Magnetic Resonance Imaging (MRI) is a non-invasive medical imaging technique that uses strong magnetic fields and radio waves to generate detailed images of the inside of the body.
One application of MRI is to indirectly measure concentrations and metabolism of glucose in the body, through the drop in signal intensity of a product of glucose metabolism, such as lactate or pyruvate.
Here’s a detailed, technical explanation of how this is done:
- MRI is based on the physical principle of nuclear magnetic resonance, which is the phenomenon whereby certain atomic nuclei, such as those of hydrogen, have a magnetic moment that can be aligned with an external magnetic field.
- When a person is placed in the MRI scanner, the magnetic moments of the hydrogen nuclei in their body are aligned with the strong magnetic field of the scanner.
- Radio waves are then applied to the body, causing the magnetic moments of the hydrogen nuclei to flip, or precess, out of alignment with the external magnetic field.
- As the nuclei relax back to their original alignment, they emit radio waves that can be detected by the MRI scanner and used to generate images of the body.
- The signal intensity of the MRI image is proportional to the number of hydrogen nuclei in the tissue being imaged.
- Glucose is a type of sugar that is used by the body for energy. When glucose is metabolized in the body, it is broken down into simpler molecules such as pyruvate and lactate.
- Both pyruvate and lactate are products of glucose metabolism that can be detected by MRI, and their concentrations can be indirectly measured by observing the drop in signal intensity of the MRI image.
- To measure the concentration and metabolism of glucose in the body, a contrast agent containing hyperpolarized pyruvate is administered to the patient. Hyperpolarization is a technique that increases the magnetic properties of the pyruvate molecules, making them easier to detect by MRI.
- The hyperpolarized pyruvate is then metabolized by the body, producing hyperpolarized lactate, which can also be detected by MRI.
- The drop in signal intensity of the MRI image is proportional to the concentration of hyperpolarized lactate in the tissue being imaged, which is in turn proportional to the concentration and metabolism of glucose in the body.
- By measuring the drop in signal intensity over time, it is possible to track the metabolism of glucose in the body, and to detect changes in glucose metabolism associated with disease or injury.
- This technique, known as hyperpolarized MRI, is a promising new tool for studying metabolic processes in the body, and has the potential to improve our understanding of diseases such as cancer, diabetes, and heart disease.
More in deep ….
- Hyperpolarization of Pyruvate: In order to measure glucose metabolism using MRI, a contrast agent containing hyperpolarized pyruvate is administered to the patient. Hyperpolarization is a technique that increases the magnetic properties of the pyruvate molecules, making them easier to detect by MRI. The hyperpolarized pyruvate is then injected into the patient’s bloodstream, and rapidly circulates throughout the body.
- Metabolism of Pyruvate: Once in the body, the hyperpolarized pyruvate is metabolized by cells, primarily in the liver, kidneys, and other organs. Pyruvate can be metabolized in several ways, but two main pathways are the conversion of pyruvate to lactate by lactate dehydrogenase (LDH) and the conversion of pyruvate to acetyl-CoA by pyruvate dehydrogenase (PDH).
- Detection of Lactate and Pyruvate: As pyruvate is metabolized, it produces hyperpolarized lactate or hyperpolarized acetyl-CoA. The drop in signal intensity of the MRI image is proportional to the concentration of hyperpolarized lactate or hyperpolarized acetyl-CoA in the tissue being imaged, which is in turn proportional to the concentration and metabolism of glucose in the body. The drop in signal intensity is due to the fact that the hyperpolarized molecules rapidly lose their polarization as they are metabolized.
- Detection of Lactate: Lactate is the primary product of pyruvate metabolism in many tissues, and can be easily detected by MRI. The drop in signal intensity of the MRI image is proportional to the concentration of hyperpolarized lactate in the tissue being imaged, which is in turn proportional to the concentration and metabolism of glucose in the body. This technique can be used to measure glucose metabolism in a variety of tissues, including the brain, heart, and tumors.
- Detection of Pyruvate: In addition to lactate, hyperpolarized pyruvate can also be used to measure glucose metabolism indirectly. The drop in signal intensity of the MRI image is proportional to the concentration of hyperpolarized pyruvate in the tissue being imaged, which is in turn proportional to the concentration of glucose in the body. This technique has been used to measure glucose metabolism in the liver, where pyruvate is primarily metabolized by PDH.
- Advantages and Limitations: The use of hyperpolarized MRI to measure glucose metabolism has several advantages over other techniques, such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS). Hyperpolarized MRI is non-invasive and does not require the injection of radioactive tracers, which can be harmful to the patient. However, hyperpolarized MRI has some limitations, including the short half-life of hyperpolarized molecules, which limits the amount of time available to image their metabolism, and the need for specialized equipment and expertise.
