Contrast agents are pharmaceuticals that increase the information content of diagnostic images. They serve to improve the sensitivity and specificity of diagnostic images by altering the intrinsic properties of tissues, which influence the fundamental mechanisms of contrast. Strategic localization of the agent can regionally change the tissue properties and result in preferential enhancement. MRI is unique among diagnostic modalities because it uses more than one intrinsic property of the tissue being imaged. All other diagnostic imaging modalities depend on one inherent tissue property for image formation. Further, MRI is neither quantitatively nor parametrically singular in its contrast mechanism, as is computed tomography.
The determinants of signal intensity and contrast in MRI are spin density (p), susceptibility (x), proton relaxation (T and T), and motion (diffusion and perfusion). Each is a tissue characteristic that influences MRI signal intensity and, in theory, a parameter that can be manipulated pharmacologically for the purpose of contrast enhancement. All four contrast agents approved for clinical use alter the relaxation times of tissues.
Three MRI contrast agents have been approved for clinical use in the United States as of 1994. Six more MRI contrast agents were approved by FDA for clinical use from 1995 through 2017: gadopentetate dimeglumine (gadolinium diethylene triamine pentaacetic acid (Gd-DTPA), Magnevist®, gadodiamide (gadolinium diethylene triamine penta-acetic acid bis-methylamide (GD-DTPA-BMA), OmniScan®, Gadoteridol (Gadolinium-1,4,7- tris (carboxymethyl)-10-(2' hydroxypropyl)-1, 4, 7 -10-tetraazacyclododecane (Gd-HPD03A]), ProHance®, gadoterate meglumine (gadolinium-tetraazacyclododecane tetra acetic acid (Gd-DOTA), Dotarem®, gadobenate dimeglumine, gadoversetamide, (OptiMARK, Covidien, Dublin, Ireland); gadobutrol.
Two other agents that are not approved for Contrast-Enhanced MR imaging of the CNS (gadofosveset trisodium and gadoxetic acid have distinct properties that render them unsuitable for this indication. Ablavar is an intravascular “blood-pool” agent approved for MR angiography of the aorto-iliac vessels, whose strong binding to serum albumin (and large effective molecular size) restricts permeability across the open blood-brain barrier, which limits CNS suitability applications, while Eovist is an approved liver-specific agent inappropriate for CNS applications because 50% of the injected dose is taken up and eliminated by hepatocytes. Although numerous studies published in peer-reviewed journals have confirmed the safety and efficacy of the seven gadolinium-based, MRI contrast agents approved for CNS imaging, differences among these agents and the impact these differences may have on clinical decision-making and diagnostic sensitivity remain misunderstood and sometimes underappreciated.
These agents are broadly similar - highly water-soluble gadolinium chelates that extracellularly distributed and eliminated rapidly through renal glomerular filtration. Differences in physicochemical properties are structural design features, i.e., the presence or absence of overall negative charge on the Gd-chelate complex, use of linear or macrocyclic frameworks for the organic chelating ligands. These differences lead to the greater formulation and dosing flexibility for the uncharged or neutral charged chelates and reduced Gd-chelate dissociation for those built around a macrocyclic ligand framework (Ibrahim MA, Ph.D. Dissertation MCW, Milwaukee, WI, 1994).
Gd-DTPA and Gd-DOTA are ionic (charged), with -2 and -1 charge in solution, respectively. Gd-HP-D03A and Gd-DTPA-MBA are non-ionic (uncharged or with a zero net charge). Gd-DTPA and Gd-DTPA-BMA are based on the same linear triamine framework. Gd-DOTA and Gd-HPD03A are based on a macrocyclic tetramine framework. The molecular weight (547-573) and their relaxivity (3.6-3.8 mMs at 20 MHz, 4.5 mMs at 63 MHz) are very similar in solution and in plasma (4.5-5.5 mMs at 42 MHz) (44-46). Osmolarity and viscosity are widely different, generally higher for the ionic than the non-ionic agents.
Gadolinium is one of the metals in the Lanthanide series, the metal of the chelate complexes, has a 4f7 sub-orbital configuration add a spin quantum number of7/2. This implies a coordination number of 8 and seven unpaired electrons.
Image contrast is the difference in brightness between an area of interest and the surroundings. The larger the difference in brightness between different tissue types, the easier it usually is to differentiate them from each other.
