Magnetic resonance imaging
|Magnetic resonance imaging|
|Synonyms||nuclear magnetic resonance imaging (NMRI), magnetic resonance tomography (MRT)|
Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio waves to generate images of the organs in the body. MRI does not involve X-rays or the use of ionizing radiation, which distinguishes it from CT or CAT scans and PET scans. Magnetic resonance imaging is a medical application of nuclear magnetic resonance (NMR). NMR can also be used for imaging in other NMR applications such as NMR spectroscopy.
While the hazards of X-rays are now well controlled in most medical contexts, an MRI scan may still be seen as a better choice than a CT scan. MRI is widely used in hospitals and clinics for medical diagnosis, staging of disease and follow-up without exposing the body to radiation. An MRI may yield different information compared with CT. Risks and discomfort may be associated with MRI scans. Compared with CT scans, MRI scans typically take longer and are louder, and they usually need the subject to enter a narrow, confining tube. In addition, people with some medical implants or other non-removable metal inside the body may be unable to undergo an MRI examination safely.
MRI was originally called NMRI (nuclear magnetic resonance imaging), but "nuclear" was dropped to avoid negative associations. Certain atomic nuclei are able to absorb and emit radio frequency energy when placed in an external magnetic field. In clinical and research MRI, hydrogen atoms are most often used to generate a detectable radio-frequency signal that is received by antennas close to the anatomy being examined. Hydrogen atoms are naturally abundant in people and other biological organisms, particularly in water and fat. For this reason, most MRI scans essentially map the location of water and fat in the body. Pulses of radio waves excite the nuclear spin energy transition, and magnetic field gradients localize the signal in space. By varying the parameters of the pulse sequence, different contrasts may be generated between tissues based on the relaxation properties of the hydrogen atoms therein.
Since its development in the 1970s and 1980s, MRI has proven to be a versatile imaging technique. While MRI is most prominently used in diagnostic medicine and biomedical research, it also may be used to form images of non-living objects. MRI scans are capable of producing a variety of chemical and physical data, in addition to detailed spatial images. The sustained increase in demand for MRI within health systems has led to concerns about cost effectiveness and overdiagnosis.
- 1 Mechanism
- 2 Diagnostics
- 2.1 Usage by organ or system
- 2.2 Contrast agents
- 2.3 Sequences
- 2.4 Other specialized configurations
- 3 Economics
- 4 Safety
- 5 Artifacts
- 6 Non-medical use
- 7 History
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
Construction and physics
To perform a study, the person is positioned within an MRI scanner that forms a strong magnetic field around the area to be imaged. In most medical applications, hydrogen nuclei, which consist solely of a proton, that are in tissues create a signal that is processed to form an image of the body. First, energy from an oscillating magnetic field is temporarily applied to the patient at the appropriate resonance frequency. The excited hydrogen atoms emit a radio frequency signal, which is measured by a receiving coil. The radio signal may be made to encode position information by varying the main magnetic field using gradient coils. As these coils are rapidly switched on and off they create the characteristic repetitive noise of an MRI scan. The contrast between different tissues is determined by the rate at which excited atoms return to the equilibrium state. Exogenous contrast agents may be given to the person to make the image clearer.
The major components of an MRI scanner are the main magnet, which polarizes the sample, the shim coils for correcting shifts in the homogeneity of the main magnetic field, the gradient system which is used to localize the MR signal and the RF system, which excites the sample and detects the resulting NMR signal. The whole system is controlled by one or more computers.
MRI requires a magnetic field that is both strong and uniform. The field strength of the magnet is measured in teslas – and while the majority of systems operate at 1.5 T, commercial systems are available between 0.2 and 7 T. Most clinical magnets are superconducting magnets, which require liquid helium. Lower field strengths can be achieved with permanent magnets, which are often used in "open" MRI scanners for claustrophobic patients. Recently, MRI has been demonstrated also at ultra-low fields, i.e., in the microtesla-to-millitesla range, where sufficient signal quality is made possible by prepolarization (on the order of 10–100 mT) and by measuring the Larmor precession fields at about 100 microtesla with highly sensitive superconducting quantum interference devices (SQUIDs).
