How do MRI machines work?
MRIs employ powerful magnets which produce a strong magnetic field that forces protons in the body to align with that field. When a radiofrequency current is then pulsed through the patient, the protons are stimulated, and spin out of equilibrium, straining against the pull of the magnetic field. When the radiofrequency field is turned off, the MRI sensors are able to detect the energy released as the protons realign with the magnetic field. The time it takes for the protons to realign with the magnetic field, as well as the amount of energy released, changes depending on the environment and the chemical nature of the molecules. Researchers and physicians are able to tell the difference between various types of tissues based on these magnetic properties.
Coils – what are they?
Radiofrequency coils (RF coils) are the “antennae” of the MRI system, broadcasting the RF signal to the subject and/or receiving the return signal. RF coils can be receive-only, in which case the coil is used as a transmitter; or transmit and receive (transceiver).
One of the most common types of receive-only coils is the surface coil. Surface coils are the simplest design of coil, and are frequently used by the Merritt lab. They are simply a loop of wire, either circular or rectangular, that is placed over the region of interest. A coil is usually a physically small antenna. The depth of the image of a surface coil is generally limited to about one radius. Surface coils are commonly used for small scan areas, such as imaging rodents. The radio frequency signal coming out of the subject is transmitted as data to a computer which then generates images. Coils are part of the hardware of MRI machines and are used to create a magnetic field or to detect a changing magnetic field by voltage induced in the wire. The perfect coil produces a uniform magnetic field without significant radiation.
The receiver coils detect the electromagnetic radiation produced by the process of nuclear relaxation inside the subject as a result of the transmitted electromagnetic field. The receiver coil is capturing the oscillating net magnetic flux from the excited spin system when an induced electric current is generated. This information is amplified, quantified and filtered to extract frequency and phase. The type of receiver coil used can be specified for the specific type of imaging required. Two of the factors which will determine the ability of a coil to receive signal are the proximity to the signal and the diameter of the coil (the larger the diameter, the less sensitive the coil).
By their nature, surface coils have good signal-to-noise ratio (SNR) for the tissue adjacent to the coil. They also allow for smaller voxel size which in turn allows for improved image resolution. A voxel is a portmanteau of contractions of the two words ‘volume’ and ‘element’ and was coined as a 3D equivalent of a pixel. It is an individual point in space on a 3-dimensional, regular matrix. The location of each voxel is encoded by its relative relationship to other voxels.
The sensitivity decreases greatly as the distance from the coil is increased. Hence, surface coils have a smaller field of view. Hence, the placement and selection of surface coils is dependent on the type of imaging required, and are particularly useful in subject regions where relatively superficial anatomy is being studied
Some things that can impact the SNR include the following:
- Amount of data acquired at one time.
- Type of sequence.
- Use of surface coils.
- Size of the field of view.
- Size of the matrix.
- Slice thickness.
One factor that can impact the SNR during a scan is the type of coil used. Hard, rigid coils like the traditional form of the object may result in a decreased SNR. This is primarily because they are not able to be shaped against the body. If the subject is smaller than the coil, the SNR is decreased, because the coil is farther from the source of the signal.
An imaging coil must resonate, or efficiently store energy, at the Larmor frequency. All imaging coils are composed of an inductor, or inductive elements, and a set of capacitive elements. The resonant frequency, ν, of an RF coil is determined by the inductance (L) and capacitance (C) of the inductor capacitor circuit.
How are deuterated compounds used?
Deuterium metabolic imaging or DMI is a recently described, innovative MR-based method to map metabolism non-invasively in 3D. DMI allows imaging of substrates and their metabolic products enriched with the non-radioactive and biocompatible deuterium (semi-heavy, or 2H) isotope. Common 2H-enriched substrates include [6,6-2H2]-glucose and 2H3-acetate to study pathways involved in energy metabolism such as glycolysis and the tricarboxylic acid (TCA) or citric acid cycle.
A typical DMI study is composed of three main steps. As a first step, the 2H-enriched substrate must be administered to the subject. Ideally the substrate is administered via intravenous infusion in order to achieve and maintain a high and stabile level of 2H-enriched substrate in the blood. Over time the 2H-enriched substrate will be broken down and converted into a range of metabolic products, for example glutamate and lactate in the case of glucose. In the brain these metabolic processes can take between 45 and 90 min to reach steady-state. The build-up of metabolic products can be dynamically followed over time or detected when steady-state has been reached. The dynamic option allows the calculation of absolute rates through metabolic pathways, whereas the steady-state option only allows one to detect the presence of an active metabolic pathway.
