Gadolinium, When a “Harmless” MRI Can Rob You of Your Health

Gadolinium, When a "Harmless" MRI Can Rob You of Your Health

Gadolinium, When a “Harmless” MRI Can Rob You of Your Health or Worse

Magnetic resonance imaging (MRI) is believed to be a safer type of medical imagining. Having an MRI does not expose the patient to excessive X-rays or ionizing radiation from computed tomography (CT) scan or positron-emission tomography. In addition, MRI imagining is noninvasive unless the use of a contrast agent is needed. The primary contrast agent used for MRI imaging is gadolinium contrast, which was once believed to be safe and did not retain within the body. However, multiple anecdotal reports over the past few years and recent studies show otherwise. So, what are the known health issues associated with gadolinium contrast usage?

All About Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) is an imaging technology used to visualize internal structures of the body in great detail. Even though MRI use has been associated with nonnative magnetic field exposure, I still believe that it is a safer alternative to CT scan because of its ionizing radiation. During an MRI, a person lies on a movable platform that moves the person into a tunnel. A powerful magnet forms a strong magnetic field, shim coils that correct shifts in the primary magnetic field, gradient system that locates the magnetic resonance signal and the radio frequency return signal from your cells, and imaging equipment that are all housed within the chassis.1 2 3 4

At the start of the scan energy from an oscillating magnetic field temporarily is applied to the patient at the appropriate resonance frequency. The excited hydrogen atoms emit a radio frequency signal because protons within most of our tissues contain water molecules which vibrate forming an image of the area of the body being scanned. A receiving coil then measures the radio frequency signal. The radio signal may be made to encode position information by varying the primary magnetic field using gradient coils. As these coils are rapidly switched on and off, they create the 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. Contrast agents including gadolinium may be given to make the image clearer. Finally, the image is transmitted from the MRI machine to computers in a different room for the radiologist to examine.5 6 7

Each tissue returns to its equilibrium state after excitation by the independent relaxation processes of T1 and T2. T1 is spin-lattice; magnetization in the same direction as the static magnetic field and T2 is spin-spin; transverse to the static magnetic field. Magnetization is allowed to recover before measuring the magnetic resonance signal by changing the repetition time, creating a T1 image. Magnetization is allowed to decay before measuring the magnetic resonance signal by changing the echo time, creating a T2 image. The signal of the T1 and T2 images can be modified from high to low to show different organ systems and components of our body. For example, T1-weighted images are better at showing fatty tissue, melanin, gadolinium contrast areas, the gray matter within the brain, the cerebral cortex, and slow flowing blood. T-2 weighted images are better at showing edema, inflammation, the white matter within the brain, and paramagnetic material including iron and ferritin.8 9 10

An MRI provides good contrast images between different soft tissues of the body. There are some complications of using an MRI, however. MRI machines are not as widely available as CT scans, are slower at imaging, and the cost of the scan can be more significant. Artifacts, anomalies that appear on MRI scan results that occur during the imaging process which may cause misdiagnosis. In addition, if you have any ferromagnetic material in your body, an MRI is contraindicated because the magnetic field might rapidly heat or pull ferromagnetic material out of your body causing severe injuries or death. Tattoos that contain ferromagnetic material have been known to heat up and cause burns as well. Some people might have claustrophobia when they are within the MRI machine because you are moved into a “tunnel” during imaging. More “open” MRI machines exist that may help people suffering from claustrophobia. However, they are not common. MRI’s maybe safer than CT scans (fetuses are very susceptible to ionizing radiation) if needed during pregnancy, yet the effects of MRI have not been studied extensively on their health effects on fetuses. The use of gadolinium contrast is also not improved by the United States Food and Drug Administration for pregnant women. Finally, there have been reports of people becoming seriously or fatally injured from ferromagnetic material (oxygen tanks for example) being left in the MRI room, so make sure your technician spot checks that all ferromagnetic material is removed from the room before your MRI starts.11 12 13 14 15 16 17

What is Gadolinium?