T1 and T2
Each tissue returns to its equilibrium state after excitation by the independent relaxation processes of T1 (spin-lattice; that is, magnetization in the same direction as the static magnetic field) and T2 (spin-spin; transverse to the static magnetic field). To create a T1-weighted image, magnetization is allowed to recover before measuring the MR signal by changing the repetition time (TR). This image weighting is useful for assessing the cerebral cortex, identifying fatty tissue, characterizing focal liver lesions, and in general obtaining morphological information, as well as for post-contrast imaging. To create a T2-weighted image, magnetization is allowed to decay before measuring the MR signal by changing the echo time (TE). This image weighting is useful for detecting edema and inflammation, revealing white matter lesions, and assessing zonal anatomy in the prostate and uterus.
The standard display of MRI images is to represent fluid characteristics in black and white images, where different tissues turn out as follows:
|Inter- mediate||Gray matter darker than white matter||White matter darker than grey matter|
Usage by organ or system
MRI has a wide range of applications in medical diagnosis and more than 25,000 scanners are estimated to be in use worldwide. MRI affects diagnosis and treatment in many specialties although the effect on improved health outcomes is uncertain.[obsolete source]
MRI is the investigative tool of choice for neurological cancers over CT, as it offers better visualization of the posterior cranial fossa, containing the brainstem and the cerebellum. The contrast provided between grey and white matter makes MRI the best choice for many conditions of the central nervous system, including demyelinating diseases, dementia, cerebrovascular disease, infectious diseases, Alzheimer's disease and epilepsy. Since many images are taken milliseconds apart, it shows how the brain responds to different stimuli, enabling researchers to study both the functional and structural brain abnormalities in psychological disorders. MRI also is used in guided stereotactic surgery and radiosurgery for treatment of intracranial tumors, arteriovenous malformations, and other surgically treatable conditions using a device known as the N-localizer.
Cardiac MRI is complementary to other imaging techniques, such as echocardiography, cardiac CT, and nuclear medicine. Its applications include assessment of myocardial ischemia and viability, cardiomyopathies, myocarditis, iron overload, vascular diseases, and congenital heart disease.
Liver and gastrointestinal
Hepatobiliary MR is used to detect and characterize lesions of the liver, pancreas, and bile ducts. Focal or diffuse disorders of the liver may be evaluated using diffusion-weighted, opposed-phase imaging, and dynamic contrast enhancement sequences. Extracellular contrast agents are used widely in liver MRI and newer hepatobiliary contrast agents also provide the opportunity to perform functional biliary imaging. Anatomical imaging of the bile ducts is achieved by using a heavily T2-weighted sequence in magnetic resonance cholangiopancreatography (MRCP). Functional imaging of the pancreas is performed following administration of secretin. MR enterography provides non-invasive assessment of inflammatory bowel disease and small bowel tumors. MR-colonography may play a role in the detection of large polyps in patients at increased risk of colorectal cancer.
Magnetic resonance angiography (MRA) generates pictures of the arteries 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 that recently moved into that plane (see also FLASH MRI).
Techniques involving phase accumulation (known as phase contrast angiography) can also be used to generate flow velocity maps easily and accurately. Magnetic resonance venography (MRV) is a similar procedure that is used to image veins. In this method, the tissue is now excited inferiorly, while the signal is gathered in the plane immediately superior to the excitation plane—thus imaging the venous blood that recently moved from the excited plane.
MRI for imaging anatomical structures or blood flow do not require contrast agents as the varying properties of the tissues or blood provide natural contrasts. However, for more specific types of imaging, exogenous contrast agents may be given intravenously, orally, or intra-articularly. The most commonly 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%. 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.
