(USPIO) The class of the ultrasmall superparamagnetic iron oxide includes several chemically and pharmacologically very distinct materials, which may or may not be interchangeable for a specific use. Some ultrasmall SPIO particles (median diameter less than 50nm) are used as MRI contrast agents (Sinerem®, Combidex®), e.g. to differentiate metastatic from inflammatory lymph nodes. USPIO shows also potential for providing important information about angiogenesis in cancer tumors and could possibly complement MRI helping physicians to identify dangerous arteriosclerosis plaques.
Because of the disadvantageous large T2*//T1 ratio, USPIO compounds are less suitable for arterial bolus contrast enhanced magnetic resonance angiography than gadolinium complexes. The tiny ultrasmall superparamagnetic iron oxides do not accumulate in the RES system as fast as larger particles, which results in a long plasma half-life. USPIO particles, with a small median diameter (less than 10 nm), will accumulate in lymph nodes after an intravenous injection by e.g. direct transcapillary passage through endothelial venules. Once within the nodal parenchyma, phagocytic cells of the mononuclear phagocyte system take up the particles.
As a second way, USPIOs are subsequently taken up from then interstitium by lymphatic vessels and transported to regional lymph nodes. A lymph node with normal phagocytic function takes up a considerable amount and shows a reduction of the signal intensity caused by T2 shortening effects and magnetic susceptibility. Caused by the small uptake of the USPIOs in metastatic lymph nodes, they appear with less signal reduction, and permit the differentiation of healthy lymph nodes from normal-sized, metastatic nodes.

See also Superparamagnetic Contrast Agents, Superparamagnetic Iron Oxide, Very Small Superparamagnetic Iron Oxide Particles, Blood Pool Agents, Intracellular Contrast Agents.

A contrast medium (or contrast agent) is a chemical substance introduced to the anatomical or functional region being imaged, to increase the differences between different tissues or between normal and abnormal tissue, by altering the relaxation times.
The chemical composition of the contrast media determines the specific usage. Similar to nuclear imaging is the intention in development of MR contrast media a high affinity to different organs or even tumors (e.g. necrosis avid contrast agent).
In 'contrast' to nuclear imaging contrast agents MR contrast media do not contain radiopharmaceuticals and the concentrations are about 100 times higher. Nuclear imaging contrast agents are direct contrast agents;; they are directly visible caused by their radioactivity. MR contrast agents affect the targeted tissue; they are indirect contrast agents.
See also Contrast Agents, the info sheet gives an overview and more in-depth information about different types of MRI contrast medium.

Generic name: Liposomes, central moiety: different, contrast effect: paramagnetic, distribution: different
Liposomes are lipid containing nanoparticles, or fat molecules, surrounding a water core. Liposomes were the first type of nanoparticles created to be used as carriers for lipophilic MRI contrast agents with novel characteristics.
Liposomes loaded with gadolinium-containing chelates have potential as blood pool agents, caused by modifications of the surface (e.g., with polyethylene glycol) leading to longer blood retention times.
The incorporation of contrast agents into either the the bilayer membrane or the aqueous inner cavity is possible. These MRI contrast agents has been used to image the lymph nodes using liposomes containing Gd-DTPA as well as dextran coated iron oxide particles.
To image the liver or the hepatobiliary system, liposomes containing Gd-HPDO3A, or MnDPDP, have been tested.
Liposomes containing gadolinium were conjugated to antibodies and targeted to a specific organ system.
A method of targeting tumors with ultrasound that also uses MRI to watch the cell destroying, uses liposomes loaded with cytotoxic drugs and also with gadolinium to make them show up in MRI. As well as used as an imaging technique, ultrasound can also be used to destroy cancer cells. Once the drugs have been administered, focusing the ultrasound on the target area makes blood vessels permeable. The liposomes leak out of the blood vessel into the target area, watched by MRI, where the cytotoxic drug can then go to work.

See also Memosomes, Superparamagnetic Iron Oxide, Classifications, Characteristics, etc. and Mangafodipir Trisodium.

