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References
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- Jansen, Backes. 1H MR spectroscopy of the brain: absolute quantification of metabolites. Radiology. 2006 Aug;240(2):318-32.
- Burtscher and Holtas. Proton MR spectroscopy in clinical routine. J Magn Reson Imaging. 2001 Apr;13(4):560-7.
- Dydak and Schar. MR spectroscopy and spectroscopic imaging:
comparing 3.0 T versus 1.5 T. Neuroimaging clinics of North America.
2006 May;16(2):269-83, x.
- Mullins. MR spectroscopy: truly molecular imaging; past, present and
future. Neuroimaging clinics of North America. 2006 Nov;16(4):605-18,
viii.
- Kwock. Localized MR spectroscopy: basic principles. Neuroimaging clinics of North America. 1998 Nov;8(4):713-31.
- Pohmann, von Kienlin. Theoretical evaluation and comparison of fast
chemical shift imaging methods. J Magn Reson. 1997 Dec;129(2):145-60.
- Bartella, Morris. Proton MR spectroscopy with choline peak as
malignancy marker improves positive predictive value for breast cancer
diagnosis: preliminary study. Radiology. 2006 Jun;239(3):686-92.
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viii.
Published on Sunday 15 February 2009
by Denis Hoa
Magnetic resonance spectroscopy allows noninvasive
and in vivo exploration of the molecular composition of tissue. It
identifies certain molecular constituents - the metabolites - involved
in physiological or pathological processes. Even though spectroscopy can
be performed on different nuclei, we will focus here on the
spectroscopy of the hydrogen nucleus, by far the most widely studied in
clinical MRI.
Published on Sunday 15 February 2009
by Denis Hoa
 Chemical shift corresponds to a change in the
resonance frequency of the nuclei within the molecules, in function of
their chemical bonds. The presence of an electron cloud constitutes an
electronic shield that slightly lowers the B0 magnetic field to which
the nucleus would normally be subjected. The resonance frequency
difference is expressed as parts per million or ppm, a value that is
independent of the amplitude of the magnetic field. The value of the
chemical shift thus provides information about the molecular group
carrying the hydrogen nuclei.
Chemical shift value
For a given molecule, the chemical shift in ppm versus the reference molecule is defined by the relationship:
With:
- ωm: resonance frequency of the studied molecule
- ωref: resonance frequency of the reference molecule
- dm: chemical shift value in ppm
In chemical shift, the difference in frequency compared to the
reference molecule is proportional to the amplitude of the B0 magnetic
field.
Interaction between the atomic nuclei of
neighboring chemical groups translates as each peak breaking down into a
complex peak (doublet, triplet, multiplet): this is spin-spin coupling.
The spacing between these peaks has a fixed frequency value (Hz),
called the J-coupling constant, independent of magnetic field amplitude.
A spectrum is represented:
- as an abscissa: metabolite position according to chemical shift.
Tetramethylsilane is used as the axis origin reference, a molecule used
in in-vitro NMR, which is conventionally at 0 ppm. This axis is
orientated from right to left.
- as an ordinate: peak amplitude.
The area below the peak curve will basically be determined by
metabolite concentration. The width of the peak is inversely
proportionate to T2* relaxation time.
Published on Sunday 15 February 2009
by Denis Hoa
In-vivo MRS uses MRI apparatus that is virtually identical to that used in imaging, but nevertheless requires:
- A sufficiently strong and very homogenous magnetic field, to distinguish resonance peaks (at least 1.5 T, shimming)
- Specific sequences for spectroscopic signal acquisition. There are
two types of MRS: either SVS: Single Voxel Spectroscopy which receives
the spectrum from a single voxel only, or spectroscopic imaging (CSI:
Chemical Shift Imaging) which measures spectra in projection (1D), on a
slice (2D) or a volume (3D).
- Adapted data processing software
- An adapted radiofrequency sustem (in the resonance frequency of the studied nucleus).
Published on Sunday 15 February 2009
by Denis Hoa
Analysis of the differences in metabolite resonance frequency can only
be performed in the presence of a highly homogenous magnetic field. A
heterogeneous magnetic field leads to resonance frequency dispersion,
spreading out the peaks or even causing them to disappear into the
background noise.
Prior to any MRS acquisition, the magnetic field is homogenized
(shimming) in the region of interest. The bigger the region, the harder
it is to homogenize the magnetic field throughout. Close to the bone,
calcifications or hemorrhagic zones, spectroscopic quality will be
poorer due to perturbations in the field generated by the differences in
magnetic susceptibility compared to soft tissue. The precession
frequency of the water must be optimized to adequately suppress the
water peak, using selective frequency pulses and dephasing gradients.
The other problem with MRS concerns the weak signal-to-noise ratio.
