RES contrast agents were colloid suspensions consisting of small (30-200 nm) clusters of iron-containing molecules forming single magnetic domains and known generically as ferrites, magnetites, ferumoxides, or superparamagnetic iron oxides (SPIOs). Superparamagnetism is a property exhibited by certain metal complexes stronger than paramagnetism but not as powerful as ferromagnetism. These particles were phagocytized by macrophages of the RES, accumulating in normal liver, spleen and lymph nodes but seldom in neoplasms.
Although SPIOs shortened T1, their dominant effect was to reduce T2 and T2*. The mechanism of preferential T2/T2* shortening by these particles derived from bulk susceptibility effects and distortions of the local magnetic field. Water molecules diffusing near these particles became dephased by the local field inhomogeneities, and signal loss ensued. When a T2- or T2*-weighted pulse sequence was performed, normal areas of liver and spleen (that naturally accumulated the contrast agents) showed reduced signal intensity, while tumors, cysts, and other lesions did not change intensity and remained bright.
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Having lived through the first SPIO era in the 1990's, I must say that I am not particularly disappointed that Feridex® and its cousins are no longer available.
Feridex® was a disgusting thick reddish-black solution that had to be mixed into a bag of saline and administered by slow intravenous infusion over 30 minutes. From an aesthetic perspective alone, I can tell you that patients do not like watching a bag of black goo being infused in their veins! In clinical trials, a relatively high number (~0.5%) of moderate to severe anaphylactic and allergic reactions occurred. These events included dyspnea, other respiratory symptoms, angioedema, generalized urticaria, and hypotension; many required treatment.
An even larger number (10% or more) of patients experienced nonallergic but severe acute back, leg or groin pain, often severe enough to cause interruption or discontinuation of the infusion. In some patients the pain was so severe necessitating treatment with corticosteroids, intravenous narcotics, or muscle relaxants.
Hori M, Murakami T, Kim T, et al. Detection of hypervascular hepatocellular carcinoma: comparison of SPIO-enhanced MRI with dynamic helical CT. J Comput Assist Tomogr 2002; 26:701-710.
Senéterre E, Taourel P, Bouvier Y, et al. Detection of hepatic metastases: ferumoxides-enhanced MR imaging versus unenhanced MR imaging and CT during arterial portography. Radiology 1996; 200:785-92.