# Magnetic resonance imaging

(Redirected from MRI)
Magnetic Resonance Image showing a vertical (sagittal) cross section through a human head.

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 composition of 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 scanners used in medicine cost approximately \$1 million USD per Tesla for each unit (typical field strength ranges from 0.3 to 3 Teslas, although field strengths as high as 9.4T are used in research scanners [2] ), with several hundred thousand dollars per year for maintenance. A man from Fraserburgh, Scotland, with terminal liver cancer become the first patient in the world to receive an MRI body scan in Aberdeen, U.K.

## Background

### Nomenclature

Magnetic Resonance Imaging was developed from knowledge gained in the study of Nuclear Magnetic Resonance. Paul Lauterbur, one of the inventors of MRI, coined the term Zeugmatography<ref>Lauterbur, P.C., Nature, 1973; 242:190-191.</ref> , for the technique based on the Greek term meaning "that which is used for joining". The term was meant to highlight the interaction between the static and the gradient magnetic fields that are critical to image formation, but the nomenclature never caught on. In its early years the medical technology was called 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.

### MRI vs CT

A Computed Tomography (CT) scanner uses ionizing radiation, X-rays, to acquire its images, making it a good tool for dense tissue (bone) exams. MRI, on the other hand, uses non-ionizing, radio frequency signals to acquire its images. MRI is best suited for soft (non-calcified) tissue exams.

Both CT and MRI scanners can generate multiple two-dimensional cross-sections or slices of tissue and three-dimensional reconstructions. Unlike CT, which uses only X-ray attenuation to generate image contrast, MRI has a long list of properties that may be used to generate image contrast. By variation of scanning parameters, tissue contrast can be altered and enhanced in various ways to demonstrate different features. (See Application below)

MRI can generate cross-sectional images in any plane (including oblique planes). CT is limited to acquiring images in the axial (or near axial) plane. However, the development of multi-detector CT scanners with near-isotropic resolution, has reduced the impact of this as isotropic data can be retrospectively reconstructed in any plane with minimal loss of image quality.

### Technique

Image:Modern 3T MRI.JPG
Modern high field clinical MRI scanner.

Medical MRI most frequently relies on the relaxation properties of excited hydrogen nuclei in water and fat. When the object to be imaged is placed in a powerful, uniform magnetic field the spins of the atomic nuclei with non-integer spin numbers within the tissue all align either 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. (For comparison, the Earth's magnetic field on average is around 50 μT, that is more than 100 000 times lower.)

In a 1.5 tesla magnetic field (at room temperature), an excess of only one in a million nuclei align themselves with the magnetic field since the thermal energy far exceeds the energy difference between the parallel and antiparallel states. 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 though, 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. 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 pulses) 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 (volume picture elements) of the subject, 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 one dimension, a linear phase with respect to position can be obtained by collecting data in the presence of a magnetic field gradient. In three dimensions (3D), a plane can be 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 two dimensions (2D). 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 (resolution) in order to provide additional sensitivity to relaxation processes that cause incoherence of transverse magnetization. Applications of T2* imaging include functional MRI (fMRI) or evaluation of baseline vascular perfusion (e.g. cerebral blood flow (CBF)) and cerebral blood volume (CBV) using injected agents as described above; in these cases, there is an inherent trade-off between image quality and detection sensitivity. Because T2*-weighted sequences are sensitive to magnetic inhomogeneity (as can be caused by deposition of Fe-containing blood-degradation products), such sequences are utilized to detect subtle areas of recent or chronic intracranial hemorrhage ("Heme sequence").

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, i.e. white matter) to appear white, congregations of neurons (i.e. gray matter) 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.

Diffusion Weighted Imaging (DWI) uses very fast scans with an additional series of gradients (diffusion gradients) rapidly turned on and off. Protons from water diffusing randomly within the brain, via Brownian motion, lose phase coherence and, thus, signal during application of diffusion gradients. Within acutely infarcted brain, water diffusivity is impaired, and signal loss on DWI sequences is less than in normal brain. DWI is the most sensitive method of detecting cerebral infarction (stroke) and can identify an infarct within 30 minutes of ictus.

