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This review on brain multiparametric quantitative MRI (MP-qMRI) focuses on the primary subset of quantitative MRI (qMRI) parameters that represent the mobile ("free") and bound ("motion-restricted") proton pools. Such primary parameters are the proton densities, relaxation times, and magnetization transfer parameters. Diffusion qMRI is also included because of its wide implementation in complete clinical MP-qMRI application. MP-qMRI advances were reviewed over the past 2 decades, with substantial progress observed toward accelerating image acquisition and increasing mapping accuracy. Areas that need further investigation and refinement are identified as follows

Human brain mapping 43(11), 3386-3403 (2022). doi:10.1002/hbm.25855, Published by Wiley-Liss, New York, NY

Purpose: Brain water content provides rich tissue contrast comparable to that of longitudinal relaxation time T1, but mapping is usually performed at modest resolution. In particular, the slice thickness in 2D mapping methods is limited. Here, we combine super-resolution reconstruction techniques with a fast water content mapping method to acquire high and isotropic resolution (0.75 mm) water content maps at 3 Tesla. Methods: A high-resolution multi-echo gradient echo image is super-resolution–reconstructed from 3 low-resolution, orthogonal multi-echo gradient echo image acquisitions, followed by water content mapping. The mapping accuracy and SNR of the proposed method are assessed using numerical simulations, phantom studies, and in vivo data acquired from 6 healthy volunteers at 3 Tesla. A high-resolution acquisition with an established mapping method is used as a reference. Results: Whole-brain water content maps with 0.75 mm isotropic resolution are demonstrated. No bias in the water content values was seen following super-resolution reconstruction. In the in vivo experiments, a lower SD of the mean water content values was observed with the proposed method compared to the reference method. Conclusions: Super-resolution reconstruction of multi-echo gradient echo data is demonstrated, enabling whole-brain water content mapping with high and isotropic resolution. The accuracy of the proposed method is shown using phantoms and 6 healthy volunteers and was found to be unchanged compared to the conventional acquisition. The proposed method could increase the sensitivity of water content mapping sufficiently to enable the detection of very small lesions, such as cortical lesions in multiple sclerosis.

The simultaneous quantification of TThis work presents a novel 10-echo GE-SE EPIK (EPI with keyhole) sequence for the rapid quantification of TIn comparison with repeated single-echo SE, multi-echo GE, and spectroscopy methods, the GE-SE EPIK sequence shows good agreement in quantifying TGE-SE EPIK provides increased resolution and more echoes, including two SEs, than comparable sequences. Moreover, GE-SE EPIK achieves this within an acquisition time of 57 s for 20 slices (matrix size = 128×128; FOV = 24 cm) and with a reasonably short TE for the final echo (114 ms). The sequence can dynamically track OEF changes in a breath-hold experiment.

Simultaneous [18 F]-fluorodeoxyglucose positron emission tomography and functional magnetic resonance imaging (FDG-PET/fMRI) provides the capability to image two sources of energetic dynamics in the brain – cerebral glucose uptake and the cerebrovascular haemodynamic response. Resting-state fMRI connectivity has been enormously useful for characterising interactions between distributed brain regions in humans. Metabolic connectivity has recently emerged as a complementary measure to investigate brain network dynamics. Functional PET (fPET) is a new approach for measuring FDG uptake with high temporal resolution and has recently shown promise for assessing the dynamics of neural metabolism. Simultaneous fMRI/fPET is a relatively new hybrid imaging modality, with only a few biomedical imaging research facilities able to acquire FDG PET and BOLD fMRI data simultaneously. We present data for n = 27 healthy young adults (18–20 yrs) who underwent a 95-min simultaneous fMRI/fPET scan while resting with their eyes open. This dataset provides significant re-use value to understand the neural dynamics of glucose metabolism and the haemodynamic response, the synchrony, and interaction between these measures, and the development of new single- and multi-modality image preparation and analysis procedures., Measurement(s) glucose import • haemodynamic response • functional brain measurement Technology Type(s) FDG-Positron Emission Tomography • Blood Oxygen Level-Dependent Functional MRI Factor Type(s) resting human brain Sample Characteristic - Organism Homo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.12994508

Translational Psychiatry 12, 36 (2022). doi:10.1038/s41398-022-01787-3, Published by Nature Publishing Group, London