Gadolinium-based contrast agent concentration in a certain tissue depends on the pharmacokinetics of the contrast agent, the structure of an agent, charge on the structure of an agent, magnetic field strength, tissue and organs’ environment, and organ and tissue architecture. In vitro, the contrast agent concentration is considered to be linearly related to relaxivity (R). In vivo, however, this is limited by additional relaxation effects.
Gadolinium-based contrast agents are paramagnetic, that is, these atoms act like ferromagnetic and superparamagnetic substances, and have a positive magnetic susceptibility. The effect of paramagnetic substances is several order of magnitude weaker than that of other substances with positive susceptibility. Paramagnetic atoms have independent magnetically diffused moments. The induced magnetization returns to zero when the applied magnetic field is turned off.
Enhancement in-vivo is achieved by an increase in the tissues signal intensity (SI), but a decrease in Longitudinal Relaxation time (T1) and Transverse Relaxation time (T2). Paramagnetic atoms exert their influence on the MR signal by this mechanism and improve the efficiency of T1 and T2 relaxation. Although, both T1 and T2 relaxation efficiency are improved, T1 effects predominate, in most situations.
Most MRI contrast agents are chelates of the rare-earth element gadolinium and produce an increased signal (“positive contrast”) on T1-weighted images (the effect on T2-weighted images is generally negligible).
Negative MRI contrast agents, such as superparamagnetic iron oxide (SPIO), are not currently in widespread use. Gadolinium-based contrast agents can be classified by their primary use as well as their chemical structure. The latter can be helpful in determining the safety profile of gadolinium-based agents and will be discussed later (see Safety). For practical purposes, gadolinium contrast agents can be classified as extracellular, blood pool, or hepatobiliary.
Extracellular agents: These are the most commonly used. They are typically small molecular weight compounds with nonspecific distribution in blood and extracellular space of the body and are used in in the imaging of tumors and inflammation, as well as in magnetic resonance angiography (MRA). They can also be used as intra-articular agents in magnetic resonance arthrography (also MRA, but not confused with magnetic resonance angiography due to the context). It must be noted that intra-articular use of gadolinium agents is considered off-label in the United States.
Blood Pool Agents: These agents are used almost exclusively in magnetic resonance angiography. While the aforementioned extracellular agents are commonly used, image timing must be precise to capture the first pass of these agents in the arterial system. Blood-pool contrast agents, on the other hand, have longer intravascular half-lives, allowing the imaging time to be extended far beyond the short arterial first-pass phase. These agents are further subdivided as macromolecular and low-molecular-weight agents. Macromolecular agents are currently not in clinical use. The most important of the low-molecular-weight agents is Gadofosveset trisodium (Ablavar, formerly Vasovist), a monomer which noncovalently binds to albumin in human plasma, making it a blood pool agent.
Hepatobiliary Agents: These agents were designed to improve the discrimination and diagnosis of focal hepatic lesions, and include gadobenate dimeglumine (Gd-BOPTA, MultiHance) and Gadoxetic acid (Gd-EOB-DTPA, Eovist, Primovist). Gd-BOPTA has a lipophilic moiety that allows uptake through the sinusoidal and canalicular side of hepatocytes. Its hepatic uptake is less than 5% of the injected dose, which can be highlighted on delayed images, at which point the intravascular component has mostly been excreted by the kidneys. Therefore, in the first few minutes after administration, Gd-BOPTA acts as a conventional extracellular agent; however, there is a marked and long-lasting enhancement of normal liver parenchyma 40 to 120 minutes after administration, at which point focal hepatic lesions will stand out as dark lesions in contrast to the enhancing normal liver. The obvious downside is having to wait 40 minutes to obtain diagnostic images.
MRI is the preferred study to diagnose a vast number of neurological & neurodegenerative diseases, infections, and other abnormal disorders in many areas of human body. In general, MRI generates images that show subtle differences between pathologic and healthy tissues. Physician-scientists, Physicians, and scientists use MRI to evaluate abdomen, pelvic region, breast, blood vessels, heart; the brain, spine and spinal cord (Central Nervous System), joints (shoulder, wrist, knee, ankle and hip, musculoskeletal and other human body areas).
MR Imaging is a procedure, without the use of x-rays and "ionizing" radiation for obtaining comprehensive images of tissues and organs throughout the human body. In contrast to CT that uses x-ray beams, MRI employs a high strength main magnetic field, magnetic field gradients, radio waves, and a computer to generate images that show if there is a disease process, or pathological condition and an injury present.
