Gadolinium Magnetic Resonance Imaging

Indications

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.[8][9][10]

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.

Contraindications

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:

• A metallic foreign body within or near the eye (these objects could be seen on an x-ray; metal or machine shop workers have this problem)

• Some implanted or external medication pumps (insulin delivery, analgesic drugs, or chemotherapy pumps)

• Ferromagnetic metallic vascular clips placed to prevent bleeding from intracranial aneurysms

• Some neurostimulation systems

• Some cochlear (inner ear) implants

• Catheters with metallic components

• Bullets, metal shrapnel or another type of metallic fragment

• Certain cardiac pacemakers or implantable cardioverter defibrillators (ICDs)

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:

• Any article of clothing that has metallic fibers or threads, metallic zippers, buttons, snaps, hooks, or underwire
• Hair barrettes, hairpins
• Beepers and cell phones
• Hearing aids
• Paper clips, coins, pens, keys
• Belt buckles, shoes, safety pins
• Watches, metallic jewelry
• Purse, money clip, wallet, cards with magnetic strips, credit/debit cards

The following objects, if near to the areas being imaged, may interfere with the image quality generated:

• Dental fillings (may distort images of the brain or facial areas; the same is true for orthodontic retainers and braces)

• Plates, screws, pins, or metallic mesh used in repairing a joint or bone

• Some tattoos or tattooed eyeliner (these distort MR images, and there is a chance of skin swelling or irritation of which black and blue pigments are the most troublesome)

• Metallic jewelry including those used for body modification or body piercing

• Joint replacement or prosthesis

• Makeup, another cosmetic with metallic components, nail polish

• Metallic spinal rod

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.

Side Effects:

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.

• Cardiovascular: Hypotension, hypertension, tachycardia, migraine, syncope, vasodilatation, pallor.

• Gastrointestinal: Abdominal discomfort, teeth pain, increased salivation, abdominal pain, vomiting, diarrhea.
• Nervous System: Agitation, anxiety, thirst, somnolence, diplopia, loss of consciousness, convulsions (including grandmal seizure), paresthesia.
• Respiratory System: Throat irritation, rhinitis, sneezing.
• Skin: Rash, sweating (hyperhidrosis), pruritus, urticaria (hives), facial edema.
• Special Senses: Conjunctivitis, taste abnormality, dry mouth, lacrimation, eye irritation, eye pain, ear pain.
• The effects of Gadolinium deposition in the brain are still unknown, although lawyers are now bringing suit.  The actor, Chuck Norris, is suing for $10 million for the “poisoning” of his wife by MRI Gadolinium!!  We tend to use Macrocyclic Gadolinium-Based agents, since these agents appear not to deposit much in the basal ganglia (Kanda, et al., AJNR Letter to the Editor, Feb 26, 2016).

Postmarketing Experience:

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.

• Anaphylactic shock, respiratory distress, and laryngeal edema [see Warnings and Precautions]
• Cardiac/respiratory arrest, shock
• Nephrogenic systemic fibrosis [see Warnings and Precautions]

The most frequently reported adverse reactions in the postmarketing experience were nausea, vomiting, urticaria, and rash.

Equipment

 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.[11][12]

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.

Personnel

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:

• Level 1 MR personnel: Those who have passed minimal safety educational efforts to ensure their own safety as they work within Zone III will be referred to henceforth as level 1 MR personnel.
• Level 2 MR personnel: Those who have been more extensively trained and educated in the broader aspects of MR safety issues, including, for example, issues related to the potential for thermal loading or burns and direct neuromuscular excitation from rapidly changing gradients, will be referred to henceforth as level 2 MR personnel. It is the responsibility of the MR medical director not only to identify the necessary training, but also to identify those individuals who qualify as level 2 MR personnel. It is understood that the medical director will have the necessary education and experience in MR safety to qualify as level 2 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.

MR Technologist

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.

Preparation

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)

Technique or Treatment

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.

Complications

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.

Clinical Significance

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.

Enhancing Healthcare Team Outcomes

MRI is the preferred study to diagnose a vast number of neurological & neurodegenerative diseases, infections, and other abnormal disorders in many areas of the human body. In general, MRI generates images that show subtle differences between pathologic and healthy tissues. Physician-scientists, nurse practitioners, 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). It is important for healthcare workers to know when to order an MRI and its limitations.