In December 2017, the Food and Drug Administration (FDA) in the United States, announced in a drug safety communication that new warnings were to be included on all gadolinium-based contrast agents (GBCAs). The FDA also called for increased patient education and requiring gadolinium contrast vendors to conduct additional animal and clinical studies to assess the safety of these agents. 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, which may be linked to the use of certain gadolinium-containing agents. The most frequently linked is gadodiamide, but other agents have been linked too. 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 to remove the agent from the body promptly.
In Europe, where more gadolinium-containing agents are available, a classification of agents according to potential risks has been released. Recently,[needs update] a new contrast agent named gadoxetate, brand name Eovist (US) or Primovist (EU), was approved for diagnostic use: this has the theoretical benefit of a dual excretion path.
This table does not include uncommon and experimental sequences.
|Group||Sequence||Abbr.||Physics||Main clinical distinctions||Example|
|Spin echo||T1 weighted||T1||Measuring spin–lattice relaxation by using a short repetition time (TR) and echo time (TE)||
Standard foundation and comparison for other sequences
|T2 weighted||T2||Measuring spin–spin relaxation by using long TR and TE times||
Standard foundation and comparison for other sequences
|Proton density weighted||PD||Long TR (to reduce T1) and short TE (to minimize T2)||Joint disease and injury.|
|Gradient echo (GRE)||Steady-state free precession||SSFP||Maintenance of a steady, residual transverse magnetisation over successive cycles.||Creation of cardiac MRI videos (pictured).|
|T2*||Postexcitation refocused GRE with small flip angle.||Low signal from hemosiderin deposits (pictured) and hemorrhages.|
|Inversion recovery||Short tau inversion recovery||STIR||Fat suppression by setting an inversion time where the signal of fat is zero||High signal in edema, such as in more severe stress fracture Shin splints pictured:|
|Fluid-attenuated inversion recovery||FLAIR||Fluid suppression by setting an inversion time that nulls fluids||High signal in lacunar infarction, multiple sclerosis (MS) plaques, subarachnoid haemorrhage and meningitis (pictured).|
|Double inversion recovery||DIR||Simultaneous suppression of cerebrospinal fluid and white matter by two inversion times||High signal of multiple sclerosis plaques (pictured)|
|Diffusion weighted (DWI)||Conventional||DWI||Measure of Brownian motion of water molecules||High signal within minutes of cerebral infarction (pictured).|
|Apparent diffusion coefficient||ADC||Reduced T2 weighting by taking multiple conventional DWI images with different DWI weighting, and the change corresponds to diffusion||Low signal minutes after cerebral infarction (pictured)|
|Diffusion tensor||DTI||Mainly tractography (pictured) by an overall greater Brownian motion of water molecules in the directions of nerve fibers|
|Perfusion weighted (PWI)||Dynamic susceptibility contrast||DSC||Gadolinium contrast is injected, and rapid repeated imaging (generally gradient-echo echo-planar T2 weighted) quantifies susceptibility-induced signal loss||In cerebral infarction, the infarcted core and the penumbra have decreased perfusion (pictured).|
|Dynamic contrast enhanced||DCE||Measuring shortening of the spin–lattice relaxation (T1) induced by a gadolinium contrast bolus|
|Arterial spin labelling||ASL||Magnetic labeling of arterial blood below the imaging slab, which subsequently enters the region of interest It does not need gadolinium contrast.|
|Functional MRI (fMRI)||Blood-oxygen-level dependent imaging||BOLD||Changes in oxygen saturation-dependent magnetism of hemoglobin reflects tissue activity.||Localizing highly active brain areas before surgery, also used in research of cognition|
|Magnetic resonance angiography (MRA) and venography||Time-of-flight||TOF||Blood entering the imaged area is not yet magnetically saturated, giving it a much higher signal when using short echo time and flow compensation.||Detection of aneurysm, stenosis, or dissection|
|Phase-contrast magnetic resonance imaging||PC-MRA||Two gradients with equal magnitude, but opposite direction, are used to encode a phase shift, which is proportional to the velocity of spins.||Detection of aneurysm, stenosis, or dissection (pictured)|
|Susceptibility-weighted||SWI||Sensitive for blood and calcium, by a fully flow compensated, long echo, gradient recalled echo (GRE) pulse sequence to exploit magnetic susceptibility differences between tissues||Detecting small amounts of hemorrhage (diffuse axonal injury pictured) or calcium|
Other specialized configurations
Magnetic resonance spectroscopy
Magnetic resonance spectroscopy (MRS) is used to measure the levels of different metabolites in body tissues, which can be achieved through a variety of single voxel or imaging-based techniques. The MR signal produces a spectrum of resonances that corresponds to different molecular arrangements of the isotope being "excited". This signature is used to diagnose certain metabolic disorders, especially those affecting the brain, and to provide information on tumor metabolism.