During an MRI procedure, the patient is positioned inside of the large, cylinder-shaped magnet that is open at both ends, called the MR scanner. The high strength main magnetic field aligns mobile hydrogen protons that exist in most tissues of human body. A specific radio wave frequency was applied to cause these mobile protons to produce signals that would be picked up by receiver coils associated with the MR scanner. The collected signals are specifically characterized by using the gradient magnetic fields, and with the aid of computer software and processing, images of tissues are created as the field-of-view "slices" that could be visualized and evaluated for pathologies.
There is no known tissue damage produced by the electromagnetic fields of the MRI, nor causes pain during an examination. MRI scanner does make loud knocking, tapping, and other noises, which can be characterized as rhythmic musical sounds during the patient’s procedure. These noises could be attenuated by using earplugs. During the patient’s scanner procedure and with the aid of an intercommunication system, the patient will be monitored, communicated with, and the patient will be able to speak with the MR scanner operator or MRI technologist by other means.
To help improve the visualization of normal and abnormal tissues seen on the MR images, Gadolinium-based, MRI contrast agent, would be injected into a hand or wrist vein, during some MRI studies. In Contrast with iodinated contrast agents used in computed tomography (CT) and x-ray studies, gadolinium-based MRI contrast agents, do not contain iodine. Hence, would rarely cause an adverse effect or allergic reaction. However, if patients have a history of a kidney transplant, kidney disease, kidney failure, liver disease, those patients should inform the Radiologist and/or MRI technologist before the administration of gadolinium-based, MRI contrast agents. If the patients are not sure about their allergic reaction status, patients are advised and encouraged to discuss these issues with the Radiologist and/or MRI technologist before the MRI procedure.
Patients are required to fill out a screening form prior to an MRI procedure, asking about any foreign substance that might interfere or create a health risk with image acquisition. Objects that may create a problem or health hazard during an MRI clinical evaluation include:
It is important to note that some items, such as certain neurostimulation systems, medication pumps, and cardiac pacemakers are acceptable for MRI. However, the radiologist and MRI technologist must know the appropriate type that patients have in order to ensure safety.
Patients and other individuals must remove the following items before entering the MRI scanner room:
The following objects, if near to the areas being imaged, may interfere with the image quality generated:
If patients are suspected to be pregnant or pregnant, the MRI technologist and/or radiologist should be informed of this during the screening process, conducted prior to the MRI procedure. There is no known adverse effect of using MRI without gadolinium-based contrast agents, in pregnant patients to date. Nonetheless, MRI without gadolinium-based contrast agents, is used in pregnant patients only to address suspected abnormalities or very important problems. It has been observed in clinical studies, MRI without gadolinium-based contrast agents, is safer for the fetus than with computed tomography (CT) and x-rays modalities.
Patients about to undergo MRI study, should inform radiologists and MRI technologists if and whether breast-feeding at the time of MRI procedure scheduling, in case gadolinium-based MRI contrast agent is required for the evaluation. If this situation arose, patients may pump and save breast milk before the study. Patients may resume breast-feeding about 24-48 hours following the injection gadolinium-based contrast material. Patients who are breast-feeding should request for additional information from the radiologists regarding this issue.
Atomic Gadolinium is very toxic, but tolerated during MRI by surrounding chemical “clathrate.”
Gadolinium is one of the metals in the lanthanide series of the periodic table that have a general depressant activity on all systems. Death is usually due to cardiovascular collapse and respiratory paralysis.
The following additional adverse reactions have been identified during postmarketing use of Gadolinium-based contrast agents. Because these reactions are reported voluntarily from a population of uncertain size, it is not possible to reliably estimate the frequency or establish a direct causal relationship to drug exposure.
The most frequently reported adverse reactions in the postmarketing experience were nausea, vomiting, urticaria, and rash.
MRI, is a process of generating detailed images of tissues and organs of the human body without the application of "ionizing" radiation and/or x-rays. In contrast, MRI employs powerful central or main magnetic field, gradient magnetic fields, radio frequency waves, and a computer to create images that show normal and abnormal processes, infections or inflammatory conditions.
