Magnetic resonance imaging

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Magnetic resonance imaging (MRI), formerly referred to as magnetic resonance tomography (MRT) and, in scientific circles, nuclear magnetic resonance imaging (NMRI) or NMR zeugmatography imaging, is a non-invasive method used to render images of the inside of an object. It is primarily used in medical imaging to demonstrate pathological or other physiological alterations of living tissues. MRI also has uses outside of the medical field, such as detecting rock permeability to hydrocarbons and as a non-destructive testing method to characterize the quality of products such as produce and timber.^[1]

MRI should not be confused with the NMR spectroscopy technique used in chemistry, although both are based on the same principles of nuclear magnetic resonance.

The scanners used in medicine have a typical magnetic field strength of 0.3 to 3 teslas. Construction costs approximately US$ 1 million per tesla, and maintenance an additional several hundred thousand dollars per year.

Contents

• 1 Background
  • 1.1 MRI vs CT
  • 1.2 Image formation
  • 1.3 Scanner construction and operation
    • 1.3.1 Magnet
    • 1.3.2 RF system
    • 1.3.3 Gradients
    • 1.3.4 Contrast enhancement
• 2 The k-space formalism
• 3 Application
  • 3.1 Specialized MRI scans
    • 3.1.1 Diffusion MRI
    • 3.1.2 Magnetic resonance angiography
    • 3.1.3 Magnetic resonance spectroscopy
    • 3.1.4 Functional MRI
    • 3.1.5 Interventional MRI
    • 3.1.6 Radiation therapy simulation
    • 3.1.7 Current density imaging
    • 3.1.8 Magnetic resonance guided focused ultrasound
    • 3.1.9 Multinuclear imaging
    • 3.1.10 Experimental MRI techniques
• 4 Safety
  • 4.1 Contrast agents
  • 4.2 Pregnancy
  • 4.3 Claustrophobia and discomfort
  • 4.4 Guidance
  • 4.5 The European Physical Agents Directive
• 5 2003 Nobel Prize
  • 5.1 Controversy
• 6 Footnotes
• 7 See also
• 8 References
• 9 External links

[edit] Background

[edit] 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 tissuecomposed of elements of a relatively higher atomic number than thetissue surrounding them, such as bone and calcifications (calciumbased) 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 agentscontaining elements of a higher atomic number than the surroundingflesh (iodine, barium). Contrast agents for MRI are those which have paramagnetic properties. One example is gadolinium.

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

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

For purposes of tumor detection and identification, MRI is generally superior^[2][3][4].However, CT usually is more widely available, faster, much lessexpensive, and may be less likely to require the person to be sedatedor anesthetized.

[edit] Image formation

In order to selectively image different voxels (volume picture elements) of the subject, orthogonalmagnetic gradients are applied. Although it is relatively common toapply gradients in the principal axes of a patient (so that the patientis imaged in x, y, and z from head to toe), MRI allows completelyflexible orientations for images. All spatial encoding is obtained byapplying magnetic field gradients which encode position within thephase of the signal. In one dimension, a linear phase with respect toposition can be obtained by collecting data in the presence of amagnetic field gradient. In three dimensions (3D), a plane can bedefined by "slice selection", in which an RF pulse of defined bandwidthis applied in the presence of a magnetic field gradient in order toreduce spatial encoding to two dimensions (2D). Spatial encoding canthen be applied in 2D after slice selection, or in 3D without sliceselection. Spatially-encoded phases are recorded in a 2D or 3D matrix; this data represents the spatial frequencies of the image object. Images can be created from the matrix using the discrete Fourier transform (DFT). Typical medical resolution is about 1 mm³, while research models can exceed 1 µm³.

[edit] Scanner construction and operation

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

[edit] Magnet

The magnet is the largest and most expensive component of thescanner, and the remainder of the scanner is built around the magnet.Just as important as the strength of the main magnet is its precision.The straightness of flux lines within the centre or, as it is known as,the iso-centre of the magnet, need to be almost perfect. This is knownas homogeneity. Fluctuations or, non-homogeneities in the fieldstrength, within the scan region, should be less than threeparts-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 4K (-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 slowlyboil off. Such magnets, therefore, require regular topping-up withhelium. Generally a Cryocooler,also known as a Coldhead is used to recondense some helium vapour backinto the liquid helium bath. Several manufacturers now offer‘cryogenless‘ scanners, where instead of being immersed in liquidhelium the magnet wire is cooled directly by a cryocooler.

