The Essentials of a Successful MRS ExamThe Essentials of a Successful MRS Exam

Ulrike Dydak, Ulrike Dydak, PhDPhDSchool of Health Sciences, Purdue UniversitySc oo o ea t Sc e ces, u due U e s ty

Department of Radiology and Imaging Sciences, IU School of Medicine

Outline

Motivation with clinical examples

Review: Basics of MRS

Meet the MetabolitesMeet the Metabolites

Workflow of an MRS exam – planning of the VOI

Important Scan Parameters

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Why Spectroscopy?

ChCho

Lactate

NAACr

4 3 2 1

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MR SpectroscopyMR Spectroscopy

…offers to study biochemistry in vivo!

GPC 31P

α-ATPγ-ATP

GPE

Pi

31P MRS

NAA

β-ATPPCrPC

PE

1H

Cho tCrtCr

MRS

GlxInsGlx Gln

NAA

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Tumor: assessment?

1.5T TE 35 PRESS spectra

high-grade glioma

normal contralateralnormal contralateral

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Abcess

Lipids & LactateTE 35 ms

• Elevated lactate• Elevated amino acids around lactate

f

Courtesy: Kim M Cecil, PhD, Cincinnati

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• Near absence of metabolites

Response to radiation therapy?

Before After

Cho

Cho

NAACr

LactateNAA

Cr Lactate

4 3 2 1 4 3 2 1

C t D t f R di l U i it f B G

CholineCholine CholineCholine

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Courtesy: Dept. of Radiology, University of Bonn, Germany

Cerebral Infarction: acute or subacute?

Subacute NormalSubacute Normal

Acute Normal

FLAIR - ROIs 2D CSI

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Courtesy: Howard RowleyCourtesy: Howard Rowley

Epilepsy: side of epileptic focus?

Epileptic focusEpileptic focus

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Epilepsy: side of epileptic focus?

Right hemisphere

Left hemispherehemisphere hemisphere

3.04.0 2.0 1.0 3.04.0 2.0 1.0

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Courtesy: Dept. of Radiology, Courtesy: Dept. of Radiology, University of Bonn, Germanyof Bonn, Germany

NAA

Neonatal Hypoxia

In these cases the level of In these cases the level of Lactate is important and will determine the prognosis of the infantprognosis of the infant.

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Lymphoma in the Spinal Cord

NAAChoLac

Cre

UD 2011Courtesy: IBT, University and ETH Zurich, Switzerland

Breast Cancer

Benign Focal FibrosisInfiltrating ductal carcinoma

ChoCho

Jacobs MA, Barker PB, et al. Proton magnetic resonance spectroscopic imaging of human breast cancer a preliminar st d J Magn Reson Imaging 2004 Jan 19(1) 68 75

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cancer: a preliminary study. J Magn. Reson Imaging. 2004 Jan;19(1):68-75

Prostate: patient case @ 3T

TE = 140 ms

Cit

TE 140 ms

ChoCr

UD 2011Courtesy : IBT, University and ETH Zurich, Switzerland

Prostate: patient case @ 3T

single voxel

TE = 132 ms

TR = 1800 ms

100 averages

VOI = 2.5x1.5x1.6

= 6 mlcholine

citrate multiplet missing

C

lipids

Cr

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Courtesy: Dept. of Radiology, Courtesy: Dept. of Radiology, University of Bonn, Germanyof Bonn, Germany

Calf muscle: 1H MRS

3T PRESSSENSE-8 knee coil10×10×10 mm

voxelTE 38 TR 2000NSA 64

IMCL

EMCL

CTMA

Cr

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Calf muscle: 31P MRS

31P, muscle

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Calf muscle: 31P MRS - functional MRS / time series

PCr

31P SV31P SVCalf muscle

Stimulus: Pedal pushing

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Pi

1H MRS of exogenous compounds

NAACr

ChoCho

GlxLip

CrLip

TE = 30 ms, 192 avgs,

VOI = 30x30x20 mm3

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Some Basics of MRS

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The basic MRS SequenceThe basic MRS Sequence

90° excitation pulse90 excitation pulse

RF (send)

Free Induction Decay (FID)RF (receive)

no gradients during acquisitionGx Gy Gz

The sequence in this form contains no localization of the signal!