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

#### Contrast Enhancement

Both T1-weighted 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). There have been concerns raised recently regarding the toxicity of gadolinium-based contrast agents and their impact on persons with impaired kidney function. Special actions may be taken, such as hemodialisis following MR examination, for renally-impaired patients who are given gadolinium contrast agents.

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.

## The k-space formalism

In 1983 Ljunggren<ref>Ljunggren S. J Magn Reson 1983; 54:338.</ref> and Tweig<ref>Template:Cite journal</ref> independently introduced the k-space formalism, a technique that proved invaluable in unifying different MR imaging techniques. They showed that the demodulated MR signal $S(t)$ generated by spins freely precessing in the presence of a linear magnetic field gradient $G$ equals the Fourier transform of the effective spin density $\rho_{eff}\$ i.e.

$S(t) = {\tilde \rho}_{\mathrm{effective}}( {\vec k}(t) ) \equiv \int d^3x \ \rho( {\vec x} ) \cdot e^{2 \pi \imath \ {\vec k}(t) \cdot {\vec x} }$

where:

${\vec k}(t) \equiv \int_0^t {\vec G}(t')\ dt'$

In other words, as time progresses the signal traces out a trajectory in k-space with the velocity vector of the trajectory proportional to the vector of the applied magnetic field gradient. By the term effective spin density we mean the true spin density $\rho({\vec x})$ corrected for the effects of $T_1$ preparation, $T_2$ decay, dephasing due to field inhomogeneity, flow, diffusion, etc. and any other phenomena that affect that amount of transverse magnetization available to induce signal in the antenna.

From the basic k-space formula, it follows immediately that we reconstruct an image $I({\vec x})$ simply by taking the inverse Fourier transform of the sampled data viz.

$I({\vec x}) = \int d^3 k \ S( {\vec k}(t) ) \cdot e^{-2 \pi \imath \ {\vec k}(t) \cdot {\vec x} }$

Using the k-space formalism, a number of seemingly complex ideas become simple. For example, it becomes very easy to understand the role of phase encoding (the so-called spin-warp method). In a standard spin echo or gradient echo scan, where the readout (or view) gradient is constant (e.g. $G_x$), a single line of k-space is scanned per RF excitation. When the phase encoding gradient is zero, the line scanned is the $k_x$ axis. When a non-zero phase-encoding pulse is added in between the RF excitation and the commencement of the readout gradient, this line moves up or down is k-space i.e. we scan the line $k_y$=constant. The k-space formalism also makes it very easy to compare different scanning techniques. In single-shot EPI, all of k-space is scanned in a single shot, following either a sinusoidal or zig-zag trajectory. Since alternate lines of k-space are scanned in opposite directions, this must be taken into account in the reconstruction. Multi-shot EPI and fast spin echo techniques acquire only part of k-space per excitation. In each shot, a different interleaved segment is acquired, and the shots are repeated until k-space is sufficiently well-covered. Since the data at the center of k-space represent lower spatial frequencies than the data at the edges of k-space, the $T_E$ value for the center of k-space determines the image's $T_2$ contrast.

The importance of the center of k-space in determining image contrast can be exploited in more advanced imaging techniques. One such technique is spiral acquisition - a rotating magnetic field gradient is applied, causing the trajectory in k-space to trace out spiral out from the center to the edge. Due to $T_2$ and $T_2*</Math> decay the signal is greatest at the start of the acquisition, hence acquiring the center of k-space first improves contrast to noise ratio (CNR) when compared to conventional zig-zag acquisitions, especially in the presence of rapid movement. Since [itex]\vec x$ and $\vec k$ are conjugate variables (with respect to the Fourier transform) we can use the Nyquist theorem to show that the step in k-space determines the field of view of the image (maximum frequency that is correctly sampled) and the maximum value of k sampled determines the resolution i.e.

$FOV \propto \frac{1}{\Delta k} \qquad \mathrm{Resolution} \propto |k_{\max}|$

(these relationships apply to each axis (X, Y, and Z) independently).