Magnetic resonance spectroscopic imaging (MRSI) combines both spectroscopic and imaging methods to produce spatially localized spectra from within the sample or patient. The spatial resolution is much lower (limited by the available SNR), but the spectra in each voxel contains information about many metabolites. Because the available signal is used to encode spatial and spectral information, MRSI requires high SNR achievable only at higher field strengths (3 T and above). The high procurement and maintenance costs of MRI with extremely high field strengths inhibit their popularity. However, recent compressed sensing-based software algorithms (e.g., SAMV) have been proposed to achieve super-resolution without requiring such high field strengths.
Real-time MRI refers to the continuous imaging of moving objects (such as the heart) in real time. One of the many different strategies developed since the early 2000s is based on radial FLASH MRI, and iterative reconstruction. This gives a temporal resolution of 20–30 ms for images with an in-plane resolution of 1.5–2.0 mm. Balanced steady-state free precession (bSSFP) imaging has a better image contrast between the blood pool and myocardium than the FLASH MRI, yet it will produce severe banding artifact when the B0 inhomogeneity is strong. Real-time MRI is likely to add important information on diseases of the heart and the joints, and in many cases may make MRI examinations easier and more comfortable for patients, especially for the patients who cannot hold their breathings or who have arrhythmia.
The lack of harmful effects on the patient and the operator make MRI well-suited for interventional radiology, where the images produced by an MRI scanner guide minimally invasive procedures. Such procedures use no ferromagnetic instruments.
A specialized growing subset of interventional MRI is intraoperative MRI, in which an MRI is used in surgery. Some specialized MRI systems allow imaging concurrent with the surgical procedure. More typically, the surgical procedure is temporarily interrupted so that MRI can assess the success of the procedure or guide subsequent surgical work.
Magnetic resonance guided focused ultrasound
In guided therapy, high-intensity focused ultrasound (HIFU) beams are focused on a tissue, that are controlled using MR thermal imaging. Due to the high energy at the focus, the temperature rises to above 65 °C (150 °F) which completely destroys the tissue. This technology can achieve precise ablation of diseased tissue. MR imaging provides a three-dimensional view of the target tissue, allowing for the 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.
Hydrogen has the most frequently imaged nucleus in MRI because it is present in biological tissues in great abundance, and because its high gyromagnetic ratio gives a strong signal. However, any nucleus with a net nuclear spin could potentially be imaged with MRI. Such nuclei include helium-3, lithium-7, 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 and 19F can be administered in sufficient quantities in liquid form (e.g. 17O-water) that hyperpolarization is not a necessity. Using helium or xenon has the advantage of reduced background noise, and therefore increased contrast for the image itself, because these elements are not normally present in biological tissues.
Moreover, the nucleus of any atom that has a net nuclear spin and that is bonded to a hydrogen atom could potentially be imaged via heteronuclear magnetization transfer MRI that would image the high-gyromagnetic-ratio hydrogen nucleus instead of the low-gyromagnetic-ratio nucleus that is bonded to the hydrogen atom. In principle, hetereonuclear magnetization transfer MRI could be used to detect the presence or absence of specific chemical bonds.