This entails multiplying the number of measurements (NSA) and limits
spatial resolution (voxel of a minimum volume of roughly 3.5 cm3 i.e. of
dimensions 1.5 x 1.5 x 1.5 cm).
Spectrum quality is evaluated according to two main criteria:
- signal-to-noise ratio (height of metabolite peaks in relation to background noise)
- spectral resolution (peak width, which determines whether the different metabolites can be separated).
Spectral resolution will depend on the homogeneity of the magnetic
field B0 and on digital resolution, i.e. the precision with which the
signal is sampled, determined according to sampling time (Te = 1/Fe) and
the total number of points measured.
Published on Sunday 15 February 2009
by Denis Hoa
Metabolites explored and TE
Only a limited number of molecules with protons are observable in MRS.
In brain MRS, the principle molecules that can be analyzed are (fig. 15.1):
- N-acetyl-asparate (NAA) (molecule present in healthy neurones) at 2.0 ppm
- Creatine/phosphocreatine (Cr) (energy metabolism molecules) at 3.0 ppm
- Choline compounds (Cho) (marker in the synthesis and breakdown of cell membranes) at 3.2 ppm
- Myo-inositol (mI) (only found in glial tissue) at 3.5 ppm (figure 15.2)
- Glutamine-Glutamate-GABA complex (Glx) (neurotransmitters) between 2.1 and 2.5 ppm
- Lactate (Lac) (anaerobic metabolism): doublet at 1.35 ppm (figure 15.3)
- Free lipids (Lip): wide resonance, doublet at 1.3 and 0.9 ppm
In prostatic MRS, the citrate peak is also looked for at 2.6 ppm.
The
number of discernable metabolites will vary according to the TE of the
spectroscopy sequence: the longer the TE (135 or 270 ms), the more long
T2 metabolites are selected. With short TE (15 to 20 ms), the spectrum
will be more complex because of the greater number of superimposed
peaks, producing a number of problems for quantification and
interpretation.
Principal metabolites
| Metabolite
| Freq. (ppm)
|
short
T2
|
long
T2
| Role
| Anomalies
|
| mI
| myoInositol
| 3,6
| ●
|
| Glial marker
|
↑ : gliomas, MS reactional gliosis
↓ : herpetic encephalitis
|
| Cho
| Choline
| 3,2
| ●
| ●
| Cell membrane metabolism marker
| ↑ : tumors, demyelinization
|
Cr
Pcr
|
Creatine
Phosphocreatine
| 3,0
| ●
| ●
| Energy metabolism marker, serves as reference peak as it is ~ constant
|
|
| Glx
|
GABA, Glutamate
Glutamine
| 2,1-2,5
| ●
|
| Intracellular neurotransmitter marker
| ↑ : hepatic encephalopathy
|
| NAA
| N-Acetyl-Aspartate
| 2,0
| ●
| ●
| Healthy neuron marker
|
↑ : Canavan's disease
↓ : neuronal distress
|
| Succ
| Succinate
| 2,4
| ●
| ●
|
D
I
S
E
A
S
E
S
| Pyogenic abscess
|
|
| Ac
| Acetate
| 1,9
| ●
| ●
| Abscess
|
|
| Ala
| Alanine
| 1,5 (doublet)
| ●
| ●
| Meningioma, Abscess
|
|
| Lac
| Lactate
|
1,3
(doublet)
| ● +
| ● –
| Ischemia, convulsions, tumors, mitochondrial cytopathies
| ↑ : anaerobic metabolism
|
| Lip
| Free lipids
|
0,9
1,4
| ●
| ●
| Necrotic tumor (high grade)
|
|
| aa
| Aminoacids
| 0,97
| ●
| ○
| Pyogenic abscess
|
|
Published on Sunday 15 February 2009
by Denis Hoa
In SVS, the signal is received of a volume limited
to a single voxel. This acquisition is fairly fast (1 to 3 minutes) and a
spectrum is easily obtained. It is performed in three steps:
- Suppression of the water signal: the quantity of hydrogen nuclei in
the water molecules in the human body is such that the water peak at 4.7
ppm “drowns” and masks the spectroscopic signal from the other
metabolites. It is therefore vital to suppress the water peak to observe
the metabolites of interest.
- Selection of the voxel of interest
- Acquisition of the spectrum, for which two types of sequence are
available (PRESS: Point-RESolved Spectroscopy, STEAM: STimulated Echo
Acquisition Mode)
Water signal suppresion
The
most commonly used method to suppress the water peak is CHESS (CHEmical
Shift Selective). CHESS consists in applying three couples (90° RF
pulses + dephasing gradients) in each spatial direction. The bandwidth
of these RF pulses is narrow and centered on the resonance frequency of
the water peak in order to saturate the water signal and preserve the
signal from the other metabolites.
