RF heating measurement using MR thermometry and field monitoring: Methodological considerations and first in vivo results.

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.

fMRI detects bilateral brain network activation following unilateral chemogenetic activation of direct striatal projection neurons.

Abnormal structural and functional connectivity in the striatum during neurological disorders has been reported using functional magnetic resonance imaging (fMRI), although the effects of cell-type specific neuronal stimulation on fMRI and related behavioral alterations are not well understood. In this study, we combined DREADD technology with fMRI ("chemo-fMRI") to investigate alterations of spontaneous neuronal activity. These were induced by the unilateral activation of dopamine D1 receptor-expressing neurons (D1-neurons) in the mouse dorsal striatum (DS). After clozapine (CLZ) stimulation of the excitatory DREADD expressed in D1-neurons, the fractional amplitude of low frequency fluctuations (fALFF) increased bilaterally in the medial thalamus, nucleus accumbens and cortex. In addition, we found that the gamma-band of local field potentials was increased in the stimulated DS and cortex bilaterally. These results provide insights for better interpretation of cell type-specific activity changes in fMRI.

Differential effects of aquaporin-4 channel inhibition on BOLD fMRI and diffusion fMRI responses in mouse visual cortex.

The contribution of astrocytes to the BOLD fMRI and DfMRI responses in visual cortex of mice following visual stimulation was investigated using TGN-020, an aquaporin 4 (AQP4) channel blocker, acting as an astrocyte function perturbator. Under TGN-020 injection the amplitude of the BOLD fMRI response became significantly higher. In contrast no significant changes in the DfMRI responses and the electrophysiological responses were observed. Those results further confirm the implications of astrocytes in the neurovascular coupling mechanism underlying BOLD fMRI, but not in the DfMRI responses which remained unsensitive to astrocyte function perturbation.

Diffusion MRI reveals in vivo and non-invasively changes in astrocyte function induced by an aquaporin-4 inhibitor.

The Glymphatic System (GS) has been proposed as a mechanism to clear brain tissue from waste. Its dysfunction might lead to several brain pathologies, including the Alzheimer's disease. A key component of the GS and brain tissue water circulation is the astrocyte which is regulated by acquaporin-4 (AQP4), a membrane-bound water channel on the astrocytic end-feet. Here we investigated the potential of diffusion MRI to monitor astrocyte activity in a mouse brain model through the inhibition of AQP4 channels with TGN-020. Upon TGN-020 injection, we observed a significant decrease in the Sindex, a diffusion marker of tissue microstructure, and a significant increase of the water diffusion coefficient (sADC) in cerebral cortex and hippocampus compared to saline injection. These results indicate the suitability of diffusion MRI to monitor astrocytic activity in vivo and non-invasively.

Author Correction: The impact of fasting on resting state brain networks in mice.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Systematic Analysis of the Improvements in Magnetic Resonance Microscopy with Ferroelectric Composite Ceramics.

The spatial resolution and signal-to-noise ratio (SNR) attainable in magnetic resonance microscopy (MRM) are limited by intrinsic probe losses and probe-sample interactions. In this work, the possibility to exceed the SNR of a standard solenoid coil by more than a factor-of-two is demonstrated theoretically and experimentally. This improvement is achieved by exciting the first transverse electric mode of a low-loss ceramic resonator instead of using the quasi-static field of the metal-wire solenoid coil. Based on theoretical considerations, a new probe for microscopy at 17 T is developed as a dielectric ring resonator made of ferroelectric/dielectric low-loss composite ceramics precisely tunable via temperature control. Besides the twofold increase in SNR, compared with the solenoid probe, the proposed ceramic probe does not cause static-field inhomogeneity and related image distortion.

The impact of fasting on resting state brain networks in mice.

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.

Investigation of lithium distribution in the rat brain ex vivo using lithium-7 magnetic resonance spectroscopy and imaging at 17.2 T.

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.

Sedation agents differentially modulate cortical and subcortical blood oxygenation: evidence from ultra-high field MRI at 17.2 T.

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.

Characterization of glioma microcirculation and tissue features using intravoxel incoherent motion magnetic resonance imaging in a rat brain model.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: Quantitative non-Gaussian diffusion and perfusion MRI can provide valuable information on microvasculature and tissue structure to improve characterization of brain tumors.

A new sequence for single-shot diffusion-weighted NMR spectroscopy by the trace of the diffusion tensor.

Diffusion-weighted spectroscopy is a unique tool for exploring the intracellular microenvironment in vivo. In living systems, diffusion may be anisotropic, when biological membranes exhibit particular orientation patterns. In this work, a volume selective diffusion-weighted sequence is proposed, allowing single-shot measurement of the trace of the diffusion tensor, which does not depend on tissue anisotropy. With this sequence, the minimal echo time is only three times the diffusion time. In addition, cross-terms between diffusion gradients and other gradients are cancelled out. An adiabatic version, similar to localization by adiabatic selective refocusing sequence, is then derived, providing partial immunity against cross-terms. Proof of concept is performed ex vivo on chicken skeletal muscle by varying tissue orientation and intra-voxel shim. In vivo performance of the sequence is finally illustrated in a U87 glioblastoma mouse model, allowing the measurement of the trace apparent diffusion coefficient for six metabolites, including J-modulated metabolites. Although measurement performed along three separate orthogonal directions would bring similar accuracy on trace apparent diffusion coefficient under ideal conditions, the method described here should be useful for probing intimate properties of the cells with minimal experimental bias.

High sensitivity 19F MRI of a perfluorooctyl bromide emulsion: application to a dynamic biodistribution study and oxygen tension mapping in the mouse liver and spleen.

We have recently developed an optimized multi-spin echo (MSE) sequence dedicated to perfluorooctyl bromide (PFOB) imaging yielding an excellent sensitivity in vitro. The aim of the present study was to apply this sequence to quantitative measurements in the mouse liver and spleen after intravenous (i.v.) injection of PFOB emulsions. We first performed oxygenation maps 25.5 min after a single infusion of emulsion and, contrary to previous studies, shortly after injection. The signal-to-noise ratio (SNR) in the liver and spleen was as high as 45 and 120, respectively, for 3-min images with 11.7-µL pixels. Values of oxygen tension tended to be slightly higher in the spleen than in the liver. Dynamic biodistribution experiments were then performed immediately after intravenous (i.v.) injection of PFOB emulsions grafted with different quantities of polyethylene glycol (PEG) for stealth. Images were acquired every 7 min for 84 min and the SNR measured in the liver and spleen was at least four from the first time point. Uptake rates could be assessed for each PEG amount and, in spite of high standard deviations (SDs) owing to interanimal variability, our data confirmed that increasing quantities of PEG allow more gradual uptake of the emulsion particles by the liver and spleen. In conclusion, our method seems to be a powerful tool to non-invasively perform accurate in vivo quantitative measurements in the liver and spleen using (19)F MRI.