For the Magnetic Resonance Imaging procedure, the patient is positioned in the wide, tube-like device, called the MR scanner, which is open at both ends. The high strength, central or main magnetic field, aligns mainly mobile hydrogen protons, which exist in most tissues of human body. Radio frequency waves are then applied by the transmit coil to cause these mobile protons to produce response signals which are picked up by a receiver or a transmit-receiver coil that is a component of the MR scanner. These response signals are specifically characterized using the gradient magnetic field, in conjunction with computer software processing, tissues and organs images are generated as a field of view "slices" that could be visualized and evaluated by the radiologists in the sagittal, coronal, transverse and oblique orientation.
MRI procedures cause no pain, and no known tissue damage is produced by the central or main and gradient magnetic fields. During the MR scanning procedure, knocking and/or tapping, and other noises are produced; these noises are musical in rhythm. Earplugs could prevent most of this noise problem occurring during the scanning procedure. Patients are monitored continuously, and patients are able to communicate with the MR scanner operator or technologist using an intercommunication system during the procedure.
MR personnel and non-MR personnel:
All individuals working within at least Zone III of the MR environment should be documented as having successfully completed at least one of the MR safety live lectures or prerecorded presentations approved by the MR medical director. Attendance should be repeated at least annually, and appropriate documentation should be provided to confirm these ongoing educational efforts. These individuals shall be referred to henceforth as MR personnel.
There are two levels of MR personnel:
All those are not having successfully complied with these MR safety instruction guidelines shall be referred to henceforth as non-MR personnel. Specifically, non-MR personnel will be the terminology used to refer to any individual or group who has not within the previous 12 months undergone the designated formal training in MR safety issues defined by the MR safety director of that installation.
1. MR technologists should be ARRT registered technologists (RTs). Furthermore, all MR technologists must be trained as level 2 MR personnel during their orientation, prior to being permitted free access to Zone III.
2. All MR technologists will maintain current certification in American Heart Association basic life support at the healthcare provider level.
3. Except for emergent coverage, there should be a minimum of 2 MR technologists or one MR technologist and at least one other individual with the designation of MR personnel in the immediate Zone II through Zone IV environment. For emergent coverage, the MR technologist should scan with no other individuals in their Zone II through Zone IV environment as long as there is readily available emergent coverage by the designated department of radiology MR personnel (e.g., radiology house staff or Radiology Attendings). (ACR WHITE PAPER ON MAGNETIC RESONANCE (MR) SAFETY Combined Papers of 2002 and 2004)
4. MRI is always “on” and potentially dangerous regarding loose ferromagnetic materials that can fly into magnet bore, thus the four classic zones (I, the hallway, II MRI reception, III MRI tech control area, and IV, the magnet room itself.
The patient will be issued a gown to wear during his/her MRI procedure. Before entering the MR scanner room, patient and any accompanying relative and/or friends will be asked screening questions with a screening form pertaining to the presence of metallic devices and implants, and if present, patients are instructed to remove all metallic jewelry and metallic objects from their pockets and hair. Any accompanying individual will be instructed to fill out a screening form too, in order to ensure that he or she will be safe in the MR scanner room. If patients have additional questions and concerns, it should be brought to the radiologists and/or MRI technologists prior to MR procedure.
When a patient is prescribed MRI with contrast agent, an IV catheter line is inserted in a vein in the arm or an accessible limb, during the initial preparation and positioning of that patient. Following the placement of the IV line, it is flushed with heparin to prevent clogging of the vein. In general, a set of noncontrast enhanced images will be obtained first, before the contrast-enhanced images will be collected. Patients are injected with a specific Gadolinium-based contrast agent in a dose of 0.10 mmole/kg for the examination. Following the injection of the contrast agent, the IV line will be flushed with some saline. Gadolinium-based MRI contrast agent is administered intravenously in approximately, 0.2 mL/kg (0.1 mmoles/ kg) at a rate of 10 mL per 15 seconds.
Gadolinium-based MRI contrast agents come from the manufacturer in following packages:
1. Single-dose vials (5, 10, 15, 20 ml)
2. Single-dose, prefilled syringes (10, 15, 20 ml)
3. Pharmacy Bulk Packages (50, 100 ml)
MRI patient study is carried out in a specific room that houses the MR system, called "scanner room." Patients are lead into the scanner room by an MRI technologist and placed on a padded, comfortable table that slowly glides patient into and out of the scanner when done. Typically, scanners are a tube-like machine that opens at both ends.