## Application

In clinical practice, MRI is used to distinguish pathologic tissue (such as a brain tumor) from normal tissue. One advantage of an MRI scan is that it is harmless to the patient. It uses 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 risk 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 randomly according to Brownian motion. In biological tissues however, the diffusion may be anisotropic. For example a molecule inside the axon of a neuron has a low probability of crossing the myelin membrane. Therefore the molecule will move principally along the axis of the neural fiber. If we know that molecules in a particular voxel diffuse principally in one direction we can make the assumption that the majority of the fibers in this area are going parallel to that direction.

The recent development of Diffusion Tensor Imaging (DTI) enables diffusion to be measured in multiple directions and the Fractional Anisotropy in each direction to be calculated for each voxel. This enables researchers to make brain maps of fiber directions to examine the connectivity of different regions in the brain (using 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, DWI is highly sensitive to the pathophysiological changes occurring in the lesion (Moseley ME et al., Magn Reson Med 1990;14:330–346). It is speculated that increases in restriction (barriers) to water diffusion, as a result of cytotoxic edema (cellular swelling), is responsible for the increase in signal on a DWI scan. Other theories, including acute changes in cellular permeability and loss of energy-dependent (ATP) cytoplastic streaming, have been proposed to explain the phenomena. The DWI enhancement 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. CT, due to its insensitivity to acute ischemia, is typically employed to rule out hemorragic stroke, which would entirely prevent the use of tissue plasminogen activator (tPA). Further, coupled with scans sensitized to cerebral perfusion, researchers can highlight regions of "perfusion/diffusion mismatch" that may indicate regions capable of salvage by reperfusion therapy.

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.

Like many other specialized applications, this technique is usually coupled with a fast image acquisition sequence, such as Echo Planar Imaging sequence.

#### Magnetic Resonance Angiography

Image:Mra1.jpg
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. Magnetic Resonance Venography (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
A fMRI scan showing regions of activation in orange, including the primary visual cortex (V1, BA17).

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.

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 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, though highly specialized protocols have been developed to permit scanning of select pacing devices. Several cases of arrhythmias or death have been reported in patients with pacemakers who have undergone MRI scanning without appropriate precautions. Other electronic implants have varying contraindications, depending upon scanner technology, implant properties, scanning protocols and anatomy being imaged. Consult your referring physician or radiologist to identify the safety or hazards of any implant.

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 radio-frequency induction heating of the object, or failure of an implanted device. These issues are especially problematic when dealing with the eye. Most MRI centers require an orbital x-ray be performed on anyone who suspects they may have small metal fragments in their eyes, perhaps from a previous accident, something not uncommon in metalworking.

Because of its non-ferromagnetic nature and poor electrical conductivity, titanium and its alloys are useful for long term implants and surgical instruments intended for use in image-guided surgery. In particular, not only is titanium safe from movement from the magnetic field, but artifacts around the implant are less frequent and less severe than with more ferromagnetic materials e.g. stainless steel. Artifacts from metal frequently appear as regions of empty space around the implant - frequently called 'black-hole artifact' e.g. a 3mm titanium alloy coronary stent may appear as a 5mm diameter region of empty space on MRI, whereas around a stainless steel stent, the artifact may extend for 10-20 mm or more.

In 2006, a new classification system for implants and ancillary clinical devices has been developed by ASTM International and is now the standard supported by the US Food and Drug Administration:

MR-Safe: The device or implant is completely non-magnetic, non-electrically conductive, and non-RF reactive, eliminating all of the primary potential threats during an MRI procedure.
MR-Conditional: A device or implant that may contain magnetic, electrically conductive or RF-reactive components that is safe for operations in proximity to the MRI, provided the conditions for safe operation are defined and observed (such as 'tested safe to 1.5 Tesla' or 'safe in magnetic fields below 500 Gauss in strength').
MR-Unsafe: Nearly self-explanatory, this category is reserved for objects that are significantly ferromagnetic and pose a clear and direct threat to persons and equipment within the magnet room.

