![]() This has been demonstrated in dedicated MR studies of the liver, brain tumors, and the vascular system. HSA (13 nm in diameter, 67,000 Da) serves as a macromolecule carrier for Gd-BOPTA demonstrating a stronger enhancing effect at equivalent dose and serum concentration to conventional extracellular contrast agents. Studies by Cavagna and colleagues showed that Gd-BOPTA (gadobenate dimeglumine, MultiHance ®, Bracco, Princeton, NJ, USA) leads to a stronger T1 shortening because of its weak affinity for human serum albumin (HSA) (Fig. Usually after intravenous bolus injection or infusion, GBCA do not cross the blood/brain barrier (BBB), but in the event of BBB disruption, increased extravasation of contrast medium into the CNS can occur quite rapidly. Excretion is predominantly renal and 1 % or less via the hepatobiliary system. These Gd-chelates do not show any cellular uptake or any characteristics to bind serum proteins. Using a T1-weighted MR sequence, these agents increase signal-to-noise ratio (SNR) of perfused tissue and improve contrast-to-noise ratio (CNR). All of them are paramagnetic i.e., they gain magnetic properties in a strong magnetic field reducing the T1 and T2 relaxation times of nearby water protons. The ECF MRCM currently approved in Europe for the diagnosis of, e.g., CNS diseases and in regular use are Gd-DTPA, Gd-HP-DO3A (gadoteridol ProHance ®, Bracco, Princeton, NJ, USA), Gd-DTPA-BMA (gadodiamide Omniscan ®, GE Healthcare, Princeton, NJ, USA), Gd-DOTA (gadoterate meglumine Dotarem ®, Guerbet, Villepinte, France), Gd-BT-DO3A (gadobutrol Gadovist ®, Bayer HealthCare, Montville, NJ, USA), and Gd-DTPA-BMEA (gadoversetamide OptiMARK ®, Covidien, Mansfield, MA, USA). Additional six Gd-based contrast agents (GBCA) were developed and are now routinely used in many countries. The first MR contrast agent, gadopentetate dimeglumine (Gd-DTPA Magnevist ®, Bayer HealthCare, Montville, NJ, USA), entered clinical trials of MRI brain studies and was initially marketed in parts of Europe and Asia in 1998 and later on in the USA. ![]() Ġ.5 M contrast agents with paramagnetic properties were the first to be introduced for clinical use. An iso-osmolar contrast medium (IOCM) is considered to have least toxicity. In the end there are nonionic dimers containing 6 iodine atoms each molecule (ratio 1:6). The osmolality depends also on the iodine concentration, which typically ranges from 300 mg I/mL (=670 mOsm/kg H 2O) to 370 mg I/mL (=800 mOsm/kg H 2O) (Appendix 15.1). Nonionic iodinated monomers (ratio 1:3) are also of less osmolar than ionic because of fewer particle number in water, i.e., nonionic agents do not require an accompanying cation and therefore have lower osmolality and belong to the group of low-osmolar CM, short LOCM. Then there are ionic dimers containing 6 iodine atoms (ratio 1:3) and having less osmolality than HOCM. ![]() These agents belong to the group of high-osmolality contrast medium, short HOCM. This means that each ionic monomer will dissociate into two particles due their ionicity, so the ratio is 2:3. The ionic iodinated contrast agents contain three iodine atoms (in a monomer unit) and are having higher osmolality than blood. Normal human reference range of osmolality in plasma is about 280–300 milliosmoles per kilogram. Some MR contrast media have characteristics of two classes, e.g., the majority of the molecules take an extracellular path being excreted via the kidney and the minor amount presents an intracellular pathway, e.g., liver-specific metallochelates are partially excreted via the biliary system. CM with intracellular uptake provide tissue-specific characteristics, e.g., they are taken up by lymphatic cells or hepatocytes, e.g., Gd-EOB-DTPA. For this class of agents (ECF compounds), there is no intracellular uptake described. These are often called “unspecific agents” and allow the evaluation of physiological parameters, such as the status or existence of the blood/brain barrier or the renal function. First-generation MR contrast agents distribute within the intravascular space and due to its small molecule size diffuse into the interstitial space of extracellular fluid (ECF) and according to the law of equilibrium back into the intravascular compartment. Intravenously (IV)-injected CM behave differently. Contrast agents are used to enhance image contrast between pathological or anatomical structures of interest and their surrounding tissue or liquid.
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