Magnetic Resonance Spectroscopy

1. Magnetic Resonance Spectroscopy
Santoshi Parajuli
Msc. MIT 2ndyear
NAMS, Bir Hospital

2. Content
 Basics
 Introduction
 Types
 Techniques
 Effects of gadolinium on MRS
 Artifacts
 Applications
 Limitations
 Recent advancements
 Summary
 References

3. Background
 Purcell and Bloch (1952) first detected NMR signals from
magnetic dipoles of nuclei when placed in an external
magnetic field.


5. Chemical shift
 1H nuclei resonate at a characteristic frequency
dependent on the magnetic field strength B
 Within a given applied field B, 1H nuclei in different
chemical environments experience a slightly different
effective field due to chemical shielding from
surrounding electrons

6. Horizontal axis Frequency (ppm)
Vertical axis Area proportional to
concentration
Chemical shift: Methanol

7.  Interactions of nuclei with the surrounding molecules
change in the local magnetic field
-change on the spin frequency of the atom
σ = diamagnetic screening
constant
B = Bo (1-σ)

8. Magnitude of σ depends on
local electron density => chemical
environment
• Adjacent atoms
• Bonds
• This causes the 1H nuclei to
resonate at slightly different
frequencies => chemical shift
ν = (γ/2π) Bo (1-σ)

9. Parts per million (ppm)
 The value of difference in RF by each hydrogen proton with in a
molecule gives information about the molecular group and is expressed
in ppm
 The chemical shift when expressed in Hz is B0 dependent
 Expressed in parts-per-million (ppm) the frequency shift is independent
of B0
 δppm = (ν-νref)/νref x 106
where vref is typically the resonant frequency of tetra-methyl silane (TMS)

10.  An NMR spectrum is a plot of signal intensity versus chemical
shift
x axis-metabolite frequency in
ppm according to the chemical
shift
y axis that corresponds to the
peak amplitude
 while the separation of the
peaks represents their
chemical shift difference.

11. Fourier transformation FT
 A mathematical function
 Decreases the time required for a scan by allowing a
range of frequencies to be explored at the same time.
 converts time-dependent pattern of free induction
decay into a frequency- dependent pattern, revealing
the NMR spectrum.

14. Introduction
 MR spectroscopy is a noninvasive technique used to analyze
the chemical composition of tissues which are very small in
number (mM concentrations) from much larger voxels which is
possible by excluding the overwhelming signals from water
and fat.
 Used for chemical analysis of different metabolites that enables
the identification and quantification of metabolites which are
biomarkers of certain pathology.

15. MR spectroscopy may be performed by using the
signals from a number of different nuclei, including
phosphorus (31P),
carbon (13C), and
fluorine (19F),

16. 1H-MR spectroscopy (proton MR spectroscopy) has become the
most prevalent since the early 1990s because of
its higher signal sensitivity,
better spatial resolution, and
the fact that (unlike other nuclei) no special hardware beyond that
found on standard MR imaging scanners is required.

17.  These metabolites can be differentiated because they
resonate at slightly different frequencies based on their local
chemical environments.
 The degree of frequency separation between two molecular
species is characterized by their chemical shift (δ), a small
number displayed on the horizontal axis below their spectra.

18. Difference between MRI and MRS
 In conventional MRI, frequency differences between voxels are
used for spatial encoding.
 This is typically accomplished by applying a frequency-encoding
gradient during signal evolution and unwinding this effect using a
readout gradient during data acquisition.
 In MR spectroscopy, however, frequency changes cannot be used
for spatial encoding as this information must used to identify
chemical shifts between molecular species.
 Accordingly, spatial gradients are not played during signal readout
in an MRS study. ​

20. Techniques
 Anatomical images-select a volume of interest (VOI)-
spectrum will be acquired
Different techniques
 Single- voxel
 Multi-voxel imaging using both long and
 short echotimes (TE)

21. Short TE vs Long TE
Short TE: Long TE
30 ms, higher SNR and less
signal loss,
from 135 to 288 ms: worse
SNR,.
More metabolies peaks, such
as myoinositol and
glutamine-glutamate (not
detected with long TE) .
More simple spectra due to
suppression of some signals
Since more peaks are shown
on the spectrum, overlap in
quantifying the peaks of
metabolites
spectra are less noisy but
have a limited number of
sharp resonances

23. Suppression
Brain metabolite concentrations are on the order of 10 mM
or less, compared with the approximately 80 M
concentration of water protons.
• Lipids also present in high concentrations within skull,
marrow, and extra cranial fat .
• Therefore essential to suppress the water and the lipid
peaks to reliably measure the metabolite contractions.