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 60,000 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.<ref>Randal C. Archibold, "Hospital Details Failures Leading to M.R.I. Fatality", The New York Times, 2001 August 22.</ref> It is for this reason that ferrous objects and devices are prohibited in proximity to the MRI scanner, with non ferro-magnetic versions of many of these objects typically retained by the scanning facility. The magnetic field remains a permanent hazard — the superconductive MRI magnet retains its magnetic field at all times. The proliferation of ferromagnetic materials makes screening them out a significant challenge. New ferromagnetic-only detection devices are supplementing conventional screening techniques in many leading hospitals and imaging centers.
• Radio frequency energy: A powerful radio transmitter is needed for excitation of proton spins. This can heat the body significantly, with the risk of hyperthermia in patients, particularly the obese or patients with thermoregulation disorders. Several countries have issued restrictions on the maximum specific absorption rate that a scanner may produce.
• Peripheral nerve stimulation (PNR): The rapid switching (on and off) of the magnetic field gradients needed for imaging is capable of causing nerve stimulation. Volunteers report a twitching sensation when exposed to rapidly switched fields, particularly in their extremities. The reason the peripheral nerves are stimulated is that the changing field increases with distance from the center of the gradient coils (which more or less coincides with the center of the magnet). Note however that when imaging the head, the heart is far off-center and induction of even a tiny current into the heart must be avoided at all costs. Although PNR was not a problem for the slow, weak gradients used in the early days of MRI, the strong, rapidly-switched gradients used in techniques such as EPI, fMRI, diffusion MRI, etc. are indeed capable of inducing PNR. American and European regulatory agencies insist that manufacturers stay below specified dB/dt limits (dB/dt is the change in field per unit time) or else prove (via clinical studies) that no PNR is induced for any imaging sequence. As a result of dB/dt limitation software and/or hardware, commercial MRI systems cannot use the full rated power of their gradient amplifiers.
• Acoustic noise: Loud noises and vibrations are produced by forces resulting from rapidly switched magnetic gradients interacting with the main magnetic field, in turn causing minute expansions and contractions of the coil itself. 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.

### Contrast agents

The most frequently used intravenous contrast agents are based on chelates of gadolinium. In general, these agents have proved safer than the iodinated contrast agents used in X-ray radiography or CT. Anaphylactoid reactions are rare occuring in approx 0.03-0.1%. <ref>Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR 1996; 167:847-849</ref>. Of particular interest is the lower incidence of nephrotoxicity, compared with iodinated agents, when given at usual doses - this has made contrast-enhanced MRI scanning an option for patients with renal impariment, who would otherwise not be able to undergo contrast-enhanced CT. <ref>"ACR guideline, 2005"</ref>

### Pregnancy

No 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.

### Claustrophobia

Due to the construction of MRI scanners they are potentially unpleasant to lie in. The part of the body being imaged needs to lie at the center of the magnet (which is often a long, narrow tube). Because scan times may be long, people with even mild claustrophobia may be unable to tolerate an MRI scan. Potential solutions may range from simple preparation (e.g. visiting the scanner to see the room and practice lying on the table), the use of open-bore design scanners, use of sedation or, for the most severe cases, general anesthesia.

### 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. The ACR White Paper on MR Safety is scheduled to be amended and updated on a biannual basis.

### The European Physical Agents Directive

The European Physical Agents (Electromagnetic Fields) Directive is European legislation that has been adopted in European legislature. By 2008 each individual state within the European Union must include this directive in its own law.

The directive applies to occupational exposure to electromagnetic fields (not medical exposure) and was intended to limit workers’ acute exposure to strong electromagnetic fields, as may be found near electricity substations, radio or television transmitters or industrial equipment. However, the regulations impact significantly on MRI, with separate sections of the regulations limiting exposure to static magnetic fields, changing magnetic fields and radio frequency energy. Field strength limits are given which may not be exceeded for any period of time. An employer may commit a criminal offence by allowing a worker to exceed an exposure limit if that is how the Directive is implemented in a particular Member State.