The suppression of motion artefacts from MR images is a challenging task. The purpose of this paper was to develop a standalone novel technique to suppress motion artefacts in MR images using a data-driven deep learning approach. A simulation framework was developed to generate motion-corrupted images from motion-free images using randomly generated motion profiles. An Inception-ResNet deep learning network architecture was used as the encoder and was augmented with a stack of convolution and upsampling layers to form an encoder-decoder network. The network was trained on simulated motion-corrupted images to identify and suppress those artefacts attributable to motion. The network was validated on unseen simulated datasets and real-world experimental motion-corrupted in vivo brain datasets. The trained network was able to suppress the motion artefacts in the reconstructed images, and the mean structural similarity (SSIM) increased from 0.9058 to 0.9338. The network was also able to suppress the motion artefacts from the real-world experimental dataset, and the mean SSIM increased from 0.8671 to 0.9145. The motion correction of the experimental datasets demonstrated the effectiveness of the motion simulation generation process. The proposed method successfully removed motion artefacts and outperformed an iterative entropy minimization method in terms of the SSIM index and normalized root mean squared error, which were 5-10% better for the proposed method. In conclusion, a novel, data-driven motion correction technique has been developed that can suppress motion artefacts from motion-corrupted MR images. The proposed technique is a standalone, post-processing method that does not interfere with data acquisition or reconstruction parameters, thus making it suitable for routine clinical practice.

Journal of magnetic resonance imaging : JMRI 55(5), 1340-1356 (2022). doi:10.1002/jmri.28029, Published by Wiley-Liss, New York, NY

Simultaneous MR-PET/-SPECT is an emerging technology that capitalises on the invaluable advantages of both modalities, allowing access to numerous sensitive tracers and superior soft-tissue contrast alongside versatile functional imaging capabilities. However, to optimise these capabilities, concurrent acquisitions require the MRI antenna located inside the PET/SPECT field-of-view to be operated without compromising any aspects of system performance or image quality compared to the stand-alone instrumentation. Here, we report a novel gamma-radiation-transparent antenna concept. The end-fed J-shape antenna is particularly adept for hybrid ultra-high field MR-PET/-SPECT applications as it enables all highly attenuating materials to be placed outside the imaging field-of-view. Furthermore, this unique configuration also provides advantages in stand-alone MR applications by reducing the amount of coupling between the cables and the antenna elements, and by lowering the potential specific absorption rate burden. The use of this new design was experimentally verified according to the important features for both ultra-high field MRI and the 511 keV transmission scan. The reconstructed attenuation maps evidently showed much lower attenuation ( ∼ 15 %) for the proposed array when compared to the conventional dipole antenna array since there were no high-density components. In MR, it was observed that the signal-to-noise ratio from the whole volume obtained using the proposed array was comparable to that acquired by the conventional array which was also in agreement with the simulation results. The unique feature, J-shape array, would enable simultaneous MR-PET/-SPECT experiments to be conducted without unduly compromising any aspects of system performance and image quality compared to the stand-alone instrumentation.

The glutamate and γ-aminobutyric acid neuroreceptor subtypes mGluR

PLOS ONE 16(11), e0246709 (2021). doi:10.1371/journal.pone.0246709, Published by PLOS, San Francisco, California, US

Understanding how the living human brain functions requires sophisticated in vivo neuroimaging technologies to characterise the complexity of neuroanatomy, neural function, and brain metabolism. Fluorodeoxyglucose positron emission tomography (FDG-PET) studies of human brain function have historically been limited in their capacity to measure dynamic neural activity. Simultaneous [18 F]-FDG-PET and functional magnetic resonance imaging (fMRI) with FDG infusion protocols enable examination of dynamic changes in cerebral glucose metabolism simultaneously with dynamic changes in blood oxygenation. The Monash vis-fPET-fMRI dataset is a simultaneously acquired FDG-fPET/BOLD-fMRI dataset acquired from n = 10 healthy adults (18–49 yrs) whilst they viewed a flickering checkerboard task. The dataset contains both raw (unprocessed) images and source data organized according to the BIDS specification. The source data includes PET listmode, normalization, sinogram and physiology data. Here, the technical feasibility of using opensource frameworks to reconstruct the PET listmode data is demonstrated. The dataset has significant re-use value for the development of new processing pipelines, signal optimisation methods, and to formulate new hypotheses concerning the relationship between neuronal glucose uptake and cerebral haemodynamics., Measurement(s)brain activityTechnology Type(s)functional magnetic resonance imaging • FDG-Positron Emission TomographySample Characteristic - OrganismHomo sapiens Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14977851