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. Multinuclear imaging holds the potential to chart the distribution of lithium in the human brain, this element finding use as an important drug for those with conditions such as bipolar disorder.
Molecular imaging by MRI
MRI has the advantages of having very high spatial resolution and is very adept at morphological imaging and functional imaging. MRI does have several disadvantages though. First, MRI has a sensitivity of around 10−3 mol/L to 10−5 mol/L, which, compared to other types of imaging, can be very limiting. This problem stems from the fact that the population difference between the nuclear spin states is very small at room temperature. For example, at 1.5 teslas, a typical field strength for clinical MRI, the difference between high and low energy states is approximately 9 molecules per 2 million. Improvements to increase MR sensitivity include increasing magnetic field strength, and hyperpolarization via optical pumping or dynamic nuclear polarization. There are also a variety of signal amplification schemes based on chemical exchange that increase sensitivity.
To achieve molecular imaging of disease biomarkers using MRI, targeted MRI contrast agents with high specificity and high relaxivity (sensitivity) are required. To date, many studies have been devoted to developing targeted-MRI contrast agents to achieve molecular imaging by MRI. Commonly, peptides, antibodies, or small ligands, and small protein domains, such as HER-2 affibodies, have been applied to achieve targeting. To enhance the sensitivity of the contrast agents, these targeting moieties are usually linked to high payload MRI contrast agents or MRI contrast agents with high relaxivities. A new class of gene targeting MR contrast agents (CA) has been introduced to show gene action of unique mRNA and gene transcription factor proteins. This new CA can trace cells with unique mRNA, microRNA and virus; tissue response to inflammation in living brains. The MR reports change in gene expression with positive correlation to TaqMan analysis, optical and electron microscopy.
This section needs to be updated.July 2019)(
In the UK, the price of a clinical 1.5-tesla MRI scanner is around £920,000/US$1.4 million, with the lifetime maintenance cost broadly similar to the purchase cost. In the Netherlands, the average MRI scanner costs around €1 million, with a 7-T MRI having been taken in use by the UMC Utrecht in December 2007, costing €7 million. Construction of MRI suites could cost up to US$500,000/€370.000 or more, depending on project scope. Pre-polarizing MRI (PMRI) systems using resistive electromagnets have shown promise as a low-cost alternative and have specific advantages for joint imaging near metal implants; however, they are likely unsuitable for routine whole-body or neuroimaging applications.
MRI scanners have become significant sources of revenue for healthcare providers in the US. This is because of favorable reimbursement rates from insurers and federal government programs. Insurance reimbursement is provided in two components, an equipment charge for the actual performance and operation of the MRI scan and a professional charge for the radiologist's review of the images and/or data. In the US Northeast, an equipment charge might be $3,500/€2,600 and a professional charge might be $350/€260, although the actual fees received by the equipment owner and interpreting physician are often significantly less and depend on the rates negotiated with insurance companies or determined by the Medicare fee schedule. For example, an orthopedic surgery group in Illinois billed a charge of $1,116/€825 for a knee MRI in 2007, but the Medicare reimbursement in 2007 was only $470.91/€350. Many insurance companies require advance approval of an MRI procedure as a condition for coverage.
In the United States, an MRI of the brain with and without contrast billed to Medicare Part B entails, on average, a technical payment of US$403/€300 and a separate payment to the radiologist of US$93/€70. In France, the cost of an MRI exam is approximately €150/US$205. This covers three basic scans including one with an intravenous contrast agent as well as a consultation with the technician and a written report to the patient's physician. In Japan, the cost of an MRI examination (excluding the cost of contrast material and films) ranges from US$155/€115 to US$180/€133, with an additional radiologist professional fee of US$17/€12.50.
