MRI SPECTROSCOPY

Magnetic resonance spectroscopy (MRS) is used to measure the levels of different metabolites in body tissues. The MR signal produces a spectrum of resonances that correspond to different molecular arrangements of the isotope being "excited". This signature is used to diagnose certain metabolic disorders, especially those affecting the brain, and to provide information on tumor metabolism.
Magnetic resonance spectroscopic imaging (MRSI) combines both spectroscopic and imaging methods to produce spatially localized spectra from within the sample or patient. The spatial resolution is much lower (limited by the available SNR), but the spectra in each voxel contains information about many metabolites. Because the available signal is used to encode spatial and spectral information, MRSI requires high SNR achievable only at higher field strengths (3 T and above).

Sequences

(MRS / MRSI - Magnetic Resonance Spectroscopic Imaging) A method using the NMR phenomenon to identify the chemical state of various elements without destroying the sample. MRS therefore provides information about the chemical composition of the tissues and the changes in chemical composition, which may occur with disease processes.
Although MRS is primarily employed as a research tool and has yet to achieve widespread acceptance in routine clinical practice, there is a growing realization that a noninvasive technique, which monitors disease biochemistry can provide important new information for the clinician.
The underlying principle of MRS is that atomic nuclei are surrounded by a cloud of electrons, which very slightly shield the nucleus from any external magnetic field. As the structure of the electron cloud is specific to an individual molecule or compound, then the magnitude of this screening effect is also a characteristic of the chemical environment of individual nuclei.
In view of the fact that the resonant frequency is proportional to the magnetic field that it experiences, it follows that the resonant frequency will be determined not only by the external applied field, but also by the small field shift generated by the electron cloud. This shift in frequency is called the chemical shift (see also Chemical Shift). It should be noted that chemical shift is a very small effect, usually expressed in ppm of the main frequency. In order to resolve the different chemical species, it is therefore necessary to achieve very high levels of homogeneity of the main magnetic field B0. Spectra from humans usually require shimming the magnet to approximately one part in 100. High resolution spectra of liquid samples demand a homogeneity of about one part in 1000.
In addition to the effects of factors such as relaxation times that can affect the NMR signal, as seen in magnetic resonance imaging, effects such as J-modulation or the transfer of magnetization after selective excitation of particular spectral lines can affect the relative strengths of spectral lines.
In the context of human MRS, two nuclei are of particular interest - H-1 and P-31. (PMRS - Proton Magnetic Resonance Spectroscopy) PMRS is mainly employed in studies of the brain where prominent peaks arise from NAA, choline containing compounds, creatine and creatine phosphate, myo-inositol and, if present, lactate; phosphorus 31 MR spectroscopy detects compounds involved in energy metabolism (creatine phosphate, adenosine triphosphate and inorganic phosphate) and certain compounds related to membrane synthesis and degradation. The frequencies of certain lines may also be affected by factors such as the local pH. It is also possible to determine intracellular pH because the inorganic phosphate peak position is pH sensitive.
If the field is uniform over the volume of the sample, "similar" nuclei will contribute a particular frequency component to the detected response signal irrespective of their individual positions in the sample. Since nuclei of different elements resonate at different frequencies, each element in the sample contributes a different frequency component. A chemical analysis can then be conducted by analyzing the MR response signal into its frequency components.

Binomial Pulses
A sequence of two or more pulses with a null response at a particular frequency used to suppress the water signal in localized proton spectroscopy.

Chemical Shift Imaging
(CSI) Chemical shift imaging is an extension of MR spectroscopy, allowing metabolite information to be measured in an extended region and to add the chemical analysis of body tissues to the potential clinical utility of Magnetic Resonance. The spatial location is phase encoded and a spectrum is recorded at each phase encoding step to allow the spectra acquisition in a number of volumes covering the whole sample. CSI provides mapping of chemical shifts, analog to individual spectral lines or groups of lines.
Spatial resolution can be in one, two or three dimensions, but with long acquisition times od full 3D CSI. Commonly a slice-selected 2D acquisition is used. The chemical composition of each voxel is represented by spectra, or as an image in which the signal intensity depends on the concentration of an individual metabolite. Alternatively frequency-selective pulses exite only a single spectral component.
There are several methods of performing chemical shift imaging, e.g. the inversion recovery method, chemical shift selective imaging sequence, chemical shift insensitive slice selective RF pulse, the saturation method, spatial and chemical shift encoded excitation and quantitative chemical shift imaging.