Gadolinium was discovered in 1880 by Jean Galissard de Marginac of Switzerland is a chemical element with the atomic number of sixty-four on the periodic table. Gadolinium is named after Johan Gadolin, a Finnish chemist and geologist. In 1792 he isolated the first known rare earth compound, yttrium oxide, from a black mineral that had been discovered at Ytterby, Sweden. A few years later this ore, which contained several lanthanides, was named gadolinite, which contains gadolinium. Gadolinium is silvery-white, it is malleable, paramagnetic at temperatures above twenty degrees Celsius has radioactive isotopes and is a rare earth metal. The element is moderately reactive to air, water, and acids. Gadolinium is usually a constituent of other minerals including monazite and bastnasite and is mined in the United States, Russia, China, Australia, and India.18 19 20

Gadolinium is used in alloys that produce magnets, electronic components, and data storage disks. The use of even one percent of gadolinium for metallurgy can significantly improve the workability and resistance to oxidation at high temperatures of iron, chromium, and other metals. It is used in the core of nuclear reactors and neutron radiography shielding because it absorbs neutrons. Gadolinium compounds are also used for making green phosphors for color cathode ray tubes that were used in older televisions and computer monitors. Ligand bonded gadolinium is mainly used now as an injectable MRI contrast agent for enhancing imaging. Gadolinium itself has no known human biological role, and free ions of gadolinium are incredibly toxic.21 22

What Health Issues Arise From Using Gadolinium-based contrast agents Why I Do Not Recommend Their Use

Gadolinium-based contrast agents are widely used during MRI procedures throughout the world and “over 30 million doses of GBCAs are consumed worldwide, and more than 300 million doses have been administrated since their introduction.” Many radiologists claim that gadolinium is safe as long as you have normal kidney function, at most you may get a rash from its use at the intravenous site. Many also state that since gadolinium-based contrast agents are bonded to ligands, therefore, they are safe and do not accumulate within the body. But are gadolinium-based contrast agents as safe as they claim?23 24

Gadolinium-based contrast agents are bonded by a ligand because as I mentioned above gadolinium has no known human biological role and free ions of gadolinium that is not bonded are incredibly toxic. One of the main questions asked of the safety of gadolinium-based contrast agents is do the agents stay bonded to their ligands or are they frequently separated and gadolinium accumulates within our cells? Recent research indicates that gadolinium retention from the use of gadolinium-based contrast agents are more likely than we believed previously. Transmetallation from zinc and iron can occur and attract the ligand away from the gadolinium releasing toxic free gadolinium ions that may accumulate in the brain, skin, bones, eyes, liver, and kidney’s causing injury and inflammation.25 26 27 28 29

There are nine United States Food and Drug Administration approved gadolinium-based contrast agents. There are different types of contrast agents, and they are either linear, macrocyclic, and ionic, or nonionic. Linear chelates are flexible open chains which do not strongly bond to gadolinium and transmetallation is more likely to occur. Macrocyclic chelates are preorganized rigid rings of an almost optimal size that create strong bonds with the gadolinium which lead to less transmetallation. There is a difference in stability between the gadolinium-based contrast agents, for example, the linear nonionic agents OMNISCAN (approved for use by the United States Food Drug Administration in 1999) and OptiMARK (approved for use by the United States Food Drug Administration in 1992) are less stable because they are more susceptible to transmetallation because they are linear nonionic agents and are more likely to cause the condition, nephrogenic systemic fibrosis and gadolinium retention. ProHance (approved for use by the United States Food Drug Administration in 1992) and Dotarem (approved for use by the United States Food Drug Administration in 2013) are both macrocyclic gadolinium-based contrast agents and are less likely to be affected by transmetallation and cause nephrogenic systemic fibrosis and gadolinium retention, but it can still occur.30 31 32 33