Magnets are available in a variety of shapes. However, permanentmagnets are most frequently ‘C‘ shaped, and superconducting magnetsmost frequently cylindrical. However, C-shaped superconducting magnetsand 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 fieldstrengths require more costly magnets with higher maintenance costs,and have increased safety concerns. 1.0 - 1.5 T field strengths are agood compromise between cost and performance for general medical use.However, for certain specialist uses (e.g., brain imaging) then fieldstrengths up to 3.0T may be desirable.

[edit] RF system

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

A recent development in MRI technology has been the development of sophisticated multi-element phased arraycoils which are capable of acquiring multiple channels of data inparallel. This ‘parallel imaging‘ technique uses unique acquisitionschemes that allow for accelerated imaging, by replacing some of thespatial coding originating from the magnetic gradients with the spatialsensitivity of the different coil elements. However the increasedacceleration also reduces SNR and can create residual artifacts in theimage reconstruction. Two frequently used parallel acquisition andreconstruction schemes are SENSE^[5] and GRAPPA^[6]. A detailed review of parallel imaging techniques can be found here: ^[7]

[edit] Gradients

Magnetic gradients are generated by three orthogonal coils, orientedin the x, y and z directions of the scanner. These are usuallyresistive electromagnets powered by sophisticated amplifiers whichpermit rapid and precise adjustments to their field strength anddirection. Typical gradient systems are capable of producing gradientsfrom 20 mT/m to 100 mT/m (i.e. in a 1.5 T magnet, when a maximal z-axisgradient is applied the field strength may be 1.45 T at one end of a 1mlong bore, and 1.55 T at the other). It is the magnetic gradients thatdetermine the plane of imaging - because the orthogonal gradients canbe 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 permitfaster scanning. However, gradient performance is limited by safetyconcerns over nerve stimulation.

In order to understand MRI contrast, it is important to have some understanding of the time constantsinvolved in relaxation processes that establish equilibrium followingRF excitation. As the high-energy nuclei relax and realign they emitenergy at rates which are recorded to provide information about thematerial they are in. The realignment of nuclear spins with themagnetic 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 echotechnique, in which spins are refocused to compensate for localmagnetic field inhomogeneities. T2* imaging is performed withoutrefocusing. This sacrifices some image integrity (resolution)but provides additional sensitivity to relaxation processes that causeincoherence of transverse magnetization. Applications of T2* imaginginclude functional MRI (fMRI) or evaluation of baseline vascular perfusion (e.g. cerebral blood flow(CBF)) and cerebral blood volume (CBV) using injected agents; in thesecases, there is an inherent trade-off between image quality anddetection 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 intracranial hemorrhage ("Heme sequence").

Image contrast is created by using a selection of image acquisitionparameters that weights signal by T1, T2 or T2*, or no relaxation time("proton-density images"). In the brain, T1-weighting causes the nerveconnections of white matter to appear white, and the congregations of neurons of gray matter to appear gray, while cerebrospinal fluidappears dark. The contrast of "white matter," "gray matter‘" and"cerebrospinal fluid" is reversed using T2 or T2* imaging, whereasproton-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 (diffusiongradients) rapidly turned on and off. Protons from water diffusingrandomly 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 diffusionis impaired, and signal loss on DWI sequences is less than in normalbrain. DWI is the most sensitive method of detecting cerebralinfarction (stroke) and works within 30 minutes of the ictus.

[edit] Contrast enhancement

Both T1-weighted and T2-weighted images are acquired for mostmedical examinations; However they do not always adequately show the anatomyor pathology. The first option is to use a more sophisticated imageacquisition 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 althoughsubstances with specific magnetic properties may be used. Mostcommonly, a paramagnetic contrast agent (usually a gadolinium compound^[10][11])is given. Gadolinium-enhanced tissues and fluids appear extremelybright on T1-weighted images. This provides high sensitivity fordetection of vascular tissues (e.g. tumors) and permits assessment ofbrain perfusion (e.g. in stroke). There have been concerns raisedrecently regarding the toxicity of gadolinium-based contrast agents andtheir impact on persons with impaired kidney function. Special actionsmay 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 livertissue retains the agent, but abnormal areas (e.g. scars, tumors) donot. 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 such as barium sulfate have been studied for potential use in the gastrointestinal tract, but are less frequently used.

