The current study aims to evaluate the feasibility of creatine (Cr) chemical exchange saturation transfer (CEST)‐weighted MRI at 7 T in the human brain by optimizing the saturation pulse parameters and computing contrast using a Z‐spectral fitting approach. The Cr‐weighted (Cr‐w) CEST contrast was computed from phantoms data. Simulations were carried out to obtain the optimum saturation parameters for Cr‐w CEST with lower contribution from other brain metabolites. CEST‐w images were acquired from the brains of four human subjects at different saturation parameters. The Cr‐w CEST contrast was computed using both asymmetry analysis and Z‐spectra fitting approaches (models 1 and 2, respectively) based on Lorentzian functions. For broad magnetization transfer (MT) effect, Gaussian and Super‐Lorentzian line shapes were also evaluated. In the phantom study, the Cr‐w CEST contrast showed a linear dependence on concentration in physiological range and a nonlinear dependence on saturation parameters. The in vivo Cr‐w CEST map generated using asymmetry analysis from the brain represents mixed contrast with contribution from other metabolites as well and relayed nuclear Overhauser effect (rNOE). Simulations provided an estimate for the optimum range of saturation parameters to be used for acquiring brain CEST data. The optimum saturation parameters for Cr‐w CEST to be used for brain data were around B1rms = 1.45 μT and duration = 2 seconds. The Z‐spectral fitting approach enabled computation of individual components. This also resulted in mitigating the contribution from MT and rNOE to Cr‐w CEST contrast, which is a major source of underestimation in asymmetry analysis. The proposed modified z‐spectra fitting approach (model 2) is more stable to noise compared with model 1. Cr‐w CEST contrast obtained using fitting was 6.98 ± 0.31% in gray matter and 5.45 ± 0.16% in white matter. Optimal saturation parameters reduced the contribution from other CEST effects to Cr‐w CEST contrast, and the proposed Z‐spectral fitting approach enabled computation of individual components in Z‐spectra of the brain. Therefore, it is feasible to compute Cr‐w CEST contrast with a lower contribution from other CEST and rNOE.

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The authors describe a novel multifunctional magneto-fluorescent MFCSNPs-FA-CHI-5FU nanocarrier that consists of magneto-fluorescent nanoparticles (MFCSNPs) targeted with folic acid (FA), modified with chitosan (CHI), and loaded with a 5-flouoruracil (5-FU) in dual mode imaging and targeted drug delivery. Multifunctional magneto-fluorescent nanocarriers show multicolor emission and superparamagnetic behavior which are advantageous for bioimaging and magnetic resonance (MR) imaging, respectively. In-vitro drug release studies show a pH-activated drug release with 92% of loaded 5-FU released in 30 h and MR imaging exhibiting excellent dose-dependent signal enhancement in T 2-weighted images. This suggests that MFCSNPs-FA-CHI-5FU nanocarriers can be used as T 2-weighted negative contrast agents in cancer diagnosis. In-vitro cytotoxicity and anticancer activity of the synthesized MFCSNPs-FA-CHI-5FU nanocarriers were evaluated on three cancer cell lines having different percentages of folate receptors viz. A375, MCF-7, and HeLa cells. The results show a very sensitive drug targeting response. Confocal laser scanning microscopy imaging (CLSM) displays targeted cellular internalization of MFCSNPs-FA-CHI-5FU nanocarriers in cancer cells. The biocompatibility of MFCSNPs-FA-CHI-5FU nanocarriers was ascertained ex-vivo by hemolysis and serum stability studies. The in vivo biodistribution studies were evaluated by radiolabeling MFCSNPs-FA-CHI-5FU nanocarriers with 99m technetium (99mTc). Thus, the synthesized nanocarriers, a dual mode imaging probe, show great potential in targeted drug delivery to improve the existing cancer theranostics.