Magnetic resonance imaging

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Magnetic resonance imaging (MRI), formerly referred to as magnetic resonance tomography (MRT) or nuclear magnetic resonance (NMR), is a method used to visualize the inside of living organisms as well as to detect the amount of bound water in geological structures. It is primarily used to demonstrate pathological or other physiological alterations of living tissues and is a commonly used form of medical imaging. MRI has also found many novel applications outside of the medical and biological fields such as rock permeability to hydrocarbons and certain non-destructive testing methods such as produce and timber quality characterization. [1] The devices used in medicine are expensive, costing approximately $1 million USD per tesla for each unit, with several hundred thousand dollars per year upkeep costs.

Contents

Background information

Nomenclature

Magnetic resonance imaging was developed from knowledge gained in the study of nuclear magnetic resonance. The original name for the medical technology is nuclear magnetic resonance imaging (NMRI), but the word nuclear is almost universally dropped. This is done to avoid the negative connotations of the word nuclear, and to prevent patients from associating the examination with radiation exposure, which is not one of the safety concerns for MRI. Scientists still use NMR when discussing non-medical devices operating on the same principles.

Technique

Image:User-FastFission-brain.gif Medical MRI most frequently relies on the relaxation properties of excited hydrogen nuclei in water. When the object to be imaged is placed in a powerful, uniform magnetic field, the spins of the atomic nuclei with non-zero spin numbers within the tissue all align in one of two opposite directions: parallel to the magnetic field or antiparallel. Common magnetic field strengths range from 0.3 to 3 teslas, although research instruments range as high as 20 teslas, and commercial suppliers are investing in 7 tesla platforms.

Only one in a million nuclei align themselves with the magnetic field. Yet, the vast quantity of nuclei in a small volume sum to produce a detectable change in field. Most basic explanations of NMR and MRI will say that the nuclei align parallel or anti-parallel with the static magnetic field; however, because of quantum mechanical reasons beyond the scope of this article, the individual nuclei are actually set off at an angle from the direction of the static magnetic field, although the bulk collection of nuclei can be partitioned into a set whose sum spin are aligned parallel and a set whose sum spin are anti-parallel.

The magnetic dipole moment of the nuclei then precesses around the axial field. While the proportion is nearly equal, slightly more are oriented at the low energy angle. The frequency with which the dipole moments precess is called the Larmor frequency. The tissue is then briefly exposed to pulses of electromagnetic energy (RF pulse) in a plane perpendicular to the magnetic field, causing some of the magnetically aligned hydrogen nuclei to assume a temporary non-aligned high-energy state. The frequency of the pulses is governed by the Larmor equation.

In order to selectively image different voxels (picture elements) of the material in question, orthogonal magnetic gradients are applied. Although it is relatively common to apply gradients in the principal axes of a patient (so that the patient is imaged in x, y, and z from head to toe), MRI allows completely flexible orientations for images. All spatial encoding is obtained by applying magnetic field gradients which encode position within the phase of the signal. In 1 dimension, a linear phase with respect to position can be obtained by collecting data in the presence of a magnetic field gradient. In 3 dimensions, a plane can defined by "slice selection", in which an RF pulse of defined bandwidth is applied in the presence of a magnetic field gradient in order to reduce spatial encoding to 2 dimensions. Spatial encoding can then be applied in 2D after slice selection, or in 3D without slice selection. In either case, a 2D or 3D matrix of spatially-encoded phases is acquired, and these data represent the spatial frequencies of the image object. Images can be created from the acquired data using the Discrete Fourier Transform (DFT).

In order to understand MRI contrast, it is important to have some understanding of the time constants involved in relaxation processes that establish equilibrium following RF excitation. As the high-energy nuclei relax and realign, they emit energy at rates which are recorded to provide information about their environment. The realignment of nuclear spins with the magnetic field is termed longitudinal relaxation and the time (typically about 1 sec) required for a certain percentage of the tissue nuclei to realign is termed "Time 1" or T1. T2-weighted imaging relies upon local dephasing of spins following the application of the transverse energy pulse; the transverse relaxation time (typically < 100 ms for tissue) is termed "Time 2" or T2. A subtle but important variant of the T2 technique is called T2* imaging. T2 imaging employs a spin echo technique, in which spins are refocused to compensate for local magnetic field inhomogeneities. T2* imaging is performed without refocusing. This sacrifices some image integrity in order to provide additional sensitivity to relaxation processes that cause incoherence of transverse magnetization. Applications of T2* imaging include function MRI (fMRI) or evaluation of baseline perfusion (CBF and CBV) using injected agents as described above; in these cases, there is an inherent trade-off between image quality and detection sensitivity.