[edit] The k-space formalism

See main article K-space

In 1983 Ljunggren^[14] and Tweig^[15]independently introduced the k-space formalism, a technique that provedinvaluable in unifying different MR imaging techniques. They showedthat 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 atrajectory in k-space with the velocity vector of the trajectoryproportional to the vector of the applied magnetic field gradient. Bythe term effective spin density we mean the true spin density corrected for the effects of T₁ preparation, T₂decay, dephasing due to field inhomogeneity, flow, diffusion, etc. andany other phenomena that affect that amount of transverse magnetizationavailable 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 ideasbecome simple. For example, it becomes very easy to understand the roleof phase encoding (the so-called spin-warp method). In a standard spinecho or gradient echo scan, where the readout (or view) gradient isconstant (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_xaxis. When a non-zero phase-encoding pulse is added in between the RFexcitation and the commencement of the readout gradient, this linemoves 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 differentscanning techniques. In single-shot EPI, all of k-space is scanned in asingle shot, following either a sinusoidal or zig-zag trajectory. Sincealternate lines of k-space are scanned in opposite directions, thismust be taken into account in the reconstruction. Multi-shot EPI andfast spin echo techniques acquire only part of k-space per excitation.In each shot, a different interleaved segment is acquired, and theshots are repeated until k-space is sufficiently well-covered. Sincethe data at the center of k-space represent lower spatial frequenciesthan 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 imagecontrast can be exploited in more advanced imaging techniques. One suchtechnique is spiral acquisition - a rotating magnetic field gradient isapplied, causing the trajectory in k-space to trace out spiral out fromthe center to the edge. Due to T₂ and T₂ *decay the signal is greatest at the start of the acquisition, henceacquiring the center of k-space first improves contrast to noise ratio(CNR) when compared to conventional zig-zag acquisitions, especially inthe presence of rapid movement.

Since and are conjugate variables (with respect to the Fourier transform) we can use the Nyquist theoremto show that the step in k-space determines the field of view of theimage (maximum frequency that is correctly sampled) and the maximumvalue of k sampled determines the resolution i.e.

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

[edit] 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 harmlessto the patient. It uses strong magnetic fields and non-ionizingradiation 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 smalldistance from each other as separate), MRI provides comparableresolution with far better contrast resolution(the ability to distinguish the differences between two arbitrarilysimilar but not identical tissues). The basis of this ability is thecomplex 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 willtake on the property of T2-weighting. On a T2-weighted scan, fat-,water- and fluid-containing tissues are bright (most modern T2sequences are actually fast T2 sequences). Damaged tissue tends to develop edema,which makes a T2-weighted sequence sensitive for pathology, andgenerally able to distinguish pathologic tissue from normal tissue.With the addition of an additional radio frequency pulse and additionalmanipulation of the magnetic gradients, a T2-weighted sequence can beconverted to a FLAIRsequence, in which free water is now dark, but edematous tissues remainbright. This sequence in particular is currently the most sensitive wayto evaluate the brain for demyelinating diseases, such as multiple sclerosis.

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

[edit] Specialized MRI scans

[edit] Diffusion MRI

Diffusion MRI measures the diffusion of water molecules in biological tissues.^[16] 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 myelinmembrane. Therefore the molecule will move principally along the axisof the neural fiber. If we know that molecules in a particular voxeldiffuse principally in one direction we can make the assumption thatthe majority of the fibers in this area are going parallel to thatdirection.

The recent development of diffusion tensor imaging(DTI) enables diffusion to be measured in multiple directions and thefractional anisotropy in each direction to be calculated for eachvoxel. This enables researchers to make brain maps of fiber directionsto 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 (MoseleyME et al., Magn Reson Med 1990;14:330–346). It is speculated thatincreases in restriction (barriers) to water diffusion, as a result ofcytotoxic edema (cellular swelling), is responsible for the increase insignal on a DWI scan. Other theories, including acute changes incellular permeability and loss of energy-dependent (ATP) cytoplasticstreaming, have been proposed to explain the phenomena. The DWIenhancement 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 4-6hours) and remains for up to two weeks. CT, due to its insensitivity toacute 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 todetect minute changes in extracellular water diffusion and thereforecould be used as a tool for fMRI. The nerve cell body enlarges when itconducts an action potential, hence restricting extracellular watermolecules from diffusing naturally. Although this process works intheory, 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.

