Molecular Imaging is a rapidly evolving field combining conventional imaging methodologies such as PET/CT, NIR, US or MRI with targeted biosensors responsive to a particular biochemical event. MRI offers a number of attractive features for molecular imaging applications: it provides excellent anatomical resolution at any depth, involves no ionizing irradiation, and is intrinsically sensitive to morphological and chemical rearrangements. The latter is typically manifested in MRI as image contrast. One of the common ways to improve contrast sensitivity is to use contrast agents, such as exogenous complexes of Gd3+, iron oxide particles or endogenous metabolic groups. Various applications of MRI molecular imaging are currently under development, such as cell tracking and imaging of receptors, gene expression, enzyme activity and pH. To achieve the full potential of molecular MRI it is crucial to have """"""""smart"""""""" and highly sensitive MRI contrast. Recently, PARACEST agents were introduced in which complexes of PARAmagnetic lanthanides are used for Chemical Exchange Saturation Transfer (CEST) MRI. One of the potential advantages of these agents is the ability to turn the contrast """"""""on"""""""" and """"""""off"""""""" via application of RF irradiation. If the RF is """"""""off"""""""" the agent will not interfere with conventional MR imaging sequences. If the RF is """"""""on"""""""" contrast will be generated in areas of agent concentration. In the conventional PARACEST experiment, an RF saturation pulse is applied on the frequency position of the lanthanide-bound exchanging protons. This approach, when applied to fast exchanging and fast relaxing lanthanides like Tm3+ and Dy3+, may require power deposition exceeding FDA guidelines and thus render many new developments inapplicable in-vivo. Recently, an alternative methodology was introduced for the detection of these agents, in which an RF preparation train is applied on the free water resonance: On resonance PARamagnetic CHemical Exchange Effects (OPARACHEE). Using WALTZ-16* as the preparation train a Tm3+ agent was successfully detected invitro and in-vivo. The advantages of OPARACHEE include much lower RF power deposition and elimination of the need to know a priori the exact frequency of the lanthanide-bound proton resonances. In principle, the paramagnetic complexes can be very sensitive to the environment of the agent. In particular, targeted agents are under development, which change their chemical exchange properties in the presence of metabolites, such as glucose, lactose, hydroxyapetite or albumin. Hence, it is important to be able to not only detect the presence of the agent, but also to provide quantitative information about the exchange characteristics and the concentration of the agent in-vivo. Today, there is no adequate paradigm connecting OPARACHEE effect magnitudes measured in the experiment with the exchange rates and concentration. We propose to develop such a paradigm starting from the basic theoretical model all the way through to successful quantitative detection in-vivo. ? ? ?
| Vinogradov, Elena; Soesbe, Todd C; Balschi, James A et al. (2012) pCEST: Positive contrast using Chemical Exchange Saturation Transfer. J Magn Reson 215:64-73 |
