Contrast Agents in Magnetic Resonance Imaging PDF

Al- Farahidi University College of Medical Techniques Department of Radiology &Sonar CONTRAST AGENTS IN MAGNATIC RESONANCE IMAGING MECHANISM OF ACTION / GADOLINIUM GASTROINTESTINAL CONTRAST AGENTS...

Al- Farahidi University College of Medical Techniques Department of Radiology &Sonar CONTRAST AGENTS IN MAGNATIC RESONANCE IMAGING MECHANISM OF ACTION / GADOLINIUM GASTROINTESTINAL CONTRAST AGENTS LECTURE 3 SECOND YEAR 2024 /2025DR. HALA AL-BAGHDADI  CONTRAST AGENTS IN MAGNETIC RESONANCE IMAGING ❖ HISTORICAL DEVELOPMENT Shortly after the introduction of clinical MRI, the first contrast enhanced human MRI studies were reported in 1981 using ferric chloride as a contrast agent in the gastrointestinal tract. In 1984, Carr et al. first demonstrated the use of a gadolinium compound as a diagnostic intravascular MRI contrast agent. Currently, around one quarter of all MRI examinations are performed with contrast agents. MECHANISM OF ACTION Whilst radiographic contrast agents use a direct alteration in tissue density to allow thevisualization of structures, the MRI contrast agents act indirectly by altering the magnetic properties of hydrogen ions (protons) in water and lipid which form the basisof the image in MRI. To enhance the inherent contrast between tissues, MRI contrast agents must alter the rate of relaxation of protons within the tissues. The changes in relaxation vary and, therefore, different tissues produce differentialenhancement of the signal. If the T1 relaxation is more rapid then a larger signal is obtained (brighter images), but theopposite is true for T2 relaxation, where more rapid relaxation produces reduced signal intensity (darker images). There are different means by which these effects on protons can beproduced using a range of MRI contrast agents. MRI contrast agents must exert a large magnetic field density (a property imparted by their unpaired electrons) to interact with the magnetic moments of the protons in the tissues and soshorten their T1 relaxation time which will produce an increase in signal intensity (see Fig. 2.3). The electron magnetic moments also cause local changes in the magnetic field, which promotesmore rapid proton dephasing and so shortens the T2 relaxation time. All contrast Intravascular contrast media agents shorten both T1 and T2 relaxation times but some will predominantly affect T1 (longitudinal relaxation rate) and other predominantly T2 (transverse relaxation rate). Agents with unpaired electron spins are potential contrast agents in MRI. These may beclassified under three headings: 1. Ferromagnetic. These retain magnetism even when the applied field is removed. This maycause particle aggregation and interfere with cell function, making them unsafe for clinical useas MRI contrast agents. 2. Paramagnetic – e.g. gadolinium. These contrast agents have magnetic moments whichalign to the applied field, but once the gradient field is turned off, thermal energy within the tissue is enough to overcome the alignment. Gadolinium compounds may be made soluble bychelation and can, therefore, either be injected intravenously or used as an oral preparation. Their maximum effect is on protons in the water molecule, shortening the T1 relaxation time and hence producing increased signal intensity (white) on T1 images (Fig. 2.3). 3. Superparamagnetic – e.g. particles of iron oxide (Fe3O4). These cause abrupt changes inthe local magnetic field which results in rapid proton dephasing and reduction in the T2 relaxation time, and hence producing decreased signal intensity (black) on T2 images (Fig. 2.4). Superparamagnetic compounds were initially produced only as large particles in a colloid suspension for gastrointestinal contrast. However, more recently they have become available assmall particles of iron oxide (SPIO) agents and ultrasmall particles of iron oxide (USPIO) agents. Both SPIO and USPIO agents have submicron global particle diameters and are small enough toform a stable solution which can be injected intravenously. GADOLINIUM The gadolinium (GD) chelates represent the largest group of MRI contrast media and areavailable in three forms: 1. Extrsacellular fluid (ECF) agent: by far the most commonly used form of gadolinium. Includes (i) Gd-diethylenetriaminepentaaceticacid (DTPA), dimeglumine gadopentetate (Magnevist,Schering), (ii) Gadodiamide (Gd-DTPA-bismethylamide) (Omniscan, Nycomed Amersham) and (iii) Gd-DO3A, Gadoteridol (ProHance, Bracco, Merck, Squibb). They all contain gadolinium, an 8-coordinate ligand binding to gadolinium and a singlewater molecule coordination site to gadolinium and all have a molecular weight similar to iodinated contrast agents. After intravenous injection they circulate within the vascular systemand are excreted unchanged by the kidneys. The ECF agents do not cross the normal blood–brain barrier but do cross the abnormalblood–brain barrier. ECF agents are used for angiography but rapidly leak out of the vascular space into the interstitial space so are used only for dynamic arterial studies. There is a wide range of indications for these contrast media including improved detection rates and more accurate delineation andcharacterization of tumours. 