[edit] 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 toevaluate the arteries of the neck and brain, the thoracic and abdominalaorta, the renal arteries, and the legs (called a "run-off"). A varietyof techniques can be used to generate the pictures, such asadministration of a paramagnetic contrast agent (gadolinium) or using atechnique known as "flow-related enhancement" (e.g. 2D and 3Dtime-of-flight sequences), where most of the signal on an image is dueto blood which has recently moved into that plane, see also FLASH MRI.Magnetic resonance venography (MRV) is a similar procedure that is usedto image veins. In this method the tissue is now excited inferiorlywhile signal is gathered in the plane immediately superior to theexcitation plane, and thus imaging the venous blood which has recentlymoved from the excited plane.

[edit] 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-richinformation obtainable from NMR. That is to say, MRI allows one tostudy a particular region within an organism or sample, but givesrelatively little information about the chemical or physical nature ofthat region--its chief value is in being able to distinguish theproperties of that region relative to those of surrounding regions. MRspectroscopy, however, provides a wealth of chemical information aboutthat region, as would an NMR spectrum of that region.

[edit] Functional MRI

Main article: Functional magnetic resonance imaging

Functional MRI (fMRI) measures signal changes in the brain that are due to changing neuralactivity. The brain is scanned at low resolution but at a rapid rate(typically once every 2-3 seconds). Increases in neural activity causechanges in the MR signal via T2* changes^[17]; 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(haemoglobin) relative to deoxygenated hemoglobin. Because deoxygenatedhemoglobin attenuates the MR signal, the vascular response leads to asignal increase that is related to the neural activity. The precisenature of the relationship between neural activity and the BOLD signalis a subject of current research. The BOLD effect also allows for thegeneration of high resolution 3D maps of the venous vasculature withinneural tissue.

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

[edit] Interventional MRI

Main article: Interventional MRI

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

[edit] Radiation therapy simulation

Because of MRI‘s superior imaging of soft tissues, it is now beingutilized to specifically locate tumors within the body in preparationfor radiation therapy treatments. For therapy simulation, a patient isplaced in specific, reproducible, body position and scanned. The MRIsystem then computes the precise location, shape and orientation of thetumor mass, correcting for any spatial distortion inherent in thesystem. The patient is then marked or tattooed with points which, whencombined with the specific body position, will permit precisetriangulation for radiation therapy.

[edit] Current density imaging

Current density imaging(CDI) endeavors to use the phase information from images to reconstructcurrent densities within a subject. Current density imaging worksbecause electrical currents generate magnetic fields, which in turnaffect the phase of the magnetic dipoles during an imaging sequence. Todate no successful CDI has been performed using biological currents,but several studies have been published which involve applied currentsthrough a pair of electrodes.

[edit] Magnetic resonance guided focused ultrasound

In MRgFUStherapy, ultrasound beams are focused on a tissue - guided andcontrolled using MR thermal imaging - and due to the significant energydeposition at the focus, temperature within the tissue rises to morethan 65°C, completely destroying it. This technology can achieve precise "ablation"of diseased tissue. MR imaging provides a three-dimensional view of thetarget tissue, allowing for precise focusing of ultrasound energy. TheMR imaging provides quantitative, real-time, thermal images of thetreated area. This allows the physician to ensure that the temperaturegenerated during each cycle of ultrasound energy is sufficient to causethermal ablation within the desired tissue and if not, to adapt theparameters to ensure effective treatment.

[edit] Multinuclear imaging

Hydrogen is the most frequently imaged nucleus in MRI because it ispresent in biological tissues in great abundance. However, any nucleuswhich has a net nuclear spin could potentially be imaged with MRI. Suchnuclei 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 imagingof 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.

[edit] Experimental MRI techniques

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

[edit] Safety

Implants and foreign bodies: Pacemakers are generally considered an absolute contraindicationtowards MRI scanning, though highly specialized protocols have beendeveloped to permit scanning of select pacing devices. Several cases ofarrhythmiasor death have been reported in patients with pacemakers who haveundergone MRI scanning without appropriate precautions. Otherelectronic implants have varying contraindications, depending uponscanner technology, implant properties, scanning protocols and anatomybeing imaged.