To measure glucose metabolism using MRI, a high-field MRI scanner is required. High-field MRI scanners operate at field strengths greater than 3 Tesla (T), with 7-Tesla (7T) MRI scanners being the most powerful available.
Illustration of the difference between a 3-tesla MRI and a 7-tesla MRI image with the same resolution. On the left: Temporal signal-to-noise ratio. On the right: activations for a paradigm developed in the laboratory. The color scale corresponds to the intensity of activations and the statistical power, that is, the level of confidence in the detection of activations. A similar improvement is expected between a 7-tesla MRI and an 11.7-tesla MRI. © Neurospin / CEA
The main difference between a 7T MRI scanner and lower-field MRI scanners is the strength of the magnetic field. A higher magnetic field strength increases the sensitivity of the MRI scanner, allowing for higher spatial resolution and improved contrast. This makes 7T MRI scanners ideal for imaging small structures, such as the brain, and for detecting subtle changes in tissue function.
However, there are also some challenges associated with using 7T MRI scanners. The increased sensitivity of the scanner can make it more susceptible to artifacts, which can affect the quality of the images. Additionally, 7T MRI scanners require specialized equipment and expertise, which can make them more expensive and less accessible than lower-field MRI scanners.
Other types of MRI scanners include:
- 1.5-Tesla MRI scanner: This is the most common type of MRI scanner used in clinical settings. It provides good spatial resolution and contrast, but may not be sensitive enough for some applications.
- 3-Tesla MRI scanner: This is a higher-field MRI scanner that provides improved spatial resolution and contrast compared to a 1.5T MRI scanner. It is commonly used for imaging the brain, spine, and musculoskeletal system.
- Open MRI scanner: Unlike traditional MRI scanners, which use a closed bore, open MRI scanners have a larger opening that can be more comfortable for patients who are claustrophobic or obese. However, open MRI scanners may not provide the same image quality as closed-bore MRI scanners.
- Functional MRI (fMRI): This is a type of MRI that is used to measure changes in blood flow in the brain, which can indicate changes in brain activity. fMRI is commonly used in research to study brain function and to diagnose neurological disorders.
- Diffusion MRI: This is a type of MRI that is used to measure the movement of water molecules in tissues, which can provide information about tissue structure and organization. Diffusion MRI is commonly used to diagnose and monitor the progression of stroke and other neurological disorders.
The 11.7 T MRI scanner at CEA-Paris-Saclay, also known as the “Iseult” project, is currently the most powerful MRI scanner for medical use in the world, surpassing the previous record of 7T held by Philips Healthcare.
The 11.7 T MRI scanner utilizes a superconducting magnet with a weight of 132 tonnes, and is capable of producing a magnetic field of 11.7 T inside a 0.9 m diameter and 5 m long volume. This allows for improved spatial resolution and signal-to-noise ratio compared to lower-field MRI scanners, which can enable researchers to study the structure and function of the brain and other organs in greater detail.
In season On account of its multiple textures and resemblance to brain tissue, a pumpkin was the natural choice to showcase MRI’s capabilities at 11.7 T. Credit: CEA
The initial images of a pumpkin as a brain-like subject produced by the Iseult project demonstrate an initial resolution of 400 microns in three dimensions, which is unprecedented for medical research.
A consortium of seven partners, led by the Donders Institute for Brain, Cognition and Behaviour (Radboud University), has received a €19 million Roadmap grant from NWO. It will be used to build the world’s first MRI scanner with a magnetic field strength of 14 Tesla in Nijmegen.
The new scanner is of great importance for research into brain disorders, explains Anja van der Kolk, neuroradiologist/clinician-scientist at Radboud university medical centre. ‘The number of people with brain disorders is large and will only increase in the upcoming years. For many of these disorders no effective treatment is currently available, because we do not know how they develop. With the 14T MRI-scanner, we will be able to see in great detail, without needing surgery, what happens to the brain when it becomes ill, even at an early stage. With this information we hope to find new options for treatment, or even prevention, of these disorders.’
On the importance of this new scanner for the field of medicine, Dennis Klomp, professor in High precision structural and metabolic imaging at UMC Utrecht says: ‘This world’s strongest MRI provides us a unique non-invasive window inside the human body to see metabolism in diseases and how this can be influenced by medication. Using the high spectral and spatial resolution of the 14T MRI, we will study the effect of new treatments in heterogeneous tissues like tumors.’
For the field of neuroscience ‘we expect that the new 14 Tesla MRI-scanner will revolutionize non-invasive neuroscience by enabling the mapping of neural circuits in humans at an unprecedented level of spatial resolution. This highly detailed data will be essential for testing existing models of neural computation and for developing and refining novel, more realistic models’, says Elia Formisano, professor for Neural Signal Analysis at Maastricht University.