24. • A CHESS (chemically selective suppression) pulse selectively
rotates water magnetization into the transverse plane where it is
immediately dephased by application of a strong spoiler
gradient. (destroy the net magnetization of water)

25. • For MR spectroscopy a single CHESS pulse provides
insufficient water suppression, so 3 CHESS pulses are
used in the typical clinical implementation.
• To insure frequency selectivity, CHESS pulses are
relatively long (20-30 ms).
• Water suppression can be accomplished by using a
chemical shift selective saturation pulse on the water
signal at 4.7 ppm, thereby suppressing the water signal
1,000- to 10,000-fold.

26. • MR vendors offer automated water suppression
procedures that iteratively evaluate and optimize flip
angles based on the residual water signal.

27.  Lipids can be avoided by
placing the VOI completely
inside the brain, excluding
skull, to avoid signal from
marrow and subcutaneous fat.
 OVS bands are spatially but not frequency specific,
reducing or eliminating signals from all tissues (not just
lipids).

28.  They can be even thicker than
the ones shown in the fig. and
brought down close to the
edges of a single voxel even at
the center of the brain,
completely surrounding it.
 They are also commonly
placed in the planes above and
below the volume of interest .

29.  OVS bands are usually sufficient for brain spectroscopy, but for
body applications (especially prostate, breast and skeletal muscle
MRS) additional fat suppression methods may be necessary.
 Inversion recovery methods widely used in conventional MR
imaging may be employed, including STIR (Short TI Inversion
Recovery) and SPIR (Spectral Presaturation with Inversion
Recovery).
 A current popular choice is SPAIR (SPectral Attenuated
Inversion Recovery),

30. Types
 Spatial localization methods for 1H-MR spectroscopy
consist of single-voxel techniques, in which spectral
data are acquired from 1 location at a time,
 In multivoxel spectroscopy, referred to as MRSI or
chemical shift imaging, spectra from multiple regions
are acquired simultaneously.

31. Single-voxel spectroscopy
(SVS)
 In this technique, a
single sample volume is
selected and a spectrum
obtained from it are the
simplest to acquire and
interpret, and hence are
the most widely used.

32. Advantages of SVS
 They provide high signal-to-noise in a relatively short
scan time.
 Because the imaged region is compact, excellent
shimming can be obtained with resultant high-quality
spectra suitable for quantitative analysis.
 SMR spectroscopy is readily available on nearly all
MR imaging scanners, is rapid and relatively easy to
perform,

33. Disadvantage
 Only a single spectrum is obtained.
 The placement of the volume of interest (VOI) becomes critical
and may lead to errors of interpretation if not done correctly.
 For instance, single-voxel MR spectroscopy studies of the brain
are often limited to 1 or 2 regions and therefore cannot assess
the spatial distribution of metabolites.
 single-voxel MR spectroscopy studies are very limited in terms
of both coverage and spatial resolution.

34. Multiple-Voxel (Spectroscopic Imaging)
 In this technique spectra are
obtained from multiple voxels in a
single slab of tissue.
 In MRSI, spectra of all voxels are a
acquired simultaneously, and spatial
distributions of various metabolites
can be obtained in a single experiment.
 Due to this there is significant weakening in the signal-to-noise ratio and
a longer scan time.

35. Multi-voxel techniques offer two potential advantages over
SVS:
 1) a larger total coverage area (since the size of the entire
multivoxel slab is greater), eliminating the sampling error to an
extent.
2) higher spatial resolution (since the individual voxels are
smaller).
 A wide coverage area is important for large, heterogenous
lesions

36. Disadvantages of multi-voxel CSI include:
1) Longer set-up and imaging time;
2) difficulties obtaining homogenous shim over the entire
region;
3) lower signal-to-noise and spectral quality for individual
voxels;
4) spectral contamination from adjacent voxels.

38. Technique
 Both SVS and multi-voxel imaging utilize specialized
MR pulse sequences. The two most widely used are the
 Point Resolved Excitation Spin-echo Sequence
(PRESS) and
 STimulated Echo Acquisition Mode (STEAM)
technique.

39. Stimulated Echo Acquisition Mode
(STEAM)
It is a spectroscopic technique using
3 slice-selective 90º-pulses applied
concurrently with 3 orthogonal
gradients (x, y and z).
The STEAM signal is a stimulated echo
(STE) derived only from protons that have experienced all 3
RF-pulses.
These protons are located in a cuboid-shaped voxel where the
3 planes overlap.

