Gadolinium-Based MR Contrast Agents in Imaging Brain and Spine - Essay Example

Name : xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx Tutor :xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx Title : Gadolinium-Based MR Contrast Agents (GBMCA) in imaging of the brain and spine. Institution : xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx Date :xxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxxx @ 2011 Introduction MRI contrast agents refers to a collection of contrast media which are used in the improvement of body structures found within the body in magnetic resonance imaging. Gadolinium based compounds happen to be the most widely used in enhancing contrast. When it has been injected inside the person gadolinium contrast medium normally makes some tissues, disease processes or abnormalities to become more visible on magnetic resonance imaging scans. The gadolinium based contrast medium can at times be referred to as an MRI agent or contrast medium. The gadolinium contrast medium has complex molecules with atoms arranged in them and held one to the other by chemical bonding. A carrier molecule and a gadolinium ion which is the active part of the MRI make up the chemical bonds. The word chelating agent is used to refer to the carrier molecule and it does the modification of gadolinium distribution in the body to counter its toxicity and at the same maintain the contrast properties within it. It has to be injected inside the vein as it goes together with the MRI scan. Gadolinium based MRI contrast agents change the times of relaxation for body cavities and tissues in which they occur. This can provide a lower or higher signal and this depends on image weighting. Many of the MRI contrast agents operate by reducing T1 relaxation time for those protons that are situated nearby Reimer, Parizel and Stichnoth (1999). The T1 shortening results from increased rates in stimulated emission from the high states of energy to the states with low energy. Thermal vibration in the metal ions with strong magnetism produces the stimulation. These ions form magnetic fields that oscillate at certain frequencies that correspond with the difference in energy between spin states. GBMCA can be administered into the body through injections or by oral means depending on the subject that has the interest. Oral administration works best with G.I tract scans whereas intravascular administration is used more for many of the other scans. A number of agents for these two types can enhance the scans routinely. Those GBMCA which are delivered via the blood happen to be chelated metals. Gadolinium based MRI contrast agents happen to be the most widely used in enhancing vessels in MR angiography or for then enhancement of brain tumor which is involved in degrading the blood brain barrier. For the bigger vessels like aorta and the branches on it the dose for gadolinium can be low to the tune of 0.1 mmol/kg of body mass. High concentrations are applicable to vasculature that is finer. Because they are very hydrophilic gadolinium chelates don’t cross the blood brain barrier. Therefore these can be vital in the enhancement of tumors and lesions where there is leaking of the GD. In the other part of body the Gd at first is left within the circulation but later distributes within the interstitial space if not eliminated through the kidneys. When in the form of free ions the toxicity of gadolinium is very high. It was believed to be safe when it is administered in the form of a chelated compound before utilization of certain Gd chelates was found to have an association with a severe and rare complication called nephrogenic systemic fibrosis and is responsible for causing fibrosis in several organs and tissues inside the body. Patients that have a bad renal function have higher risks of nephrogenic systemic fibrosis. The classification of the compounds is done on the basis of whether they posses linear geometry or are macro cyclic and if they are ionic or not ionic. Those ionic Gd compounds that are cyclical are believed to be he ones with the lowest chances of releasing the Gd ion and therefore they are safer than all the rest. Various ranges of contrast agents that have gadolinium occur in various territories. Within the U.S for example those Gd chelated contrast agents approved by the Food and Drug Administration include gadodiamide, gadobenic acid, gadopentetic acid, gadoteridol, gadofosveset, gadoversetamide and gadoxetic acid. Apart from those contrast agents containing gadolidium which have the FDA approval and approval from other organizations fro marketing there exists certain others which have been given generic names from the World Health Organization. These names are gatobutrol, gadocoletic acid, gadodenterate, gadomelitol, gadopenamide and gadoteric acid. Gadolinium contrast medium is applicable in about 30 percent of the MRI scans to help in making the scanned pictures or images of the internal structures of the body more clear. This helps to improve the MRI scan’s diagnostic accuracy. For instance it can make the inflammation, growth, tumor, blood vessels and the scarring on the cardiac muscle more visible as it also does assessment for the flow of blood to the organs like the heart and the brain. The patient is given advice before receiving the MRI scan that in the course of the scan there will be injection of gadolinium contrast medium. The injection is given by a radiologist or nurse performing the MRI scan. Gadolinium contrast medium is normally given via a needle into the bloodstream on the arm (Reamer et al 1999). MRI contrast agents which are gadolinium based are useful in improving accuracy of diagnosis in certain conditions like inflammation and some infectious diseases in the brain, soft tissues, bones and spine because they make work easier for the radiologist to identify where and what the problem is. Industrial guidelines and Safety implications Gadolinium contrast medium has been found to be generally safe. There are no common reactions or side effects although they can occur sometimes. Sometimes adverse reactions such as slight headache, dizziness and nausea may occur immediately after the injection. This normally happens in 1 percent to 5 percent of injections. Sometimes a cold feeling can take place at the site of the injection. Allergic reactions can occur although they ar5e very rear. These types of severe reactions that can sometimes have difficulty breathing and swollen lips and the mouth as well take place in approximately 1 out of every 10 people treated with gadolinium. Such severe reactions on general terms