Frontiers in neurology 12, 680254 (2021). doi:10.3389/fneur.2021.680254, Published by Frontiers Research Foundation, Lausanne

EPI with Keyhole (EPIK) is a hybrid imaging technique that overcomes many of the performance disadvantages associated with EPI. Previously, EPIK was shown to provide a higher temporal resolution and fewer image distortions than EPI whilst maintaining comparable performance for the detection of BOLD-based signals. This work carefully examines the putative enhanced sensitivity of EPIK in a typical fMRI setting by using a robust fMRI paradigm – visually guided finger tapping – to demonstrate the advantages of EPIK for fMRI at 3 T. The data acquired were directly compared to the community standard fMRI protocol using single-shot EPI to ascertain a clear comparison. Each sequence was optimised to offer its highest possible spatial resolution for a given set of imaging conditions, i.e., EPIK and EPI achieved an in-planar resolution of 2.08 × 2.08 mm2 with 32 slices and 3.13 × 3.13 mm2 with 36 slices, respectively. EPIK demonstrated a number of clear improvements, such as superior spatial resolution with favourable robustness against susceptibility artefacts. Both imaging sequences revealed robust activation within primary motor, premotor and visual regions, although significantly higher BOLD amplitudes were detected using EPIK within the primary and supplementary motor areas. Dynamic causal modelling, in combination with Bayesian model selection, identified identical winning models for EPIK and EPI data. Coupling parameters reflecting task-related modulations and the connectivity of fixed connections were comparably robust for both sequences. However, fixed connections from the left motor cortex to the right visual cortex were estimated as being significantly more robust for EPIK data.

BACKGROUND Body mass index (BMI) is increasing in a large number of elderly persons. This increase in BMI is known to put one at risk for many "diseases of aging," although less is known about how a change in BMI may affect the brains of the elderly. PURPOSE To investigate the relationship between BMI and quantitative water content, T1 , T2 *, and the semi-quantitative magnetization transfer ratio (MTR) of various structures in elderly brains. STUDY TYPE Cross-sectional. SUBJECTS Forty-two adults (BMI range: 19.1-33.5 kg/m2 , age range: 58-80 years). FIELD STRENGTH 3T MRI (two multi-echo gradient echoes, actual flip angle imaging, magnetization prepared rapid gradient echo, fluid attenuated inversion recovery). ASSESSMENT The 3D two-point method was used to derive (semi-)quantitative parameters in global white (WM) and gray matter (GM) and their regions as defined by the Johns Hopkins University and the Montreal Neurological Institute atlases. STATISTICAL TESTS Multivariate linear regression with BMI as principal regressor, corrected for the additional regressors age, gender, and glycated hemoglobin. Spearman correlation between quantitative parameters of the regions showing significant changes and the lipid spectra / C-reactive protein (CRP). Voxel-based morphometry and analysis of covariance (ANCOVA) to explore changes in the GM volume. RESULTS T1 increased significantly (P

PURPOSE To investigate the correlation between electrical conductivity and sodium concentration, both measured in vivo, in the human brain. METHODS Conductivity measurements were performed on samples with different sodium (Na+ ) and agarose concentrations using a dielectric probe, and the correlation between conductivity and Na+ content was evaluated. Subsequently, brain conductivity and total Na+ content maps were measured in 8 healthy subjects using phase-based MREPT and sodium MRI, respectively. After co-registration and spatial normalization to the 1 mm 152 MNI brain atlas, the relationship between conductivity and tissue sodium concentration (TSC) was examined within different brain regions. RESULTS The conductivities of agarose gels increased linearly with NaCl concentration, while remaining almost independent of agarose content. When measured in healthy subjects, conductivities showed positive correlation with total tissue sodium concentration (R = 0.39, P < 0.005). The same trend was found in gray matter (R = 0.36, P < 0.005) and in white matter (R = 0.28, P < 0.05). CONCLUSION Tissue conductivity shows a positive correlation with total sodium concentration. Conductivity might serve as a novel technique to visualize the total tissue electrolyte concentration, although refinements in the consideration of e.g., tissue water content, would be necessary to improve the quantitative value.

