MRI (Magnetic Resonance Imaging): An Important tool for Biological Science

Magnetic resonance imaging (MRI), nuclear magnetic resonance imaging (NMRI), ormagnetic resonance tomography (MRT) is a medical imaging technique used in radiologyto image the anatomy and the physiological processes of the body in both health and disease. MRI scanners use strong magnetic fields, radio waves, and field gradients to form images of the body. MRI is based upon the science of Nuclear Magnetic Resonance (NMR). Certain atomic nuclei can 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 in close proximity to the anatomy being examined. Hydrogen atoms exist naturally in people and other biological organisms in abundance, 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 are used to 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 can be generated between tissues based on the relaxation properties of the hydrogen atoms therein. Since its early development in the 1970s and 1980s, MRI has proven to be a highly versatile imaging modality. While MRI is most prominently used in diagnostic medicine and biomedical research, it can also 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. MRI is widely used in hospitals and clinics for medical diagnosis, staging of disease and follow-up without exposing the body to ionizing radiation. MRI has a wide range of applications in medical diagnosis and over 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. 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 can be more expensive, time-consuming, and claustrophobia-exacerbating). MRI is in general a safe technique but the number of incidents causing patient harm has risen. Contraindications to MRI include most cochlear implants and cardiac pacemakers, shrapnel and metallic foreign bodies in the eyes. The safety of MRI during the first trimester of pregnancy is uncertain, but it may be preferable to other options. The sustained increase in demand for MRI within the health care industry has led to concerns about cost effectiveness and over-diagnosis. MRI is the investigative tool of choice for neurological cancers, as it has better resolution than CT and offers better visualization of the posterior fossa. The contrast provided between grey and white matter makes it the best choice for many conditions of the central nervous system, including  demyelinating diseases, dementia, infectious diseases and epilepsy. Since many images are taken milliseconds apart, it shows how the brain responds to different stimuli; researchers can then study both the functional and structural brain abnormalities in psychological disorders.  

MRI and Time

Magnetic resonance imaging was invented by Paul C. Lauterbur in September 1971; he published the theory behind it in March 1973. The factors leading to image contrast (differences in tissue relaxation time values) had been described nearly 20 years earlier by Erik Odeblad (physician and scientist).  In 1950, spin echoes were first detected by Erwin Hahn and in 1952, Herman Carr produced a one-dimensional NMR spectrum as reported in his Harvard PhD thesis. In the Soviet Union, Vladislav Ivanov filed (in 1960) a document with the USSR State Committee for Inventions and Discovery at Leningrad for a Magnetic Resonance Imaging device, although this was not approved until the 1970s. In a March 1971 paper in the journal Science, Raymond Damadian, an Armenian-American physician and professor at the Downstate Medical Center State University of New York (SUNY), reported that tumors and normal tissue can be distinguished in vivo by nuclear magnetic resonance ("NMR"). He suggested that these differences could be used to diagnose cancer, though later research would find that these differences, while real, are too variable for diagnostic purposes. Damadian's initial methods were flawed for practical use, relying on a point-by-point scan of the entire body and using relaxation rates, which turned out not to be an effective indicator of cancerous tissue. While researching the analytical properties of magnetic resonance, Damadian created a hypothetical magnetic resonance cancer-detecting machine in 1972. He filed the first patent for such a machine, U.S. Patent 3,789,832 on March 17, 1972, which was later issued to him on February 5, 1974. The US National Science Foundation notes "The patent included the idea of using NMR to 'scan' the human body to locate cancerous tissue." However, it did not describe a method for generating pictures from such a scan or precisely how such a scan might be done. Meanwhile, Paul Lauterbur at Stony Brook University expanded on Carr's technique and developed a way to generate the first MRI images, in 2D and 3D, using gradients. In 1973, Lauterbur published the first nuclear magnetic resonance image and the first cross-sectional image of a living mouse in January 1974. In the late 1970s, Peter Mansfield, a physicist and professor at the University of Nottingham, England, developed the echo-planar imaging (EPI) technique that would lead to scans taking seconds rather than hours and produce clearer images than Lauterbur had. Damadian, along with Larry Minkoff and Michael Goldsmith, obtained an image of a tumor in the thorax of a mouse in 1976. They also performed the first MRI body scan of a human being on July 3, 1977, studies which they published in 1977. In 1979, Richard S. Likes filed a patent on k-space U.S. Patent 4,307,343.