Chemical Shift Selective Imaging Sequence
(CHESS) A sequence for water suppression in proton MR spectroscopy and for water or fat suppression in MR imaging. This technique uses a frequency-selective 90° pulse to selectively excite the water signal, followed by a spoiler gradient to dephase the resulting magnetization. The gradients may be repeated several times in different directions to increase its effectiveness.

Depth Resolved Spectroscopy
(DRESS) Depth resolved surface spectroscopy is a localization method that employ gradients to select the region from which spectra are acquired.

Point Resolved Spectroscopy
(PRESS) Point resolved spectroscopy is a multi echo single shot technique to obtain spectral data. PRESS is a 90°-180°-180° (slice selective pulses) sequence. The 90° radio frequency pulse rotates the spins in the yx-plane, followed by the first 180° pulse (spin rotation in the xz-plane) and the second 180° pulse (spin rotation in the xy-plane), which gives the signal.
With the long echo times used in PRESS, there is a better visualization of metabolites with longer relaxation times. Many of the metabolites depicted by stimulated echo technique are not seen on point resolved spectroscopy, but PRESS is less susceptible to motion, diffusion, and quantum effects and has a better SNR than stimulated echo acquisition mode (STEAM).

Spectroscopy Evaluation
Integrated software package with extensive graphical display functionality to evaluate and post-process spectroscopy acquisition data.
Features
Display of CSI data as colored metabolite images or spectral overview maps, overlaid on anatomical image
Export of spectroscopy data to a user-accessible file format
Relative quantification of spectra, compilation of the data to result table
Automated peak normalization tissue, water or reference
New dedicated SVS breast evaluation protocols

1. Load the SVS data set into the Spectroscopy application. The metabolite spectrum will automatically be shown in the first segment.
2. Select single data set mode. This will allow for creation of tables in the empty segments.
3. View the localizer. Double clicking on a localizer image puts this image in the large segment.
4. Activate an empty segment and right click select results table. This table will give you a ratio of metabolite integrals, where you select the denominator.
5. Save the results. Activate a segment and select save as, choose "selected results". This can be viewed or sent to PACs from the patient browser.

1. Load the CSI data set into the Spectroscopy Application.
2. Select Spectral Map on an empty segment. This will provide spectral graphs for all voxel within the Vol.
3. Zoom and pan the image to the desired size.
4. Select the last empty segment and select metabolite map. Create a ratio map to show levels of a desired metabolite compared to another.
5. Zoom and pan this image to the desired size.
6. Select the Save Data icon, Selected Results, to save maps.
7. Individual voxel graphs can be viewed by selecting a voxel on the localizer

Single Voxel Spectroscopy
Software package with sequences and protocols for single voxel proton spectroscopy.
Features
Streamlined for easy push-button operation
Matrix Spectroscopy – phase-coherent signal combination from several coil elements for maximum SNR based on the head matrix coil
Spectral suppression (user definable parameter) to avoid lipid superposition in order to reliably detect e.g. choline in the breast
Up to 8 regional saturation (RSat) bands for outer volume suppression can be defined by the user
Physiological triggering (ECG, pulse, respiratory or external trigger) in order to avoid e.g. CSF pulsation artifacts


	SVS shows increased Choline signal in the lesion of the right parietal lobe, proving malignancy

Step by step:

1. Run localizers, and open the svs_se_135 sequence. This is found in the exam explorer, under; Spectroscopy, Head, SVS.
2. Position the VOI on one image and go to scroll, nearest. This will align the VOI in plane for all orientations.
3. Notice that the VOI has solid borders. This means that the VOI intersects in all three planes.
4. Select "Reference Lines". This will show where the slices intersect the VOI.
5. Apply the sequence.
6. Notice in this example that the sequence name has been changed from the factory default nomenclature.
This will disable the automatic postprocessing protocol when loaded into Spectroscopy Evaluation. To correct this ensure the scanned sequence stays the same as the factory default.

