for regions outside the central nervous system, also the lipid signal. One can perform this by applying appropriate preparatory RF pulses before the main sequence.

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Proton Spectroscopy
1000 25 800 20 600

15

400

10 5

200

0 0

This figure demonstrates the importance of suppressing the water signal. The metabolites of interest have a signal one hundred times smaller than that of the water peak, and without water suppression would be poorly resolved Scott & White 2004

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Proton Spectroscopy (SVS with PRESS)

For one acquisition scheme Point RESolved Spectroscopy (PRESS)
Basic diagram of SVS with spin echo (ref #1) Water-suppression The 90 pulse excites a slice. The first 180 pulse refocuses the transverse magnetization in a row of tissue within the slice. The second 180 pulse refocuses the magnetization within a column of the row, leaving a single voxel. Then, the signal represents a combination of spins in that voxel precessing at slightly different frequencies (function of time). Fourier transform of signal number of spins at a given frequency in a voxel (function of frequency). Scott & White 2004

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Proton Spectroscopy (SVS with PRESS)

The effect of echo time in SE single voxel spectroscopy (SVS). Left: TE=30ms; Right: TE=144 ms. TE controls the T2 contrast of the spectral peaks in the same way tissue T2 contrast is controlled in MR imaging. As shown, Glx (glutamine) and myoinositol (mI) have short T2 values and are not visible on long TE spectra.

Scott & White 2004

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Proton Spectroscopy (SVS with PRESS)

Major healthy brain metabolite peaks: long TE spectra: 1) N-acetylaspartate (NAA) at 2.02 ppm, 2) choline (Cho) at 3.20 ppm, and 3) creatine (Cr) at 3.02 ppm and 3.9 ppm. short TE spectra (addl peaks): 4) myoinositol (mI) at 3.56 ppm, 5) glutamine and glutamate (Glx) between 2.05-2.5 ppm and 3.65-3.8 ppm, and 6) glucose at 3.43 ppm.

Scott & White 2004

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Proton Spectroscopy (SVS with STEAM)

Basic diagram of SVS with STEAM:

Water-suppression The 90 pulse excites a slice. A second 90 pulse refocuses the transverse magnetization in a row of tissue within the slice. A third 90 pulse refocuses the magnetization within a column of the row, leaving a single voxel.
Negative to STEAM: rephasing only about 50% of the original generated transverse magnetization (low SNR). ~ (sort of ) Positive to STEAM: shorter echo times than PRESS sequence.
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Scott & White 2004

Multivoxel Spectroscopy (Chemical Shift Imaging)

Phase encoding gradients can be utilized, as in imaging, in order to encode spatial information. Figure 4 illustrates a simple 2D chemical shift imaging (CSI) acquisition scheme. Selective 90 RF pulse and slice-select gradient generates a transverse magnetization within the slice. Orthogonal magnetic field gradients of short duration serve to phase-encode the data in 2D. Data are sampled at multiple times. 3D Fourier inverse transform gives frequency information over the 2D slice.

146

Figure 4
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Scott & White 2004

Multivoxel Spectroscopy (Chemical Shift Imaging)

Figure 5 illustrates the imaging setup for a 2D CSI acquisition. A single slice is defined through the area of interest, and then a box is specified within this (white lines). Spectra will then be generated for all voxels within the box.

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Figure 5

This figure presents the spectra for a low grade brainstem glioma. SE CSI acquisition: two spectra (TE=30 ms--second column, and 144 ms--third column). The first column shows the voxel corresponding to the spectra on the same row. Rows: 1st=lesion spectra, 2nd= normal brain spectra.
Scott & White 2004
149

Figure 5

The lesion spectra demonstrate decreased NAA (a marker of neuronal integrity) and increased choline (a marker of myelin breakdown). The short TE spectrum demonstrates elevated myo-inositol (a marker of glial cells). Figure 6 (next slide) presents a color-coded choline metabolite map. Scott & White 2004

150

Multivoxel Spectroscopy

Figure 6

Scott & White 2004

151

Proton MRS is able to detect the following metabolites: N-Acetyl Aspartate (NAA) at 2 ppm: Marker of neuronal density and viability Creatine (Cr) at 3 ppm: Energy metabolism, generation of ATP Choline (Cho) at 3.2 ppm: Pathological alterations in membrane turnover, increased in tumors Lipids (Lip) between 0.8 1.5 ppm: Breakdown of tissue, elevated in brain tumors - lipids indicate necrosis

Brain Spectroscopy
The clinical utility of the brain spectrum rests upon 2 important properties:
The nature and concentration of brain chemicals identified is remarkably constant
A normal brain spectrum is readily recognized

The particular neurochemicals concerned are of clinical relevance in healthy and diseased brain.