41.  The time of appearance of the STE depends on the spacing of the 3
RF-pulses.
 If the first 2 pulses are separated by time TE/2, the peak of the STE
will occur precisely at TE/2 after the third RF-pulse.
 The interval between the 2nd and 3rd pulses, TM, is called the
mixing time, which is usually kept at a minimum.
 During this period the magnetization is "stored" along the z-axis
and does not undergo T2 decay.
 Thus the echo time (TE) for the sequence is defined as TE/2 + TE/2
and does not include TM).

42. Advantages
 1) the sequence TE can be made very short (down to ~7
msec in practice), allowing detection of short T2
metabolites.
 2) the exclusive use of 90º- (rather than 180º-) pulses
allows for better voxel edge definition,
 higher bandwidth → less chemical shift displacement
artifact and lower tissue energy deposition smaller
SARs

43. Disadvantages
 STEAM has a major signal-to-noise penalty ,the
maximum signal from STEAM is only half as large as
from PRESS.
 For this reason alone, STEAM has continually lost
popularity over the last decade, especially for ¹H
spectroscopy at 3.0T and below.
 Use only for estimation of hepatic fat fraction in ¹H-liver
MRS

44. Point Resolved Spectroscopy (PRESS)
 It is the dominant method used for ¹H spectroscopy at 1.5T and
3.0T.
 The core sequence consists of three slice-selective RF-pulses
(90º−180º−180º) applied concurrently with three orthogonal
gradients (x, y and z).
 The PRESS signal at time TE is a spin echo derived only from
protons that have experienced all 3 RF-pulses.
 These protons are located in a cuboid-shaped voxel where the
three imaging planes overlap.

46. Advantages
 The PRESS sequence is relatively easy to program
and implement.
 It is not restricted to single voxel spectroscopy
(SVS) but can be used with phase-encoding gradients
in chemical shift imaging (CSI)allowing subdivision
into multiple smaller voxels.

47. Disadvantages
 Limitation of its minimum achievable TE.
In practice, TE's of 30-35 msec are commonly used, and
values below 25 msec are difficult to attain.
The relatively high minimum TE directly follows from
the pulse sequence structure -- multiple RF-pulses and
waiting for spin-echoes takes time

48.  The practical implication is that metabolites with short T2's
will be difficult to resolve using PRESS.
 Thus PRESS cannot be used for ³¹P spectroscopy at all (where
all the relevant metabolites have very short T2s).
 And since T2 values decrease with increasing field strength,
PRESS is less useful even for ¹H spectroscopy at 7T and
above.

49.  A final minor limitation of PRESS is the potential for tissue
heating.
 The multiple 180º-pulses deposit considerable energy, and in
some instances specific absorption rate (SAR) limits may be
exceeded.
 In these cases the less commonly used STimulated Echo
Acquisition Mode (STEAM) method may offer lower energy
deposition (as well as shorter TE's) than PRESS and be
preferred.

51. Gadolinium Effect on MRS
 Gadolinium-based contrast agents produce susceptibility-induced
distortions of local magnetic fields in tissues where they
accumulate.
 This results in potential line broadening and height loss for all
spectral lines, especially at longer TE values.
 In clinical practice, however, only the choline peak is noticeably
affected, whose area may be significantly reduced depending on
the organ, degree of enhancement, and type of contrast agent
used.

52. Choline structure N-methyl protons (blue) are responsible for
its main spectral line. The positive charge at this end of the
molecule may make it more attracted to negatively charged
gadolinium chelates.

53.  Gadolinium contrast does not cross an intact blood-brain-
barrier, so no spectral effects are observed in non-enhancing
brain lesions.
 Even for markedly enhancing brain tumors, relativly little
qualtitative effect can be noticed on short TE single voxel
studies, an approximately 15% reduction in choline peak area
has been reported in brain tumors using 2D-CSI.

54.  In body imaging gadolinium contrast rapidly accumulates in
both normal and abnormal tissues and its effects are greater.
 In breast imaging, for example, gadolinium may reduce the
area under the choline peak as much as 40%.
 Because the N-methyl group of choline is postitively charged,
this phenomenon is more prominent when negatively charged
chelates (such as Magnevist, MultiHance, and Dotarem) are
used instead of neutral ones (e.g., Omniscan, ProHance).