Techniques applying a
180° inversion pulse with adapted TI, like those used in FLAIR and STIR
sequences, can also be used to eliminate the water signal (WEFT: Water
Elimination Fourier Transform) or suppress the fat signal in breast
spectroscopy, for example. In practice, CHESS is more commonly used than
WEFT.
Principles of volume selection
The
analyzed volume is selected by a succession of three selective
radiofrequency pulses (accompanied by gradients) in the three directions
in space. These pulses determine three orthogonal planes whose
intersection corresponds to the volume studied. Only the signal of this
voxel will be recorded, by selecting only the echo resulting from the
series of three radiofrequency pulses.
PRESS and STEAM sequences
Acquisition of the signal from the selected voxel can be performed using two different types of sequence:
STEAM (Stimulated Echo Acquisition Mode)
The
three voxel-selection RF pulses have flip angles of 90°. The stimulated
echo is recorded from the cumulated effect of the three pulses, thus
corresponding to the signal from the only voxel of interest (cf. chapter
6.7.2. Hahn echo and stimulated echo). The TE of the stimulated echo
corresponds to double the time interval between the first two pulses.
The delay between the second and third RF pulses is the mix time TM.
This technique is particularly adapted to short TE spectral
acquisitions.
PRESS (Point RESolved Spectroscopy)
In
the PRESS method, the RF pulses have flip angles of 90° - 180° - 180°.
The signal emitted by the voxel of interest is thus a spin echo. The
amplitude of this spin echo is two times greater than the stimulated
echo obtained by STEAM. The PRESS technique thus offers a better
signal-to-noise ratio than STEAM. It can be used with short TE (15 – 20
ms) or long TE (135 – 270 ms).
Whatever the case spectroscopic signal recording does not use a
frequency encoding readout gradient, as the frequency is used to
constitute the spectrum (rather than the position), after Fourier
transform of the signal.
Published on Sunday 15 February 2009
by Denis Hoa
Metabolic imaging (CSI) consists in recording the
spectroscopic data for a group of voxels, in slice(s) (2D) or by volume
(3D). It is based on a repetition of STEAM or PRESS type sequences to
which is added spatial phase encoding. The number and direction of phase
encodings depend on the number of dimensions explored (1D, 2D or 3D),
adding on to acquisition time. The duration of the sequence is equal to
TR ∙ Nph1D ∙ Nph2D ∙ Nph3D ∙ NSA (NphxD number of phase encoding steps
in direction x).
To reduce acquisition time, variants of the basic sequence have been proposed:
- Multiple Slice CSI accelerates the acquisition of several slices compared to 2D CSI
- Turbo CSI (several echoes received by rewinding the phase encoding
gradient before each additional echo, derived from the repetition of the
last spin echo pulse and the gradient)
- Fast CSI provides an important speed gain compared to 2D CSI, by
performing spatial encoding in one direction during signal acquisition,
by means of oscillating gradients, similar to spatial encoding in an
echo planar sequence. These techniques are less sensitive than the
classic CSI sequence. The speed gain is particularly useful in 3D
spectroscopic imaging or in the case of motion artifacts.
- CSI with parallel acquisition (SENSE CSI).
Signal processing calls on Fourier transforms (1 for each
phase-encoded dimension phase + 1 for spectral analysis) and requires
data correction (correction of the baseline, phase, smoothing truncation
artifacts…).
The results appear in the form of parametric images
(«metabolic maps ») or a matrix of the spectra of the regions to be
studied
Published on Sunday 15 February 2009
by Denis Hoa
Extracting a quality spectrum from the signal involves several processing steps:
- Zero-filling or apodization filtering to complete the digitized FID signal
- Phase correction to obtain the real part of the spectrum (absorption spectrum)
- Baseline correction
In vivo metabolite quantification
- Relative quantification: The results of the MRS are generally
expressed as concentration ratios. Creatine peak or comparison with the
healthy controlateral zone often serve as the reference values.
- Absolute quantification: Measuring the true concentration of
metabolites by MRS comes up against several technical difficulties: the
peak area has to be determined accurately then converted into
concentration after calibration.
Published on Sunday 15 February 2009
by Denis Hoa
With greater feasibility in the clinical practice
setting, the indications for MRS are multiplying. In brain MRS, it
yields diagnostic data for:
- Tumoral pathologies: choline, myo-inositol (gliomas), free lipids
(necrotic tumor: glioblastoma, metastasis…), alanine (meningioma),
lactate
- Demyelinizing inflammatory pathologies: myo-inositol,
- Infectious diseases: free acetate and aminoacids in certain abscesses, reduction of NAA and VIH encephalopathy
- Metabolic pathologies: myo-inositol and glutamine / glutamate in hepatic encephalopathy, lactate and diffuse cerebral distress
- Epilepsy, brain maturation and degenerative diseases…
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