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Brain Spectroscopy
Important brain metabolites: NAA (N-acetyl aspartate) considered to be present only in neurons and dendrites, reflects health of neurons (neuronal marker) --decreased in global brain disease, or large necrotic tumor -- ~2.0 ppm Cr (creatine/phosphocreatine) a reservoir for high energy phosphate for generation of adenosine triphosphate [ATP] (energy metabolism marker) usually used as a reference peak to generate NAA/Cr and Cho/Cr ratios ~3.0 ppm 154

Brain Spectroscopy
Important brain metabolites: Cho choline/phosphocholine/glycerophosphorylcholine)

associated with glial cell membrane integrity (cell membrane marker)-shows cell destruction-elevated in tumor, ischemia, MSits abundant, so it can be used to monitor MS or tumor 155 ~ 3.25 ppm

Brain Spectroscopy
Important brain metabolites: Glx (Glutamine/Glutamate)neurotransmitter --elevated in stroke, lymphoma, hypoxia ~ 2.1-2.5 ppm
mI (Myo-inositol)- cell membrane marker (shows cell destruction) elevated in Alzheimers, diabetes, recovered hypoxia ~3.56 ppm

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Brain Spectroscopy
Important brain metabolites: Lipidindicates tissue necrosis ~ .9 1.4 ppm
Lactateindicates hypoxiaelevated in infarcts, abscess, mitochondrial disorders, malignant tumors, MS plaques ~ 1.33 ppm
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Brain Spectroscopy
Single Voxel prescription:
Avoid blood, blood products, air, CSF, fat, metal, calcification and bone. Sometimes useful to place another voxel in the contralateral normal appearing tissue for reference

158

References:

Reviews in Urology 2006

Carroll, et. al., Magnetic Resonance Imaging and Spectroscopy of Prostate Cancer; REVIEWS IN UROLOGY Vol. 8 Suppl. 1 2006 Scott & White 2004 Runge,VM, Nitz,WR, et al. The Physics of Clinical MR, for Neuroradiology, Taught Through Images. Radiology 2007 Bartella, et al., Enhancing Nonmass Lesions in the Breast: Evaluation with Proton (1H) MR Spectroscopy Radiology Volume 245 (1) October 2007
159

References:

Reviews in Urology 2006

Carroll, et. al., Magnetic Resonance Imaging and Spectroscopy of Prostate Cancer; REVIEWS IN UROLOGY Vol. 8 Suppl. 1 2006 Scott & White 2004 Runge,VM, Nitz,WR, et al. The Physics of Clinical MR, for Neuroradiology, Taught Through Images. Radiology 2007 Bartella, et al., Enhancing Nonmass Lesions in the Breast: Evaluation with Proton (1H) MR Spectroscopy Radiology Volume 245 (1) October 2007
160

Ethanol spectrum

OH CH2

CH3
161

Proton Spectroscopy
1000 25 800 20 600

15

400

10 5

200

0 0

This figure demonstrates the importance of suppressing the water signal. The metabolites of interest have a signal one hundred times smaller than that of the water peak, and without water suppression would be poorly resolved
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Proton Spectroscopy (SVS with PRESS)

The effect of echo time in SE single voxel spectroscopy (SVS). Left: TE=30ms; Right: TE=144 ms. TE controls the T2 contrast of the spectral peaks in the same way tissue T2 contrast is controlled in MR imaging. As shown, Glx (glutamine) and myoinositol (mI) have short T2 values and are not visible on long TE spectra.

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This figure presents the spectra for a low grade brainstem glioma. SE CSI acquisition: two spectra (TE=30 ms--second column, and 144 ms--third column). The first column shows the voxel corresponding to the spectra on the same row. Rows: 1st=lesion spectra, 2nd= normal brain spectra.
164

The lesion spectra demonstrate decreased NAA (a marker of neuronal integrity) and increased choline (a marker of myelin breakdown). The short TE spectrum demonstrates elevated myo-inositol (a marker of glial cells).
165

In vivo MR Spectroscopy
Representative MRS of a normal human brain @3T 4000
NAA
3000

Y Axis Title

2000

Cho
1000

Cr Glu/ Gln
Lipids, macromolecules

MI

600

X Axis Title

Multivoxel Spectroscopy

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Brain Spectroscopy

Voxel placement

Spectrum
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Brain Spectroscopy

Voxel placement With saturation bands

Spectrum from GBM Elevated choline, lactate decreased NAA 169

Spectroscopy at 3T vs 1.5T

3T

1.5T

170

Mutlivoxel spectroscopy

2D CSI of phantom --processed result

171

Spectroscopy of the Prostate

172

Spectroscopy of the Prostate

Prostate cancer is associated with proportionately lower levels of citrate and higher levels of choline and creatine than are seen in benign prostatic hyperplasia (BPH) or in normal prostate tissue.
173

Spectroscopy of the Prostate

174

Reviews in Urology 2006

Spectroscopy of the Prostate

(From image on previous slide) Combined magnetic resonance imaging, diffusion tensor imaging, and 3-D magnetic resonance spectroscopic imaging (MRSI) of the prostate at 1.5 tesla. A. Axial T2-weighted image and 3-dimensional MRSI spectral grid. The arrows indicate a region of prostate cancer. B. Corresponding 3-dimensional MRSI spectral array, showing the presence of an aggressive-appearing tumor (very elevated choline and reduced citrate) on the left side of the gland (right side of the image). C. Image of the mean diffusional coefficient of water demonstrates a region of prostate cancer (arrows) in the same location as the T2weighted image and MRSI. D. Representative spectra taken from the region of healthy prostate tissue and prostate cancer. PPM, parts per million 175 Reviews in Urology 2006

