Combidex® is the brand name (same as Sinerem®) for an ultrasmall superparamagnetic iron oxide (USPIO) in the development pipeline to detect metastatic disease in lymph nodes. Metastatic lymph nodes show less uptake of this MRI contrast agent, which results in less signal decrease and allows the differentiation of normal lymph nodes from normal-sized, metastatic nodes. Combidex® has also potential to be used as a functional molecular imaging agent.
In March 2005, AMAG Pharmaceuticals Inc received an approvable letter from the U.S. Food and Drug Administration with respect to Combidex subject to certain conditions.
See also Ferumoxtran, Drug Development and Approval Process USA, Molecular Imaging and Classifications, Characteristics, etc.

Contrast enhanced MRI is a commonly used procedure in magnetic resonance imaging. The need to more accurately characterize different types of lesions and to detect all malignant lesions is the main reason for the use of intravenous contrast agents.
Some methods are available to improve the contrast of different tissues. The focus of dynamic contrast enhanced MRI (DCE-MRI) is on contrast kinetics with demands for spatial resolution dependent on the application. DCE-MR imaging is used for diagnosis of cancer (see also liver imaging, abdominal imaging, breast MRI, dynamic scanning) as well as for diagnosis of cardiac infarction (see perfusion imaging, cardiac MRI). Quantitative DCE-MRI requires special data acquisition techniques and analysis software.
Contrast enhanced magnetic resonance angiography (CE-MRA) allows the visualization of vessels and the temporal resolution provides a separation of arteries and veins. These methods share the need for acquisition methods with high temporal and spatial resolution.
Double contrast administration (combined contrast enhanced (CCE) MRI) uses two contrast agents with complementary mechanisms e.g., superparamagnetic iron oxide to darken the background liver and gadolinium to brighten the vessels. A variety of different categories of contrast agents are currently available for clinical use.
Reasons for the use of contrast agents in MRI scans are:
Common Indications:
Brain MRI : Preoperative/pretreatment evaluation and postoperative evaluation of brain tumor therapy, CNS infections, noninfectious inflammatory disease and meningeal disease.
Spine MRI : Infection/inflammatory disease, primary tumors, drop metastases, initial evaluation of syrinx, postoperative evaluation of the lumbar spine: disk vs. scar.
Breast MRI : Detection of breast cancer in case of dense breasts, implants, malignant lymph nodes, or scarring after treatment for breast cancer, diagnosis of a suspicious breast lesion in order to avoid biopsy.

For Ultrasound Imaging (USI) see Contrast Enhanced Ultrasound at Medical-Ultrasound-Imaging.com. See also Blood Pool Agents, Myocardial Late Enhancement, Cardiovascular Imaging, Contrast Enhanced MR Venography, Contrast Resolution, Dynamic Scanning, Lung Imaging, Hepatobiliary Contrast Agents, Contrast Medium and MRI Guided Biopsy.

(DICOM) DICOM is the industry standard for transferral of radiologic images and other medical information between computers. Patterned after the Open System Interconnection of the International Standards Organization, DICOM enables digital communication between diagnostic and therapeutic equipment and systems from various manufacturers.
The DICOM 3.0 standard evolved from versions 1.0 (1985) and 2.0 (1988) of a standard developed by the American College of Radiology (ACR) and National Electrical Manufacturers Association (NEMA). To support the implementation and demonstration of DICOM 3.0, the RSNA Electronic Communications Committee began to work with the ACR-NEMA MedPacs ad hoc section in 1992.
Also Picture Archiving and Communication Systems (PACS), which are connected with the Radiology Information System (RIS) use commonly the DICOM standard for the transfer and storage of medical images.

The Dixon technique is a MRI method used for fat suppression and/or fat quantification. The difference in magnetic resonance frequencies between fat and water-bound protons allows the separation of water and fat images based on the chemical shift effect.
This imaging technique is named after Dixon, who published in 1984 the basic idea to use phase differences to calculate water and fat components in postprocessing. Dixon's method relies on acquiring an image when fat and water are 'in phase', and another in 'opposed phase' (out of phase). These images are then added together to get water-only images, and subtracted to get fat-only images. Therefore, this sequence type can deliver up to 4 contrasts in one measurement: in phase, opposed phase, water and fat images. An additional benefit of Dixon imaging is that source images and fat images are also available to the diagnosing physician.
The original two point Dixon sequence (number of points means the number of images acquired at different TE) had limited possibilities to optimize the echo time, spatial resolution, slice thickness, and scan time; but Dixon based fat suppression can be very effective in areas of high magnetic susceptibility, where other techniques fail. This insensitivity to magnetic field inhomogeneity and the possibility of direct image-based water and fat quantification have currently generated high research interests and improvements to the basic method (three point Dixon).
The combination of Dixon with gradient echo sequences allows for example liver imaging with 4 image types in one breath hold. With Dixon TSE/FSE an excellent fat suppression with high resolution can be achieved, particularly useful in imaging of the extremities.
For low bandwidth imaging, chemical shift correction of fat images can be made before recombination with water images to produce images free of chemical shift displacement artifacts. The need to acquire more echoes lengthens the minimum scan time, but the lack of fat saturation pulses extends the maximum slice coverage resulting in comparable scan time.

Different stages of the drug development and approval process in the USA, lead from preclinical trials (testing in animals), first application in humans through limited and broad clinical tests, to postmarketing studies.

By Dale E. Wierenga, Ph.D. and C. Robert Eaton
Office of Research and Development
Pharmaceutical Manufacturers Association

'In reviewing this report, it is important to keep in mind the realities of the drug discovery and development process. The U.S. system of new drug approvals is perhaps the most rigorous in the world. On average, it costs a company $359 million to get one new medicine from the laboratory to the pharmacist's shelf, according to a February 1993 report by the Congressional Office of Technology Assessment.'

See also Phase 1 2 3 4 Drug Trials, Food and Drug Administration, and European Medicines Agency.