During the 1970s a team led by John Mallard built the first full body MRI scanner at the University of Aberdeen. On 28 August 1980 they used this machine to obtain the first clinically useful image of a patient's internal tissues using Magnetic Resonance Imaging (MRI), which identified a primary tumour in the patient's chest, an abnormal liver, and secondary cancer in his bones. It was later used at St Bartholomew's Hospital, in London, from 1983 to 1993. Mallard and his team are credited for technological advances that led to the widespread introduction of MRI. In 1975, the University of California, San Francisco Radiology Department founded the Radiologic Imaging Laboratory (RIL). With the support of Pfizer, Diasonics, and later Toshiba America MRI, the lab developed new imaging technology and installed systems in the US and worldwide. In 1981 RIL researchers, including Leon Kaufman and Lawrence Crooks, published Nuclear Magnetic Resonance Imaging in Medicine. In the 1980s the book was considered the definitive introductory textbook to the subject. In 1980 Paul Bottomley joined the GE Research Center in Schenectady, NY. His team ordered the highest field-strength magnet then available — a 1.5T system — and built the first high-field device, overcoming problems of coil design, RF penetration and signal-to-noise ratio to build the first whole-body MRI/MRS scanner.

 In 1982, Bottomley performed the first localized MRS in the human heart and brain. After starting a collaboration on heart applications with Robert Weiss at Johns Hopkins, Bottomley returned to the university in 1994 as Russell Morgan Professor and director of the MR Research Division. Although MRI is most commonly performed at 1.5 T, higher fields such as 3T are gaining more popularity because of their increased sensitivity and resolution. In research laboratories, human studies have been performed at up to 9.4 T and animal studies have been performed at up to 21.1T.

Reflecting the fundamental importance and applicability of MRI in medicine, Paul Lauterbur of the University of Illinois at Urbana-Champaign and Sir Peter Mansfield of the University of Nottingham were awarded the 2003 Nobel Prize in Physiology or Medicine for their "discoveries concerning magnetic resonance imaging". The Nobel citation acknowledged Lauterbur's insight of using magnetic field gradients to determine spatial localization, a discovery that allowed rapid acquisition of 2D images. Mansfield was credited with introducing the mathematical formalism and developing techniques for efficient gradient utilization and fast imaging. The actual research that won the prize was done almost 30 years before while Paul Lauterbur was a professor in the Department of Chemistry at Stony Brook University in New York.

Important Applications

D- MRI

Diffusion MRI measures the diffusion of water molecules in biological tissues. Clinically, diffusion MRI is useful for the diagnoses of conditions (e.g., stroke) or neurological disorders (e.g., multiple sclerosis), and helps better understand the connectivity of white matter axons in the central nervous system. In anisotropic medium (inside a glass of water for example), water molecules naturally move randomly according to turbulence and Brownian motion. In biological tissues however, where the Reynolds number is low enough for flows to be laminar, 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 moves principally along the axis of the neural fiber. If it is known that molecules in a particular voxel diffuse principally in one direction, the assumption can be made that the majority of the fibers in this area are parallel to that direction.

MAGNETIC RESONANCE ANGIOGRAPHY

Magnetic resonance angiography (MRA) generates pictures of the arteries to evaluate them forstenosis (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.

MAGNETIC RESONANCE SPECTROSCOPY

Magnetic resonance spectroscopy (MRS) is used to measure the levels of different metabolites in body tissues. 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).

FUNCTIONAL MRI

Functional MRI (fMRI) measures signal changes in the brain that are due to changing neural activity. Compared to anatomical T1W imaging, the brain is scanned at lower spatial resolution but at a higher temporal resolution (typically once every 2–3 seconds). Increases in neural activity cause changes in the MR signal via T*
2 changes; 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.

REAL-TIME MRI

Real-time MRI refers to the continuous monitoring ("filming") of moving objects in real time. While many different strategies have been developed over the past two decades, a recent development reported a real-time MRI technique based on radial FLASH and iterative reconstruction that yields a temporal resolution of 20 to 30 milliseconds for images with an in-plane resolution of 1.5 to 2.0 mm. The new method promises to add important information about diseases of the joints and the heart. In many cases MRI examinations may become easier and more comfortable for patients.

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 (150 °F), 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, 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.

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, andhyperpolarization via optical pumping or dynamic nuclear polarization. There are also a variety of signal amplification schemes based on chemical exchange that increase sensitivity.

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