DMI is a MR-based method and as such the 2H-enriched substrate and products are detected with 2H MR acquisition methods. A standard DMI acquisition is executed as MR spectroscopic imaging (MRSI) with a simple pulse-acquire sequence extended with phase-encoding gradients to obtain spatial information.
The sensitivity of 2H NMR and thus DMI was recently shown to increase supralinearly with the magnetic field strength (Fig. 2A). For small animal surface coils (~ 30 mm) the sensitivity between 4.0 T and 11.7 T scaled at the theoretical maximum (SNR ~ B01.75), whereas for larger human surface coils (~ 80 mm) the sensitivity between 4.0 T and 7.0 T scaled as B01.65. In addition to the higher sensitivity, DMI at higher magnetic fields also displayed the anticipated increased spectral dispersion.
DMI has previously been demonstrated to provide 3D metabolic images in rats and humans. The availability of genetically modified mouse models and the need for in vivo metabolic phenotyping tools provides incentive to extend DMI to mice. Using a small (8 x 12 mm), arched DMI coil and uniformly deuterated glucose, high-resolution (5µL) DMI maps could be generated on mouse brain at 11.7 T. Fig. 3B shows a Lac/Glx ratio map in a mouse model of glioblastoma, highlighting the Warburg effect in the brain tumor.
13C and hyperpolarization – how is this done and why?
Hyperpolarization is a technique for “supercharging” the spin polarization of MRI tracers that can enhance their MRI signal up to 50,000 times. It involves first freezing a sample to the liquid helium temperature of -452°F to eliminate thermal motion. The sample also contains a polarizing agent—a chemical containing a single stable electron that is already highly polarized at this temperature. When the polarizing agent is bombarded with microwaves, it absorbs energy and transfers it to the molecule of interest for MRI, thereby hyperpolarizing it. This process is called dynamic nuclear polarization (DNP).
When thawed, a hyperpolarized sample retains a significant amount of this supercharged property for up to several minutes before undergoing “relaxation.” Thus, researchers can inject hyperpolarized versions of specially synthesized labeled molecules into the subject to act as chemical tracers. As these tracers undergo reactions in the subject’s biochemical pathways, researchers can follow the flow of these pathways—for example, analyzing the hyperactive metabolic machinery of tumors.
One widely used atom in hyperpolarization studies is the heavier isotope of carbon, 13C, whose nucleus contains one more neutron than the common 12C. Researchers are using hyperpolarized 13C-labeled compounds to track the metabolic machinery of cancer, diabetes, obesity, heart and liver diseases, and other disorders. They are also using such tracers to measure the neural metabolic pathways responsible for synthesizing neurotransmitters, the signaling molecules by which one neuron triggers its neighbor to launch a nerve impulse.
Magnetic Resonance Spectroscopy – what does this tell us about metabolism?
Magnetic Resonance (MR) spectroscopy is a noninvasive diagnostic test for measuring biochemical changes in the brain, especially the presence of tumors. While magnetic resonance imaging (MRI) identifies the anatomical location of a tumor, MR spectroscopy compares the chemical composition of normal brain tissue with abnormal tumor tissue. This test can also be used to detect tissue changes in stroke and epilepsy.
MR spectroscopy is conducted on the same machine as conventional MRI. The MRI scan uses a powerful magnet, radio waves, and a computer to create detailed images. Spectroscopy is a series of tests that are added to the MRI scan of a subject to measure the chemical metabolism of a suspected tumor.
MR spectroscopy analyzes molecules such as hydrogen ions or protons. Proton spectroscopy is more commonly used. There are several different metabolites, or products of metabolism, that can be measured to differentiate between tumor types:
- Amino acids
- Lipid
- Lactate
- Alanine
- N-acetyl aspartate
- Choline
- Creatine
- Myoinositol
The frequency of these metabolites is measured in units called parts per million (ppm) and plotted on a graph as peaks of varying height. By measuring each metabolite’s ppm and comparing it to normal brain tissue, the neuroradiologist can determine the type of tissue present.
MR spectroscopy can be used to determine tumor type and aggressiveness, and distinguish between tumor recurrence and radiation necrosis. Different metabolites can indicate:
- Glioma: lower than normal N-acetyl aspartate levels, elevated choline and lipid levels, and lactate peaks.
- Radiation necrosis: does not have elevated choline levels
- Meningioma: elevated alanine levels