Building on the success of positron emission tomography (PET)/CT scanners, a hybrid imaging technology, combining PET with the versatile attributes of magnetic resonance imaging (MRI), has been in use for over ten years. At the Forschungszentrum Julich, one of the four prototypes available worldwide, combining a commercial 3T MRI with a newly developed BrainPET insert, was installed in 2008, allowing simultaneous data acquisition with PET and MRI. Here, we report on our ten-year-long experience of the methods and technology developed through this paper with numerous patients and volunteers. In the course of our research, a number of different radiotracers, such as [18F]Fluoroethyltyrosine, [11C]Flumazenil, [11C]Raclopride, and [15O]H2O, have been applied while simultaneously measuring several different MR sequences. The PET data obtained with the BrainPET has demonstrated higher image quality and superior resolution capability compared to the stand-alone PET scanner, ECAT Exact HR+. Furthermore, the simultaneous acquisition of MR images alongside BrainPET scans, using different sequences, showed an excellent quality without any relevant artifacts and provided useful complementary information. Our experiences with the hybrid 3T MR-BrainPET indicate a promising basis for further developments of this unique technique, allowing simultaneous brain imaging in a clinical setting.

A deep learning framework is presented that transforms the task of MR image reconstruction from randomly undersampled k-space data into pixel classification. A DL network was trained to remove incoherent undersampling artifacts from MR images. The underlying, fully sampled, target image was represented as a discrete quantized image. The quantization step enables the design of a convolutional neural network (CNN) that can classify each pixel in the input image to a discrete quantized level. The reconstructed image quality of the proposed DL classification model was compared with conventional compressed sensing (CS) and a DL regression model. The reconstructed images using the DL classification model outperformed the state-of-the-art compressed sensing and DL regression models with a similar number of parameters assessed using quantitative measures. The experiments reveal that the proposed deep learning method is robust to noise and is able to reconstruct high-quality images in low SNR scenarios where conventional CS reconstructions and DL regression networks perform poorly. A generic design framework for transforming MR image reconstruction into pixel classification is developed. The proposed method can be easily incorporated into other DL-based image reconstruction methods.

Frontiers in neuroscience 15, 537666 (2021). doi:10.3389/fnins.2021.537666, Published by Frontiers Research Foundation, Lausanne

Simultaneous MR-PET is an increasingly popular multimodal imaging technique that is able to combine metabolic information obtained from PET with anatomical/functional information from MRI. One of the key technological challenges of the technique is the integration of a PET-transparent MR coil system, a solution to which is demonstrated here for a double-tuned

Translational Psychiatry 11(1), 60 (2021). doi:10.1038/s41398-020-01160-2, Published by Nature Publishing Group, London

Magnetic resonance in medicine : MRM 85(5), 2892-2903 (2021). doi:10.1002/mrm.28597, Published by Wiley-Liss, New York, NY [u.a.]

Scientific reports 11(1), 11564 (2021). doi:10.1038/s41598-021-91056-y, Published by Macmillan Publishers Limited, part of Springer Nature, [London]

NeuroImage 252, 119014 (2022). doi:10.1016/j.neuroimage.2022.119014, Published by Academic Press, Orlando, Fla.

Purpose A recent study reported on high, longer lasting and finally reversible cerebral uptake of O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) induced by epileptic activity. Therefore, we examined cerebral [18F]FET uptake in two chemically induced rat epilepsy models and in patients with focal epilepsy to further investigate whether this phenomenon represents a major pitfall in brain tumor diagnostics and whether [18F]FET may be a potential marker to localize epileptic foci. Procedures Five rats underwent kainic acid titration to exhibit 3 to 3.5 h of class IV–V motor seizures (status epilepticus, SE). Rats underwent 4× [18F]FET PET and 4× MRI on the following 25 days. Six rats underwent kindling with pentylenetetrazol (PTZ) 3 to 8×/week over 10 weeks, and hence, seizures increased from class I to class IV. [18F]FET PET and MRI were performed regularly on days with and without seizures. Four rats served as healthy controls. Additionally, five patients with focal epilepsy underwent [18F]FET PET within 12 days after the last documented seizure. Results No abnormalities in [18F]FET PET or MRI were detected in the kindling model. The SE model showed significantly decreased [18F]FET uptake 3 days after SE in all examined brain regions, and especially in the amygdala region, which normalized within 2 weeks. Corresponding signal alterations in T2-weighted MRI were noted in the amygdala and hippocampus, which recovered 24 days post-SE. No abnormality of cerebral [18F]FET uptake was noted in the epilepsy patients. Conclusions There was no evidence for increased cerebral [18F]FET uptake after epileptic seizures neither in the rat models nor in patients. The SE model even showed decreased [18F]FET uptake throughout the brain. We conclude that epileptic seizures per se do not cause a longer lasting increased [18F]FET accumulation and are unlikely to be a major cause of pitfall for brain tumor diagnostics.

