Basics of MR Spectroscopy I

Cho

Cr NAA

Lactate

ppm

4

3

2

1

Imaging Science Educational Workshop 2008 Ulrike Dydak, PhD

Lecture Outline Part I: Chemical Shift J-coupling Localization Parameters Part II Spectroscopic Imaging Processing Quantification
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Magnetic Resonance Imaging

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Basics of MRS

MR Imaging and Spectroscopy share the same physical principle!

MRI looks at the geometrical distribution of water molecules

MRS looks at the chemical composition of the tissue of interest and displays it in a spectrum
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Larmor Frequency

f0 = γ* x B0

B0

γ (γ * = ) 2π
Lamor frequency:

γ: property of nucleus γ*H = 42.577 MHz/T γ*P = 17.235 MHz/T

1.5 T
1H 31P

3T 127.73 MHz 51.7 MHz
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63.86 MHz 25.85 MHz

Basics of MR Spectroscopy
What is necessary to obtain an MR signal? – magnetic moment ≠ 0 – high gyromagnetic ratio γ => enough sensitivity – natural abundance of the isotope – concentration ≥ mmol/l in the body

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Nuclei of biological interest
Spinquantum number Gyromagnetc ratio γ*=γ/2π 42.58 10.71 3.08 5.77 40.06 11.26 17.24 1.99 2.87 Natural abundance [%] Relative sensitivity corrected for natural abundance

1

H C N 0

1/2 1/2 1 5/2 1/2 3/2 1/2 3/2 7/2

99.98 1.11 99.64 0.04 100.00 100.00 100.00 93.08 0.14

1.00 1.8 10
-4

13 14

1.0 10-3 1.1 10-5 8.3 10
-1

17 19 23

F

Na P

9.3 10-2 6.6 10-2 4.7 10
-4

31 39 43

K

Ca

9.3 10-6

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Nuclei of biological interest
1H

metabolites: Problems:

1-11 mmol/l in the body, high sensitivity water suppression (110 mol/l !!), fat suppression overlapping of metabolite peaks

31P

~ 10 mmol/l, important for studying energy metabolism Problems: low sensitivity (100* lower than 1H MRS) basic atom in organic molecules Problems: only 1% natural abundance of 13C => very low sensitivity

13C

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The MRS Experiment
B0 Lamor frequency f0 = γ* x B0
1H 31P

1.5 T
63.86 MHz 25.85 MHz

3T
127.73 MHz 51.7 MHz

RF Excitation pulse

FT

f0

Free Induction Decay (FID)
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FID and Spectrum

FT

ms

Hz / ppm

Time domain

Frequency domain

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FID and Spectrum

FT

ms

Hz / ppm

Time domain

Frequency domain
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Fourier Transform

NAA

Spectrum FID
Cre t Cho Cho Cre NAA f

Time domain FT

Frequency domain

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MR Spectroscopy

H2 O

MRS Experiment

Protons (1H) from water show peak at specific frequency
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MR Spectroscopy
BUT:

CH3CH2OH

Looking more closely there are more peaks…revealing the real nature of the drink

CH2 CH3

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1H

MR Spectroscopy in vivo

=> We are interested in the small peaks
Water suppression

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Chemical Shift

H2O O H H

Different chemical environment of 1H nuclei => slightly different local magnetic field => slightly different Larmor frequency f Resonance frequency shift is called chemical shift Causes of chemical shift: – shielding/deshielding of the electron shell – J-coupling/spin-spin coupling (effect of neighbour)
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Chemical Shift
Chemical environment ⇒ shielding

water

fat

O H
ion bonding H deprived from electron weak shielding => sense higher B0-field

H H

C H

H

covalent bonding shared electrons strong shielding => sense lower B0-field
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Chemical shift
δ [Hz] = f - fref
H2O unit: ppm (parts per million = 10-6)

