Lithium is the first-line mood stabilizer for the treatment of patients with bipolar disorder. However, its mechanisms of action and transport across the blood-brain barrier remain poorly understood. The contribution of lithium-7 magnetic resonance imaging (7 Li MRI) to investigate brain lithium distribution remains limited because of the modest sensitivity of the lithium nucleus and the expected low brain concentrations in humans and animal models. Therefore, we decided to image lithium distribution in the rat brain ex vivo using a turbo-spin-echo imaging sequence at 17.2 T. The estimation of lithium concentrations was performed using a phantom replacement approach accounting for B1 inhomogeneities and differential T1 and T2 weighting. Our MRI-derived lithium concentrations were validated by comparison with inductively coupled plasma-mass spectrometry (ICP-MS) measurements ([Li]MRI = 1.18[Li]MS , R = 0.95). Overall, a sensitivity of 0.03 mmol/L was achieved for a spatial resolution of 16 μL. Lithium distribution was uneven throughout the brain (normalized lithium content ranged from 0.4 to 1.4) and was mostly symmetrical, with consistently lower concentrations in the metencephalon (cerebellum and brainstem) and higher concentrations in the cortex. Interestingly, low lithium concentrations were also observed close to the lateral ventricles. The average brain-to-plasma lithium ratio was 0.34 ± 0.04, ranging from 0.29 to 0.39. Brain lithium concentrations were reasonably correlated with plasma lithium concentrations, with Pearson correlation factors ranging from 0.63 to 0.90.
In this contribution, we present a new radiofrequency probe, a dual dielectric resonator used for transmission and reception of RF signals in Magnetic Resonance Microscopy. The probe is designed as a pair of magnetically coupled ceramic rings with the permittivity of 530 resonating at the Larmor frequency of protons at the magnetic field 17 T (730 MHz). The resonators are made of a unique low-loss ferroelectric composite ceramics, which allows doubling the scanned volume with increased signal-to-noise ratio in comparison to a metal solenoid probe. By adjusting the distance between the resonators and the position of the loop feed placed between them, the probe can be tuned and impedance-matched and does not require capacitors.
Background Sedation agents affect brain hemodynamic and metabolism leading to specific modifications of the cerebral blood oxygenation level. We previously demonstrated that ultra-high field (UHF) MRI detects changes in cortical blood oxygenation following the administration of sedation drugs commonly used in animal research. Here we applied the UHF-MRI method to study clinically relevant sedation drugs for their effects on cortical and subcortical (thalamus, striatum) oxygenation levels. Methods We acquired T2*-weighted images of Sprague-Dawley rat brains at 17.2T in vivo. During each MRI session, rats were first anesthetized with isoflurane, then with a second sedative agent (sevoflurane, propofol, midazolam, medetomidine or ketamine-xylazine) after stopping isoflurane. We computed a T2*-oxygenation-ratio that aimed at estimating cerebral blood oxygenation level for each sedative agent in each region of interest: cortex, hippocampus, thalamus and striatum. Results The T2*-oxygenation-ratio was consistent across scan sessions. This ratio was higher with inhalational agents than with intravenous agents. Under sevoflurane and medetomidine, T2*-oxygenation-ratio was homogenous across the brain regions. Intravenous agents (except medetomidine) induced a T2*-oxygenation-ratio imbalance between cortex and subcortical regions: T2*-oxygenation-ratio was higher in the cortex than the subcortical areas under ketamine-xylazine; T2*-oxygenation-ratio was higher in subcortical regions than in the cortex under propofol or midazolam. Conclusion Preclinical UHF MRI is a powerful method to monitor the changes in cerebral blood oxygenation level induced by sedative agents across brain structures. This approach also allows for a classification of sedative agents based on their differential effects on cerebral blood oxygenation level.
Abstract Although abnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we successfully combined DREADD-technology with fMRI (chemo-fMRI) to investigate the alterations of spontaneous neuronal activity induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). We compared the effects of two different DREADD ligands, clozapine (CLZ) and clozapine-N-oxide (CNO), on behavior and fMRI. We found that the effects of CLZ on behavior were more rapid than those of CNO. In fMRI, both systemic CLZ and CNO administrations, which evoked unilateral activations of D1-neurons in DS, increased the fractional amplitude of low frequency fluctuations (fALFF) in the thalamus and bilateral cortex. In addition, we found the increased gamma-band of local field potentials in DS and bilateral cortex after CLZ-evoked unilateral activation of D1-neuron in the striatum. These results provide bases for better interpretation of cell type-specific activity changes in fMRI.