One of the leading theories for gadolinium toxicity is the role of transmetallation where endogenous metals such as iron and zinc attract the ligand to release free gadolinium that deposits in the tissue as gadolinium phosphate. Lower thermodynamic stability of the GBCM will facilitate easier transmetallation with endogenous metals such as iron or zinc In support of transmetallation, animal and human studies have demonstrated increased zincuria after linear GBCM administration, particularly at toxic doses. Further, animal models of NSF also demonstrate increased urinary zinc excretion Zinc-dependent transmetallation could not fully explain NSF pathogenesis as exogenous zinc supplementation did not exaggerate the severity of fibrosis in animal models of NSF.34

Our studies and others have demonstrated iron mobilization in a subset of patients exposed to linear GBCM. In our prospective observation of 2 CKD patients, we observed that GBCM triggered iron mobilization, transferrin oversaturation and induced substantial elevations in serum ferritin. One of these patients required hemodialysis that normalized the iron studies but the patient eventually developed NSF.35

In a retrospective analysis, we could also confirm that transferrin saturation and serum ferritin levels were higher in ESKD patients with established NSF than in control ESKD patients. In an autopsy study of NSF patients, we further demonstrated that NSF is associated with tissue accumulation of not only gadolinium but also of significant amounts of iron. Using energy filtering transmission electron microscope, confirmed our observations by demonstrating juxtaposition of gadolinium and iron particles in the tissues of patients with NSF. Collectively, these observations pointed to a role of iron mobilization and tissue iron accumulation in the pathogenesis of gadolinium chelate toxicity.36

Free gadolinium ions are able to generate excessive amounts of oxidative stress within our mitochondria and our cells by increasing the formation of reactive oxygen species, mobilization of cellular iron, triggering apoptosis, transmetallation that occurs from zinc and iron stores, and competition with Ca2+ (calcium ions) in cellular processes causing a disruption of calcium homeostasis. Gadolinium has been shown in studies to trigger the release of multiple cytokines (IL-4, IL-6, IL-13 for example) which would trigger excessive inflammation and trigger the development of tissue fibrosis. Gadolinium has a similar ionic radius compared to calcium ions and it competes with calcium ions in cellular and biochemical processes, causing issues with calcium homeostasis. Gadolinium is capable of inhibiting stretch-activated and voltage-gated calcium channels, causing inappropriate cellular calcium influx, triggering oxidative stress and apoptosis. It can also block calcium ion dependent enzymes such as S-transferases, dehydrogenases, kinases, ATPase, and glutathione, causing further mitochondrial dysfunction.37 38 39 40

Gadolinium-based contrast agent administration induces mobilization of iron causing transmetallation of gadolinium and causing gadolinium deposits to occur. Gadolinium increases iron concentration within CD163+ macrophages that process and recycle our iron, inhibiting proper iron homeostasis. Inhibition of iron homeostasis increases labile iron pooling which leads to increased mitochondrial damage, tissue injury, and fibrosis. The labile iron pool is within the cytoplasm of our cells and can generate free radicals when iron homeostasis is disrupted, and too much free iron ions comprise the pool instead of bounded iron (ferritin for example). Iron from the labile pool can be taken up by mitochondria via mitoferrin to synthesize Fe-S clusters and heme groups for proper respiration.41 42

Gadolinium exposure is the only known cause of a condition known as nephrogenic systemic fibrosis. Symptoms of nephrogenic systemic fibrosis usually occur within two to ten weeks of the use of gadolinium-based contrast agents but may occur months or years after exposure. One instance of the condition occurred as late as eight years after contrast exposure in the reported literature. Symptoms of the condition include thickening and hardening (fibrosis) of the skin, subcutaneous tissues, and, sometimes, underlying skeletal muscle. If the skeletal muscle is affected pain, loss of range of motion, contractures, or loss of function may occur. Skin swelling, pain, and itching may occur. The areas of the body that are mainly affected include the arms and the legs, but the trunk may be affected as well.43 44 45