Image contrast is created by using a selection of image acquisition parameters that weights signal by T1, T2 or T2*, or no relaxation time ("proton-density images"). In the brain, T1-weighting causes fiber tracts (nerve connections) to appear white, congregations of neurons to appear gray, and cerebrospinal fluid to appear dark. The contrast of "white matter," "gray matter'" and "cerebrospinal fluid" is reversed using T2 or T2* imaging, whereas proton-weighted imaging provides little contrast in normal subjects. Additionally, functional information (CBF, CBV, blood oxygenation) can be encoded within T1, T2, or T2*; see functional MRI (fMRI) and the section below.

Typical medical resolution is about 1 mm3, while research models can exceed 1 µm3.

Contrast-enhancement

Both T1- and T2-weighted images are acquired for most medical examinations. However, these 2 sets of images are not always sufficient to adequately show anatomy or pathology. One option is to use a more sophisticated image acquisition technique - e.g. fat suppression, chemical-shift imaging. The other is to administer a contrast agent to delineate areas of interest.

A contrast agent may be as simple as water, taken orally, for imaging the stomach and small bowel. Alternatively, substances with specific magnetic properties may be used.

Most commonly, a paramagnetic contrast agent (usually a gadolinium compound) is given. Gadolinium-enhanced tissues and fluids appear extremely bright on T1-weighted images. This provides high sensitivity for detection of vascular tissues (e.g. tumors) and permits assessment of brain perfusion (e.g. in stroke).

More recently, superparamagnetic contrast agents (e.g. iron oxide nanoparticles) have become available. These agents appear very dark on T2*-weighted images. These agents may be used for liver imaging - normal liver tissue retains the agent, but abnormal areas (e.g. scars, tumors) do not. They can also be taken orally, to improve visualisation of the gastrointestinal tract, and to prevent water in the gastrointestinal tract from obscuring other organs (e.g. pancreas).

Diamagnetic agents e.g. barium sulfate have been studied for potential use in the GI tract, but are less frequently used.

Application

Image:3Dbrain.gif In clinical practice, MRI is used to distinguish pathologic tissue (such as a brain tumor) from normal tissue. One of the advantages of an MRI scan is that, according to current medical knowledge, it is harmless to the patient. It utilizes strong magnetic fields and non-ionizing radiation in the radio frequency range. Compare this to CT scans and traditional X-rays which involve doses of ionizing radiation and may increase the chance of malignancy, especially in a fetus.

While CT provides good spatial resolution (the ability to distinguish two structures an arbitrarily small distance from each other as separate), MRI provides comparable resolution with far better contrast resolution (the ability to distinguish the differences between two arbitrarily similar but not identical tissues). The basis of this ability is the complex library of pulse sequences that the modern medical MRI scanner includes, each of which is optimized to provide image contrast based on the chemical sensitivity of MRI.

For example, with particular values of the echo time (TE) and the repetition time (TR), which are basic parameters of image acquisition, a sequence will take on the property of T2-weighting. On a T2-weighted scan, fat-, water- and fluid-containing tissues are bright (most modern T2 sequences are actually fast T2 sequences). Damaged tissue tends to develop edema, which makes a T2-weighted sequence sensitive for pathology, and generally able to distinguish pathologic tissue from normal tissue. With the addition of an additional radio frequency pulse and additional manipulation of the magnetic gradients, a T2-weighted sequence can be converted to a FLAIR (Fluid Light Attenuation Inversion Recovery) sequence, in which free water is now dark, but edematous tissues remain bright. This sequence in particular is currently the most sensitive way to evaluate the brain for demyelinating diseases, such as multiple sclerosis.

The typical MRI examination consists of 5-20 sequences, each of which are chosen to provide a particular type of information about the subject tissues. This information is then synthesized by the interpreting physician.

Specialized MRI scans

Diffusion MRI

Diffusion MRI measures the diffusion of water molecules in biological tissues. In an isotropic medium (inside a glass of water for example) water molecules naturally move according to Brownian motion. In biological tissues however, the diffusion is very often anisotropic. For example a molecule inside the axon of a neuron has a low probability to cross a myelin membrane. Therefore the molecule will move principally along the axis of the neural fiber. Conversely if we know that molecules locally diffuse principally in one direction we can make the assumption that this corresponds to a set of fibers.