Gx, Gy, Gz

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The sequence in this form contains no localization of the signal!

The MRS ExperimentThe MRS Experiment

B0

f0 = γ* x B0

Lamor frequency 1.5 T 3 T1H 63.86 MHz 127.73 MHz31P 25.85 MHz 51.7 MHz

Excitationpulse

water

FT

pulse suppression

f0

Free Induction Decay (FID) spectrum spectrum

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Free Induction Decay (FID) spectrum spectrum

The MRS ExperimentThe MRS Experiment

1. The amplitude of the first point of the FID corresponds to the area under the peak => concentration=> concentration

2. The resonance frequency determines the position on the spectral axis

3. The longer the FID acquisition, the better the spectral resolution!

4. The faster the FID decays, the lower and broader the peak

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peak. => importance of shimmingHz

Chemical ShiftChemical Shift

B0

freq = γ* x B0

Lamor frequency

NAA

All i l f 1HAll signal from 1H

Glx

Cho tCr

Ins

tCr

NAA

BUT

=> Chemical Shift causes GlxGlx Gln signal from different molecules

to resonate at (slightly) different frequencies

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Chemical ShiftChemical Shift

Owater N-Acetylaspartate

O O

C-CH2-CH-C H HC

fat

H HC CH2 CH C

O NH O

C=O

H HC

HCH3

⇒ different chemical environment of protonsppm = parts per million

(normalized difference of⇒ different chemical environment of protons

⇒ different shielding of B0

⇒ different resonance frequency => chemical shift

(normalized difference of resonance frequency)

H2O NAA lipids

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Hz Scaling

3T3T

1.5T

0 -100 -200 -300 -400 -500 Hz

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Frequency Hz

ppm Scaling

NAA1.5T 3T

NAA

Cho tCr

I

tCr

Ins

GlxGlxGln

NAACho tCr

NAANAA

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Brain Metabolites seen inBrain Metabolites seen in 11H MR SpectroscopyH MR Spectroscopy

Ascorbic acidLactate

Aspartate

GABACreatineCholine

GlutamateGlutamineGlucoseGABA

myoInositol

Glycine

LactateGlutathione

Taurine

NAA

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JJ--couplingcoupling

Line splitting due to influence of neighboring nuclei:Example: Lactate

O H

C C CH

or

C-C-CH3

O OH

CH : doubletCH3: doublet

CH: quartet

CH3CH

weak coupling

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Physical parameters of MRS

Characteristics of a spectrum:p

resonance frequency (chemical shift)

coupling constant J (Hz)

area/size of the signals (peaks) => concentration of metabolites

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Meet the Metabolites

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NAA (N-Acetyl AspartatetCr (total Creatine)

Brain metabolites Brain metabolites detected by 1H MRSdetected by 1H MRSNAA (N-Acetyl AspartateFunction: neuronal marker (neuronal density, function)

normal conc.: ~6-12 mM

tCr (total Creatine) (Creatine & Phosphocreatine)

Function: energy buffer,energy shuttle

normal conc : 6 12 mMCho (Choline containing

NAA

normal conc.: ~6-12 mMCho (Choline containing compounds)

reflects: membrane synthesis and degradation Lactate

F ti d d t f

Cho tCr

InstCr

normal conc.: ~2 mM Function: end product of anaerobic glycolysis

normal conc.: <1 mM

(M )I it l InsGlxGlx

GlnNAA

Glutamate / Glutaminefunction: excitatory neurotransmitter

(Myo-)InositolFunction: osmolite, glialmarker, necessary for cell growth

normal conc.: ~12 mM

GABA (γ- aminobutyric acid)GSH (Glutathione)