δ [ppm] =

f - fref fref

·106
1.5 T: Δ = 177 Hz 3 T: Δ = 354 Hz

NAA

Δ = 2.7 ppm

1H: 31P:

fref = fTMS fref = fPCr

TMS: tetramethylsilane Si(CH3)4 => fNAA = 2.02 ppm

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Chemical shift
IMPORTANT: • The chemical shift expressed in ppm is independent of the magnetic field strength ! - e.g. NAA is always at 2 ppm • The value of 1ppm in Hz is different at different field strength and for different nuclei:
1.5 T 1H : 31P : 1ppm = 63.87 Hz 1ppm = 25.86 Hz 3T 1ppm = 127.74 Hz 1ppm = 51.72 Hz

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Hz Scaling

3T

0

-100

-200

-300

-400

-500

Hz

1.5T

0

-100

-200

-300 Frequency

-400

-500

Hz
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ppm Scaling
1.5T 3T

NAA

NAA Cho tCr tCr Ins Glx

Cho tCr

NAA

Glx Gln

NAA

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Metabolites seen in 1H MR Spectroscopy
Lactate Ascorbic acid Aspartate Choline Creatine GABA Glucose Glutamine Glutamate Glycine Glutathione Lactate myoInositol NAA Taurine

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J-coupling
Line splitting due to influence of neighboring nuclei:
Example: Lactate
or

O

H C-C-CH3

O

OH

CH3: doublet CH: quartet

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE O H C-C-CH3 CH3 O OH

OH rest CH

3 1

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE O H C-C-CH3 CH3 O OH

OH rest CH

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE O H C-C-CH3 CH3 O OH

OH rest CH

1:1

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE O H C-C-CH3 CH3 O OH

OH rest CH

1:1

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE O H C-C-CH3 CH3 O OH

OH rest CH

1:1 1:3:3:1

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J-coupling

-

Fine structure
1H SPECTRUM OF LACTATE

CH3: doublet at 1.31 ppm CH: quartet at 4.10 ppm

O

H C-C-CH3

O

OH

CH3 weak coupling CH

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J-coupling

-

Fine structure

31P Spectrum from the calf muscle:

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J-coupling

-

Fine structure

Effect of echo time on evolution of coupled spins:

=> multiplet looks up at TE = n/J with even n with odd n

down at TE = n/J

J-COUPLING IS EQUAL AT ALL FIELD STRENGTHS !
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Meet some of the Metabolites

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N-Acetyl Aspartate = NAA

~ 6-12 mM

O C-CH2-CH-C O NH C=O CH3

O

O

CH3 CH2 CH

2.02 ppm 2.69 & 2.49 ppm 4.39 ppm

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N-Acetyl Aspartate = NAA

Function:

1. Neuronal marker i.e. concentration correlates with neuronal density 2. Neuronal function, i.e. synthesis is energy-dependent, therefore concentration correlates with neuronal function

NAA Decrease: NAA Increase:

Tumor, Stroke, Epilepsy, Hyp-/Anoxia, Inflammation, Dementia, Trauma Brain Development and Maturation Canavan’s Disease (aspartoacylase deficiency)
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Example: Epilepsy

Right hemisphere

Left hemisphere

4.0

3.0

2.0

1.0

4.0

3.0

2.0

1.0

NAA
Courtesy: Dept. of Radiology, University of Bonn, Germany
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Creatine / Phosphocreatine = Cre

~ 6-12 mM

H3C-N-CH2-COOC=NH2+ NH2

CH3 CH2

3.03 ppm 3.93 ppm

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Creatine / Phosphocreatine = Cre

Function:

1. Energy Buffer: H + PCr + ADP ⇔ ATP + Cr 2. Energy shuttle: “Energy transport” from production (mitochondria) to energy utilizing sites

The CRE peak is often stable and therefore may serve as an internal reference
Exceptions: Cr/PCr Decrease: Acute and subacute stroke, Brain tumor, Brain metastasis, Abscesses, Inborn errors of Creatine synthesis
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Example: Abcess
TE 35 ms

Lipids & Lactate

• Elevated lactate • Elevated amino acids around lactate • Near absence of metabolites