PLOS ONE 16(2), 1-16 (2021). doi:10.1371/journal.pone.0247552, Published by PLOS, San Francisco, California, US

The use of hybrid PET/MR imaging facilitates the simultaneous investigation of challenge-related changes in ligand binding to neuroreceptors using PET, while concurrently measuring neuroactivation or blood flow with MRI. Having attained a steady state of the PET radiotracer using a bolus-infusion protocol, it is possible to observe alterations in ligand neuroreceptor binding through changes in distribution volumes. Here, we present an iterative procedure for establishing an administration scheme to obtain steady state [

With the increasing availability of ultra-high field MRI systems, studying non-proton nuclei (X-nuclei), such as 23Na and 31P has received great interest. X-nuclei are able to provide insight into important cellular processes and energy metabolism in tissues and by monitoring these nuclei closely it is possible to establish links to pathological conditions and neurodegenerative diseases. In order to investigate X-nuclei, a well-designed radiofrequency (RF) system with a multi-tuned RF coil is required. However, as the intrinsic sensitivity of non-proton nuclei is lower compared to 1H, it is important to ensure that the signal-to-noise ratio (SNR) of the X-nuclei is as high as possible. This review aims to give a comprehensive overview of previous efforts, with particular focus on the design concept of multi-tuned coils, predominantly for brain applications. In order to guide the readers, the main body of the review is categorised into two parts: state-of-the art according to the single or multiple design structures and emerging technologies. A more detailed description is given in each subsection relating to the specific design approaches of, mostly, double-tuned coils, including using traps, PIN-diodes, nested and metamaterial, together with explanations of their novelties, optimal solutions and trade-offs.

Prostate cancer is one of the most common cancers among men and its early detection is critical for its successful treatment. The use of multimodal imaging, such as MR-PET, is most advantageous as it is able to provide detailed information about the prostate. However, as the human prostate is flexible and can move into different positions under external conditions, it is important to localise the focused region-of-interest using both MRI and PET under identical circumstances. In this work, we designed five commonly used linear and quadrature radiofrequency surface coils suitable for hybrid MR-PET use in endorectal applications. Due to the endorectal design and the shielded PET insert, the outer face of the coils investigated was curved and the region to be imaged was outside the volume of the coil. The tilting angles of the coils were varied with respect to the main magnetic field direction. This was done to approximate the various positions from which the prostate could be imaged. The transmit efficiencies and safety excitation efficiencies from simulations, together with the signal-to-noise ratios from the MR images were calculated and analysed. Overall, it was found that the overlapped loops driven in quadrature were superior to the other types of coils we tested. In order to determine the effect of the different coil designs on PET, transmission scans were carried out, and it was observed that the differences between attenuation maps with and without the coils were negligible. The findings of this work can provide useful guidance for the integration of such coil designs into MR-PET hybrid systems in the future.

Cognitive decline is a symptom of healthy ageing and Alzheimer's disease. We examined the effect of real-time fMRI based neurofeedback training on visuo-spatial memory and its associated neuronal response. Twelve healthy subjects and nine patients of prodromal Alzheimer's disease were included. The examination spanned five days (T1-T5): T1 contained a neuropsychological pre-test, the encoding of an itinerary and a fMRI-based task related that itinerary. T2-T4 hosted the real-time fMRI neurofeedback training of the parahippocampal gyrus and on T5 a post-test session including encoding of another itinerary and a subsequent fMRI-based task were done. Scores from neuropsychological tests, brain activation and task performance during the fMRI-paradigm were compared between pre and post-test as well as between healthy controls and patients. Behavioural performance in the fMRI-task remained unchanged, while cognitive testing showed improvements in visuo-spatial memory performance. Both groups displayed task-relevant brain activation, which decreased in the right precentral gyrus and left occipital lobe from pre to post-test in controls, but increased in the right occipital lobe, middle frontal gyrus and left frontal lobe in the patient group. While results suggest that the training has affected brain activation differently between controls and patients, there are no pointers towards a behavioural manifestation of these changes. Future research is required on the effects that can be induced using real-time fMRI based neurofeedback training and the required training duration to elicit broad and lasting effects.

