Magnetic resonance imaging (MRI) is primarily used in medical imaging to visualise the structure and function of the body. It provides detailed images of the body in any plane. MR has much greater soft tissue contrast than CT making it especially useful in neurological, musculoskeletal, cardiovascular and oncolological diseases. Unlike CT it uses no ionizing radiation. The scanner creates a powerful magnetic field which aligns the magnetization of hydrogen atoms in the body. Radio waves are used to alter the alignment of this magnetization. This causes the hydrogen atoms to emit a weak radio signal which is amplified by the scanner. This signal can be manipulated by additional magnetic fields to build up enough information to reconstruct an image of the body.

Magnetic resonance spectroscopy is used to measure the levels of different metabolites in body tissues. The MR signal produces spectrum of difference resonances that correspond to different molecular arrangements of the isotope being "excited". This signature is used to diagnose certain metabolic disorders, especially those affecting the brain,^[1] as well as to provide information on tumor metabolism. ^[2]

The scanners used in medicine have a typical magnetic field strength of 0.2 to 3 teslas. Construction costs approximately US$ 1 million per tesla and maintenance an additional several hundred thousand dollars per year. Research using MRI scanners operating at ultra high field strength (up to 21.1 tesla) can produce images of the mouse brain with a resolution of 18 micrometres ^[3].

Background

Nomenclature

Magnetic resonance imaging was developed from knowledge gained in the study of nuclear magnetic resonance. In its early years MRI was referred to as nuclear magnetic resonance imaging (NMRI), but the word nuclear has been associated with ionizing radiation exposure, which is not used in an MRI, so to prevent patients from making a negative association between MRI and ionizing radiation, the word has been almost universally removed. Scientists still use the term NMRI when discussing non-medical devices operating on the same principles.

One of the inventors of MRI, Paul Lauterbur, originally named the technique zeugmatography, a Greek term meaning "that which is used for joining".^[4] The term referred to the interaction between the static and the gradient magnetic fields necessary to create an image, but the nomenclature never caught on.

Principle

Magnetism

Elementary subatomic particles such as protons have the quantum mechanical property of spin. If the number of nucleons within an isotope is even then there is no net spin. Nuclei such as ¹H or ³¹P which have an odd number of nucleons will have a non–zero spin and therefore a magnetic moment.

When these spins are placed in an external magnetic field they start to precess around the direction of that field. The magnetic field also creates two energy states that the protons can occupy which are separated by a quantum of energy. The thermal energy of the sample causes the molecules to tumble leaving only a very small excess of protons to cause magnetic polarization.

Resonance

The energy difference between the proton energy states corresponds to electromagnetic radiation at radio frequency wavelengths. Resonant absorption of energy by the protons due to an external oscillating magnetic field (radio wave) will occur at the Larmor frequency.

The net magnetization vector has two components. The longitudinal magnetization is due to an excess of protons in the higher energy state. This gives a net polarization antiparallel to the external field. The transverse magnetization is due to coherences forming between the two proton energy states. This gives a net polarization perpendicular to external field in the transverse plane. The recovery of longitudinal magnetization is called T1 relaxation and the loss of phase coherence in the transverse plane is called T2 relaxation.

When the radio frequency pulse is turned off, the transverse vector component produces an oscillating magnetic field which induces a small current in the receiver coil. This free induction decay (FID) lasts only a few milliseconds before the thermal equilibrium of the spins is restored. The actual signal that is measured by the scanner is formed by a refocusing gradient or radio wave to create a gradient or spin-echo.

Imaging

Slice selection is achieved by applying a magnetic gradient in addition to the external magnetic field during the radio frequency pulse. Only one plane within the object will have protons that are on–resonance and contribute to the signal.

A real image can be considered as being composed of a number of spatial frequencies at different orientations. A two–dimensional Fourier transformation of a real image will express these waves as a matrix of spatial frequencies known as k–space. Low spatial frequencies are represented at the center of k–space and high spatial frequencies at the periphery. Frequency and phase encoding are used to measure the amplitudes of a range of spatial frequencies within the object being imaged. The frequency encoding gradient is applied during readout of the signal and is orthogonal to the slice selection gradient. During application of the gradient the frequency differences in the readout direction progressively change. At the midpoint of the readout these differences are small and the low spatial frequencies in the image are sampled filling the center of k-space. Higher spatial frequencies will be sampled towards the beginning and end of the readout filling the periphery of k-space.

