MRI Contrast Agents Jerry Allison Ph.D Chris Wright B.S Tom Lavin B.S Nathan Yanasak Ph.D Tom Hu Ph.D MBA December 12th, 2007 Outline • Introduction to MR Contrast Agents        Exogenous Paramagnetic Agents Superparamagnetic Agents Ferromagnetic Agents Positive Contrast Agents Negative Contrast Agents Route of Administration • Clinical Based MRI Contrast Agents/Examples Outline • Introduction to MR Contrast Agents        Exogenous Paramagnetic Agents Superparamagnetic Agents Ferromagnetic Agents Positive Contrast Agents Negative Contrast Agents Route of Administration • Clinical Based MRI Contrast Agents/Examples Contrast Agents • • • • • • • Exogenous Paramagnetic Agents Superparamagnetic Agents Ferromagnetic Agents Positive Contrast Agents Negative Contrast Agents Route of Administration Contrast Agents • Contrast agents are useful for detection of tumors, infection, inflammation, infarction and lesions Contrast agents alter T1, T2, or T2* of various tissues, producing contrast • Barium and iodine compounds are used to enhance contrast in xray procedures These compounds are sometimes referred to as contrast “media” since their presence appears directly in the images • MRI contrast is enhanced using contrast “agents” since the contrast is not directly imaged but rather the effect that the magnetic properties of the contrast agent has on the relaxation of tissues is imaged Contrast Agents (Exogenous) • A variety of paramagnetic, superparamagnetic and ferromagnetic contrast agents can be administered i.v., orally or rectally to manipulate tissue contrast • Contrast agents are generally described by their magnetic properties or contrast enhancement  paramagnetic agents  ferromagnetic agents  superparamagnetic agents Contrast Agents (Exogenous) • Paramagnetic substances have positive magnetic susceptibility due to the presence of one or more unpaired electrons:  Gd3+ unpaired electrons  Dy3+ unpaired electrons  Fe2+ unpaired electrons  Mn3+ unpaired electrons Contrast Agents (Exogenous) • Ferromagnetic substances are solids with crystalline structures that develop small magnetic domains When placed in an external magnetic field (B0), the multitude of magnetic domains will align with the field and retain that magnetism when removed from the Bo field  Iron, Nickel and Cobalt have ferromagnetic properties Contrast Agents (Exogenous) • Superparamagnetic substances are smaller solid particles each of which develop a “single domain” Like ferromagnetic substances, the domains align in the external magnetic field; unlike ferromagnetic particles, the alignment disperses when the paramagnetic substance is removed from the external field  Magnetite Fe3O4 (i.v or oral) Contrast Agents Positive contrast agents: • Positive contrast agents cause hyperintensity on T1 weighted images The presence of a positive agent stimulates an increase in spin flip transitions resulting in reduced T1 values and increased brightness on T1 weighted images Gd-based MR Contrast Agents • OptiMARK by Mallinckrodt Inc  Gd-DTPA-BMEA: gadoversetamide  dose: 0.1 mmol/kg / 0.2 mL/kg Indications and Usage • Central Nervous System • Extracranial/Extraspinal Tissue • Body Relative Concentration for Indications • The concentration of MRI contrast is intermediate to x-ray and nuclear medicine contrast  10-3 to 10-2 mmol/kg X-ray (iodine)  10-5 to 10-3 mmol/kg MRI  < 10-7 mmol/kg Nuclear Medicine Mn-based MR Contrast Agents • Manganese dipyridoxyl-diphosphate (MnDPDP; Teslascan) Fe-Based MR Contrast ... OptiMARK) Gd-based MR Contrast Agents • MultiHance by Bracco Diagnostics  Gd-BOPTA: gadobenate dimeglumine  dose: 0.05 mmol/kg for Liver MRI; 0.1 mmol/kg for CNS Gd-based MR Contrast Agents... Fibrosing Dermopathy (NFD)” • International Society for Magnetic Resonance in Medicine (ISMRM; www.ismrm.org) • Gadobenate Dimeglumine (marketed as MultiHance) • Gadodiamide (marketed as Omniscan)... Contrast Agents Negative Contrast Agents Route of Administration • Clinical Based MRI Contrast Agents/Examples Gd-based MR Contrast Agents • • • • • Gadobenate Dimeglumine (marketed as MultiHance)