Assessment of a clinically feasible Bayesian fitting algorithm using a simplified description of Chemical Exchange Saturation Transfer (CEST) imaging.

Fitting a model based on the Bloch-McConnell (BM) equations to Chemical Exchange Saturation Transfer (CEST) spectra allows for the quantification of metabolite concentration and exchange rate as well as simultaneous correction of field inhomogeneity, direct water saturation and magnetization transfer. Employing a Bayesian fitting approach permits the integration of prior information into the analysis to incorporate expected parameter distributions and to prevent over-fitting. However, the analysis can be time consuming if a general numerical solution of the BM equations is applied. In this study, we combined a Bayesian fitting algorithm with approximate analytical solutions of the BM equations to achieve feasible computational times. To evaluate the accuracy and speed of the suggested approach, phantoms including Iodipamide, Taurine and Creatine were tested in addition to simulated data with continuous-wave (CW) and pulsed saturation with Gaussian pulses. A significant reduction of computational time was achieved when fitting CW data (about 50-fold) and pulsed saturation data (more than 100-fold) with the analytical model while the estimated parameters were largely consistent with the parameters from the general numerical solution. The increased speed of the algorithm facilitates the Bayesian analysis of CEST data within clinically feasible processing times. Other analytical models valid for different parameter regimes may be employed to extend the applicability to a wider range of CEST agents.

An efficient MRI agent targeting extracellular markers in prostate adenocarcinoma.

PURPOSE: Prostate cancer (PCa) is the most widespread tumor affecting males in Western countries. We propose a novel MRI molecular tetrameric probe based on the heptadentate gadolinium (Gd)-AAZTA (6-amino-6-methylperhydro-1,4-diazepinetetraacetic acid) that is able to in vivo detect PCa through the recognition of the fibrin-fibronectin (FB-FN) complex. METHODS: The peptide CREKA (Cys-Arg-Glu-Lys-Ala), targeting the FB-FN complex in the reactive stroma of the tumor, was synthesized by solid phase peptide synthesis (SPPS) and conjugated to the tetramer dL-(Gd-AAZTA)4 . The resulting probe was characterized by 1 H relaxometry, tested in vitro on FB clots and in vivo on an orthotopic mouse model of PCa. RESULTS: CREKA-dL-(Gd-AAZTA)4 showed a remarkable relaxivity of 18.2 m MGd-1s-1 (0.47 T, 25°C) because of the presence of 2 water molecules (q = 2) in the inner coordination sphere of each Gd3+ ion, whose rotational motion (τR ) is lengthened as the result of the relatively high molecular weight. The probe displayed a detectable affinity for plasma-derived FB clots. On intravenous injection of the probe in an orthotopic mouse model of PCa, a significant increase in the prostate T1 contrast (~40%) was observed. The MRI signal appears statistically higher either with respect to the one observed for the control probes and to the one detected when CREKA-dL-(Gd-AAZTA)4 was administered to healthy animals. CONCLUSIONS: This study demonstrated the ability of the CREKA-dL-(Gd-AAZTA)4 probe to specifically localize in prostate tumor after injection. The high relaxivity of the probe allows the reduction of the injected dose to 20 µmolGd /kg, yielding a good in vivo contrast enhancement in the region of prostate tumor.