Phase encoding is applied in the remaining orthogonal plane and uses the same principle of sampling the object for different spatial frequencies. However, it is applied for a brief period before the readout and the strength of the gradient is changed incrementally between each radio frequency pulse. For each phase encoding step a line of k–space is filled.

Scanner construction and operation

The three systems described above form the major components of an MRI scanner: a static magnetic field, an RF transmitter and receiver, and three orthogonal, controllable magnetic gradients.

Magnet

The magnet is the largest and most expensive component of the scanner, and the remainder of the scanner is built around it. Just as important as the strength of the main magnet is its precision. The straightness of magnet lines within the center or, as it is known as, the iso-center of the magnet, need to be almost perfect. This is known as homogeneity. Fluctuations or, non-homogeneities in the field strength, within the scan region, should be less than three parts per million (3 ppm). Three types of magnet have been used:

• Permanent magnet: Conventional magnets made from ferromagnetic materials (e.g., steel) can be used to provide the static magnetic field. These are extremely bulky (the magnet can weigh in excess of 100 tonnes), but once installed require little costly maintenance. Permanent magnets can only achieve limited field strength (usually < 0.4 T) and have limited stability and precision. There are also potential safety issues, as the magnetic field cannot be removed in case of entrapment.
• Resistive electromagnet: A solenoid wound from copper wire is an alternative to a permanent magnet. The advantages are low cost, but field strength is limited, and stability is poor. The electromagnet requires considerable electrical energy during operation which can make it expensive to operate. This design is essentially obsolete.
• Superconducting electromagnet: When a niobium-titanium alloy is cooled by liquid helium at 4 K (−269 °C, −452 °F) it becomes superconducting where it loses all resistance to flow of electrical current. By building an electromagnet from superconducting wire, it is possible to develop extremely high field strengths, with very high stability. The construction of such magnets is extremely costly, and the cryogenic helium is expensive and difficult to handle. However, despite its cost, helium cooled superconducting magnets are the most common type found in MRI scanners today.

Most superconducting magnets have their coils of superconductive wire immersed in liquid helium, inside a vessel called a cryostat. Despite thermal insulation, ambient heat causes the helium to slowly boil off. Such magnets, therefore, require regular topping-up with helium. Generally a cryocooler, also known as a coldhead is used to recondense some helium vapor back into the liquid helium bath. Several manufacturers now offer 'cryogenless' scanners, where instead of being immersed in liquid helium the magnet wire is cooled directly by a cryocooler.

Magnets are available in a variety of shapes. However, permanent magnets are most frequently 'C' shaped, and superconducting magnets most frequently cylindrical. However, C-shaped superconducting magnets and box-shaped permanent magnets have also been used.

Magnetic field strength is an important factor determining image quality. Higher magnetic fields increase signal-to-noise ratio, permitting higher resolution or faster scanning. However, higher field strengths require more costly magnets with higher maintenance costs, and have increased safety concerns. 1.0 - 1.5 T field strengths are a good compromise between cost and performance for general medical use. However, for certain specialist uses (e.g., brain imaging), field strengths up to 3.0 T may be desirable.

RF system

The RF transmission system consists of a RF synthesizer, power amplifier and transmitting coil. This is usually built into the body of the scanner. The power of the transmitter is variable, but high-end scanners may have a peak output power of up to 35 kW, and be capable of sustaining average power of 1 kW. The receiver consists of the coil, pre-amplifier and signal processing system. While it is possible to scan using the integrated coil for transmitting and receiving, if a small region is being imaged then better image quality is obtained by using a close-fitting smaller coil. A variety of coils are available which fit around parts of the body, e.g., the head, knee, wrist, or internally, e.g., the rectum.

A recent development in MRI technology has been the development of sophisticated multi-element phased array coils which are capable of acquiring multiple channels of data in parallel. This 'parallel imaging' technique uses unique acquisition schemes that allow for accelerated imaging, by replacing some of the spatial coding originating from the magnetic gradients with the spatial sensitivity of the different coil elements. However the increased acceleration also reduces the signal-to-noise ratio and can create residual artifacts in the image reconstruction. Two frequently used parallel acquisition and reconstruction schemes are SENSE^[5] and GRAPPA^[6]. A detailed review of parallel imaging techniques can be found here: ^[7]

Gradients

Magnetic gradients are generated by three orthogonal coils, oriented in the x, y and z directions of the scanner. These are usually resistive electromagnets powered by sophisticated amplifiers which permit rapid and precise adjustments to their field strength and direction. Typical gradient systems are capable of producing gradients from 20 mT/m to 100 mT/m (i.e. in a 1.5 T magnet, when a maximal z-axis gradient is applied the field strength may be 1.45 T at one end of a 1 m long bore, and 1.55 T at the other). It is the magnetic gradients that determine the plane of imaging - because the orthogonal gradients can be combined freely, any plane can be selected for imaging.

