In 1988, the first contrast agent specifically designed for magnetic resonance imaging (MRI), gadopentetate dimeglumine (Magnevist®), became available for clinical use. Since then, a plethora of studies have investigated the potential of MRI contrast agents for diagnostic imaging across the body, including the central nervous system, heart and circulation, breast, lungs, the gastrointestinal, genitourinary, musculoskeletal and lymphatic systems, and even the skin. Today, after 25 years of contrast-enhanced (CE-) MRI in clinical practice, the utility of this diagnostic imaging modality has expanded beyond initial expectations to become an essential tool for disease diagnosis and management worldwide. CE-MRI continues to evolve, with new techniques, advanced technologies, and novel contrast agents bringing exciting opportunities for more sensitive, targeted imaging and improved patient management, along with associated clinical challenges. This review aims to provide an overview on the history of MRI and contrast media development, to highlight certain key advances in the clinical development of CE-MRI, to outline current technical trends and clinical challenges, and to suggest some important future perspectives.FundingBayer HealthCare.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0275-4) contains supplementary material, which is available to authorized users.

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The aim was to investigate the effects of echo time (TE) on diffusion quantification of brain white matter. Seven rhesus monkeys (all males; age, 4 -6 years; weight, 5-7 kg) underwent diffusion tensor imaging (DTI) with a series of TEs in 1.5T and 3.0T MR scanners. The mean diffusivity (MD), fractional anisotropy (FA), primary ( 1 ), and transverse eigenvalues ( 23 ) were measured in a region of interest at the bilateral internal capsule. Pearson correlation showed that the FA and 1 increased and 23 decreased with TE both at 1.5T and 3.0T except for the MD. Repeated measurement analysis of variance (ANOVA) also showed significantly higher FA and lower MD and 23 at 3.0T than those at 1.5T (P < 0.01), but no statistical differences were found in 1 between these two field strengths (P ‫؍‬ 0.709). Diffusion tensor imaging (DTI) is a noninvasive method that measures the random motion of water molecules and provides information about cellular integrity and pathology (1). Within a highly oriented brain white matter (WM) tract, water molecules diffuse faster along the tract than the directions perpendicular to it. The diffusion properties can be evaluated by some quantitative indices derived from DTI data, which contain a set of diffusion-weighted images with the diffusion sensitive gradients in at least six noncollinear directions. The mean diffusivity (MD) and fractional anisotropy (FA) are two popular indices, which reflect the mean magnitude and the directionality of molecular motion, respectively. These two indices are calculated from three diffusion tensor eigenvalues, representing the apparent diffusion coefficients (ADC) along the primary, median, and minimum axes of the diffusion ellipsoid. The primary eigenvalue ( 1 ) is the diffusion coefficient along the direction of maximum diffusion. The transverse eigenvalue ( 23 ) is generated by averaging the median ( 2 ) and minimum eigenvalues ( 3 ), which reflects the average diffusivity perpendicular to the direction of maximum diffusion. In recent years, DTI has been widely used in the evaluation of WM in different physiological and pathologic states, such as brain development (2), aging (3), tumors (4), multiple sclerosis (5), plasticity (6), and degeneration (7).Because the signal intensity from DTI reflects an average contribution of water diffusion in all compartments separated by the cellular microstructures (for example, the axonal membranes and myelin sheaths) (8), the diffusion tensor-derived indices may depend on the microscopic tissue properties, such as the cell size, orientation, tortuosity of the extracellular space, relaxation times, and cell membrane permeability (9 -11). Previous studies have demonstrated that the diffusion indices can be influenced by some MRI parameters, including diffusion time (11), echo time (9,12), and b-value (13). The dependence of the diffusion indices on the MRI parameters might decrease the comparability and generality of DTI studies on a certain disease with different parameters or MR scanners. As a result, it is critica...

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