Brain metabolites and glioma pattern
Spectroscopy provides a non-biopsy insight into tissue biochemistry. The analysis is performed using voxels—three-dimensional pixels that make up a volumetric image. For the brain, three groups of molecules serve as key markers:
- Choline-containing molecules (Cho)
- Creatine (Cr)
- N-acetylaspartate (NAA): this metabolite is concentrated predominantly in neurons. If the NAA peak on the spectrogram drops, it directly indicates the death or damage of nerve cells.
The classic pattern of a low-grade glioma (low-grade glioma) is a marked decrease in the NAA peak against the background of a pathologically high Cho level (compared to the stable Cr peak). Such metabolic shifts serve as a reliable marker of neoplasm aggressiveness.
Application of various nuclei in MRS
Although MRS most commonly analyzes protons (^1H), the use of other nuclei opens up additional diagnostic windows.
- Phosphorus-31 (^31P): indispensable for calculating intracellular pH. The reference point is the peak of pH-sensitive inorganic phosphate. A scenario where extracellular acidification is recorded is very characteristic of growing tumors.
- Fluorine-19 (^19F): used in pharmacokinetic studies. In particular, it helps track the distribution of fluorinated chemotherapeutic agents, such as 5-fluorouracil (5-fluorouracil).
- Carbon-13 (^13C): allows for a detailed study of the metabolism of carbon-containing structures (e.g., the tricarboxylic acid cycle). Since metabolic abnormalities precede structural ones, this is a powerful tool for early diagnosis. However, the natural abundance of carbon-13 in the body is only about 1%, making classical ^13C-MRS a method with extremely low sensitivity.
Overcoming limitations: Hyperpolarization technology
Basic MRS protocols suffer from two main problems: low sensitivity and insufficient spatial resolution. The solution has been hyperpolarization technology (Hyperpolarisation), which multiplies the signal intensity.
- Hyperpolarized gases: used primarily in pulmonology for detailed visualization of lung microstructure.
- Hyperpolarized ^13C: involves the intravenous administration of a labeled agent followed by tracking of both the molecule itself and its decay products. This allows fundamental biochemical pathways to be observed in real time.
The most promising agent today is considered to be ^13C-labeled pyruvate. Its metabolism is successfully visualized during examinations of the healthy heart, as well as prostate and brain cancer. The main clinical value of hyperpolarized pyruvate is the ability to instantly assess treatment response by detecting rapid changes in tumor metabolism immediately after radiation or chemotherapy.
Related method: Diffusion-weighted imaging
In addition to spectroscopy, a powerful tool for cancer detection is diffusion-weighted imaging (Diffusion-Weighted Imaging, DWI). This method generates contrast based on the random Brownian motion of water molecules.
Unlike MRS, which evaluates biochemistry, DW-MRI focuses on tissue cellularity (tissue cellularity).
- Low cellularity: water moves freely. This yields a low signal on DW-MRI and a high apparent diffusion coefficient (Apparent Diffusion Coefficient, ADC).
- High cellularity (cancer): cells are densely packed, water movement is restricted. The images show a high signal and low ADC.
Advanced DW-MRI protocols are currently used to detect and stage oncological processes, study tumor compartments and heterogeneity, and monitor treatment efficacy.
Briefly: answers to topical questions
Which chemotherapy drugs can be tracked using fluorine-19 MR spectroscopy?
^19F-MR spectroscopy is used to study the pharmacokinetics of fluorinated drugs, such as 5-fluorouracil.
Which metabolites, besides choline, creatine, and N-acetylaspartate, are detected in brain MR spectroscopy?
In addition to choline, creatine, and N-acetylaspartate, brain MR spectroscopy detects the following additional metabolites:
- Lipids (Lipids) — released during cell membrane damage.
- Lactate (Lactate) — a marker of anaerobic metabolism.
- Myo-inositol (myo-inositol) — detected using a short echo time.
- Glutamate (glutamate) — also detected with a short echo time.
- Glutamine (glutamine) — determined together with other metabolites at a short echo time.
What does the appearance of a lactate peak on a brain MR spectrogram indicate?
The appearance of a lactate peak on a brain MR spectrogram indicates the development of anaerobic metabolism (glycolysis). In clinical practice, such changes may indicate the following pathological conditions:
- Ischemic brain injury (ischemic brain suffering) — accompanied by the appearance of a lactate doublet on the spectrogram.
- MELAS syndrome (Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes) — the lactate peak is detected in lesion sites, visually normal areas of the brain, and the cerebrospinal fluid of the lateral ventricles.
Class and exam questions
How does MRS differentiate normal brain tissue from glioma?
In healthy tissue, the N-acetylaspartate (NAA) peak is high. In glioma, this peak decreases due to neuronal damage, and the level of choline-containing molecules (Cho) increases relative to creatine (Cr).
Why use phosphorus-31 spectroscopy?
Evaluation of the inorganic phosphate peak allows determination of intracellular pH. This is critically important because acidification of the extracellular space is frequently observed in tumors.
What does the apparent diffusion coefficient (ADC) show in DWI-MRI?
It reflects the cell density within the tissue. In malignant tumors, high cellularity restricts water molecule diffusion, resulting in a low ADC and high signal intensity on scans.
What is the advantage of hyperpolarized ^13C-pyruvate?
This molecule serves as a reliable biomarker of early treatment response. It allows for in vivo visualization of ultra-fast metabolic changes in the tumor immediately after chemotherapy.
What else to study on this topic
- Pharmacokinetics of 5-fluorouracil using ^19F-MRS
- Technique for quantitative assessment of the apparent diffusion coefficient (ADC)
- Visualization of lung microstructure using hyperpolarized gases
- Assessment of the tricarboxylic acid cycle using ^13C-MRS
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