To prepare for the MRI clinical study, patients are given earplugs or headphones to wear in order to protect patients’ hearing because, when scanners are in operation, loud noises are produced. These loud noises, which are musically rhythmic in nature are normal and should be of less concern for the patient.
During some MRI clinical procedures, a gadolinium-based, contrast agent will be injected into a vein to help acquire an enhanced and clearer picture of the area being imaged. At some point during the MRI clinical study, an MRI technologist or a nurse, will pull the table out of the scanner in order to inject the contrast agent. Injection of the gadolinium-based contrast agent is performed through a small an intravenous catheter that is placed in a hand vein or an arm vein of the patient. A normal saline solution plus heparin is instilled through the intravenous line to prevent clotting until at some point, when the gadolinium-based contrast agent is injected during the MRI procedure.
Most MRI studies will last between 15 to 45 minutes depending on the human body areas imaged and how many images are to be collected, although some may take as long as 60 minutes or longer. The most important thing for the patient to do is to lie still and relax. Patients are told before the start of the clinical study the duration of each scanning protocol.
Patients are asked to remain motionless during the image acquisition time. In between imaging protocols, some minor movement are allowed. The MRI technologist will advise patient on when he or she could move or not move.
When the MRI protocol begins, the patient could breathe normally. However, for some specific evaluations, it may be necessary for the patient to hold his/her breathing for a short time period.
During patients MRI procedure, the MRI technologists will be able to talk to and hear the patient, and observe patient all the time. Patients are also able to communicate with the MRI technologists at all times.
When the MRI evaluation is complete, patients may be required to wait until the images are examined in order to determine if additional images are required. After the scanning procedure, there are no restrictions on the patient, and could go about his/her normal activities. Patients who are injected with gadolinium-based, MRI contrast agents are advised to drink additional water for few hours after the procedure, in order to clear the contrast agent from their bodies.
After the MRI procedure is completed, radiologists will review and evaluate the images, and will send a report of the scans to the patients’ primary physician.
MR Imaging study produced a complex reaction between mobile hydrogen protons in biologic tissues, a main, static magnetic field (static field), and excitation energy in the form of radiowaves (Rf) of a specific frequency introduced by transmitting coils positioned next to the human body areas of interest. Images from areas of interest are produced by computer processing of resonance data received from protons in the body's field of view. The field strength of the main, static magnet is directly related to signal-to-noise ratio (SN/R) of the images acquired; the higher the field strength, the higher the signal-to-noise ratio. While 1.5-T static, main magnets are now the standard high-field MRI units, 3.0-T static, main magnets are now widely used and have distinct advantages in the musculoskeletal systems and brain because of higher signal-to-noise ratio and increased soft tissue differentiation.
Spatial localization of the body's areas of interest is obtained by gradient magnetic fields inserted and/or surrounding the main magnet field, which produce minor changes in the magnetic field throughout the imaging volume. Radiofrequency pulses momentarily excite the energy state of the mobile hydrogen protons of the body's areas of interest. Radiofrequency pulse is applied at a frequency specific for the main magnetic field strength. For example, for a 1.5T magnetic field strength, the frequency is 63.85 MHz. The mobile hydrogen protons subsequent return to equilibrium energy state (relaxation) and resulted in a release of radiofrequency energy (the echo), which are detected by the receive coils or a transmit-receive coils. Fourier transform analysis is applied to the echo signals into data used to form the acquired MR images. The MR images acquired consist of a map of the distribution of mobile hydrogen protons, with signal intensity produced by both differences in the relaxation times and density of hydrogen protons on different molecules. Although clinical MRI procedure makes use of the abundant mobile hydrogen protons, research into carbon and sodium imaging and spectroscopy are being pursued by several researchers.