The recent development of Diffusion Tensor Imaging (DTI) enables diffusion to be measured in multiple directions (currently up to 99) and the Fractional Anisotropy in each direction to be calculated for each voxel. This enables researchers to make axonal maps to examine the structural connectivity of different regions in the brain (tractography) or to examine areas of neural degeneration and demyelinaton in diseases like Multiple Sclerosis.

Another application of diffusion MRI is diffusion-weighted imaging (DWI). Following an ischemic stroke, brain cells die. It is speculated that resultant areas of restricted diffusion are detectable. This finding appears within 5-10 minutes of the onset of stroke symptoms (as compared with computed tomography, which often does not detect changes of acute infarct for up to 4-6 hours) and remains for up to two weeks. As such, DWI sequences are extraordinarily sensitive for acute stroke.

Finally, it has been proposed that diffusion MRI may be able to detect minute changes in extracellular water diffusion and therefore could be used as a tool for fMRI. The nerve cell body enlarges when it conducts an action potential, hence restricting extracellular water molecules from diffusing naturally. Although this process works in theory, evidence is only moderately convincing.

Magnetic resonance angiography

Magnetic resonance angiography (MRA) is used to generate pictures of the arteries in order to evaluate them for stenosis (abnormal narrowing) or aneurysms (vessel wall dilatations, at risk of rupture). MRA is often used to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, the renal arteries, and the legs (called a "run-off"). A variety of techniques can be used to generate the pictures, such as administration of a paramagnetic contrast agent (gadolinium) or using a technique known as "flow-related enhancement" (e.g. 2D and 3D time-of-flight sequences), where most of the signal on an image is due to blood which has recently moved into that plane. MRV is a similar procedure that is used to image veins. In this method the tissue is now excited inferiorly while signal is gathered in the plane immediately superior to the excitation plane, and thus imaging the venous blood which has recently moved from the excited plane.

Magnetic resonance spectroscopy

Magnetic resonance spectroscopy (MRS), also known as MRSI (MRS Imaging) and Volume Selective NMR Spectroscopy, is a technique which combines the spatially-addressable nature of MRI with the spectroscopically-rich information obtainable from nuclear magnetic resonance (NMR). That is to say, MRI allows one to study a particular region within an organism or sample, but gives relatively little information about the chemical or physical nature of that region--its chief value is in being able to distinguish the properties of that region relative to those of surrounding regions. MR spectroscopy, however, provides a wealth of chemical information about that region, as would an NMR spectrum of that region.

Functional MRI

Image:FMRI.jpg Functional MRI (fMRI) measures signal changes in the brain that are due to changing neural activity. The brain is scanned at low resolution but at a rapid rate (typically once every 2-3 seconds). Increases in neural activity cause changes in the MR signal via a mechanism called the BOLD (blood oxygen level-dependent) effect. Increased neural activity causes an increased demand for oxygen, and the vascular system actually overcompensates for this, increasing the amount of oxygenated hemoglobin (haemoglobin) relative to deoxygenated hemoglobin. Because deoxygenated hemoglobin attenuates the MR signal, the vascular response leads to a signal increase that is related to the neural activity. The precise nature of the relationship between neural activity and the BOLD signal is a subject of current research. The BOLD effect also allows for the generation of high resolution 3D maps of the venous vasculature within neural tissue.

While BOLD signal is the most common method employed for neuroscience studies in human subjects, the flexible nature of MR imaging provides means to sensitize the signal to other aspects of the blood supply. Alternative techniques employ arterial spin labeling (ASL) or weight the MRI signal by cerebral blood flow (CBF) and cerebral blood volume (CBV). The CBV method requires injection of a class of MRI contrast agents that are now in human clinical trials. Because this method has been shown to be far more sensitive than the BOLD technique in pre-clinical studies, it may potentially expand the role of fMRI in clinical applications. The CBF method provides more quantitative information than the BOLD signal, albeit at a significant loss of detection sensitivity.