respond well to treatment with drugs in an emergency. In those patients that have normal functioning of the kidney a big portion of the gadolinium contrast medium is that is injected passes out almost wholly through the urine in 24 hours Edelman, Hesselink, and Zlatkin, (1996). Gadolinium contrast medium should not be used in patients that have kidney failure which is acute or chronic or reduced kidney function and another condition called hepatorenal syndrome in which the functioning of the kidneys and liver is reduced. A nephrogenic systemic fibrosis which is a debilitating disease that forms skin contractures or tightening and thickening of he skin and the damage of internal organs has been seen in certain gadolinium based contrast agents in a small number of portions with preexisting abnormalities in the functioning of the kidneys. As indicated earlier the gadolinium based agents do not have nephrotoxicity that is associated with contrast media that is iodinated. Therefore they are safe. Slight adverse effects take place in an infrequent manner and among them is taste pervasion and nausea and hives. Although it is not possible to differentiate these agents based on slight adverse effects they have differences in the ability of the chelates because clinical lab abnormalities are known with those agents that are less stable. Worth to emphasize about the MR contrast agent safety is Laili’s work in which he published a study whereby hypnotic suggestion could be seen to effectively reduce adverse reactions from urographic contrast agents to a big level. In the study the emesis and nausea incidences fell from 9.5 percent to 1.5 percent. The conclusion here was that the factor with the most importance is the fear of reactions from the urographic contrast media that are undesirable which the radiologist may engender or even the approach of the radiologist to the patient. The overt manifestations on the skin known as nephrogenic systemic fibrosis include the participation of muscles, lungs, liver and difficulty in hypercoagulability as well as thrombotic events. Those cutaneous lesions that are associated with NSF are the color of the skin and at times are erythematous papules which arise in symmetric ways on trunk and limbs which often progress to form brawny plaques. Patients normally complain of pruritus with sharp pains on the lesions that appear on the skin Atlas (1996). In certain cases where there are extremities fibrosing effects are normally rapid in their progression which leads to contractures in the limbs and reduced mobility. The disease may cause death and has no cure that is known. The degree of severity of renal insufficiency in those patients that are affected by NSF can vary from acute and reversible renal insufficiency to those patients that have renal failure that is chronic on long term dialysis. The current common hypothesis shows that NSF results from the instability of gadolinium chelates and particularly dechelation in vivo. Instability in some gadolinium chelates particularly omniscan is an old discussion because this issue has been referred to all through in the development of the agents. The ulceration on the skin and the degenerative lesions in the germinal epithelium of the testicles were described after repeated application of large doses of OptiMARK and Omniscan in rats in the process of preclinical studies for regulation. There are safety concerns over the serious injuries on patients that are associated with procedures of magnetic resonance. These issues include the burns caused by cables and electrodes in the process of MRI exams, certain injuries among patients with neurological stimulators implanted in them, burns in those patients with transdermal patches on, and the metallic objects that are brought inside the MR unit which fly in a room killing people. Molecular structure All the known gadolinium contrast agents happen to be chelates which have the gadolinium ion (Gd3+). There are 2 gadolinium chelate categories that are structurally distinct and they are the Cyclic chelates like gatoteridol, gadoterate meglumine in which Gd3+ occurs in a cavity. The others are the linear chelates with examples like gadopentetate dimeglumine and gadodiamide. There is excess chelate in the preparation of the contrast agent to avoid toxicity in the gadolinium (GD3+) within a solution. High concentration of chelates shows indirectly that there is likelihood that release of free gadolinium from the chelate complex will be easy. Certain gadolinium based contrast media have a higher likelihood of releasing free Gd3+ via the process known as transmetallation using endogenous ions in the body. The agents possess the biggest chelate amounts. Gadodiamide is different from the rest of the gadolinium based contrast media except gadoversetamide 2 because it carries too much chelate and has a high likelihood of releasing free Gd3+ in camparison to the rest of the agents Edelman, Hesselink, and Zlatkin, (1996). Cyclic molecules provide better binding and protection to Gd3+ when compared to linear molecules. Ionic cyclic chelates have a lesser likelihood of releasing free Gd3+. They do not require excess chelate and their half life for dissociation is the longest. Linear gadolinium chelates that are not ionic like gadodiamide have a high likelihood of releasing free Gd3+ within the body and they posses excess chelate with the highest quantity. Again the molecular charge can increase the possibility of free Gd3+ release via the present binding strength on the chelate. Conclusion In conclusion the paper carries a discussion on gadolinium based MR contrast agents as used in spine and brain imaging. Molecular structure, industrial guidelines and safety implications of the use of these contrast agents have also been discussed in detail. These contrast agents are very important in medical practice especially in scanning where they enable radiologists to identify the problem in the body and even the location of that problem. General the MRI contrast agents based on gadolinium are safe only for a few reactions that occur on certain people. however it is important that more research is carried out in order to get rid of the existing adverse reactions on people. Works cited Atlas, S. W. 1996 (Ed.) M agnetic Resonance Imaging of the Brain and Spine. Philadelphia: Lippincott Williams & Wilkins. Reimer, P., Parizel, P.M. and Stichnoth, F.-A. 1999, Clinical MR Imaging: A Practical Approach. Germany: Springer. Edelman, R.R., Hesselink, J.R. and Zlatkin, M.B. 1996, Clinical MR Imaging: Volume1, 2nd edn. Philadelphia: WB Saunders & Co. Read More