Magnetic Resonance Imaging



Magnetic resonance imaging (MRI) - also called  magnetic resonance tomography (MRT) - is a method of creating images of the inside of opaque organs in living organisms as well as detecting 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. The devices used in medicine are expensive, costing approximately $1M USD per Tesla for each unit, with several hundred thousand dollars per year upkeep costs.

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
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 0.5 to 3 Tesla, although research instruments range as high as 20 Tesla, 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 nuclei are actually set off at an angle from the direction of the static magnetic field.

The magnetic dipole moment of the nuclei then precess 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 pixels (picture elements) or voxels (3-D volume 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 apply 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 &quot;Time 1&quot; 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 &quot;Time 2&quot; or T2. A subtle but important variant of the T2 technique is called T2* imaging. Whereas T2 imaging employs "spin echoes", which are radio-frequency pulses that refocus inhomogeneities in the magnetic field, T2* imaging 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 cerebral spinal fluid to appear dark. The contrast of "white matter", "gray matter", and "cerebral spinal 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.

Both T1- and T2-weighted images are acquired for most medical examinations. Often, a paramagnetic contrast agent, a gadolinium compound, is administered, and both pre-contrast T1-weighted images and post-contrast T1-weighted images are obtained. Injections of bolus contrast agent, together with rapid imaging, enable evalution of brain perfusion; this is particularly important in patients presenting symptoms of stroke. Additionally, information provided by clinically-approved contrast agent provides information about the integrity of the blood-brain barrier, which prevents leakage of contrast in healthy subjects. Typical medical resolution is about 1 mm3, while research models can exceed 1 &micro;m3.

Application
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 children receiving multiple examinations.

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, water and fluid-containing tissues are bright (most modern T2 sequences are actually fast T2 sequences, in which case fat is also bright). 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 some more 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 now is dark, but edematous tissues remain bright. This sequence, in particular, is currently the most sensitive way to evaluate the brain for changes of multiple sclerosis.

The typical MRI examination typically 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.

Safety
The presence of a ferromagnetic foreign body (such as shell fragments) in the subject, or a metallic implant (like surgical prostheses, or pacemakers) can present a (relative or absolute) contraindication towards MRI scanning: interaction of the magnetic and radiofrequency fields with such an object can lead to: trauma due to shifting of the object in the magnetic field, thermal injury from radiofrequency induction of heating of the object, or failure of an implanted device.

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 nonmagnetic "MRI-safe" versions of many of these objects typically retained by the scanning facility. Contrary to expectations, the magnet is energized at all times, even when it is not in use. Because of this, floor cleaning machines are often a victim of the magnet. An emergency shut-down of the magnet, an operation known as a 'quench', is costly and involves dumping liquid helium from the device. The sudden expansion of the escaping cold helium liquid into its gaseous form, and the displacement of oxygen is a hazard of its own.

Many 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.

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). The main use of MRA is to evaluate the arteries of the neck and brain, the thoracic and abdominal aorta, and the kidneys. A variety of techniques can be used to generate the pictures, such as administration of a paramagnetic contrast agent (such as gadolinium) or using a technique known as "flow-related enhancement" (e.g. 2D and 3D time-of-flight sequences), where the only 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 dorsally while signal is gathered in the plane immediately ventral 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
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 &quot;interventional radiology&quot;, 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 &quot;open bore&quot; 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 tatooed 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.

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). In 1974, Damadian patented the design and use of NMR (US Patent 3,789,832 ) 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. 

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.

Reference

 * 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.