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

While these implants pose a current problem, scientist are workingon a nano coating for implants. This will screen the implants from theradio frequency waves and thus patients with future implants will beable to use MRI scanners. The current article for this is from the new scientist.

Ferromagnetic foreign bodies (e.g. shell fragments), or metallic implants (e.g. surgical prostheses, aneurysmclips) are also potential risks, and safety aspects need to beconsidered on an individual basis. Interaction of the magnetic andradiofrequency fields with such objects can lead to: trauma due tomovement of the object in the magnetic field, thermal injury fromradio-frequency induction heatingof the object, or failure of an implanted device. These issues areespecially problematic when dealing with the eye. Most MRI centersrequire an orbital x-raybe performed on anyone who suspects they may have small metal fragmentsin their eyes, perhaps from a previous accident, something not uncommonin 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 themagnetic field, but artifacts around the implant are less frequent andless severe than with more ferromagnetic materials e.g. stainlesssteel. Artifacts from metal frequently appear as regions of empty spacearound the implant - frequently called ‘black-hole artifact‘ e.g. a 3mmtitanium alloy coronary stent may appear as a 5mm diameter region ofempty space on MRI, whereas around a stainless steel stent, theartifact may extend for 10-20 mm or more.

In 2006, a new classification system for implants and ancillaryclinical devices has been developed by ASTM International and is nowthe 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 ofthe primary potential threats during an MRI procedure.

MR-Conditional: A device or implant that may containmagnetic, electrically conductive or RF-reactive components that issafe for operations in proximity to the MRI, provided the conditionsfor safe operation are defined and observed (such as ‘tested safe to1.5 teslas‘ or ‘safe in magnetic fields below 500 gauss in strength‘).

MR-Unsafe: Nearly self-explanatory, this category isreserved for objects that are significantly ferromagnetic and pose aclear and direct threat to persons and equipment within the magnet room.

In the case of pacemakers, the risk is thought to be primarily RFinduction in the pacing electrodes/wires causing inappropriate pacingof the heart, rather than the magnetic field affecting the pacemakeritself. Much research and development is being undertaken, and manytools are being developed in order to predict the effects of the RFfields 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.^[18] 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 [1], 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.

[edit] 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 contrastagents used in X-ray radiography or CT. Anaphylactoid reactions arerare occurring in approx 0.03-0.1%. ^[19].Of particular interest is the lower incidence of nephrotoxicity,compared with iodinated agents, when given at usual doses—this has madecontrast-enhanced MRI scanning an option for patients with renalimpairment, who would otherwise not be able to undergocontrast-enhanced CT. ^[20]

Although gadolinium agents have proved useful for patients withrenal impairment, there has been a newly identified risk described inpatients with severe renal failure requiring dialysis. A rare, butserious, illness affecting dialysis patients, nephrogenic systemic fibrosis,has been linked to the use of certain gadolinium containing agents: themost frequently associated is gadodiamide (Omniscan™, GE healthcare);association with some other agents has been reported. ^[21]Although a causal link has not been definitively established, currentguidelines are that dialysis patients should only receive gadoliniumagents 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. ^[22]

[edit] 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 whenessential. This is particularly the case during the first trimester ofpregnancy, as organogenesistakes place during this period. The concerns in pregnancy are the sameas for MRI in general, but the fetus may be more sensitive to theeffects—particularly to heating and to noise. However, one additionalconcern 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 away of diagnosing and monitoring disease of the fetus because it canprovide more diagnostic information than ultrasoundwithout the use of ionizing radiation. MRI is the imaging mode ofchoice for 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 babies who have defects otherwise incompatible with life.

[edit] Claustrophobia and discomfort

Due to the construction of MRI scanners, they are potentiallyunpleasant to lie in. The part of the body being imaged needs to lie atthe center of the magnet (which is often a long, narrow tube). Becausescan times may be long (perhaps one hour), people with even mild claustrophobiaare often unable to tolerate an MRI scan. Potential solutions rangefrom simple preparation (e.g., visiting the scanner to see the room andpractice lying on the table), watching DVDs with a Head-mounted displaywhile in the machine, the use of open-bore design scanners, uprightMRIs (made exclusively by FONAR), the use of sedation, or, for the mostsevere cases, general anesthesia.