Courtesy: Kim M Cecil, PhD, Cincinnati

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Choline-Containing Compounds = Cho

Cho = phosphorylcholine and glycerophosphorylcholine, no contribution from acetylcholine

~ 2 mM

CH3 HO-CH2-CH2-N-CH3 CH3

CH3 CH2

3.22 ppm 3.54 & 4.05 ppm

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Choline-Containing Compounds = Cho

Function:

Involved in pathways of phospholipid synthesis and degradation. => reflecting membrane synthesis and degradation

Cho Increase:

Brain Tumors, MS-Plaques, Stroke, Inflammation, White Matter Diseases Hepatic Encephalopathy, Necrosis
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Cho Decrease:

Lactate
TE = 144 ms = 1/J

~ 1 mM
O H C-C-CH3 O OH

TE = 288 ms = 2/J

CH3 doublet CH quartet

1.33 ppm 4.11 ppm

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Lactate = Lac

Function:

Sign of impaired energy metabolism, impaired oxygen delivery (anaerobic glycolysis). Not or hardly detectable in normal brain tissue (~1 mM)

Lac Increase:

Stroke, An-/Hypoxia, Mitochondrial diseases, Tumors (Brain and Metastases), Epileptic discharges, Abscesses/Infection, Prolonged neuronal activation (?)
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Example: Glioblastoma Multiforme
Cho
TE 288 ms

Lactate Cr NAA

ppm 4

3

2

1

0

Courtesy: Kim M Cecil, PhD, Cincinnati
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MRS: Acquisition Parameters

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Planning a Spectroscopy Scan
Typical parameters for 1H MRS (SV):
Volume selection TE TR Averages Spectral bandwidth: Samples: PRESS / STEAM 19 / 30 / 144 / 288 ms 1000 / 1500 / 2000 ms 128 / 192 / 256 / … 1000 Hz 512 / 1024 / 2024

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Influence of echo time
short TE (30 ms) long TE (144 ms)
+ clear baseline + easier quantification
NAA MI / Cre Cre Cho Gln/ Glu Cho Cre Cho Cre NAA NAA

long TE (288 ms)

- Loss of SNR with T2 - Some metabolites only visible at short TE!

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Influence of echo time
short TE (30 ms) long TE (144 ms) long TE (288 ms)

Note: difference in T2’s causes ratios to differ at different echotimes!
NAA MI / Cre Cre Cho Gln/ Glu Cho Cre Cho Cre NAA NAA

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Influence of echo time
Effect of echo time on evolution of coupled spins:
Lac TE = 144 ms Lac TE = 288 ms

J (Lac) = 6.933 Hz => multiplet looks up at down at TE = n/J TE = n/J with even n (288 ms, 576 ms, …) with odd n (144 ms, 432 ms, …)

J-COUPLING IS EQUAL AT ALL FIELD STRENGTHS !
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Glioblastoma Multiforme
Cho
TE 35 ms

mI Cr NAA

Lactate/Lipid

ppm 4

3

2

1

0

Courtesy: Kim M Cecil, PhD, Cincinnati
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Glioblastoma Multiforme
Cho
TE 288 ms

Lactate Cr NAA

ppm 4

3

2

1

0

Courtesy: Kim M Cecil, PhD, Cincinnati
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Planning a Spectroscopy Scan
Typical parameters for 1H MRS (SV):
Volume selection TE TR Averages Spectral bandwidth: Samples: PRESS / STEAM 19 / 30 / 144 / 288 ms 1000 / 1500 / 2000 ms 128 / 192 / 256 / … 1000 Hz 512 / 1024 / 2024

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Acquisition Time and Spectral Resolution
FT

Δf = 1 / T acq

Δf = BW / N

Δf

Tacq

Bandwidth

Spectral resolution Δf = 1 / T acq Spectral resolution Δf = BW / samples => acquisition time depends on spectral resolution!
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Planning a Spectroscopy Scan
Typical parameters for 1H MRS (SV):
Volume selection TE TR Averages Spectral bandwidth: Samples: PRESS / STEAM 19 / 30 / 144 / 288 ms 1000 / 1500 / 2000 ms 128 / 192 / 256 / … 1000 Hz 512 / 1024 / 2024

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MRS: Localization and Shimming

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Localization
brain (hippocampus)

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Cerebral Infarction: acute or subacute?