55. Artifacts
MRS is prone to artifacts due to.
 Motion,
 Poor water or lipid suppressions,
 Field inhomogeneity,
 Eddy currents,
 Chemical shift displacement

56. Some regions are more susceptible to this artifact:
 near bone structures and air tissue-interfaces.
 Therefore placement of the VOI should be avoided
near areas such as anterior temporal and frontal lobes
in brain.
 Paramagnetic devices

57. poor shimming can be recognized
by spectral lines that are too wide,
short, and poorly separated.
 Poor field homogeneity : a lower SNR and broadening of the
width of the peaks.

58. When water suppression fails or proves inadequate, the
metabolite spectra may be inapparent or lost in background
noise.

59. Content
 Basics
 Introduction
 Types
 Techniques
 Effects of gadolinium on MRS
 Artifacts
 Applications
 Limitations
 Future
 Summary
 References

60. Brain Metabolites Identified with MRS
 Human brain contains hundreds of metabolites but proton
MRS can only detect a few of them as least mulli-molar
concentrations are necessary for the metabolites to be
detected.
 Each metabolite appears at a specific ppm, and each one
reflects specific cellular and biochemical processes

62. The common way to analyze clinical spectra is to look at
metabolite ratios, namely
NAA/Cr,
NAA/Cho,
and Cho/Cr.

63. Hunter's angle
 Hunter's angle (or line) has been
used as a quick, semiquantitative
,visual method for assessing
whether an MRS spectrum is
normal or abnormal.
 It is named after Dr. Hunter
Sheldon Hunter's line at a 45° angle connecting the 3
major peaks of a normal MR spectrum
(Choline, Creatine, and n-acetyl-aspartate) at
short TE = 30 ms. A fourth peak, myo-Inositol,
often falls on this line as well.

65. Applications
MRS has been applied as both a research and a clinical tool
 The adaptability of MRS provides a technique that can probe a wide
range of metabolic usage across different tissues.
 Although MRS is mostly applied for brain tissue, it can be used for
 detection,
 localization,
 staging ,
 tumor aggressiveness evaluation,
 and tumor response assessment

66. Breast
 Technique Breast MRS is technically challenging.
 The nature of breast masses is that they are frequently multiple,
relatively small, spaced widely apart, and embedded in a
background of fat.
 For these reasons breast MRS is less widely used clinically than
brain or even prostate MRS at present.
 The main purpose of breast ¹H-MRS is to help distinguish
benign from malignant tumors.

67.  Utilized SVS techniques.
 Accurate sizing and placement of the voxel is critical, with
special care needed to exclude both adipose tissues and
cystic/necrotic regions.
 Although gadolinium contrast may reduce the size of the
choline peak, it is still commonly used to identify small
lesions and to define tumor margins before spectroscopy.

68. Single voxel breast MRS study showing elevated total
choline (tCho) in a malignant neoplasm. Note commonly
seen contamination from incompletely suppressed lipids.

69. Brain
 MRS will play a significant role in the diagnosis and
monitoring of psychiatric disease progression and even
evaluation of treatment response in mental disorders.
 There are many studies on the spectrum of metabolites in ASD,
SZ, PD, BD and major depressive disorder that provide
valuable information of metabolic changes in these patients

71. tNAA is decreseased
and mins is elevated

73. Prostrate
 In prostate lesion, MRS
has been proven to be a
powerful device in
diagnosis, position
delineation, classification
of tumours, evaluation of
aggressiveness and tumour
response assessment.

74. .Due to its small size and deep location embedded in pelvic
fat, MRS of the prostate is challenging.
Manual shimming is generally recommended in addition to
automated shimming to improve the quality of
spectroscopic data acquired.

75.  TR is kept short (~1000 ms)
 Imaging time, which may still exceed 20+ minutes
per acquisition, not including setup.
 TE depends both on TR and field strength, but is
usually set to ~125 ms at 1.5T.

76. Limitations of MRS
 It has less sensitivity
 Data processing is not routine and not standard protocol
 Lack of familiarity with clinicians
Operator and interpreter dependent.
• Positioning of voxel is a very important step in performing MRS,
which if not accurate will obtain contaminated or sub optimal spectra.
• Interpreter requires an overall knowledge of the biochemical
metabolites and the possible differential diagnosis.

77.  Proximity of the VOI to the scalp can result in contaminating lipid
signals. Techniques to suppress lipid signals can minimize this
problem.
 It is difficult to perform MRS on smaller lesions as partial volume
averaging will contaminate the spectra.
 Proximity of the VOI to the paranasal sinuses can result in line
broadening and susceptibility artifacts.
 Iron and minerals that accumulate in the basal ganglia cause
susceptibility broadening, resulting typically in lower-quality spectra.

