FREQUENTLY ASKED QUESTIONS ABOUT
MAGNETIC RESONANCE SPECTROSCOPY
(MRS)
Bruce M. Damon, PhD
Vanderbilt University
Thomas
B. Price, PhD, FACSM
Yale University
What do I need to know before
reading these FAQs?
Is it Magnetic Resonance
Spectroscopy or Nuclear Magnetic Resonance Spectroscopy?
Which atomic nuclei
are magnetic?
What are the components of an
in vivo MR system?
How do you observe the nuclear
magnetism?
What happens to the spins
after you pulse them with the RF magnetic field?
Does the MR signal persist
forever?
Do the spins remain in the
transverse plane forever?
How is MRS used to determine
chemical structures?
How is chemical shift
measured?
How are chemical
concentrations measured?
What are some other common
MRS terms?
What can be measured with 1H
MRS?
What can be measured with 31P
MRS?
What can be measured with 13C
MRS?
What are some the main
biomedical MRS journals?
Where can I go for more
information?
What do I need to know before reading these
FAQs?
You should be generally familiar
with the principles of electricity, magnetism, and nuclear physics that would
be taught in an introductory college Physics course and with the principles of
atomic and molecular structure that would be taught in an introductory college
Chemistry course.
What is MRS used for?
MRS is used to obtain information about chemical composition. MRS measurements are commonly made on chemical samples and tissues. In animals and humans a number of chemical concentrations can be obtained over a period of time. From this information, rates of change in specific metabolites can be determined.
Is it Magnetic Resonance Spectroscopy or
Nuclear Magnetic Resonance Spectroscopy?
Either. The word ÒnuclearÓ is often
dropped, in part to break a perceived association with ionizing radiation, and
also because it is a more general term (NMR exploits the magnetic properties of
atomic nuclei to learn about chemical structures. MR experiments can also be
conducted on electrons).
Which atomic nuclei are magnetic? And
why are they magnetic in the first place?
Any nucleus with an odd atomic
number or an odd atomic weight has a net spin. Spin is the tendency to behave
like a spinning ball of charge. Any time a charge moves, it creates a magnetic
field. Some biologically important nuclei that have spin include 1H,
13C, 17O, 23Na, and 31P. Most in
vivo MRS is done on
include 1H, 13C, and 31P.
What are the components of an in vivo MR system?
There are several, including:
- The magnet itself. The bore of the magnet may be large
enough to fit a whole person into (snugly), or it may only be large enough
to fit a small animal. The magnetic field strengths of human magnets range
from 1.5 to 7 Tesla. In general higher magnetic field strengths are more
easily obtained in magnets with smaller bores. One Tesla equals 10,000 gauss (the EarthÕs magnetic
field is about 2 gauss). The magnetic field can be generated by a
permanent magnet but more commonly a current is passed through wires. The
wires can either be resistive or superconducting. In general, magnetic
field intensity is given the symbol B; the main (or static) magnetic field
of the MR unit is called B0.
- The
RF coil. The radiofrequency (RF) coil is placed on or around the body part
to be studied and is used to transmit RF magnetic fields into the tissue
and to measure the MR response (more about this later). The RF magnetic
field is also called the B1 field.
- Other
hardware. Amplifiers, RF pulse synthesizers, digitizers, and many other
pieces of hardware also compose the MR system.
- A computer
console. Computers are used to operate the system and to process and
display data.
How do you observe the nuclear magnetism?
There are three steps. First, the
sample is introduced into the magnetic field. Nuclei that have spin (often just
called ÒspinsÓ) interact with each and their surroundings to reach an ordered
equilibrium condition. That equilibrium is characterized by:
- A
separation of spins into different energy levels (two for 1H, 13C,
and 31P).
- Precession
Ð a wobbling sort of motion undergone by spinning object subjected to an
external force. For example, a spinning top, influenced by gravity,
precesses about its own axis as it slows down.
The frequency of precession is called the Larmor frequency, and is directly proportional to the strength of the magnetic field experienced by the nucleus.