MR Imaging Relaxation Times (T1 & T2)
The time it takes to return to the equilibrium state of the excited mobile hydrogen protons is called the relaxation time. The relaxation time differs among abnormal and normal tissues. The relaxation time of a mobile hydrogen proton in a tissue is achieved by local interactions with neighboring molecules and atoms. There are two relaxation times, T1 and, T2, that affect the images' signal intensity. T1 relaxation time, (also called longitudinal relaxation times) is the time, for 63% of the excited mobile hydrogen protons to return to their normal equilibrium state. T2 (Transverse relaxation times) relaxation time. is the time for 63% of the excited mobile hydrogen protons to fan out of precession or dephased owing to reactions with nearby hydrogen protons. The intensity and image contrast of the signal acquired within various tissues can be controlled by altering acquisition parameters, such as the time between the Radiofrequency pulse and the signal reception (TE = echo time) and interval between Radiofrequency pulses (TR = repetition times). T1-weighted (T1-W) images are acquired by setting the TR and TE relatively short, whereas applying longer TR and TE times produce T2-weighted (T2-W) images. Subacute hemorrhage and fat have relatively shorter T1 relaxation rates and thus higher signal intensity than brain on T1-W images. Tissues and organs, having more water, such as edema and CSF, have long T1 and T2 relaxation rates, resulting in relatively lower signal intensity on T1W images and higher signal intensity on T2-W images. Gray matter consists of 10–15% more water than white matter, this accounts for much of the intrinsic contrast between the two tissues on MR Imaging. T2-W images are more sensitive than T1-W images to demyelination, infarction, edema and chronic hemorrhage, while T1-W MR Imaging is more sensitive to fatty tissues and subacute hemorrhage.
Some of the patients who had MRI procedures may feel frightened, closed-in, and /or confined. Approximately, one in twenty of these patients are may require and prescribed a sedative medication in order to remain calm. This subset of patients could also be scanned in one of the newer scanners with the wide-bore design. They could also be scanned in an “open scanner” design, except the open scanner design has a lower magnetic field strength. Most Magnetic Resonance Imaging centers allow a friend or relative to be present in the MR scanner room with the patient, which also decrease the level of anxiety, apprehension, and fear in these patients. If patients are instructed appropriately and know what to expect, it is possible for most clinical studies to be completed.
Some patients, generally with renal dysfunction may develop Contrast Agents-induced Nephrogenic Systemic Fibrosis. What is nephrogenic systemic fibrosis? It is a serious side effect of Gadolinium-based MRI contrast agent, where the protective “clathrate” breaks down in the kidneys in patients with renal failure. Nephrogenic systemic fibrosis (NSF) is a rare systemic disorder of unknown etiology with high morbidity and mortality rates, which is almost exclusively seen in patients with impaired renal function. While it is often discussed in the setting of gadolinium-based contrast agents, it is important to note that the diagnosis does not require a history of exposure to these agents. Renal impairment, however, is an important predisposing factor, and almost all cases of NSF have been seen in patients with stage IV or V chronic kidney disease or those with an acute renal injury. When associated with gadolinium-based contrast agents, NSF usually presents between 2 and ten weeks after administration and is more common with a particular class of gadolinium-based contrast agents. The macrocyclic agents are shaped like cages around the gadolinium ion and have a lower probability of releasing free gadolinium. They are considered more stable than other contrast agents and have a lower risk of NSF. The linear nonionic agents are the least stable, and the linear ionic agents have intermediate stability. For example, the vast majority of patients with NSF have been exposed to the linear nonionic agent, Omniscan (gadodiamide), even though it only has about 15% of the worldwide market share of gadolinium-based contrast agents.
Gadolinium-based MRI contrast agents are toxic to fetuses as well. Hence, the contraindication in pregnancy, except in rare cases where the risk-benefit ratio has to be considered.
Unlike its’ cousin Nuclear Magnetic Resonance (NMR) used in chemistry and biochemistry to characterize molecules, Magnetic Resonance Imaging does not possess high sensitivity for single imaging molecules. MRI can only detect molecular motions and compositions in relationship to the characteristics of the surrounding tissues. Gadolinium-based MRI can detect changes and differences in molecular compositions and motions and hence have a significant role in the development of MR for molecular imaging. Gadolinium-based MRI contrast agents alter one or more of their physicochemical properties dynamically when interacting with their surrounding tissues environment. A multidisciplinary research approach, scientists and physicians with a thorough understanding of molecular and cell biology, chemistry and biochemistry, physiology, biomedical engineering of imaging methods, and radiology, is often required to develop and apply Gadolinium-based MRI contrast agents to biological and/or biomedical studies.
Diagnosis and treatment planning in over 100 million patients around the world have employed gadolinium-based, MRI contrast agents in the last 25 years. Quality of MR images are enhanced using gadolinium-based contrast agents, by the perturbation of nearby water protons’ magnetic properties in the body. Gadolinium-based MRI contrast agents, aid physicians to diagnose and treat a variety of pathological processes by improving the visualization of specific organs, tissues, and blood vessels.