PurposePositron emission tomography (PET) using O-(2-[18F]fluoroethyl)-L-tyrosine ([18F]FET) improves the diagnostics of cerebral gliomas compared with conventional magnetic resonance imaging (MRI). Sodium MRI is an evolving method to assess tumor metabolism. In this pilot study, we explored the relationship of [18F]FET-PET and sodium MRI in patients with cerebral gliomas in relation to the mutational status of the enzyme isocitrate dehydrogenase (IDH).ProceduresTen patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [18F]FET-PET and sodium MRI using an enhanced simultaneous single-quantum- and triple-quantum-filtered imaging of 23Na (SISTINA) sequence to estimate total (NaT), weighted non-restricted (NaNR, mainly extracellular), and restricted (NaR, mainly intracellular) sodium in tumors and normal brain tissue. [18F]FET uptake and sodium parameters in tumors with a different IDH mutational status were compared. After biopsy or resection, histology and the IDH mutational status were determined neuropathologically.ResultsNaT (p = 0.05), tumor-to-brain ratios (TBR) of NaT (p = 0.02), NaNR (p = 0.003), and the ratio of NaT/NaR (p

Purpose Echo planar imaging is used widely for its imaging speed. However, its applications often suffer from ghost artifacts. In the community, an approach using three navigator echoes is used commonly for the artifact correction. Although this scheme is effective, as the matrix size increases for high-resolution imaging, the navigator echoes can contribute significantly to increasing the "required minimum TE." To overcome this issue, this work proposes the use of an alternative navigator echo scheme called the "TR-external" scheme. Methods The TR-external scheme reduces the required minimum TE by allocating an additional excitation loop for the navigator echoes before every main excitation loop. In this work, a detailed analysis on the TR-external scheme was performed to assess its performance in comparison to the standard scheme. Visual fMRI was performed to check the feasibility of using the TR-external scheme for detecting functional signals. Results The performance of the TR-external scheme was comparable with that of the standard scheme in terms of the SNR, elimination of ghost artifacts, and the BOLD detection. For a given matrix size (288 × 288), the TR-external scheme allowed a substantially shorter TE (5.94 ms) compared with the standard scheme, which resulted in a higher SNR. Furthermore, this feature enabled the submillimeter-resolution (0.73 × 0.73 mm2 ) fMRI measurement with a favorable TE (35 ms) at 3 T. The fMRI results revealed that activated voxels are well localized along the cortical ribbon. Conclusion A TR-external scheme for EPI phase correction was implemented at 3 T. Its feasibility for submillimeter-resolution fMRI was successfully demonstrated.

Precise and comprehensive mapping of somatotopic representations in the motor cortex is clinically essential to achieve maximum resection of brain tumours whilst preserving motor function, especially since the current gold standard, that is, intraoperative direct cortical stimulation (DCS), holds limitations linked to the intraoperative setting such as time constraints or anatomical restrictions. Non‐invasive techniques are increasingly relevant with regard to pre‐operative risk‐assessment. Here, we assessed the congruency of neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) with DCS. The motor representations of the hand, the foot and the tongue regions of 36 patients with intracranial tumours were mapped pre‐operatively using nTMS and fMRI and by intraoperative DCS. Euclidean distances (ED) between hotspots/centres of gravity and (relative) overlaps of the maps were compared. We found significantly smaller EDs (11.4 ± 8.3 vs. 16.8 ± 7.0 mm) and better spatial overlaps (64 ± 38% vs. 37 ± 37%) between DCS and nTMS compared with DCS and fMRI. In contrast to DCS, fMRI and nTMS mappings were feasible for all regions and patients without complications. In summary, nTMS seems to be the more promising non‐invasive motor cortex mapping technique to approximate the gold standard DCS results., The motor representations of the hand, the foot and the tongue regions were mapped pre‐operatively using neuronavigated transcranial magnetic stimulation (nTMS) and functional magnetic resonance imaging (fMRI) in thirty six patients with intracranial tumours and were compared with intraoperative direct cortex stimulation (DCS). We found significantly smaller Euclidean distances and better spatial overlaps between DCS and nTMS compared with DCS and fMRI. In summary, nTMS seems to be the more promising non‐invasive motor cortex mapping technique to approximate the gold standard DCS results.