Spectroscopy of the Prostate

While MR spectroscopy is already being utilized for prostate cancer detection and staging, evidence is now emerging that it may also be helpful in assessing response to treatment, most commonly with radiation and/or androgen deprivation. Areas of active research include imaging at high field strength (> 3 tesla); novel spectroscopic markers of malignancy, such as polyamines and spermine; and MRI176 guided biopsy and treatment.

Spectroscopy of the Prostate

greatly reduced citrate, elevated choline prostate cancer

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Spectroscopy of the Breast

Breast MR spectroscopy, usually performed with a single-voxel technique, may serve as a useful adjunct to breast MR imaging in distinguishing between benign and malignant lesions. The diagnostic value of MR spectroscopy is typically based on the detection of elevated levels of choline compounds, which are a marker of active tumors.
Radiology 2007
178

Spectroscopy of the Breast

Radiology 2007

179

Spectroscopy of the Breast

(From previous slide) Palpable mammographically detected and biopsy-proved invasive lobular carcinoma in left breast of 56-year-old woman. (a) Sagittal fat-suppressed T1-weighted MR image of left breast immediately after intravenous injection of gadopentetate dimeglumine shows 5-cm regional area of clumped enhancement in 12 oclock axis, circumscribed by the voxel (white box). (b) Spectrum demonstrates choline (Cho) peak at frequency of 3.2 ppm, with SNR greater than 2. This is a truepositive finding. Lac = lactate, Lip = lipid.
Radiology 2007
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Spectroscopy of the Breast

Radiology 2007

181

Spectroscopy of the Breast

Suspicious nonmass lesion detected at screening MR imaging in 38-year-old woman with BRCA-1 gene who was imaged at day 11 of her menstrual cycle. (a) Postcontrast sagittal fat-suppressed T1-weighted MR image of left breast shows focal clumped enhancement in upper inner region, circumscribed by the voxel (white box). (b) Magnified spectrum demonstrates large lipid (Lip) peak, but no choline (Cho) resonance peak was observed at frequency of 3.2 ppm. This is a true-negative finding.
Radiology 2007
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Spectroscopy of the Breast

elevated levels of choline compounds marker of active tumors.

183

References:
Proton magnetic resonance spectroscopy in the brain: Report of AAPM MR Task group #9. Drost, D.J., et al., Med Phys 29(9) Sept 2002. Questions and Answers in Magnetic Resonance Imaging (2nd Edition). Elster, A.D. and Burdette, J. H. Mosby, St. Louis 2001
184

References:
Medical Magnetic Resonance Imaging and Spectroscopy. Edited by Budinger &Margulis. Society of Magnetic Resonance in Medicine 1986 Clinical Applications of MR Spectroscopy Edited by Mukherji Wiley & Sons, New York 1998
185

References:
MRI from Picture to Proton D.W. McRobbie et al. Cambridge University Press 2003 Magnetic Resonance Spectroscopy of Neurological Diseases E. R. Danielsen Marcel Dekker, Inc. New York 1998.

186

References:

Reviews in Urology 2006

Carroll, et. al., Magnetic Resonance Imaging and Spectroscopy of Prostate Cancer; REVIEWS IN UROLOGY Vol. 8 Suppl. 1 2006 Scott & White 2004 Runge,VM, Nitz,WR, et al. The Physics of Clinical MR, for Neuroradiology, Taught Through Images. Radiology 2007 Bartella, et al., Enhancing Nonmass Lesions in the Breast: Evaluation with Proton (1H) MR Spectroscopy Radiology Volume 245 (1) October 2007
187

Spectroscopy of the Breast

188

Spectroscopy of the Breast

189

MR Spectroscopy

1.5T (in vivo)

energy
with water suppression

neurons

membranes glia

neurotransmitters Lipids/lactate

51 M s/p surgery and XRT for anasplastic astrocytoma, now with new area of enhancement

MRS: reduced NAA, increased Cho c/w normal. Dx: tumor recurrence

Increased Coverage
1H

Volumetric spiral MRSI

1.5 T, 7 yo male, TE=144ms, 1 cc voxels, 15 min acq.

NAA Cre

Cho
water

Increased Resolution
High Resolution Spiral PRESS at 3T
Central slice

Spiral PRESS CSI, TR/TE=2000/144ms, 5 surface coil, 32x32x8 matrix, 20x20x10 cm FOV, 0.5 cc voxels, 6 min 40 s acq time

Increased Information Content

Spiral CT-PRESS at 3T

Metabolic Pathways

Example Target: Pyruvate

Alanine Pyruvate

Lactate

2D Fourier transform