normal conc.: ~4-8 mM

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Function: primary inhibitory neurotransmitter

normal conc.: ~1 mM

Function: antioxidant

normal conc.: ~2-3 mM

N-Acetyl Aspartate = NAA

O O

C-CH2-CH-C

O NH O

~ 6-12 mM

O NH O

C=O

CH33

CH3 2.02 ppm

CH2 2.69 & 2.49 ppm

CH 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 d d t th fenergy-dependent, therefore

concentration correlates with neuronal function

NAA Decrease: Tumor, Stroke, Epilepsy, Hyp-/Anoxia, Inflammation Dementia TraumaInflammation, Dementia, Trauma

NAA Increase: Brain Development and MaturationCanavan’s Disease (aspartoacylase deficiency)

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Canavan s Disease (aspartoacylase deficiency)

Creatine / Phosphocreatine = Cre

H3C-N-CH2-COO-

C=NH2+

~ 6-12 mM

NH2

CH3 3.03 ppm

CH2 3.93 ppm

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Creatine / Phosphocreatine = Cre

Function: 1. Energy Buffer:

H + PCr + ADP ⇔ ATP + Cr

2. Energy shuttle: “Energy transport” from2. 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

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Brain metastasis, Abscesses, Inborn errors of Creatine synthesis

Choline-Containing Compounds = Cho

Cho = phosphorylcholine and glycerophosphorylcholine,

CH

no contribution from acetylcholine

~ 2 mM CH3

HO-CH2-CH2-N-CH3

CH3

CH 3 22 ppmCH3 3.22 ppm

CH2 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 PlMS-Plaques, Stroke, Inflammation, White Matter Diseases

Cho Decrease: Hepatic Encephalopathy,

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p p p yNecrosis

Lactate

~ 1 mMTE = 144 ms = 1/J

O H

C C CHC-C-CH3

O OH

CH3 doublet 1.33 ppm

CH quartet 4 11 ppm

TE = 288 ms = 2/J

CH quartet 4.11 ppm

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Lactate = Lac

Function: Sign of impaired energy metabolism, impaired oxygen delivery (anaerobic glycolysis).

N t h dl d t t bl i l b iNot or hardly detectable in normal brain tissue (~1 mM)

Lac Increase: Stroke, An-/Hypoxia, Mitochondrial diseases, T (B i d M )Tumors (Brain and Metastases), Epileptic discharges, Abscesses/Infection,

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,Prolonged neuronal activation (?)

The successful MRS Exam

- Workflow

Rules of Thumb for Parameters- Rules of Thumb for Parameters

- ShimmingShimming

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MR MR Spectroscopy: How to acquire a good dataset?Spectroscopy: How to acquire a good dataset?

intensity

NAA

intensity arbitrary units

Cho tCr

Ins

tCr

GlxGlxNAA

GlxGlxGln

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ppmChemical shift

Workflow of an MRS scan:

Survey Anatomical (and f nctional) imagingAnatomical (and functional) imagingAcquire fast images in at least 2 directions for planning the MRS VOI (e.g. sag and axial)VOI (e.g. sag and axial)Plan the MRS scanScan Preparation (automatic or manual)Scan Preparation (automatic or manual)Acquire the MRS dataViewing and processing

Never plan a spectroscopy scan on images acquired half an hour ago! Viewing and processing

Save/Export the data!ago!

The patient is likely to have moved in between!

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Localization

brain (hippocampus)

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Localization

brain (occiptal lobe)

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Localization

prostate

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Localization

Brain tumor

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Planning

Pl i h ti if iblPlace in homogenous tissue if possible

Stay away from air cavities (at least 5 mm!)