Abstract Fasting is known to influence learning and memory in mice and alter the neural networks that subserve these cognitive functions. We used high-resolution functional MRI to study the impact of fasting on resting-state functional connectivity in mice following 12 h of fasting. The cortex and subcortex were parcellated into 52 subregions and functional connectivity was measured between each pair of subregions in groups of fasted and non-fasted mice. Functional connectivity was globally increased in the fasted group compared to the non-fasted group, with the most significant increases evident between the hippocampus (bilateral), retrosplenial cortex (left), visual cortex (left) and auditory cortex (left). Functional brain networks in the non-fasted group comprised five segregated modules of strongly interconnected subregions, whereas the fasted group comprised only three modules. The amplitude of low frequency fluctuations (ALFF) was decreased in the ventromedial hypothalamus in the fasted group. Correlation in gamma oscillations derived from local field potentials was increased between the left visual and retrosplenial cortices in the fasted group and the power of gamma oscillations was reduced in the ventromedial hypothalamus. These results indicate that fasting induces profound changes in functional connectivity, most likely resulting from altered coupling of neuronal gamma oscillations.
Purpose A MR thermometry (MRT) method with field monitoring is proposed to improve the measurement of small temperature variations induced in brain MRI exams. Methods MR thermometry experiments were performed at 7 Tesla with concurrent field monitoring and RF heating. Images were reconstructed with nominal k‐space trajectories and with first‐order spherical harmonics correction. Experiments were performed in vitro with deliberate field disturbances and on an anesthetized macaque in 2 different specific absorption rate regimes, that is, at 50% and 100% of the maximal specific absorption rate level allowed in the International Electrotechnical Commission normal mode of operation. Repeatability was assessed by running a second separate session on the same animal. Results Inclusion of magnetic field fluctuations in the reconstruction improved temperature measurement accuracy in vitro down to 0.02°C. Measurement precision in vivo was on the order of 0.15°C in areas little affected by motion. In the same region, temperature increase reached 0.5 to 0.8°C after 20 min of heating at 100% specific absorption rates and followed a rough factor of 2 with the 50% specific absorption rate scans. A horizontal temperature plateau, as predicted by Pennes bioheat model with thermal constants from the literature and constant blood temperature assumption, was not observed. Conclusion Inclusion of field fluctuations in image reconstruction was beneficial for the measurement of small temperature rises encountered in standard brain exams. More work is needed to correct for motion‐induced field disturbances to extract reliable temperature maps.
Magnetic Resonance Microscopy (MRM) is a specialized imaging technique for visualization of samples with tiny structural details with dimensions of less than 100 μm with an extremely high resolution (voxel dimensions are typically less than 100 μm). However, in practice it is limited by the signal-to-noise ratio (SNR) of the MRM setup and can be insufficient for the required visualization resolution. In order to increase SNR as high as possible, the constant magnetic field B 0 of the MR system should be ultra high (7-21 T). Averaging of obtained images can also improve the SNR, increasing, however the overall scan time. In biomedical applications the scan time is limited by the lifetime of a biological sample. Therefore, any methods to increase SNR for the given B 0 and the scan time are of a great interest in MRM applications.
Our aim was to investigate the pertinence of diffusion and perfusion magnetic resonance imaging (MRI) parameters obtained at 17.2 T in a 9L glioma rat brain tumor model to evaluate tumor tissue characteristics.The local animal ethics advisory committee approved this study. 9L glioma cells were injected intracerebrally to 14 Fischer rats. The animals were imaged at 7 or 12 days after implantation on a 17.2-T MRI scanner, using 72 different b values (2-3025 s/mm(2)). The signal attenuation, S/So, was fitted using a kurtosis diffusion model (ADCo and K) and a biexponential diffusion model (fractions ffast and fslow and diffusion coefficients Dfast and Dslow) using b values greater than 300 s/mm(2). To bridge the 2 models, an average diffusion coefficient and a biexponential index were estimated from the biexponential model as ADCo and K equivalents, respectively. Intravoxel incoherent motion perfusion-related parameters were obtained from the residual signal at low b values, after the diffusion component has been removed. Diffusion and perfusion maps were generated for each fitted parameter on a pixel-by-pixel basis, and regions of interest were drawn in the tumor and contralateral side to retrieve diffusion and perfusion parameters. All rats were killed and cellularity and vascularity were quantitatively assessed using histology for comparison with diffusion and perfusion parameters.Intravoxel incoherent motion maps clearly highlighted tumor areas as generally heterogeneous, as confirmed by histology. For diffusion parameters, ADCo and were not significantly different between the tumor and contralateral side, whereas K in the tumor was significantly higher than in contralateral basal ganglia (P < 0.0001), as well as biexponential index (P < 0.001). ADCo and in the tumor at day 7 were significantly higher than at day 12 (P < 0.01 and P < 0.001, respectively). fIVIM in the tumor from the kurtosis diffusion model was significantly higher than in contralateral basal ganglia (P < 0.001). fIVIM in the tumor at day 7 was significantly higher than in the tumor at day 12 (P < 0.0001). There was no significant difference for D* between the tumor and contralateral side (P = 0.06). A significant negative correlation was found between tumor vascularity and fIVIM (P < 0.05) as well as between tumor cell count and (P < 0.01).Quantitative non-Gaussian diffusion and perfusion MRI can provide valuable information on microvasculature and tissue structure to improve characterization of brain tumors.