We anticipate that at magnetic fields at and above 14 T, in vivo measurements at resolutions of less than 100 µm will be feasible on timescales compatible with human tolerances. Modeling and experimental studies show that the required timing and resolution for imaging computational elements of the brain require higher magnetic fields than those currently available (Fig. 1). The highest resolution for the human brain achieved at 7 T is 0.2 mm isotropic using prospective motion compensation and lengthy averaging. Isotropic resolution of 0.65 mm has been achieved for function MRI (fMRI). Reduction of the voxel volume to 0.1 µL or less provides unprecedented biologically relevant resolution gains in a spatially non-homogeneous and curved structure such as the brain. It allows, for example, resolution of the six layers defined by the neuron types across the cortical thickness, and ~2 voxels across a column on the cortical surface, using isotropic voxel dimensions. It will also allow semi-quantitative mapping of the distribution of aggregated proteins (e.g., amyloid plaques and phosphorylated Tau protein) through susceptibility anisotropy.
Fig. 1 Existing magnets and projects are shown with the required conductor. Solid diamonds indicate magnets presently in operation. Open diamonds indicate magnets presently under construction or repair. Target magnet designs in this paper are shown as red circles
If we assume the signal-to-noise ratio (SNR) scales linearly or better with a magnetic field in the human brain, as it has been shown for up to 9.4 T  and linearly with fields from 9.4 to 21.1 T (vide infra), magnetic fields of 14 T and above will provide significant gains towards the goal of 0.1-µL volume resolution. If we consider the BOLD (blood oxygen level-dependent) effect to increase at least linearly with magnetic field magnitude , then the combined effects of SNR and BOLD contrast would translate into a quadratic gain with field magnitude or ~eightfold gain in contrast-to-noise ratio for functional mapping signals that define the ultimate resolution of the functional maps.
Ultrahigh fields open unique doors to the interrogation of individual brain metabolites. Neurotransmitters such as glutamine, glutamate, and GABA can easily be distinguished from energetic reporters such as lactate, glucose, and ATP. Also, heteronuclear MRS and MRSI measurements using stable 13C and 17O tracers and naturally abundant 31P can enable brain function maps of energetics not available to studies even at 7 T. The sensitivity boost arising from ≥14 T fields will lead to 23Na, 35Cl, 39K, and possibly other nuclide mapping at unprecedented spatial resolutions and signal strengths.
In summary, a high-field MRI scanner, such as a 7T MRI scanner, is typically required to measure glucose metabolism using MRI. While 7T MRI scanners provide improved sensitivity and spatial resolution, they also have some challenges associated with their use. Other types of MRI scanners, such as 1.5T and 3T MRI scanners, open MRI scanners, fMRI, and diffusion MRI, are also commonly used for different types of imaging applications.
- Petr Bednarik et al, 1H magnetic resonance spectroscopic imaging of deuterated glucose and of neurotransmitter metabolism at 7 T in the human brain, Nature Biomedical Engineering (2023). DOI: 10.1038/s41551-023-01035-z
- Fabian Niess et al, Noninvasive 3-Dimensional 1H-Magnetic Resonance Spectroscopic Imaging of Human Brain Glucose and Neurotransmitter Metabolism Using Deuterium Labeling at 3T, Investigative Radiology (2023). DOI: 10.1097/RLI.0000000000000953
- “Hyperpolarized MRI: Metabolic Imaging and Beyond” by Matthew E. Merritt et al. – This review article provides a comprehensive overview of hyperpolarized MRI, including its application to the study of glucose metabolism.
- “Glucose Metabolism in Vivo by Magnetic Resonance Spectroscopy and Imaging” by Rolf Gruetter et al. – This article discusses the use of magnetic resonance spectroscopy and imaging to study glucose metabolism in vivo.
- “Hyperpolarized [1-13C] Pyruvate to Lactate Conversion Is Rate-Limited by Lactate Dehydrogenase” by Ralph E. Hurd et al. – This research article describes a study using hyperpolarized pyruvate to measure glucose metabolism in tumors.
- “Glucose Metabolism in Cancer: The Saga of Pyruvate Kinase Continues” by Daniel A. Tennant et al. – This review article discusses the role of pyruvate kinase in glucose metabolism in cancer cells, and the potential of hyperpolarized MRI to study this process.
- “Magnetic Resonance Imaging of Glucose Uptake and Metabolism in Patients with Head and Neck Cancer” by David M. Wilson et al. – This research article describes a study using MRI to measure glucose uptake and metabolism in patients with head and neck cancer.