Liver imaging can be performed with sonography, computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound is, caused by the easy access, still the first-line imaging method of choice; CT and MRI are applied whenever ultrasound imaging yields vague results. Indications are the characterization of metastases and primary liver tumors e.g., benign lesions such as focal nodular hyperplasia (FNH), adenoma, hemangioma and malignant lesions (cancer) such as hepatocellular carcinomas (HCC). The decision, which medical imaging modality is more suitable, MRI or CT, is dependent on the different factors. CT is less costly and more widely available; modern multislice scanners provide high spatial resolution and short scan times but has the disadvantage of radiation exposure.
With the introduction of high performance MR systems and advanced sequences the image quality of MRI for the liver has gained substantially. Fast spin echo or single shot techniques, often combined with fat suppression, are the most common T2 weighted sequences used in liver MRI procedures. Spoiled gradient echo sequences are used as ideal T1 weighted sequences for evaluating of the liver. The repetition time (TR) can be sufficiently long to acquire enough sections covering the entire liver in one pass, and to provide good signal to noise. The TE should be the shortest in phase echo time (TE), which provides strong T1 weighting, minimizes magnetic susceptibility effects, and permits acquisition within one breath hold to cover the whole liver. A flip angle of 80° provides good T1 weighting and less of power deposition and tissue saturation than a larger flip angle that would provide comparable T1 weighting.
Liver MRI is very dependent on the administration of contrast agents, especially when detection and characterization of focal lesions are the issues. Liver MRI combined with MRCP is useful to evaluate patients with hepatic and biliary disease.
Gadolinium chelates are typical non-specific extracellular agents diffusing rapidly to the extravascular space of tissues being cleared by glomerular filtration at the kidney. These characteristics are somewhat problematic when a large organ with a huge interstitial space like the liver is imaged. These agents provide a small temporal imaging window (seconds), after which they begin to diffuse to the interstitial space not only of healthy liver cells but also of lesions, reducing the contrast gradient necessary for easy lesion detection. Dynamic MRI with multiple phases after i.v. contrast media (Gd chelates), with arterial, portal and late phase images (similar to CT) provides additional information.
An additional advantage of MRI is the availability of liver-specific contrast agents (see also Hepatobiliary Contrast Agents). Gd-EOB-DTPA (gadoxetate disodium, Gadolinium ethoxybenzyl dimeglumine, EOVIST Injection, brand name in other countries is Primovist) is a gadolinium-based MRI contrast agent approved by the FDA for the detection and characterization of known or suspected focal liver lesions.
Gd-EOB-DTPA provides dynamic phases after intravenous injection, similarly to non-specific gadolinium chelates, and distributes into the hepatocytes and bile ducts during the hepatobiliary phase. It has up to 50% hepatobiliary excretion in the normal liver.
Since ferumoxides are not eliminated by the kidney, they possess long plasmatic half-lives, allowing circulation for several minutes in the vascular space. The uptake process is dependent on the total size of the particle being quicker for larger particles with a size of the range of 150 nm (called superparamagnetic iron oxide). The smaller ones, possessing a total particle size in the order of 30 nm, are called ultrasmall superparamagnetic iron oxide particles and they suffer a slower uptake by RES cells. Intracellular contrast agents used in liver MRI are primarily targeted to the normal liver parenchyma and not to pathological cells. Currently, iron oxide based MRI contrast agents are not marketed.
Beyond contrast enhanced MRI, the detection of fatty liver disease and iron overload has clinical significance due to the potential for evolution into cirrhosis and hepatocellular carcinoma. Imaging-based liver fat quantification (see also Dixon) provides noninvasively information about fat metabolism; chemical shift imaging or T2*-weighted imaging allow the quantification of hepatic iron concentration.

See also Abdominal Imaging, Primovistâ„¢, Liver Acquisition with Volume Acquisition (LAVA), T1W High Resolution Isotropic Volume Examination (THRIVE) and Bolus Injection.

For Ultrasound Imaging (USI) see Liver Sonography at Medical-Ultrasound-Imaging.com.

Liver imaging with gadolinium contrast enhanced MRI is sometimes not sufficient for a reliable diagnosis of liver lesions. For this reasons, special liver Contrast agents that are targeted to the reticuloendothelial system (RES), have been developed to improve both detection and characterization of liver and spleen lesions. Reticuloendothelial Contrast Agents, as e.g. superparamagnetic iron oxides (SPIO), are taken up by healthy liver tissue but not tumors.
These RES targeted contrast agents provide a prolonged imaging window and enough time for high spatial resolution or multiple breath hold images. Reticuloendothelial contrast agents have an increased sensitivity for the detection of small liver lesions (e.g., metastases), compared with gadolinium enhanced MRI and spiral CT. At higher field strengths with an increased signal to noise ratio the susceptibility effect with iron oxide particles may be enhanced.
Other new agents (Gadobenate Dimeglumine, Gadoxetic Acid) have both an initial extracellular circulation and a delayed liver-specific uptake. Since a considerable part of these contrast agents is excreted in the bile, functional biliary imaging can diagnose biliary anomalies, postoperative bile leaks, and anastomotic strictures. Other agents, such as liposomes (with encapsulated Gd-DTPA) or DOTA complexes are in different development stages.

See also Hepatobiliary Contrast Agents, Gadolinium Oxide, Superparamagnetic Iron Oxide and Liposomes.