GRACE: GeneRAlized breast speCtroscopy Exam- Choline level follow up to evaluate Ca breast: (GeneRAlized breast speCtroscopy Exam)
SVS technique (spin echo sequence) optimized for breast spectroscopy.
The technique contains a special spectral lipid suppression pulse (user definable) for lipid signal reduction. Siemens unique water reference detection to visualize the normalized choline ratio.
Online frequency shift correction for reduction of breathing related artifacts, Inline implementation – no additional user interaction is required.
Clinical applications:
• Differentiating benign from malignant breast lesions
• Predicting clinical response to neoadjuvant chemotherapy in an early stage (24hours after receiving the first dose)

3D CSI (Chemical Shift Imaging):
Integrated multivoxel spectroscopy software package with sequences and protocols for 3D Chemical Shift Imaging (CSI).
Features
Matrix Spectroscopy – phase-coherent signal combination from several coil elements for maximum SNR with configurable prescan-based normalization for optimal homogeneity
3D Chemical Shift Imaging
Hybrid CSI with combined Volume selection and Field of View (FoV) encoding
Short TEs available (30 ms for SE, 20 ms for STEAM)
Automized shimming of the higher order shimming channels for optimal homogeneity of the larger CSI volumes
Weighted acquisition, leading to a reduced examination time compared to full k-space coverage while keeping SNR and spatial resolution
Outer Volume Suppression
Spectral Suppression
Protocols for prostate spectroscopy
Clinical Applications
Prostate Spectroscopy for diagnosis, localization of prostate cancer
Improved spatial localization of metabolic changes in biopsy or radiotherapy planning


Cho/Cr ratio map generated from 3D CSI measurement	Spectral nap generated from 3D CSI measurement	Increased Cho-signal in a medulloblastoma case

Step by step:
1. Perform imaging in all three planes to include the entire brain. Open the csi 3D se 135 sequence. Located in the exam explorer in the Spectroscopy, CSI, head region.
2. Scroll thru the transversal images for area of interest.
3. Copy image position. Right click on the selected transverse image, from the menu select copy image position.
4. Go to the scroll drop down menu and select scroll nearest. This will align the 3D VOI in all three orientations.
5. Rotate the VOI inplane on the transversal image to cover the area of interest.
6. Open toolbar, and and select create sat bands. Draw saturation bands around all sides of the 3D VOI to remove lipid signal from calvarium.
7. Select fully excited VOI, on the Geometry card.
Apply the sequence.

31 P Spectroscopy: Optimized for liver and heart applications.
Integrated package with RF coil, sequences and protocols for 31P spectroscopy.
Offering the same level of user friendliness and automation as 1H spectroscopy.
1H/31P transmit/ receive Heart Liver coil for 31P spectroscopy
Short TE CSI sequence and protocols optimized for heart and liver applications
NOE (Nuclear Overhauser Effect) and 1H decoupling available
ECG triggering available
Weighted acquisition available

Prostate Package #T+D

The prostate spectroscopy package is an comprehensive software package which bundles:
- Single Voxel Spectroscopy
- 2D Chemical shift Imaging
- 3D Chemical Shift Imaging
- Spectroscopy Evaluation syngo
- syngo Tissue 4D Evaluation
Sequences and protocols for proton spectroscopy, 2D and 3D proton chemical shift imaging (2D CSI and 3D CSI) to examine metabolic changes in the prostate are included. Furthermore included is the comprehensive Spectroscopy evaluation software which enables fast evaluation of spectroscopy data on the syngo Acquisition Workplace.
Tissue 4D is an application for visualizing and post-processing dynamic contrast-enhanced 3D datasets.
Tissue 4D provides two evaluation options:
- Standard curve evaluation
- Curve evaluation according to a pharmacokinetic model.