Subacute

Normal

Acute

Normal

FLAIR - ROIs
Courtesy: Howard Rowley

2D CSI

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Lymphoma in the Spinal Cord

Cho

NAA Lac

Cre

Courtesy: IBT, University and ETH Zurich, Switzerland
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Localization
prostate

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Localization by gradients

in each direction a gradient field defines one slice => the intersection of these slices is the selected volume of interest

These methods can also be used in addition to a localization with a surface coil to profit from high SNR.

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Localization Single Voxel techniques:
– – – – PRESS (selective excitation for 1H MRS) STEAM (selective excitation for 1H MRS) ISIS (encoding scheme for 31P MRS) …

Multivoxel techniques:
– Spectroscopic Imaging / Chemical Shift Imaging (CSI) – Hadamard encoding

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Localization: PRESS
PRESS = Point RESolved Spectroscopy double spin echo sequence: 90° - 180° - 180° - echo acquisition
Gx
Gy

Gz
90
o

180o

180 o

Rf

time
TE
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Localization: PRESS
PRESS = Point RESolved Spectroscopy

RF INPUT

RF OUTPUT
FID

G

1

G

2

G 3
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Localization: PRESS
PRESS = Point RESolved Spectroscopy
TE1/2

RF INPUT

T2

RF OUTPUT
FID
first echo

G

1

G

2

G

3
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Localization: PRESS
PRESS = Point RESolved Spectroscopy
TE1/2 (TE1+TE2)/2 TE1/2

RF INPUT

T2
RF OUTPUT
FID
first echo second echo

G

1

G

2

G

3
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Localization: PRESS Advantages:
good localization and strong suppression of signals outside the selected volume in one measurement => widely used for 1H spectroscopy less motion sensitive than STEAM

Disadvantages:
minimal TE: ~ 19 ms => unsuitable for 31P spectroscopy

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Localization: STEAM
STEAM = Stimulated Echo Acquisition Mode 3 slice selective 90° pulses => stimulated echo after TE + TM

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Localization: STEAM

uses 3 slice selective 90° pulses forming a stimulated echo after TE + TM

RF INPUT RF OUTPUT
FID

G

1

G

2

G3
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Localization: STEAM

uses 3 slice selective 90° pulses forming a stimulated echo after TE + TM
TE/2 TM

RF INPUT RF OUTPUT
FID

G

1

G

2

G3
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Localization: STEAM

uses 3 slice selective 90° pulses forming a stimulated echo after TE + TM
TE/2 TM TE/2

RF INPUT

T2
RF OUTPUT
FID
second echo

G

1

G

2

G3
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Localization: STEAM

Advantages:
allows shorter echo times than PRESS (~10 ms) better water suppression than PRESS less chemical shift artefacts (no 180 refocusing pulses)

Disadvantages:
signal intensities are only half of those obtained with PRESS

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finally…
intensity arbitrary units

NAA

Cho tCr tCr Ins Glx

NAA

Glx Gln

Chemical shift

ppm

perequisite for such quality: high field homogeneity within VOI
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Shimming Purpose of shimming: Reduce inhomogeneities => longer T2* => smaller linewidth and higher amplitudes This improves
– signal to noise – resolution

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Shimming

T2 *
t f

FT

Δf =

1 π T2 *

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Shimming

t

f

FT

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Shimming

t

f

FT

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Shimming

t

f

FT

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Effect of Shimming
Example: prostate spectrum

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Effect of Shimming
Example: prostate spectrum

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Effect of Shimming
Example: prostate spectrum

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Effect of Shimming
Example: prostate spectrum

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Thank you!

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