Background: The measurement of the concentration of theranostic agents in vivo is essential for the assessment of their therapeutic efficacy and their safety regarding healthy tissue. To this end, there is a need for quantitative T 1 measurements that can be obtained as part of a standard clinical imaging protocol applied to tumor patients. Purpose: To generate T 1 maps from MR images obtained with the magnetization-prepared rapid gradient echo (MPRAGE) sequence. To evaluate the feasibility of the proposed approach on phantoms, animal and patients with brain metastases. Study Type: Pilot. Phantom/Animal model/Population: Solutions containing contrast agents (chelated Gd 3+ and iron nanoparticles), male rat of Wistar strain, three patients with brain metastases. Field Strength/Sequence: A 3-T and 7-T, saturation recovery (SR), and MPRAGE sequences. Assessment: The MPRAGE T 1 measurement was compared to the reference SR method on phantoms and rat brain at 7-T. The robustness of the in vivo method was evaluated by studying the impact of misestimates of tissue proton density. Concentrations of Gd-based theranostic agents were measured at 3-T in gray matter and metastases in patients recruited in NanoRad clinical trial. Statistical Tests: A linear model was used to characterize the relation between T 1 measurements from the MPRAGE and the SR acquisitions obtained in vitro at 7-T. Results: The slope of the linear model was 0.966 (R 2 = 0.9934). MPRAGE-based T 1 values measured in the rat brain were 1723 msec in the thalamus. MPRAGE-based T 1 values measured in patients in white matter and gray matter amounted to 747 msec and 1690 msec. Mean concentration values of Gd 3+ in metastases were 61.47 μmol. Data Conclusion:The T 1 values obtained in vitro and in vivo support the validity of the proposed approach. The concentrations of Gd-based theranostic agents may be assessed in patients with metastases within a standard clinical imaging protocol using the MPRAGE sequence. Evidence Level: 2. Technical Efficacy: Stage 1.

The aim of this study was to evaluate the potential of a miniaturized implantable nuclear magnetic resonance (NMR) coil to acquire in vivo proton NMR spectra in sub-microliter regions of interest and to obtain metabolic information using magnetic resonance spectroscopy (MRS) in these small volumes. For this purpose, the NMR microcoils were implanted in the right cortex of healthy rats and in C6 glioma-bearing rats. The dimensions of the microcoil were 450 micrometers wide and 3 mm long. The MRS acquisitions were performed at 7 Tesla using volume coil for RF excitation and microcoil for signal reception. The detection volume of the microcoil was measured equal to 450 nL. A gain in sensitivity equal to 76 was found in favor of implanted microcoil as compared to external surface coil. Nine resonances from metabolites were assigned in the spectra acquired in healthy rats (n = 5) and in glioma-bearing rat (n = 1). The differences in relative amplitude of choline, lactate and creatine resonances observed in glioma-bearing animal were in agreement with published findings on this tumor model. In conclusion, the designed implantable microcoil is suitable for in vivo MRS and can be used for probing the metabolism in localized and very small regions of interest in a tumor.

The use of miniaturized NMR receiver coils is an effective approach for improving detection sensitivity in studies using MRS and MRI. By optimizing the filling factor (the fraction of the coil occupied by the sample), and by increasing the RF magnetic field produced per unit current, the sensitivity gain offered by NMR microcoils is particularly interesting when small volumes or regions of interest are investigated. For in vivo studies, millimetric or sub-millimetric microcoils can be deployed in tissues to access regions of interest located at a certain depth. In this study, the implementation and application of a tissue-implantable NMR microcoil with a detection volume of 850 nL is described. The RF magnetic field generated by the microcoil was evaluated using a finite element method simulation and experimentally determined by high spatial resolution MRI acquisitions. The performance of the microcoil in terms of spectral resolution and limit of detection was measured at 7 T in vitro and in vivo in rodent brains. These performances were compared with those of a conventional external detection coil. Proton MR spectra were acquired in the cortex of rat brain. The concentrations of main metabolites were quantified and compared with reference values from the literature. In vitro and in vivo results obtained with the implantable microcoil showed a gain in sensitivity greater than 50 compared with detection using an external coil. In vivo proton spectra of diagnostic value were obtained from brain regions of a few hundred nanoliters. The similarities between spectra obtained with the implanted microcoil and those obtained with the external NMR coil highlight the minimally invasive nature of the coil implantation procedure. These implantable microcoils represent new tools for probing tissue metabolism in very small healthy or diseased regions using MRS.