Scan speed is dependent on performance of the gradient system. Stronger gradients allow for faster imaging, or for higher resolution; similarly, gradients systems capable of faster switching can also permit faster scanning. However, gradient performance is limited by safety concerns over nerve stimulation.

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 the material they are in. The realignment of nuclear spins with the magnetic field is termed longitudinal relaxation and the time required for a certain percentage of the tissue's nuclei to realign is termed "Time 1" or T1, which is typically about 1 second. T2-weighted imaging relies upon local dephasing of spins following the application of the transverse energy pulse; the transverse relaxation time is termed "Time 2" or T2, typically < 100 ms for tissue. 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) but provides 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; 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 iron-containing blood-degradation products), such sequences are utilized to detect subtle areas of recent or chronic intra cranial 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 the nerve connections of white matter to appear white, and the congregations of neurons of gray matter to appear gray, while cerebrospinal fluid appears 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*.

Diffusion weighted imaging (DWI) ^[8] 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. In a brain with an acute infarction water diffusion 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 works within 30 minutes of the ictus.

Contrast enhancement

Both T1-weighted and T2-weighted images are acquired for most medical examinations; However they do not always adequately show the anatomy or pathology. The first option is to use a more sophisticated image acquisition technique such as fat suppression or chemical-shift imaging.^[9] 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 although substances with specific magnetic properties may be used. Most commonly, a paramagnetic contrast agent (usually a gadolinium compound^[10][11]) 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 hemodialysis following a contrast MRI scan for renally-impaired patients.

More recently, superparamagnetic contrast agents (e.g. iron oxide nanoparticles^[12][13]) have become available. These agents appear very dark on T2*-weighted images and 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 visualization of the gastrointestinal tract, and to prevent water in the gastrointestinal tract from obscuring other organs (e.g. pancreas).

Diamagnetic agents such as barium sulfate have been studied for potential use in the gastrointestinal tract, but are less frequently used.

MRI vs CT

A computed tomography (CT) scanner uses X-rays, a type of ionizing radiation, to acquire its images, making it a good tool for examining tissue composed of elements of a relatively higher atomic number than the tissue surrounding them, such as bone and calcifications (calcium based) within the body (carbon based flesh), or of structures (vessels, bowel). MRI, on the other hand, uses non-ionizing radio frequency (RF) signals to acquire its images and is best suited for non-calcified tissue.

CT may be enhanced by use of contrast agents containing elements of a higher atomic number than the surrounding flesh such as iodine or barium. Contrast agents for MRI are those which have paramagnetic properties. One example is gadolinium.

Both CT and MRI scanners can generate multiple two-dimensional cross-sections (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 detect different features. (See Application below.)

MRI can generate cross-sectional images in any plane (including oblique planes). CT was limited to acquiring images in the axial (or near axial) plane in the past. The scans used to be called Computed Axial Tomography scans (CAT scans). However, the development of multi-detector CT scanners with near-isotropic resolution, allows the CT scanner to produce data that can be retrospectively reconstructed in any plane with minimal loss of image quality.

For purposes of tumor detection and identification, MRI is generally superior.^[14][15][16] However, CT usually is more widely available, faster, much less expensive, and may be less likely to require the person to be sedated or anesthetized.

MRI is also best suited for cases when a patient is to undergo the exam several times successively in the short term, because, unlike CT, it does not expose the patient to the hazards of ionizing radiation.

The k-space formalism

In 1983 Ljunggren^[17] and Tweig^[18] 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 freely precessing nuclear spins in the presence of a linear magnetic field gradient G equals the Fourier transform of the effective spin density i.e.

where:

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 corrected for the effects of T₁ preparation, T₂ 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 RF probe.

From the basic k-space formula, it follows immediately that we reconstruct an image simply by taking the inverse Fourier transform of the sampled data viz.

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 in 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 alternating 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 T₂ 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 T₂ and T₂ * 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 and 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.

