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WIREs Nanomed Nanobiotechnol
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Magnetic resonance chemical exchange saturation transfer imaging and nanotechnology

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Abstract Chemical exchange saturation transfer (CEST) agents and paramagnetic CEST (PARACEST) agents display bound water signals that exchange protons with the bulk water. CEST magnetic resonance imaging (MRI) relies on exchangeable protons that resonate at a chemical shift that is distinguishable from the bulk water signal. In some cases, paramagnetic chelates are utilized to shift the bound water frequency further away from the bulk water. Radiofrequency prepulses applied at the appropriate frequency can saturate the exchangeable protons, which transfer into the bulk water pool and lead to reduced equilibrium magnetization. Therefore, CEST and PARACEST agents allow the image contrast to be switched ‘on’ and ‘off’ by simply changing the pulse sequence parameters. One of the main limitations with this approach is the inherent insensitivity of MRI to CEST and PARACEST agents. Nanoscale carriers have been developed to improve the limit of detection for these agents, demonstrating the feasibility of in vivo molecular or cellular MRI based on CEST or PARACEST contrast. These carriers have been based on a number of different nanoparticle constructs, such as liposomes, dendrimers, polymers, adenovirus particles, and perfluorocarbon nanoparticles. The unique MRI properties of CEST and PARACEST nanoparticle systems have spawned research into an array of potential medical applications. WIREs Nanomed Nanobiotechnol 2012, 4:389–398. doi: 10.1002/wnan.1167 This article is categorized under: Diagnostic Tools > Diagnostic Nanodevices Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > In Vivo Nanodiagnostics and Imaging

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Dual PARACEST and 19F molecular imaging of fibrin with PARACEST PFC nanoparticles. The PARACEST (a) and 19F (b) images collaboratively show nanoparticles bound to the surface of an in vitro clot. The grayscale color bar represents the PARACEST CNR depicted in (a). (c) The nanoparticle concentration (nM) is color‐coded and overlaid onto the PARACEST subtraction image to demonstrate colocalization of these two definitive signals. (Reprinted with permission from Ref 6. Copyright 2011 John Wiley & Sons)

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Mathematical simulation of PARACEST MRI signal versus bound water lifetime. The bound water lifetime for the dilute PFC nanoparticles (red triangle) is lower than for the water‐soluble chelate (blue circle), decreasing the available PARACEST contrast. When the particles bind to a target surface, the bound water lifetime increases, making the exchange kinetics more optimal, and increasing the image contrast (green square). (Reprinted with permission from Ref 6. Copyright 2011 John Wiley & Sons)

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Z‐spectra acquired from a water‐soluble PARACEST chelate and PFC PARACEST nanoparticles showing a bound water peak at +51 ppm. The experimental data (indicated by data points) was fit to the Bloch equations (fitting denoted by solid lines) for calculating the bound water lifetime of the water‐soluble chelate (290 µs) and the nanoparticles (108 µs). The water‐soluble chelate produced a stronger PARACEST effect than the nanoparticles because of the reduced bound water lifetime of the nanoparticle agent. (Reprinted with permission from Ref 6. Copyright 2011 John Wiley & Sons)

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Molecular imaging of fibrin‐targeted PARACEST (left) or control (right) PFC nanoparticles bound to plasma clots. Images obtained with saturation at −52 ppm (top) show no differences between clots treated with PARACEST or control nanoparticles. Subtraction images (middle) reveal signal enhancement on the surface of the clot treated with PARACEST nanoparticles, and no enhancement of the clot treated with control nanoparticles. The CNR at the clot surface (bottom) was significantly higher with PARACEST nanoparticles compared to control nanoparticles (*P < 0.05). (Reprinted with permission from Ref 23. Copyright 2006 Wiley‐Liss, Inc.)

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Increasing the power or duration of the MRI saturation pulse increases the image enhancement from PARACEST PFC nanoparticles. A presaturation pulse as short as 1 second can produce a 5% change in the image intensity. As the PARACEST signal continued to increase, it is likely that the bound water peak was never completely saturated under these experimental conditions. (Reprinted with permission from Ref 23. Copyright 2006 Wiley‐Liss, Inc.)

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Therapeutic Approaches and Drug Discovery > Emerging Technologies
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