The noise associated with the operation of an MRI scanner(especially the audible noise associated with the radio frequencypulses applied to the subject) can also exacerbate the discomfortassociated with the procedure.

[edit] Guidance

Safety issues, including the potential for biostimulation deviceinterference, movement of ferromagnetic bodies, and incidentallocalized 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 the new title ACR Guidance Document for Safe MR Practices.

[edit] The European Physical Agents Directive

The European Physical Agents (Electromagnetic Fields) Directive isEuropean legislation that has been adopted in European legislature. By2008 each individual state within the European Union must include thisdirective in its own law.

The directive applies to occupational exposure to electromagneticfields (not medical exposure) and was intended to limit workers’ acuteexposure to strong electromagnetic fields, as may be found nearelectricity substations, radio or television transmitters or industrialequipment. However, the regulations impact significantly on MRI, withseparate sections of the regulations limiting exposure to staticmagnetic fields, changing magnetic fields and radio frequency energy.Field strength limits are given which may not be exceeded for anyperiod of time. An employer may commit a criminal offence by allowing aworker to exceed an exposure limit if that is how the Directive isimplemented in a particular Member State.

The Directive is based on the international consensus of establishedeffects of exposure to electromagnetic fields, and in particular theadvice of the European Commissions‘s advisor, the InternationalCommission on Non-Ionizing Radiation Protection (ICNIRP). The aims ofthe Directive, and the ICNIRP guidelines upon which it is based, are toprevent exposure to potentially harmful fields. The actual limits inthe Directive are very similar to the limits advised by the Instituteof Electrical and Electronics Engineers, with the exception of thefrequencies produced by the gradient coils, where the IEEE limits aresignificantly higher.

Many Member States of the EU already have either specific EMFregulations or (as in the UK) a general requirement under workplacehealth and safety legislation to protect workers againstelectromagnetic fields. In almost all cases the existing regulationsare aligned with the ICNIRP limits so that the Directive should, intheory, have little impact on any employer already meeting their legalresponsibilities.

The introduction of the Directive has brought to light an existingpotential issue with occupational exposures to MRI fields. There are atpresent very few data on the number or types of MRI practice that mightlead to exposures in excess of the levels of the Directive. There is ajustifiable concern amongst MRI practitioners that if the Directivewere to be enforced more vigorously than existing legislation, the useof MRI might be restricted, or working practices of MRI personnel mighthave to change.

In the initial draft a limit of static field strength to 2 T wasgiven. This has since been removed from the regulations, and whilst itis unlikely to be restored as it was without a strong justification,some restriction on static fields may be reintroduced after the matterhas been considered more fully by ICNIRP. The effect of such a limitmight be to restrict the installation, operation and maintenance of MRIscanners with magnets of 2 T and stronger. As the increase in fieldstrength has been instrumental in developing higher resolution andhigher 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 nowformed a working group to examine the implications on MRI and to try toaddress the issue of occupational exposures to electromagnetic fieldsfrom MRI.

[edit] 2003 Nobel Prize

Reflecting the fundamental importance and applicability of MRI in the medical field, Paul Lauterbur and Sir Peter Mansfield of the University of Illinois, Urbana-Champaign and University of Nottingham were awarded the 2003 Nobel Prize in Medicine or Physiologyfor their "discoveries concerning magnetic resonance imaging". TheNobel Prize committee acknowledged Lauterbur‘s insight of usingmagnetic field gradients to introduce spatial localization, a discoverythat allowed rapid acquisition of 2D images. Sir Peter Mansfield wascredited with introducing the mathematical formalism and developingtechniques for efficient gradient utilization and fast imaging.