Clinical manifestation of the disease includes skin patterned plaques, your skin has a “cobblestone” appearance, marked induration (Peau d’orange), skin puckering, linear banding, superficial plaques, dermal papules, and scleral plaques. Histologic manifestation includes increased cytokine production (IL-4, IL-6, IL-13, and nuclear factor-kappa B (NFκB)-dependent chemokines CCL2, CCL8, CXCL10, CXCL11, and CXCL12, for example), increased spindle and/or epithelioid cells with few other inflammatory cells, CD34 + spindle or epithelioid cells with dendritic processes on either side of elastic fibers (tram-tracking), presence of both fine and ropey collagen surrounded by clefts, septal involvement, and preserved elastic fibers. Formation of fibrotic tissue may become systemic, extending to the pleura of the lungs and the diaphragm causing breathing issues. It may also proliferate the pericardium affecting the heart and the outermost layer of the three membranes covering the brain and spinal cord. Finally, restoration of proper kidney function if possible which is the elimination pathway for the gadolinium combined with proper plasmapheresis, improving mitochondrial health, and proper sunlight exposure may help improve the health of people suffering from nephrogenic systemic fibrosis. More information about how you might recover from gadolinium toxicity is near the end of the blog.46 47 48 49

The chance of developing nephrogenic systemic fibrosis from gadolinium-based contrast agents differs per a person’s genetics; the contrast agent used, the dosage of the contrast agent, your age, your weight, a person’s state of health, and how well your kidney’s function when attempting to clear gadolinium. However, I want to make clear that the functionality of the kidneys themselves are not the single cause of the disease, the disease is caused by gadolinium retention which can occur in someone with normal kidney function. Interestingly enough gadolinium-based contrast agents have been used in the United States since 1988, it took eighteen years before it was “discovered” they caused this dreaded disease.50 51 52 53 54

The safety record of GBCAs has been extremely impressive. Literature places the incidence of severe adverse reactions with GBCAs to be as low as 0.01%. During the first many years of their usage, until the late 1990s, GBCAs were found to be far less nephrotoxic than the iodinated contrast media. These early favorable results encouraged liberal use of GBCAs as “safe” contrast agents. In addition to their usage in MRI examinations, GBCAs also came to be used as substitutes for iodinated contrast media while carrying out conventional angiographies and contrast computed tomography in patients with deranged renal function.55

This trusting belief was, however, soon demolished by a concatenation of studies, which revealed a relationship between the use of GBCAs and the development of nephrogenic systemic fibrosis (NSF). The first report of skin fibrosis in these patients appeared in the year 2000. Six years later, two European groups suggested the causal relationship between the development of nephrogenic systemic fibrosis (NSF) and GBCAs. These studies came as a rude shock and necessitated “The Contrast Media Safety Committee of European Society of Urogenital Radiology” to establish guidelines on NSF in 2007. Since then, considerable literature has emerged which establishes a linear relationship between insufficient excretion of GBCAs in renocompromised patients and NSF due to retention of dissociated gadolinium. This risk was found to vary with the structure of each GBCA, being much higher in the case of non-ionic linear chelates than the relatively biostable macrocyclic GBCAs owing to the rapid dechelation of the former. These studies led to distinct modifications in the usage of intravenous MRI contrast agents, bringing the villain of NSF to heel.56

However, even before the fire of NSF was to go cold, new alarm bells have begun to toll. The more recent scientific literature seems to point that, despite a normal hepatobiliary function and intact blood–brain barrier, patients receiving GBCAs are liable to suffer gadolinium deposition in the neuronal cells. Specific brain regions have been found to demonstrate distinct MR signal changes due to cumulative gadolinium deposition in the wake of usage of GBCAs. Until recent, these changes were erroneously thought of as signs of specific pathologies. Much like NSF, this risk also appears to vary with the structure of GBCA used. The clinical import of this neuronal gadolinium deposition, however, still needs to be defined. Whether this would impair the neuronal function in the long run, or simply reflect a morphological artifact, remains a major clinical inquiry.57

The agents OMNISCAN, OptiMARK, and Magnevist have been implicated as the primary contrast agents that trigger nephrogenic systemic fibrosis. The European Commission has banned the use of OMNISCAN and Magnevist as intravenous MRI contrast agents in the European Union as of 2017. That being said recent research studies into the transmetallation of gadolinium-based contrast agents and multiple antidotal reports show that fibrosis and nephrogenic systemic fibrosis can occur in people with healthy kidney function as well. Wait, did the above reference study mention that gadolinium from transmetallation of gadolinium-based contrast agents can deposit within the brain as well?58 59