Clinical MRI installation in a general hospital
MRI is in general a safe technique, although injuries may occur as a result of failed safety procedures or human error. Contraindications to MRI include most cochlear implants and cardiac pacemakers, shrapnel, and metallic foreign bodies in the eyes. Magnetic resonance imaging in pregnancy appears to be safe at least during the second and third trimesters if done without contrast agents. Since MRI does not use any ionizing radiation, its use is generally favored in preference to CT when either modality could yield the same information. In certain cases, MRI is not preferred as it may be more expensive, time-consuming, and claustrophobia-exacerbating.
MRI uses powerful magnets and can therefore cause magnetic materials to move at great speeds posing risk. Deaths have occurred. However, as millions of MRIs are performed globally each year, fatalities are extremely rare.
Medical societies issue guidelines for when physicians should use MRI on patients and recommend against overuse. MRI can detect health problems or confirm a diagnosis, but medical societies often recommend that MRI not be the first procedure for creating a plan to diagnose or manage a patient's complaint. A common case is to use MRI to seek a cause of low back pain; the American College of Physicians, for example, recommends against this procedure as unlikely to result in a positive outcome for the patient.
An MRI artifact is a visual artifact, that is, an anomaly during visual representation. Many different artifacts can occur during magnetic resonance imaging (MRI), some affecting the diagnostic quality, while others may be confused with pathology. Artifacts can be classified as patient-related, signal processing-dependent and hardware (machine)-related.
MRI is used industrially mainly for routine analysis of chemicals. The nuclear magnetic resonance technique is also used, for example, to measure the ratio between water and fat in foods, monitoring of flow of corrosive fluids in pipes, or to study molecular structures such as catalysts.
In 1971, Paul Lauterbur applied magnetic field gradients in all three dimensions and a back-projection technique to create NMR images. He published the first images of two tubes of water in 1973 in the journal Nature, followed by the picture of a living animal, a clam, and in 1974 by the image of the thoracic cavity of a mouse. Lauterbur called his imaging method zeugmatography, a term which was later replaced by (N)MR imaging. In the late 1970s, physicists Peter Mansfield and Paul Lauterbur, developed MRI-related techniques, like the echo-planar imaging (EPI) technique. Mansfield and Lauterbur were awarded the 2003 Nobel Prize in Physiology or Medicine for their "discoveries concerning magnetic resonance imaging".
- Earth's field NMR
- Electron paramagnetic resonance
- High-definition fiber tracking
- High-resolution computed tomography
- History of neuroimaging
- International Society of Magnetic Resonance in Medicine
- List of neuroimaging software
- Magnetic immunoassay
- Magnetic particle imaging
- Magnetic resonance elastography
- Magnetic Resonance Imaging (journal)
- Magnetic resonance microscopy
- Nobel Prize controversies – Physiology or medicine
- Rabi cycle
- Robinson oscillator
- Sodium MRI
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|Wikimedia Commons has media related to Magnetic resonance imaging.|
- Rinck PA (ed.). "MRI: A Peer-Reviewed, Critical Introduction". European Magnetic Resonance Forum (EMRF)/The Round Table Foundation (TRTF).
- A Guided Tour of MRI: An introduction for laypeople National High Magnetic Field Laboratory
- The Basics of MRI. Underlying physics and technical aspects.
- Video: What to Expect During Your MRI Exam from the Institute for Magnetic Resonance Safety, Education, and Research (IMRSER)
- Royal Institution Lecture – MRI: A Window on the Human Body
- A Short History of Magnetic Resonance Imaging from a European Point of View
- How MRI works explained simply using diagrams
- Real-time MRI videos: Biomedizinische NMR Forschungs GmbH.
- Paul C. Lauterbur, Genesis of the MRI (Magnetic Resonance Imaging) notebook, September 1971 (all pages freely available for download in variety of formats from Science History Institute Digital Collections at digital.sciencehistory.org)