[edit] 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 entitled "The Shameful Wrong That Must Be Righted", demanding that he be awarded at least a share of the Nobel Prize. ^[23] 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) creditDamadian with describing the concept of whole-body NMR scanning, aswell 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 wasof a claim dunked in Cope‘s contrast medium, deuterium oxide. However,Damadian‘s scanner neither included the fundamental concept of afrequency-encoding magnetic field gradient, which encodes theone-dimensional intensity projection of an object in such a way that itmay be recovered by a simple Fourier transformation, nor did hedescribe a technique for true two-dimensional imaging. Instead,Damadian‘s idea of a scanner was designed to map an object sequentiallypoint by point. MR scanners currently used in medical and non-medicalpractice all rely on the gradient imaging technology first published byPaul 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 imageeach pixel, which took much longer than the gradient encoded MRImethods and differed greatly from the non-commercial scanners thatfirst Carr and then Lauterbur and Mansfield developed. The"focus-field" scanner failed to sell and was never used clinically. [2]

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.

The contribution by John Mallard and colleagues at the University of Aberdeen,who developed the spin-warp technology, as well as producing the firstclinically useful images in patients, is also often overlooked. ^{[24] [25] [26]}

[edit] Footnotes

1. ^ http://www.mri.cl/index.pl/industrial_stud#355
2. ^ Magnetic resonance and computerized tomography of posterior cranial fossa tumors in childhood. Differential diagnosis and assessment of lesion extent][Article in Italian] Colosimo C, Celi G, Settecasi C, Tartaglione T, Di Rocco C, Marano P. (1995) Radiol Med (Torino) 90(4):386-395
3. ^ The clinical and radiological evaluation of primary brain neoplasms in children, Part II: Radiological evaluation. Allen ED, Byrd SE, Darling CF, Tomita T, Wilczynski MA. (1993) J Natl Med Assoc. 85(7):546-553
4. ^ Computed tomography versus magnetic resonance imaging of the brain. A collaborative interinstitutional study. Deck MD, Henschke C, Lee BC, Zimmerman RD, Hyman RA, Edwards J, Saint Louis LA, Cahill PT, Stein H, Whalen JP. (1989) Clin Imaging 13(1):2-15
5. ^ Pruessmann KP, Weiger M, Scheidegger MB, Boesiger P. "SENSE: sensititivy encoding for fast MRI." Magn Reson Med. 1999 Nov;42(5):952-62. PMID 10542355
6. ^ Griswold MA, Jakob PM, Heidemann RM, Nittka M, Jellus V, Wang J, Kiefer B, Haase A. "Generalized autocalibrating partially parallel acquisitions (GRAPPA)." Magn Reson Med. 2002 Jun;47(6):1202-10. PMID 12111967
7. ^ http://cfmriweb.ucsd.edu/ttliu/be280a_05/blaimer05.pdf
8. ^ Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology. 1986 Nov;161(2):401-7 PMID 3763909
9. ^ Haase A., Frahm J., Hanicke W., Matthaei D. "¹H NMR chemical shift selective (CHESS) imaging." Phys Med Biol. 1985 Apr;30(4):341-4. PMID 4001160
10. ^ Weinmann HJ, Brasch RC, Press WR, Wesbey GE. "Characteristics of gadolinium-DTPA complex: a potential NMR contrast agent." AJR Am J Roentgenol. 1984 Mar;142(3):619-24. PMID 6607655
11. ^ Laniado M, Weinmann HJ, Schorner W, Felix R, Speck U. "First use of GdDTPA/dimeglumine in man." Physiol Chem Phys Med NMR. 1984;16(2):157-65. PMID 6505042
12. ^ Widdler DJ, Greif WL, Widdler KJ, Edelman RR, Brady TJ. "Magnetite Albumin Microspheres: A New MR Contrast Material." AJR Am J Roentgenol. 1987;148(2):399-404. PMID 3492120
13. ^ Weissleder R, Elizondo G, Wittenberg J, Rabito CA, Bengele HH, Josephson L. "Ultrasmall Superparamagnetic Iron Oxide: Characterization of a New Class of Contrast Agents for MR Imaging." Radiology. 1990;175(2):489-93. PMID 2326474
14. ^ Ljunggren S. J Magn Reson 1983; 54:338.
15. ^ Twieg D (1983). "The k-trajectory formulation of the NMR imaging process with applications in analysis and synthesis of imaging methods.". Med Phys 10 (5): 610-21. PMID 6646065. 
16. ^ Le Bihan D, Breton E, Lallemand D, Grenier P, Cabanis E, Laval-Jeantet M. MR imaging of intravoxel incoherent motions: application to diffusion and perfusion in neurologic disorders. Radiology. 1986 Nov;161(2):401-7 PMID 3763909
17. ^ Thulborn KR, Waterton JC, Matthews PM, Radda GK. "Oxygenation dependence of the transverse relaxation time of water protons in whole blood at high field." Biochim Biophys Acta. 1982 Feb 2;714(2):265-70. PMID 6275909
18. ^ Randal C. Archibold, "Hospital Details Failures Leading to M.R.I. Fatality", The New York Times, 2001 August 22.
19. ^ Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR 1996; 167:847-849
20. ^ "ACR guideline, 2005"
21. ^ H.S. Thomsen, S.K. Morcos and P. Dawson, Is there a causal relation between the administration of gadolinium based contrast media and the development of nephrogenic systemic fibrosis (NSF)?, Clinical Radiology, Volume 61 (11), Nov 2006, pp. 905-906.
22. ^ "FDA Public Health Advisory: Gadolinium-containing Contrast Agents for Magnetic Resonance Imaging"
23. ^ H.F. Judson, "No Nobel Prize for whining", New York Times, 20 October 2003. Accessed 2006-11-02.
24. ^ Hutchison JMS, Mallard JR, Goll CC (1974). "In-vivo imaging of body structures using proton resonance", Proceedings of the 18th Ampère Congress: Magnetic resonance and related phenomena. Oxford, Amsterdam: North-Holland Publishing Company, 283-284. 
25. ^ Edelstein WA, Hutchison JMS, Johnson G, Redpath TW (1980). "Spin-warp NMR imaging and applications to human whole-body imaging". Phys Med Biol 25: 751-756. PMID 7454767. 
26. ^ Mallard J (2006). "Magnetic resonance imaging—the Aberdeen perspective on developments in the early years". Phys Med Biol 51: R45-R60. PMID 16790917. 