The United States Food and Drug Administration released a safety announcement in 2015 that brain deposits from intravenous gadolinium-based contrast agents are possible “The U.S. Food and Drug Administration (FDA) is investigating the risk of brain deposits following repeated use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). MRIs help detect abnormalities of body organs, blood vessels, and other tissues. Recent publications in the medical literature have reported that deposits of GBCAs remain in the brains of some patients who undergo four or more contrast MRI scans, long after the last administration. It is unknown whether these gadolinium deposits are harmful or can lead to adverse health effects.” In 2017, the United States Food and Drug Administration still claimed they have not found any negative effects of toxic gadolinium brain deposits. “A U.S. Food and Drug Administration (FDA) review to date has not identified adverse health effects from gadolinium retained in the brain after the use of gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI). All GBCAs may be associated with some gadolinium retention in the brain and other body tissues. However, because we identified no evidence to date that gadolinium retention in the brain from any of the GBCAs, including GBCAs associated with higher retention of gadolinium, is harmful, restricting GBCA use is not warranted at this time. We will continue to assess the safety of GBCAs and plan to have a public meeting to discuss this issue in the future.” Interestingly, enough later in 2017 the required a new class warning for gadolinium-based contrast agents “The U.S. Food and Drug Administration (FDA) is requiring a new class warning and other safety measures for all gadolinium-based contrast agents (GBCAs) for magnetic resonance imaging (MRI) concerning gadolinium remaining in patients’ bodies, including the brain, for months to years after receiving these drugs. Gadolinium retention has not been directly linked to adverse health effects in patients with normal kidney function, and we have concluded that the benefit of all approved GBCAs continues to outweigh any potential risks.” As I have shown proof in multiple above studies that the United States Food and Drug Administration is full of bs when they state gadolinium retention has not been directly linked to adverse health effects and that the benefits of using the agents outweigh the risks, if that is true, why the stern warning? We were told that that was highly unlikely for decades, how can brain accumulation even be possible?60 61 62

Gadolinium-based contrast agents are not supposed to cross the blood-brain barrier easily. However, there are new studies that show gadolinium is able to accumulate within the brain from the use of contrast agents. Disruption of the integrity of blood-brain barrier, iron metabolism issues within the brain, and accumulation of gadolinium in cerebral spinal fluid can lead to neural gadolinium accumulation. The integrity of the blood-brain barrier can be compromised from many different health issues, some examples include gut dysbiosis (excessive endotoxins in the bloodstream for example), diabetes, heavy metal toxicity, multiple sclerosis, congenital defects of the blood brain barrier, brain cancer, meningitis, epilepsy, systemic inflammation, stroke, and Alzheimer’s disease. Seventy-six percent of stroke patients had gadolinium-basted contrast leak into their eyes during MRI procedures. The gadolinium-based contrasts crossed the blood-ocular barrier and might cause deposits within the eyes, compromising vision. Finally, gadolinium targets ferroportin-expressing iron-recycling areas of brain structures (such as cerebellar dentate nucleus and globus pallidus) that are involved in active regulation of iron and manganese metabolism to result in metal accumulation (gadolinium, iron, and manganese) causing neurotoxicity.63 64 65 66 67 68 69 70 71 72

OMNISCAN Insert73

I want to briefly cover the insert for OMNISCAN so that you can get an idea of the information that is offered by General Electric to radiologists. OMNISCAN is a commonly used gadolinium-based contrast agent for MRI imagining in the United States.

Interesting a warning on the first page that states that OMNISCAN should not be injected into the spinal canal, it should not be given to people with poor kidney health, and the dosage should be closely monitored.

In depth warnings and contraindications on the second page. Interesting there is a section on gadolinium retention and that it may occur with OMNISCAN, it fact the insert states that is occurs more often with OMNISCAN. It mentions the consequences of gadolinium retention in the brain have not been established. I believe this is an incorrect statement it has been shown in multiple studies. Finally, it mentions that adverse event can occur in people with normal kidney function.