Interventional MRI

Because of the lack of harmful effects on the patient and the operator, MR is well suited for "interventional radiology", where the images produced by an MRI scanner are used to guide a minimally-invasive procedure intraoperatively and/or interactively. However, the non-magnetic environment required by the scanner and the strong magnetic radiofrequency and quasi-static fields generated by the scanner hardware require the use of specialized instruments. Often required is the use of an "open bore" magnet which permits the operating staff better access to patients during the operation. Such open bore magnets are often lower field magnets, typically in the 0.2 tesla range, which decreases their sensitivity but also decreases the Radio Frequency power potentially absorbed by the patient during a protracted operation. Higher field magnet systems are beginning to be deployed in intraoperative imaging suites, which can combine high-field MRI with a surgical suite and even CT in a series of interconnected rooms. Specialty high-field interventional MR devices, such as the IMRIS system, can actually bring a high-field magnet to the patient within the operating theatre, permitting the use of standard surgical tools while the magnet is in an adjoining space.

Radiation therapy simulation

Because of MRI's superior imaging of soft tissues, it is now being utilized to specifically locate tumors within the body in preparation for radiation therapy treatments. For therapy simulation, a patient is placed in specific, reproducible, body position and scanned. The MRI system then computes the precise location, shape and orientation of the tumor mass, correcting for any spatial distortion inherent in the system. The patient is then marked or tattooed with points which, when combined with the specific body position, will permit precise triangulation for radiation therapy.

Current density imaging

Current density imaging is a subbranch of MRI that endeavors to use the phase information from the MRI images to reconstruct current densities within a subject. Current density imaging works because electrical currents generate magnetic fields, which in turn affect the phase of the magnetic dipoles during an imaging sequence. To date no successful CDI has been performed using biological currents, however several studies have been published which involve applied currents through a pair of electrodes.

Magnetic resonance guided focused ultrasound

In MRgFUS therapy, ultrasound beams are focused on a tissue - guided and controlled using MR thermal imaging - and due to the significant energy deposition at the focus, temperature within the tissue rises to more than 65°C, completely destroying it. This technology can achieve precise "ablation" of diseased tissue. MR imaging provides a three-dimensional view of the target tissue, allowing for precise focusing of ultrasound energy. The MR imaging provides quantitative, real-time, thermal images of the treated area. This allows the physician to ensure that the temperature generated during each cycle of ultrasound energy is sufficient to cause thermal ablation within the desired tissue and if not, to adapt the parameters to ensure effective treatment.

Multinuclear imaging

Hydrogen is the most frequently imaged nucleus in MRI because it is present in biological tissues in great abundance. However, any nucleus which has a net nuclear spin could potentially be imaged with MRI. Such nuclei include Helium-3, Carbon-13, Oxygen-17, Sodium-23, Phosphorus-31 and Xenon-129. 23Na and 31P are naturally abundant in the body, so can be imaged directly. Gaseous isotopes (3He and 129Xe) must be hyperpolarized, as their nuclear density is too low to yield a useful signal under normal conditions. 17O and 13C can be administered in sufficient quantities in liquid form (e.g. 17O-water, or 13C-glucose solutions) that hyperpolarization is not a necessity.

Multinuclear imaging is primarily a research technique at present. However, potential applications include functional imaging and imaging of organs poorly seen on 1H MRI (e.g. lungs and bones) or as alternative contrast agents. Inhaled hyperpolarized 3He can be used to image the distribution of air spaces within the lungs. Injectable solutions containing 13C or stabilized bubbles of hyperpolarized 129Xe have been studied as contrast agents for angiography and perfusion imaging. 31P can potentially provide information on bone density and structure, as well as functional imaging of the brain.

Safety

Implants and foreign bodies: Pacemakers are generally considered an absolute contraindication towards MRI scanning. Several cases of arrhythmias or death have been reported in patients with pacemakers who have undergone MRI scanning. Other electronic implants are, at least, relative contraindications.

Ferromagnetic foreign bodies (e.g. shell fragments), or metallic implants (e.g. surgical prostheses, aneurysm clips) are also potential risks, and safety aspects need to be considered on an individual basis. Interaction of the magnetic and radiofrequency fields with such objects can lead to: trauma due to movement of the object in the magnetic field, thermal injury from radiofrequency induction heating of the object, or failure of an implanted device.

In the case of pacemakers, the risk is thought to be primarily RF induction in the pacing electrodes/wires causing inappropriate pacing of the heart, rather than the magnetic field affecting the pacemaker itself.