78.  Proximity of the VOI to the scalp can result in
contaminating lipid signals. Techniques to suppress lipid
signals can minimize this problem.
 It has relatively long acquisition time
 It is only a supportive method for diagnosis.
 Many disorders have overlapping MRS features.

79. Recent advances
High-Field MR Spectroscopy
 Spectral SNR and chemical shift resolution increase with increasing
magnetic field strength (B0), though the SNR increase may sometimes be
less than the linear improvement predicted by theory.
 This outcome is most likely explained by the increase in spectral line
widths with increasing B0.
 While field homogeneity is usually measured from voxel water line widths,
typical metabolite (eg, for Cr or NAA) line widths in the human brain are
 3.5 Hz at 1.5T, 5.5 Hz at 4T, 9.5 Hz at 7T.44

80.  The metabolite line width also depends on B0 field
homogeneity and metabolite T2 relaxation time.
 It has been found that metabolite T2 relaxation times measured
in vivo decrease with increasing B0.
 For instance, the T2 of NAA drops from approximately
 300–450 ms at 1.5T
to 210–300 ms at 3T,
to 185–230 ms at 4T,
and 140 ms at 7T.

81. Therefore, high-field MR spectroscopy is best performed at short TEs
(such as ≤35 ms).
 Despite increasing line width, improved SNR and chemical
resolution of spectra are shown at 7T compared with 3T, and 3T
compared with 1.5T.
 Moreover, resonances from coupled spin systems such as GABA,
Glu, and glutamine are better demonstrated at high field.
 Therefore, performing MR spectroscopy studies at the highest field
available is recommended.

82. Advancement in applications

83. Protocols
 Commercial vendors offer optimized/streamlined protocols for
breast MRS.
 GE BREASE (BREAst Spectroscopy Examination), a single
voxel technique using PRESS and TE averaging.
 Siemens GRACE (GeneRalized breAst speCtroscopy Exam).
GRACE allows for quantitative choline measurements using
signal from tissue water as an internal calibration reference or
from an external sample fixed to the inner surface of the breast
coil itself.

84. ¹H-Liver MRS

85.  Technique
challenges
 MRS application in the hepatic system and gastrointestinal tract are
mainly limited because of respiratory motion, which can be
improved by using breath holds acquisition and abdominal
compression.
Solution single-voxel acquisition during breath holding is preferred.
 Moreover, signal preproseeing or postprocessing such as automatic
corrections of phase and frequency can diminsh motion induced
distortions.

86. Single-voxel ¹H-MRS study of the liver
shows dominant water and fat peaks. After
correction for T2 effects and modeling, the
relative areas under each peak can be
 A voxel is typically placed over
the right lobe of the liver,
avoiding larger vessels, bile
ducts, and obvious masses.
 The hepatic fat fraction can be
estimated as (AF)/(AF+AW),
where AF and AW are the areas on
the T2-corrected fat and water
peaks

87.  Neither fat nor water suppression pulses are used.
 The STEAM technique is preferred over PRESS because it is less
sensitive to J-coupling effects and provides more accurate
estimate of fat fraction.
 TR should be greater than 3000 ms to minimize T1 relaxation
effects.
 Multi-echo acquisition with different TEs allows correction for
T2 relaxation effects.
 .

88. 1H MRS for hepatic lipid quantification
 Liver and intracellular muscular lipid content reportedly
correlate with insulin resistance, which is the best
predictor for the clinical onset of T2DM.
 Thus, lipid content, as assessed by 1H MRS, can serve as a
surrogate in vivo marker for insulin sensitivity.
 which cannot be easily assessed by other imaging
methods, for example, dual-energy X-ray absorptiometry.

89.  Lipid signals can be converted to percent (%) lipid
relative to water

90. Summary
 MRS is a valuable non invasive tool to probe the chemical
composition of the brain
 Provides metabolic information complementary to the
structural information provided by MRI
 Multi-voxel technique more complex but accurate
 Proper technique should be employed.
 MRS highly sensitive but sometimes non specific

91. References
 Http://mriquestions.Com/single-v-multi-voxel.Html
 Https://radiopaedia.Org/articles/glutamine-glutamate-peak
 Interaction of gadolinium-based MR contrast agents with
choline: implications for MR spectroscopy (MRS) of the
breast.Lenkinski re1, wang x, elian m, goldberg sn.
Https://www.Ncbi.Nlm.Nih.Gov/pubmed/19365855
 https://www.nature.com/articles/emm2014101

92.  Thank you