Recommendation that a non-contrast MRI should be taken first because the use of OMNISCAN might create artifacts.

Interesting, the insert admits that OMNISCAN might interfere with iron and calcium.

OMNISCAN should not be used during pregnancy!

Or should it be given while nursing.

Finally, it should not be given to children under the age of two. A very low dose is recommended for children over the age of two.

No long term animal studies have been done to determine if OMNISCAN is carcinogenic.

Radiologists and physicians are supposed to follow these guidelines when using and recommending OMNISCAN. For people who have had a gadolinium-based contrast agent like OMNISCAN did your healthcare professional advise you of the risks of gadolinium retention like they were required to do by the insert? I would assume no because if they did you probably would not have the contrast given to you. If only healthcare professionals would read the inserts of the medications they prescribe and follow their directions, many people would not become ill or die from errors caused by medical ignorance.

What Might Be Done to Properly Detox Gadolinium?

There is much debate about how to properly detox gadolinium. The following link from The LightHouse Project gives good information on how one might test for gadolinium toxicity. However, there is not much research on how it should be done correctly. Some people recommend intravenous ethylenediaminetetraacetic acid (EDTA), but it has not been tested for his efficacy and safety when chelating gadolinium. In addition, if you are mercury burdened, then you cannot use intravenous EDTA for chelation because it can displace mercury throughout the body and not properly eliminate it. Some people recommend the Cutler protocol using oral dimercaptosuccinic acid or 2,3-dimercaptopropane-1-sulfonate and then oral alpha lipoic acid. I believe the Cutler protocol would be safer. However, it is unknown how effective it is when it comes to chelating gadolinium, and it cannot be performed if someone has any oral mercury amalgams.74

Proper sunlight exposure, infrared therapy, non GM sourced vitamin C ingestion (vital for collagen production), and Vital Proteins collagen peptide ingestion may help improve skin health that is affected by gadolinium by reducing inflammation. Epsom salt baths may also help to improve joint pain associated with gadolinium toxicity. Proper vitamin D production from the sun, vitamin K2 supplementation, and magnesium supplementation may help improve calcium homeostasis which is affected by gadolinium toxicity. Morley Robbins Root Cause Protocol may help improve ceruloplasmin levels and lower ferritin, which would improve the health of your collagen and reduce inflammation. Supplementation of ubiquinol with PQQ may help improve your mitochondrial function that is hindered by gadolinium toxicity. Proper omega 3 fatty acid ingestion, healthy saturated fat ingestion (extra virgin coconut oil, MCT oil, grass fed butter, grass fed ghee, pastured organic meat), high dose (two to three grams or more for example) Meriva curcumin supplementation, proper sleep hygiene, proper light exposure, and intravenous phospholipid therapy may help improve neural function and relieve brain inflammation. Finally, following a healthy diet like Perfect Health Diet or if needed autoimmune paleo diet may help bring some relief as well.75 76 77

Conclusion

I do not recommend the use of gadolinium-based contrast agents for MRI procedures because of gadolinium retention. Gadolinium is toxic and even the best gadolinium bonded contrast agents United States Food and Drug Administration approved, ProHance and Gadavist may cause gadolinium retention. Gadolinium retention causes fibrosis, mitochondrial dysfunction, interruption of calcium homeostasis, and brain inflammation. There are newer MRI contrasts that are currently in research for future use, but they may not be safe either. Manganese-based contrast agents may cause similar neurotoxicity issues. Gena O’Kelley, Chuck Norris’s wife, was personally affected by gadolinium toxicity and is suing multiple pharmaceutical companies and is working to spread awareness as well. I also want to thank The LightHouse Project and the MRI Gadolinium Toxicity Illnesses Facebook group for spreading awareness on the dangers of gadolinium-based contrast agents. To those who are affected or have loved ones that were affected by gadolinium toxicity, I hope you can recover and find peace.78 79 80

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