¹⁵N Heteronuclear Chemical Exchange Saturation Transfer MRI

A two-step heteronuclear enhancement approach was combined with chemical exchange saturation transfer (CEST) to magnify ¹⁵N MRI signal of molecules through indirect detection via water protons. Previous CEST studies have been limited to radiofrequency (rf) saturation transfer or excitation transfer employing protons. Here, the signal of ¹⁵N is detected indirectly through the water signal by first inverting selectively protons that are scalar-coupled to ¹⁵N in the urea molecule, followed by chemical exchange of the amide proton to bulk water. In addition to providing a small sensitivity enhancement, this approach can be used to monitor the exchange rates and thus the pH sensitivity of the participating ¹⁵N-bound protons

Single ¹⁹F Probe for Simultaneous Detection of Multiple Metal Ions Using miCEST MRI

The local presence and concentration of metal ions in biological systems has been extensively studied <i>ex vivo</i> using fluorescent dyes. However, the detection of multiple metal ions <i>in vivo</i> remains a major challenge. We present a magnetic resonance imaging (MRI)-based method for noninvasive detection of specific ions that may be coexisting, using the tetrafluorinated derivative of the BAPTA (TF-BAPTA) chelate as a ¹⁹F chelate analogue of existing optical dyes. Taking advantage of the difference in the ion-specific ¹⁹F nuclear magnetic resonance (NMR) chemical shift offset (Δω) values between the ion-bound and free TF-BAPTA, we exploited the dynamic exchange between ion-bound and free TF-BAPTA to obtain MRI contrast with multi-ion chemical exchange saturation transfer (miCEST). We demonstrate that TF-BAPTA as a prototype single ¹⁹F probe can be used to separately visualize mixed Zn²⁺ and Fe²⁺ ions in a specific and simultaneous fashion, without interference from potential competitive ions