(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 thought to be 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 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.^[19] 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 demyelination 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 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) cytoplasmic 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 hemorrhagic 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

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, see also FLASH MRI. 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

In vivo ('in the living organism') 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 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, how much fat or water is present, relative to those of surrounding regions). MR spectroscopy, however, provides a wealth of information about other biological chemicals ('metabolites') within 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 T2* changes^[20]; this mechanism is referred to as 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 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 preclinical 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

The lack of harmful effects on the patient and the operator make MRI well-suited for "interventional radiology", where the images produced by a MRI scanner are used to guide minimally-invasive procedures.

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 (CDI) endeavors to use the phase information from 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, but 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, fluorine-19, 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 such as ³He or ¹²⁹Xe must be hyperpolarized and then inhaled as their nuclear density is too low to yield a useful signal under normal conditions. ¹⁷O, ¹³C and ¹⁹F can be administered in sufficient quantities in liquid form (e.g. ¹⁷O-water, ¹³C-glucose solutions or perfluorocarbons) 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.

Experimental MRI techniques

Currently there is active research in several new MRI technologies like magnetization transfer MRI (MT-MRI), diffusion tensor MRI (DT-MRI), and proton MR spectroscopy, plus recent research in to Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure.

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 arrhythmia 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.

Though pacemakers receive significant attention, it should also be noted that many other forms of medical or biostimulation implants may be contraindicated for MRI scans. These may include Vagus nerve stimulators, implantable cardioverter-defibrillators (ICD), loop recorders, insulin pumps, cochlear implants, deep brain stimulators and many others. Medical device patients should always present complete information (manufacturer, model, serial number and date of implantation) about all implants to both the referring physician and to the radiologist or technologist before entering the room for the MRI scan.

While these implants pose a current problem, scientist are working on a nano coating for implants. This will screen the implants from the radio frequency waves and thus patients with future implants will be able to use MRI scanners. The current article for this is from New Scientist.

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 radio frequency 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 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. Much research and development is being undertaken, and many tools are being developed in order to predict the effects of the RF fields inside the body.

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.^[21] 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. A video of what happens when a ferromagnetic bottle of oxygen enters the vicinity of an MRI magnet can be viewed here [2], the bottle is violently sucked into the bore of the magnet and oscillates rapidly in midair until coming to rest at the center.
• 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 occurring in approx 0.03-0.1%.^[22] 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 impairment, who would otherwise not be able to undergo contrast-enhanced CT.^[23]

Although gadolinium agents have proved useful for patients with renal impairment, in patients with severe renal failure requiring dialysis there is a risk of a rare but serious illness, nephrogenic systemic fibrosis, that may be linked to the use of certain gadolinium-containing agents: the most frequently linked is gadodiamide, but other agents have been linked too.^[24] Although a causal link has not been definitively established, current guidelines in the United States are that dialysis patients should only receive gadolinium agents where essential, and that dialysis should be performed as soon as possible after the scan is complete, in order to remove the agent from the body promptly.^[25] In Europe where more gadolinium-containing agents are available, a classification of agents according to potential risks has been released.^[26][27]

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 congenital defects of the fetus because it can provide more diagnostic information than ultrasound and it lacks the ionizing radiation of CT. MRI without contrast is the imaging mode of choice for pre-surgical, in-utero diagnosis and evaluation of fetal tumors, primarily teratomas, facilitating open fetal surgery, other fetal interventions, and planning for procedures (such as the EXIT procedure) to safely deliver and treat babies whose defects would otherwise be fatal.

Claustrophobia and discomfort

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 (perhaps one hour), people with even mild claustrophobia are often unable to tolerate an MRI scan without management.

Management may include:

• Advance preparation
  • visiting the scanner to see the room and practice lying on the table
  • visualization techniques
  • chemical sedation
  • general anesthesia
• Coping while inside the scanner
  • holding a "panic button"
  • listening to music on headphones or watching a movie with a Head-mounted display while in the machine
• Modified scanner designs
  • open-bore design scanners.

Though open MRIs have increased in popularity as of late, they produce inferior scan quality because they operate at lower magnetic fields than closed MRIs.

·          

• upright MRIs (made exclusively by FONAR)

For babies and children, chemical sedation or general anesthesia are the norm. These MRI subjects are too young to be instructed to hold still during the scanning session. Obese patients and pregnant women may find the MRI machine to be a tight fit, and even some claustrophobics may find the experience intolerable without sedation. Pregnant women may also have difficulty lying on their back without moving for an hour or more.

The noise associated with the operation of an MRI scanner (especially the audible noise associated with the gradient pulses applied to the subject) can also exacerbate the discomfort associated with the procedure.

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 has been rewritten and was released early in 2007 under th