Second, we disrupt the equilibrium. We do this by applying a second magnetic field, which is oscillating at the Larmor frequency. The Larmor frequency happens to be in the radiofrequency band of the electromagnetic spectrum, and so this magnetic field is often called the RF pulse. The RF pulse is delivered through the RF coil.
Finally, we observe the response. The RF coil is switched from transmitter to receiver mode, and basically acts like a radio antenna. The signal is digitized and stored for later processing.
What happens to the spins after you pulse them with the RF magnetic
field?
They have already reached an
equilibrium with the main magnetic field. So their response is to precess about
the RF field. This causes them to rotate away from B0 and towards
the plane lying transverse to B0. When they enter the transverse
plane, their phases are coherent (aligned with each other). After the RF field
is shut off (itÕs typically only pulsed for a matter of milliseconds), the
spins start to precess about B0 again. As they do so, they induce a
current into the RF coil.
Does the MR signal persist forever?
No. In the sample there are minute
variations in magnetic field strength. This causes the different spins to experience
slightly different magnetic fields (and therefore different Larmor
frequencies). Because the spins are precessing at different frequencies, they
loss their phase coherence, and the signal decays. This process is called
transverse relaxation (because it happens while the spins are in the transverse
plane), and is characterized by an exponential time constant, T2.
For most biological metabolites, T2 is on the order of tens to
hundreds of ms.
The spins also lose phase coherence
(ÒdephaseÓ) because of an inhomogeneous B0 field. This occurs in
part because an imperfectly engineered magnet and also because putting the
sample into the magnet disrupts its homogeneity somewhat. Thus there is a
faster effective loss of signal, which is characterized by the time constant T2*.
Do the spins remain in the transverse plane
forever?
No. Eventually, they leave the
transverse plane and return to the equilibrium condition. This process is
called longitudinal relaxation and is characterized by an exponential time
constant, T1. For biological metabolites, T1Õs generally
range from hundreds to thousands of ms. The time required to return fully to
equilibrium is ~5 times T1.
How is the signal processed?
The signal is processed with a fast
Fourier transform (FFT). An FFT is an algorithm that transforms data from the
time domain (time is the unit on the abscissa) to the frequency domain (Hz is
the unit on the abscissa). It does this by fitting sine functions of varying
frequencies to the time domain data, and then displaying the weighted
amplitudes of sine functions as a function of frequency.
How is MRS used to determine chemical structures?
The presence of electrons around a
nucleus shields the nucleus from the applied magnetic field. Therefore the
magnetic field that is actually experienced by the nucleus will depend on the
local chemical structure. Because the nuclei experience different effective
applied magnetic fields, their Larmor frequencies vary too. Thus they
experience a shift
in Larmor frequency due to their chemical structure.
How is chemical shift measured?
Chemical shift is measured in Hz or
parts per million (ppm). The preferred unit is ppm, because it is independent
of magnetic field strength, but there are specific occasions in which it is
useful to measure the chemical shift in Hz.
How are chemical concentrations
measured?
Chemical concentrations
are measured by comparison with a standard of a known chemical concentration.
Each atom of a particular chemical compound produces a peak at a specific
chemical shift (ppm). The area underneath this peak is an indication of the
numbers of that particular atom present in the sample. Additional consideration
must be made for relaxation time differences between the chemicals. By comparing areas between the peak
corresponding to the atom of interest with that of an atom from a chemical
compound of known concentration, we can determine the chemical concentration of
the atom of interest. The standard may be internal (for example, creatine in the same 1H spectrum),
or external (for example, a glycogen solution from a different 13C
spectrum). When calculating concentrations from an external sample solution
other factors, such as sample volume and RF coil loading need to be
considered.
Because we can make a
number of concentration measurements over a period of time, rates of appearance
and disappearance can be determined for metabolites measured with 1H,
31P, or 13C.
What are some other common MRS terms?
FID (Free Induction Decay): This is the name given to the
signal recorded after a single RF field pulse. ItÕs called a free induction
decay because they are freely precessing, inducing a current into the coil, and
their signal is decaying.
