Magnetic Resonance Spectroscopic Imaging (MRS) is an advanced neuroimaging technique that provides insights into the biochemical changes in the brain. It does this by measuring the concentration of specific metabolites and neurotransmitters, such as N-acetyl aspartate (NAA) and glutamate.
Unlike conventional MRI, which focuses on structural or functional imaging, MRS detects biochemical changes, offering a unique perspective on metabolic processes and brain health.
MRS is particularly valuable for identifying biochemical markers of neurological disorders, monitoring brain metabolism, and studying neurochemical imbalances associated with conditions such as epilepsy, brain tumors, or neurodegenerative diseases (e.g., Alzheimer and multiple sclerosis).
MRS targets a specific brain region (called voxel, resembles a cube) and isolates the signal from this area. By applying a Fourier Transform to the signal, MRS identifies the frequencies contributing to the signal in the voxel. The resulting graph, known as a spectrum, highlights different frequencies, each corresponding to distinct metabolites.
Within the body, hydrogen (H) atoms in water and fat tissues dominate. Due to differences in electron shielding, at the same magnetic field strength, H atoms in water will process and resonate at slightly different frequencies compared to those of H in fat. The phenomenon of differences in processional frequencies is known as chemical shift, this creates a separation in frequencies that MRS exploits to distinguish molecules within the voxel.
To enhance clarity, MRS suppresses signals from water and fat, so that one can concentrate on the metabolites that contain hydrogen atoms. This is achieved using techniques like:
A very narrow radio frequency (RF) pulse that matches the specific frequency of water hydrogen atoms. As only this pulse matches the processional frequency of specific hydrogen atoms, it will cause only water hydrogen atoms to flip into the transverse plane.
Next, a spoiler gradient is applied, which causes the net magnetization vector to rapidly dephase in the transverse magnetization plane. When the net magnetization vector has been flipped 90 degrees, there is no longitudinal magnetization nor transverse for water. The net magnetisation for water is 0.
Afterwards, one can run a regular pulse sequence with the initial 90 degree RF pulse, all other metabolites have longitudinal magnetization and will be flipped into the transverse plane, whilst water will not. This lets us analyse only the metabolite signals.
To suppress the signal coming from fat, Short Time Inversion Recovery (STIR) is used: An RF pulse inverts fat magnetization to 180°, which means that the H atoms of fat now lie antiparallel to the main magnetic field. They will now try to recover longitudinal magnetization at the T1 rate. At a specific time point, the net magnetization vector will be zero (this means that it has the equal number of protons in the spin up and spin down state). If we run our pulse signal at that moment, we won’t get any signal coming from fat.
Here, instead of saturating tissue based on their processional frequency, one saturates them based on their location within the slice. For example, saturation bands can be placed over the fat in the scalp to prevent it from contributing to the slice.
Unlike conventional MRI, which maps images by filling k-space (a domain for storing raw MRI data) using frequency and phase encoding gradients; MRS localizes signals whithin a specific region using slice selection gradients. This process includes the following steps:
1. Selecting a region of interest (ROI) using gradients. The ROI is matched with an RF pulse, the latter is tuned to match the precessional frequencies of the protons. This isolates the signal contributions from the selected voxel.
2. To measure any signal, transverse magnetization is required. A slice selection gradient is applied in the longitudinal plane, and is matched with an RF pulse at the same frequency as the precessional frequencies of the target slice. For this reason, the observed transverse magnetization loss originates exclusively from this slice.
Similar to spin echo MRI, an additional 180 degree RF pulse is applied along the y axis . This allows to continue observing signal decay without overlap between the slices. The loss of transverse magnetization that we then see, will come from this specific slice.
3. When the y-axis and z-axis overlap, a spin echo is formed, generating a signal specific to a column of tissue. This step ensures precise localization of the signal to a column within the slice.
The process is repeated for the x-axis, completing the localization along all three spatial dimensions (x, y, z). This three-dimensional localization defines the voxel of interest, and the technique used for this is called Point Resolved Spectroscopy (PRESS).
4. Final Spectrum Generation: After isolating the voxel, the signal is analyzed to create a frequency spectrum corresponding to the metabolite composition within the voxel. Each peak in the spectrum represents a distinct metabolite, and its signal intensity reflects its concentration relative to other metabolites in the voxel.
The result is a frequency spectrum representing different metabolites in the voxel. Peaks in the spectrum correspond to specific metabolites, and the signal intensity serves as a proxy for their concentration. However, various factors influence signal intensity, including magnetic field homogeneity, molecular interactions, and T2 relaxation times.
MRS, can be considered a powerful tool for biochemical insights, it is sensitive to technical variables and background noise, requiring advanced techniques to ensure accurate metabolite quantification.
MRS is highly specialised, it focuses only on specific metabolites which often also comes at the cost of low spatial and temporal resolution.
The spatial resolution is lower than that of MRI, as MRS measures signals from larger voxels, this is necessary because the specific metabolites it measures are present at much lower concentrations than water protons, so larger voxels are needed to collect enough signal. Additionally, overlapping signals from neighbouring regions can blur spatial specificity.
The temporal resolution is also lower, as MRS requires averaging of multiple signals to improve the signal to noise ratio (SNR). A single spectrum often takes several seconds or minutes, this makes it impractical for capturing the fast dynamic changes of the brain. Furthermore, biochemical changes measured by MRS occur slowly, whilst real-time brain activity changes in milliseconds.
MRS could potentially detect metabolic changes in deception related regions, however due to its low spatial and temporal resolution, it isn't used for realt time cognitive processes. For dynamic brain function analysis, one uses fMRI.