Other significant safety issues include:

  • Projectiles: As a result of the very high strength of the magnetic field needed to produce scans (frequently up to 30,000 times the earth's own magnetic field effects), there are several incidental safety issues addressed in MRI facilities. Missile-effect accidents, where ferromagnetic objects are attracted to the center of the magnet, have resulted in injury and death. It is for this reason that ferrous objects and devices are prohibited in proximity to the MRI scanner, with non ferro-magnetic "MRI-safe" versions of many of these objects typically retained by the scanning facility. The magnetic field remains a permanent hazard—electromagnetic machines are kept energized at all times.
  • Radio frequency energy: A powerful radio transmitter is needed for excitation of proton spins. This can result in deposition of significant thermal energy in the body, with the risk of hyperthermia in children or elderly patients. Several countries have issued restrictions on the maximum Specific absorption rate that a scanner may produce.
  • Acoustic noise: Loud noises and vibrations are produced by forces resulting from rapidly switched magnetic gradients interacting with the main magnetic field. This is most marked with high-field machines and rapid-imaging techniques in which sound intensity can reach 130 dB (equivalent to a jet engine at take-off). Appropriate use of ear protection is essential. Manufacturers are now incorporating noise insulation and active noise cancellation systems on their equipment.
  • Cryogens: An emergency shut-down of a superconducting electromagnet, an operation known as "quenching," involves the rapid boiling of liquid helium from the device. If the rapidly expanding helium cannot be dissipated though external vents, it may be released into the scanner room where it may cause displacement of the oxygen and present a risk of asphyxiation. Since a quench results in immediate loss of all cryogens in the magnet, recommissioning the magnet is extremely expensive and time-consuming. Spontaneous quenches are uncommon, but can occur at any time.

Pregnancy

No reproducible harmful effects of MRI on the fetus have been demonstrated. In particular, MRI avoids the use of ionizing radiation, to which the fetus is particularly sensitive. However, as a precaution, current guidelines recommend that pregnant women undergo MRI only when essential. This is particularly the case during the first trimester of pregnancy, as organogenesis takes place during this period. The concerns in pregnancy are the same as for MRI in general, but the fetus may be more sensitive to the effects - particularly to heating and to noise. However, one additional concern is the use of contrast agents; gadolinium compounds are known to cross the placenta and enter the fetal bloodstream, and it is recommended that their use be avoided.

Despite these concerns, MRI is rapidly growing in importance as a way of diagnosing and monitoring disease of the fetus because it can provide more diagnostic information than ultrasound without the use of ionizing radiation.

Guidance

Safety issues, including the potential for biostimulation device interference, movement of ferromagnetic bodies and incidental localized heating have been addressed in the American College of Radiology's 'White Paper on MR Safety' which was originally published in 2002 and expanded in 2004.

2003 Nobel Prize

Reflecting the fundamental importance and applicability of MRI in the medical field, Paul Lauterbur and Sir Peter Mansfield were awarded the 2003 Nobel Prize in Medicine for their discoveries concerning MRI. Lauterbur discovered that gradients in the magnetic field could be used to generate two-dimensional images. Mansfield analyzed the gradients mathematically. In a controversial decision, the Nobel Committee snubbed MRI pioneer Raymond V. Damadian although Nobel rules allowed for the award to be shared with a third person. Soon after the announcement, Damadian took out expensive, full-page advertisements in major newspapers to protest the decision (New York Times ad text). Image:Damadian invention.jpg In 1974, Damadian patented the design and use of NMR (US Patent 3,789,832 [2]) for detecting cancer. This patent did not describe a method for generating pictures; however, in 1997, he successfully sued General Electric for infringement and received an award of $129 million. He later settled out of court for further millions from other MRI scanner manufacturers. In 1980, he produced the first commercial MRI scanner, though the machine failed to sell and was never used clinically. [3]

In recording the history of MRI, Mattson and Simon (1996) credit Damadian with describing the concept of whole-body NMR scanning, as well as discovering the NMR tissue relaxation differences that made this feasible. In 2001, the Lemelson-MIT program bestowed its Lifetime Achievement Award on Dr. Damadian as "the man who invented the MRI scanner".

It is still not clear if Damadian's method of detecting cancer is working, and it is not used in modern MRI imaging and diagnostics. His description of a whole body scanner only concerned itself with searching the body for cancer, and does not discuss the use of the data for generating pictures showing different tissues. The procedure as described would take a very long time to perform. There is a big difference between this scanner and contemporary MRI machines.

See also

References

  • James Mattson and Merrill Simon. The Pioneers of NMR and Magnetic Resonance in Medicine: The Story of MRI. Jericho & New York: Bar-Ilan University Press, 1996. ISBN 0961924314.

External links

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