Nutation Angle: The amount of rotation away from B0
caused by the B1 field. In NMR jargon, it is sometimes called the
ÒflipÓ angle.
Pulse Sequence: The sequence of RF pulses used to
generate desired signal characteristics.
NEX (Number of
Excitations): The
number of times the pulse sequence is repeated, for purposes of signal
averaging.
TR (Repetition Time): The time between individual
repetitions of the pulse sequence.
Partial Saturation: Applies to acquisitions in which NEX
> 1. If the TR < (5«T1), the spin system will not fully
recover from a pulse, and is said to be partially saturated. All other things
being equal, the overall signal will be reduced relative to the full
longitudinal relaxation (5«T1) condition.
Ernst Angle: The nutation angle that optimizes
the signalÐtoÐnoise ratio, taking into consideration the T1 and TR.
Spectral Width: The range of Larmor frequencies
excited by the RF field.
What can be measured with 1H MRS?
Simple 1H MRS experiments
will measure the two most plentiful protonÐcontaining compounds in the body Ð
water and lipids. Variations in lipid content are seen in diseases such as
muscular dystrophy. In order to observe proton metabolites, the water signal
must be suppressed. Some of the biochemicals that can then be seen include
NÐacetyl aspartate, creatine, carnosine, intraÐ and extraÐ myocellular lipids,
and, with some extra work, lactate. Also, the carnosine CÐ2 protonÕs chemical
shift can be used to measure intracellular pH. 1H spectra from a
frog muscle before and after exercise are shown below.
What can be measured with 31P
MRS?
With 31P MRS, peaks from
inorganic phosphate, phosphomonoesters, phosphodiesters, phosphocreatine, and
the three phosphates of ATP can be observed. In additional to concentration
measurements (typically using phosphocreatine as an internal standard), the
intracellular free Mg2+ concentration can be derived from analysis
of the ATP peaks, and the chemical shift between inorganic phosphate and
phosphocreatine is sensitive to pH. 31P spectra from a frog muscle
before and after exercise are shown below.
What can be measured with 13C
MRS?
With natural abundance 13C
MRS the CÐ1 peak of glycogen can be easily observed, and the chemical
concentration can be determined from an external glycogen standard. Other
peaks, from C=C bonds of triglycerides, ÐCH2 and ÐCH3 resonances of freeÐfatty acids, and glycerol
are more complex, representing several different atoms that cannot be easily
resolved. Therefore, determining chemical concentrations is very difficult. The
problem with 13C MRS is that the 13C atom represents only
1.1% of the total atoms; hence, signalÐtoÐnoise issues become a problem. For
example, at 4.7T a useful 13C spectrum from the human gastrocnemius
requires about 5min to collect, compared with a 31P spectrum, which
can be collected in a few seconds. By administering a 13C labeled
substrate (often 1Ð13C glucose administered intravenously) the low
signal generated by natural abundance 13C MRS enriched from 1.1%
abundance to near 100% abundance, thereby dramatically increasing the signal.
This technique can be used to trace the movement of 13C label
through various metabolic pathways. For example, a number of glycolytic and TCA
cycle intermediates can be tracked as muscle metabolism proceeds forward.
What are some the main biomedical MRS
journals?
If your institution has electronic
subscriptions to these journals, you can follow the links to go to the journal
home page and download current articles:
Magnetic Resonance in Medicine
Magnetic Resonance Materials in Physics, Biology, and
Medicine
You will also find MRS papers in
applied physiology and biochemistry journals.
Where can I go for more information?
Websites:
The International Society for
Magnetic Resonance in Medicine maintains an extensive
list of MRI tutorial and educational websites.
The spectroscopyNOW.com website has
information about MRS and many other spectroscopic methods.
Books:
In Vivo NMR Spectroscopy:
Principles and Techniques by Robin Degraaf.
Nuclear Magnetic Resonance and
Its Application to Living Systems by David Gadian.
Any organic chemistry book will have
a brief introduction to NMR spectroscopy.
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