Brain: avoid subcutaneous fat

B d MRS id t f tiBody MRS: consider movement of tissue

Avoid major vessels

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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

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

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Spectroscopic Imaging

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Spectroscopic Imaging

NAACho

NAA

CreCho

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SV versus CSI

Sequence

– SVS (single voxel spectroscopy)• global disease• complement to CSI in focal lesioncomplement to CSI in focal lesion• quantification

CSI ( h i l hift i i lti l MRS)– CSI (chemical shift imaging, multivoxel MRS)• focal lesion• focal and global heterogeneous lesions

• multislice CSI

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SV versus CSI

Location of VOI – CSI

– centre of focal lesionincluding contra lateral side

– standard locations• supraventricular WM + GMp• basal ganglia

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Planning – 2D CSI

– Make sure no part of your PRESS box covers air, lipids, etc!

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– Make use of outer volume suppression bands

Planning – 3D CSI

– Check planning from lowest to highest imaging slice within PRESS box:

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– Sat bands must cover skull in all slices!

Planning – 3D CSI

– Easier placement of sat bands without CSI grid– Display lowest and highest imaging slice within PRESS box

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Display lowest and highest imaging slice within PRESS box

Planning – 3D CSI

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MRS: Acquisition Parameters

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Summary of Parameters

We will cover only a few of the most important parameters:

1 V l l ti1. Volume selection2. TE - echo time3 TR - repetition time3. TR repetition time4. NA - number of averages5. Volume size6. BW – bandwidth of spectrum7. Samples – number of samples per spectrum

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PRESS versus STEAM

Parameters – STEAM / SESTEAM SE (PRESS)STEAM SE (PRESS)

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3T SVS ST TE 20 ms 3T SVS SE TE 30 ms

Slide courtesy: Isabella Bjørkman-Burtscher

Summary of Parameters

We will cover only a few of the most important parameters:

2 TE h ti2. TE - echo time

Typical TE choices:Typical TE choices:

- “short” TE ( 6ms, 25 ms, 30 or 35 ms)

- 144 ms (lactate doublet inverted)

- 288 ms (lactate doublet upright)

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Spin Echo ExperimentSpin Echo Experiment

90o 180o

t

∝ e− t T2

S

t

∝e− t T2*

TE/2 TE/2

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Echo Time

In the PRESS / PROBE sequence:

Gx

Gy

180o

The image part with relationship ID rId2 was not found in the file.

The image part with relationship ID rId2 was not found in the file.

Gz

The image part with relationship ID rId2 was not found in the file.

180o

90o

timeRf

TE

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Influence of echo time

long TE (144 ms)short TE (30 ms) long TE (288 ms)

+ clear baseline

+ easier quantification

NAA

MI / Cre

- Loss of SNR with T2

- Some metabolites only visible at short TE!

Cho Cre

NAAChoCre

Cre

Gln/Glu

NAACho Cre

Cho Cre

NAA

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Influence of echo time

long TE (144 ms)short TE (30 ms) long TE (288 ms)

Note: difference in T2’s causes ratios to differ at different echotimes!

NAA

MI / Cre

Cho Cre

NAAChoCre

Cre

Gln/Glu

NAACho Cre

Cho Cre

NAA

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Influence of echo time

Effect of echo time on evolution of coupled spins:Lac

TE = 288 msLac

TE = 144 ms TE 288 msTE 144 ms

J (Lac) = 6.933 Hz => multiplet looks

up at TE = n/J with even n (288 ms, 576 ms, …)

down at TE = n/J with odd n (144 ms, 432 ms, …)

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J-COUPLING IS EQUAL AT ALL FIELD STRENGTHS !

Glioblastoma Multiforme

Cho TE 35 ms

NAACr

mI Lactate/Lipid

Cr

3 14 02ppm

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Courtesy: Kim M Cecil, PhD, Cincinnati

Glioblastoma Multiforme

Cho TE 288 ms

CrLactate

NAA

3 14 02ppm

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pp

Courtesy: Kim M Cecil, PhD, Cincinnati

Summary of Parameters

We will cover only a few of the most important parameters:

1. TE- echo time2. TR- repetition time

Typical TR choices: 1s 1 5s 2sTypical TR choices: 1s, 1.5s, 2s

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Repetition Time

TRRF input

t

RF output

t

z‘

M

z‘

RFT1 relaxation

z‘t

M

M

RF

M

• Typical T1s of metabolites: ~ 1 s and longer!• Fully relaxed spectrum: use > 5 T1• Main problem with long TRs: scan time (e g 128 averages * 5s = 640 s ≈ 10 min)

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Main problem with long TRs: scan time (e.g. 128 averages 5s = 640 s ≈ 10 min) • Main problem with short TRs: saturation loss (loss in SNR)

Summary of Parameters

We will cover only a few of the most important parameters:

1. TE- echo time2. TR- repetition time3. NA - number of averages4. Volume size

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Averages and VOI size

SNR ∞ Volume SNR ∞ averages

Rule of thumb for choice of averages:

– VOI = 20 x 20 x 20 (8ml) or larger => averages = 128( ) g g– 4 ml < VOI < 8 ml => averages = 196– VOI < 10 x 20 x 20 (4ml) => averages = 256

Minimal VOI sizes:

– On Human scanners: ~ 1x1x1 cm3 = 1 ml (scan time > 10 min)( )

– At 9.4T in the rat brain: ~ 2x2x2 mm3 = 8 ul (scan time > 20 min)

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Summary of Parameters

We will cover only a few of the most important parameters:

1. TE- echo time2. TR- repetition time3. NA - number of averages4. Volume size5. BW – bandwidth of spectrum6. Samples – number of samples per spectrum

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Spectral BW and samples

FT

Δf

Tacq BandwidthN number of sample points f BW / NN number of sample points

Δf spectral resolution

BW spectral bandwidth

Δf = BW / NΔf = 1 / T acq

T acq = 1 /Δf = N / BW

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acq / /

Spectral BW and samples

To resolve two peaks with Δf = 6 Hz

=> need Δf ≤ 3Hz better Δf ≈ 1 HzΔf => need Δf ≤ 3Hz, better Δf ≈ 1 Hz

for BW = 1000 Hz Tacq ≈ 1 s

Δf

high resolution => more samples => longerTacq

we need N = BW / Δf = 1000acq

q

shortTacq => poor resolution

to avoid truncation artefacts: Tacq ≥ 5 T2*

to avoid saturation artefacts: TR ≥ 3-5 T1

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Scan preparation phases

What all could be done during scan preparation (depending on system and system settings):

Pick-up phase determinationPower optimizationpresonance frequency determinationAutomated shimming ormanual shimmingreceiver gain optimizationelectronic noise level determinationelectronic noise level determinationautomatic water suppression optimization

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Shimming

Purpose of shimming:Reduce inhomogeneities

=> longer T2* => smaller linewidth and higher amplitudes

This improves SNR and spectral resolution

Default shimming settings:11H Same coil as chosen for MRS sequence echo time as used in actual scan

Reshimming necessary when:G t (VOI) h b h d

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Geometry (VOI) has been changed

Shimming

T2*

1Δf

FTft

1π T2

*Δf =

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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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Shimming

t f

FT

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Shimming

Rule of thumb

For brain MRS:

Siemens system => try to get a linewidth <25 (20)GE system => try to get a “FWHM” < 15GE system => try to get a FWHM < 15

For body MRS:

linewidth of ~30-40 may be oklinewidth of 30 40 may be ok

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In vivo 1H MR Spectroscopy 1984

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Single Volume 1H Spectroscopy

NAA

3T3T

Cho tCr

I

tCr

Ins

GlxGlxGln

NAA

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Courtesy: Dept. of Radiology, University of Bonn, GermanyCourtesy: Dept. of Radiology, University of Bonn, Germany

Take home messages:

Make sure the subject is well fixatedInstruct the subject not to move – not even in between scans!

Take your time in placing the VOI well – it will pay off!Avoid air, lipids, large vesselsLongitudinal studies: take screenshots of setup

Keep it as simple as possible (single voxel, easy angulations, …)Don’t forget to export/save this data separately (different from MRI images!)

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