Sodium MRI is a promising method for assessing the metabolic properties of brain tumours. In a recent study, a strong relationship between semi-quantitative abnormalities in sodium MRI and the mutational status of the isocitrate dehydrogenase enzyme (IDH) with untreated cerebral gliomas was observed. Here, sodium relaxometry in brain tumour tissue was investigated in relation to molecular markers in order to reveal quantitative sodium tissue parameters and the differences between healthy tissue and brain tumour. The previous semi-quantitative approach is extended by use of suitable relaxometry methods accompanied by numerical simulation to achieve detailed quantitative analysis of intra- and extracellular sodium concentration using an enhanced SISTINA sequence at 4 T. Using optimised techniques, biexponential sodium relaxation times in tumour (T*2f , T*2s ) and in healthy contralateral brain tissue (T*2f,CL , T*2s,CL ) were estimated in 10 patients, along with intracellular sodium molar fractions (χ, χCL ), volume fractions (η, ηCL ) and concentrations (ρin , ρin,CL ). The total sodium tissue concentrations (ρT , ρT,CL ) were also estimated. The ratios T*2f /T*2f,CL (P = .05), η/ηCL (P = .02) and χ/χCL (P = .02) were significantly lower in IDH mutated than in IDH wildtype gliomas (n = 4 and n = 5 patients, respectively). The Wilcoxon rank-sum test was used to compare sodium MRI parameters in patients with and without IDH mutation. Thus, quantitative analysis of relaxation rates, intra- and extracellular sodium concentrations, intracellular molar and volume fractions based on enhanced SISTINA confirmed a relationship between abnormalities in sodium parameters and the IDH mutational status in cerebral gliomas, hence catering for the potential to provide further insights into the status of the disease.

PLOS ONE 15(8), e0237494 (2020). doi:10.1371/journal.pone.0237494, Published by PLOS, San Francisco, California, US

Simultaneous trimodal positron emission tomography/magnetic resonance imaging/electroencephalography (PET/MRI/EEG) resting state (rs) brain data were acquired from 10 healthy male volunteers. The rs‐functional MRI (fMRI) metrics, such as regional homogeneity (ReHo), degree centrality (DC) and fractional amplitude of low‐frequency fluctuations (fALFFs), as well as 2‐[18F]fluoro‐2‐desoxy‐d‐glucose (FDG)‐PET standardised uptake value (SUV), were calculated and the measures were extracted from the default mode network (DMN) regions of the brain. Similarly, four microstates for each subject, showing the diverse functional states of the whole brain via topographical variations due to global field power (GFP), were estimated from artefact‐corrected EEG signals. In this exploratory analysis, the GFP of microstates was nonparametrically compared to rs‐fMRI metrics and FDG‐PET SUV measured in the DMN of the brain. The rs‐fMRI metrics (ReHO, fALFF) and FDG‐PET SUV did not show any significant correlations with any of the microstates. The DC metric showed a significant positive correlation with microstate C (r (s) = 0.73, p = .01). FDG‐PET SUVs indicate a trend for a negative correlation with microstates A, B and C. The positive correlation of microstate C with DC metrics suggests a functional relationship between cortical hubs in the frontal and occipital lobes. The results of this study suggest further exploration of this method in a larger sample and in patients with neuropsychiatric disorders. The aim of this exploratory pilot study is to lay the foundation for the development of such multimodal measures to be applied as biomarkers for diagnosis, disease staging, treatment response and monitoring of neuropsychiatric disorders.

PURPOSE Sodium imaging delivers valuable information about in vivo metabolism and pathophysiology. Image quantification can benefit the diagnosis and characterization of existing pathologies and the clinical course of a disease. An enhanced SISTINA sequence is proposed for sodium imaging and for the estimation of sodium tissue parameters for a 2-compartment model of the brain, such as relaxation times in intracellular space and tissue, intracellular volume fraction, and intracellular molar fraction. The aim of the research is to demonstrate how a 2-compartment model can be parameterized to sufficiently describe tissue sodium concentrations and dynamics by performing relaxometry with such a sequence. METHODS Multiple quantum filtered sodium signals were detected using an enhanced SISTINA sequence (consisting of 3 consecutive RF pulses) by placing a readout train between the first and second RF pulse, and 1 after the third pulse. Semiautomatic segmentation using singular value decomposition and manual segmentation was applied to the images. RESULTS Analysis was performed on 40 healthy volunteers in a 4T scanner, yielding bi-exponential relaxation times of brain tissue, intracellular sodium molar and volume fraction, intracellular sodium concentration, as well as sodium tissue concentration in the scope of a considered model. Two models with either purely mono-exponential or bi-exponential relaxing extracellular sodium were used with and without a potential contribution of triple quantum-filtered signal from extracellular space. CONCLUSION An estimation of relaxation properties and concentrations limited to the assumed model is possible from a single sequence. The achieved results agree well with those reported in literature.