The Directive is based on the international consensus of established effects of exposure to electromagnetic fields, and in particular the advice of the European Commissions's advisor, the International Commission on Non-Ionizing Radiation Protection (ICNIRP). The aims of the Directive, and the ICNIRP guidelines upon which it is based, are to prevent exposure to potentially harmful fields. The actual limits in the Directive are very similar to the limits advised by the Institute of Electrical and Electronics Engineers, with the exception of the frequencies produced by the gradient coils, where the IEEE limits are significantly higher.

Many Member States of the EU already have either specific EMF regulations or (as in the UK) a general requirement under workplace health and safety legislation to protect workers against electromagnetic fields. In almost all cases the existing regulations are aligned with the ICNIRP limits so that the Directive should, in theory, have little impact on any employer already meeting their legal responsibilities.

The introduction of the Directive has brought to light an existing potential issue with occupational exposures to MRI fields. There are at present very few data on the number or types of MRI practice that might lead to expsoures in excess of the levels of the Directive. There is a justifiable concern amongst MRI practitioners that if the Directive were to be enforced more vigorously than existing legislation, the use of MRI might be restricted, or working practices of MRI personnel might have to change.

In the initial draft a limit of static field strength to 2 T was given. This has since been removed from the regulations, and whilst it is unlikely to be restored as it was without a strong justification, some restriction on static fields may be reintroduced after the matter has been considered more fully by ICNIRP. The effect of such a limit might be to restrict the installation, operation and maintenance of MRI scanners with magnets of 2 T and stronger. As the increase in field strength has been instrumental in developing higher resolution and higher performance scanners, this would be a significant step back. This is why it is unlikely to happen without strong justification.

Individual government agencies and the European Commission have now formed a working group to examine the implications on MRI and to try to address the issue of occupational exposures to electromagnetic fields from MRI.

## 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 magnetic resonance imaging". The Nobel Prize committee acknowledged Lauterbur's insight of using magnetic field gradients to introduce spatial localization, a discovery that allowed rapid acquisition of 2D images. Sir Peter Mansfield was credited with introducing the mathematical formalism and developing techniques for efficient gradient utilization and fast imaging.

###  Controversy

The 2003 Nobel Prize in Medicine award was vigorously protested by Raymond Vahan Damadian, who claimed that he was the inventor of MRI, and that Paul Lauterbur and Sir Peter Mansfield had merely refined the technology. Damadian, through his company Fonar took out full-page advertisements in New York Times' and The Washington Post, titled "The Shameful Wrong That Must Be Righted", demanding that he be awarded at least a share of the Nobel Prize.<ref>H.F. Judson, "No Nobel Prize for whining", New York Times, Oct 20, 2003. Accessed: Nov 02, 2006 </ref> . The Nobel Assembly at Karolinska Institutet, which picks the winner in medicine, refused to comment on Damadian's claims or change the awardees.

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 T1 differences between cancerous and normal tissue ex vivo. Damadian's first image did precede Lauterbur's first image, and it was of a clam dunked in Cope's contrast medium, deuterium oxide. However MR scanners currently used in medical practice, all rely on the gradient imaging technology published by Paul Lauterbur in his 1973, Nature paper.

In 1980, Damadian produced the first commercial MRI scanner, using a "focus-field" approach that involved repositioning the patient to image each pixel, which took much longer than the subsequence gradient encoded MRI and differed greatly from the non-commercial scanners that first Carr and then Lauterbur and Mansfield developed. The "focus-field" scanner failed to sell and was never used clinically. [3]

Some also say that the Nobel Prize also slighted the contributions of Herman Y Carr, who used magnetic field gradients to create 1D projections of NMR test tube samples. See Carr's letter to Physics Today.

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## 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 0-9619243-1-4.
• E. M. Haacke, R.W. Brown, M.L. Thompson, R. Venkatesan, Magnetic Resonance Imaging: Physical Principles and Sequence Design, John Wiley, 1999. ISBN 0-421-35128-8

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