The spectroscopy evaluation software is fully integrated in syngo MR.
Evaluation protocols adapted to the scan protocols carry out a complete and automatic evaluation of the measured data.
Optimized protocols for 3D CSI in the prostate are included.

The following functions are included:
- Subsequent water suppression with optional phase correction
- Apodization
- Zero filling
- Fourier transformation
- Base line correction
- Automatic or manual phase correction
- Curve fitting and peak labeling
- Summaries in tabular form of the essential results specifying the metabolites, their position, integrals and signal ratios in relation to a selectable reference.

Tissue 4D provides the tissue visualization features:
- 4D visualization (3D and over time)
- Color display of parametric cards (Ktrans, Kep, Ve, Vp, iAUC)
- Additional visualization of 2D or 3D morphological dataset

Post-processing features:
- Elastic 3D motion correction
- Fully automatic calculation of subtracted images

Standard curve evaluation:
- Calculation and display of enrichment curves

Pharmacokinetic model:
- Pharmacokinetic calculation on a pixel-by-pixel basis using a 2-compartment model
- Calculation is based on the Toft model. Various model functions are available.
- Manual segmentation and calculation on the result images.

The following result images can be saved as DICOM images:
- 3D motion-corrected, dynamic images
- Colored images
- Possibility for exporting results in the relevant layout format.

In (1H) Magnetic Resonance Spectroscopy each proton can be visualized at a specific chemical shift (peak position along x-axis) depending on its chemical environment. This chemical shift is dictated by neighboring protons within the molecule. Therefore, metabolites can be characterized by their unique set of 1H chemical shifts. The metabolites that MRS probes for have known (1H) chemical shifts that have previously been identified in NMR spectra. These metabolites include:
1.) N-acetyl Aspartate (NAA): with its major resonance peak at 2.02ppm, is a neuronal marker and decrease in levels of NAA indicate loss or damage to neuronal tissue, which results from many types of insults to the brain. Its presence in normal conditions indicates neuronal and axonal integrity.
2.) Choline: with its major peak at 3.2ppm, choline is known to be associated with membrane turnover, or increase in cell division. Increased choline indicates increase in cell production or membrane breakdown, which can suggest demyelination or presence of malignant tumors or inflammatory processes.
3.) Creatine & phosphocreatine: with its major peak at 3.0ppm, creatine marks metabolism of brain energy. Gradual loss of creatine in conjunction with other major metabolites indicates tissue death or major cell death resulting from disease, injury or lack of blood supply. Increase in creatine concentration could be a response to cerebral trauma. Absence of creatine may be indicative of a rare congenital disease.
4.) Lipids: with their major aliphatic peaks located in the 0.9-1.5ppm range, increase in lipids is seen is also indicative of necrosis. These spectra are easily contaminated, as lipids are not only present in the brain, but also in other biological tissue such as the fat in the scalp and area between the scalp and skull.
5.) Lactate: is a market of oxygen deficiency, reveals itself as a doublet (two symmetric peaks in one) at 1.33ppm. Normally lactate is not visible, for its concentration is lower that the detection limit of MRS, however presence of this peak indicates glycolysis has been initiated in an oxygen deficient environment. Several causes of this include ischemia, hypoxia, mitochondrial disorders, and some types of tumors.
6.) Myo-inositol: with its major peak at 3.56ppm, an increase in Myo-inositol has been seen in granulation and gliosis and patients with Alzheimer’s, dementia, and HIV patients.
7.) Glutamate and Glutamine: these amino acids are marked by a series of resonance peaks between 2.2 and 2.4ppm. Hyperammonemia, hepatic encephalopathy are two major conditions that result in elevated levels of glutamine and glutamate. MRS, used in conjunction with MRI or some other imaging technique, can be used to detect changes in the concentrations of these metabolites, or significantly abnormal concentrations of these metabolites.