2. Liver agents: the excretion pathway of the gadolinium chelates can be altered to producecompounds such as Gd-BOPTA (gadobenate, Multihance) and Gd-DTPA (Primovist), which are Intravascular contrast media _taken up by hepatocytes and cleared intact via the hepatobiliary system Another paramagneticliver specific contrast agent is the manganese chelate Mn-DPDP (Telescan). These agents are used to improve detection of liver lesions which do not contain hepatocytes(therefore do not take up the contrast), such as liver metastases, and to characterize lesions which do take up the contrast, such as hepatocellular carcinoma. They can also be used to provide positive contrast (T1 weighted) of the hepato-biliary system. 3. Blood pool agents: the blood pool agents remain longer in the vascular space than ECF agents and allow a wider range of vascular imaging. The first of these contrast agents approved forclinical use in Europe, gadofosveset trisodium (Vasovist, Bayer Schering), has recently been introduced. For ECF gadolinium agents, usually 0.1 mmol kg body weight (e.g. 0.2 ml of Magnevist kg ; up to 0.2 mmol kg Adverse reactions Gadolinium contrast agents are very safe and well tolerated; theyhave a much lower incidence of adverse reactions than iodinatedcontrast agents. Adverse reactions to gadolinium are mostly mild and self-limiting and can be divided into acute and delayed reactions.Acute adverse reactions These are rare, but the following have been described: 1. Urticaria and rash 2. Nausea/vomiting 3. Dizziness and confusion 4. Dyspnea, chest discomfort and palpitation 5. Anaphylactoid shock Patients with a history of previous adverse reaction to gadolinium contrast agents have up to aneightfold increase in likelihood of experiencing adverse reactions, and those with asthma, documented allergies or previousadverse reaction to iodinated contrast are also at increased risk of adverse reaction. Delayed adverse reactions 1. Renal impairment – when used at the standard doses given above, gadolinium contrastagents do not cause significant impairment of renal function. It was initially thought that gadolinium agents might be used as a replacement for iodinated contrast for those at increasedrisk of contrast nephrotoxicity. However, when used at the high doses required to give equivalent X-ray attenuation, gadolinium-based contrast media have more nephrotoxic potentialthan iodinated contrast. 2. Nephrogenic systemic fibrosis (NSF) – this systemic disorder, first described in 2000, is characterized by increased deposition of collagen with thickening and hardening of the skin, contractures and, in some patients, clinical involvement of other tissues. NSF only occurs in patients with renal disease and almost all patients with NSF have beenexposed to gadolinium-based contrast agents within 2–3 months prior to the onset of the disease. The mechanism by which renal failure and gadolinium-based contrast agents triggerNSF is not known. The overwhelming majority of reported cases of NSF representpatients who had previouslybeen given gadodiamide (Omnisc but there are some reports of NSF associated with other gadolinium contrast agents. Reported figures from Denmark show that 5% of all patients with severe renal impairment who had been givenOmniscan developed NSF. Precautions for prevention of adverse reactions Detailed guidelines are available from the American College of Radiology and the EuropeanSociety of Urogenital Radiology. These form the basis for the following advice. Acute adverse reactions 1. Identify patients at increased risk of reaction because of previous gadolinium reaction, asthma,allergies or previous adverse reaction to iodinated contrast. 2. For those at increased risk consider an alternative test not requiring a gadolinium agent. 3. If proceeding with i.v. gadolinium contrast: a. patients who have previously reacted to one gadolinium based contrast agent should be injected withdifferent agent if they are re-studied b. although there is no clinical evidence of the effectiveness of premedication, it is suggested that consideration be given to Intravascular contrast media the use of premedication such as oral prednisolone 30 mg orally 12 and 2 hours before contrastmedium c. those with at increased risk of adverse reaction should be monitored more closely after injection. Delayed adverse reaction: 1. Identify patients at risk of NSF because of impaired renal function (GFR