[edit] See also

• History of brain imaging
• Nobel Prize controversies
• FLASH MRI
• Functional magnetic resonance imaging
• High intensity focused ultrasound
• Relaxation and relaxometry
• Robinson oscillator
• Signal-to-noise ratio
• Contrast to noise ratio
• Contrast resolution
• Spatial resolution
• Rabi cycle
• InVesalius
• Specific absorption rate
• Neuroimaging software
• Electron-spin resonance (spin physics)

[edit] 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 0471351288

[edit] External links

• MRI - Magnetic resonance imaging Animation made by bigs.eu; contents are: spin, spin modification, induction, relaxation and precession, spin echo sequence, gradient echo sequence, inversion recovery sequence
• SCMR — Society for Cardiovascular Magnetic Resonance
• MRIONTHEWEB.NL Everything about mri. Become a member and share information and meet other mri operators.
• ‘MRI: A Window on the Human Body‘ Freeview video Royal Institution Lecture by Laurie Hall, Cambridge University by the Vega Science Trust.
• U.S. Patent 3,789,832  — Apparatus and method of detecting cancer in tissue
• International Society for Magnetic Resonance in Medicine
• e-MRI : interactive course about MRI physics (Flash player required)
• RadiologyInfo- The radiology information resource for patients: Magnetic Resonance Imaging (MRI)
• "Nobel Prizefight" — article about the 2003 Nobel Prize controversy
• Guidance Document for MR Safe Practices:2007 — ACR‘s Guidance Document (superseding the combined 2002 and 2004 White Paper on MR Safety)
• Frank Shellock‘s MRIsafety web site
• MRI-Planning.com - Website on MRI safety, suite design and operational issues
• How Stuff Works MRI article — Basic information, applications and advantages of MRI scans
• MRI Resources on the Web - reviewed links to some of the best MRI sites
• The basics of MRI - a free online textbook
• Information and images about "flying objects" in MRI
• MRI Pulse Sequences - Download Images
• Vendor Specific MRI Terminology — Acronyms and Imaging Parameters
• Example MRI
• Laboratory of Neuro Imaging at UCLA
• The Whole Brain Atlas
• Human MRI Datasets
• Database of MRI studies related to emergency medicine
• Environmental Health Criteria 232 Static Fields by the WHO (2006).
• Health effects of static fields and MRI scanners - a summary of the above WHO report by GreenFacts.
• Effects of a pacemaker implant in a generic MRI System.
• E.U. Threatens to Impose Severe MRI Restrictions DOTmed News - June 14, 2007
• Patient-Info - Your Radiology Information