Simultaneous PET/MR/EEG (Positron Emission Tomography – Magnetic Resonance – Electroencephalography), a new tool for the investigation of neuronal networks in the human brain, is presented here within the framework of the European Union Project TRIMAGE. The trimodal, cost-effective PET/MR/EEG imaging tool makes use of cutting edge technology both in PET and in MR fields. A novel type of magnet (1.5T, non-cryogenic) has been built together with a PET scanner that makes use of the most advanced photodetectors (i.e., SiPM matrices), scintillators matrices (LYSO) and digital electronics. The combined PET/MR/EEG system is dedicated to brain imaging and has an inner diameter of 260 mm and an axial Field-of-View of 160 mm.It enables the acquisition and assessment of molecular metabolic information with high spatial and temporal resolution in a given brain simultaneously. The dopaminergic system and the glutamatergic system in schizophrenic patients are investigated via PET, the same physiological/pathophysiological conditions with regard to functional connectivity, via fMRI, and its electrophysiological signature via EEG. In addition to basic neuroscience questions addressing neurovascular-metabolic coupling, this new methodology lays the foundation for individual physiological and pathological fingerprints for a wide research field addressing healthy aging, gender effects, plasticity and different psychiatric and neurological diseases.The preliminary performances of two components of the imaging tool (PET and MR) are discussed. Initial results of the search of possible candidates for suitable schizophrenia biomarkers are also presented as obtained with PET/MR systems available to the collaboration.

A new reconstruction method, coined MIRAGE, is presented for accurate, fast, and robust parameter mapping of multiple-echo gradient-echo (MEGE) imaging, the basis sequence of novel quantitative magnetic resonance imaging techniques such as water content and susceptibility mapping. Assuming that the temporal signal can be modeled as a sum of damped complex exponentials, MIRAGE performs model-based reconstruction of undersampled data by minimizing the rank of local Hankel matrices. It further incorporates multi-channel information and spatial prior knowledge. Finally, the parameter maps are estimated using nonlinear regression. Simulations and retrospective undersampling of phantom and in vivo data affirm robustness, e.g., to strong inhomogeneity of the static magnetic field and partial volume effects. MIRAGE is compared with a state-of-the-art compressed sensing method, ${{\text {L}}_{1}}$ -ESPIRiT. Parameter maps estimated from reconstructed data using MIRAGE are shown to be accurate, with the mean absolute error reduced by up to 50% for in vivo results. The proposed method has the potential to improve the diagnostic utility of quantitative imaging techniques that rely on MEGE data.

Glutamate is the major excitatory neurotransmitter in the human brain and has a central role in both intrinsic and stimulus-induced activity. We conducted a study in a cohort of healthy, male volunteers in which glutamate levels were measured in the posterior cingulate cortex (PCC) using 1H magnetic resonance spectroscopy at 3T. The advantages of simultaneous electroencephalography and magnetic resonance imaging (EEG-MRI) were exploited and the subjects were measured in the same session and under the same physiological conditions. Diffusion tensor imaging (DTI), functional MRI (fMRI) and EEG were measured in order to investigate the functional and microstructural correlates of glutamate. The concentration of glutamate (institute units) was calculated and those values were tested for correlation with the metrics of resting state fMRI, DTI, and EEG electrical sources. Our results showed that the concentration of glutamate in the PCC had a significant negative correlation with the tissue mean diffusivity in the same area. The analysis of resting state networks did not show any relationship between the concentration of glutamate and the intrinsic activity of the resting state networks. The concentration of glutamate showed a positive correlation with the electrical generators of α-1 frequency and a negative correlation with the generators of α-2 and β-1 electrical generators. © 2017 Wiley Periodicals, Inc.

Non-proton MRI has recently garnered gathering interest with the increased availability of ultra high-field MRI system. Assuming the availability of a broadband RF amplifier, performing multinuclear MR experiments essentially requires additional hardware, such as an RF resonator and a T/R switch for each nucleus. A double- or triple-resonant RF probe is typically constructed using traps or PIN-diode circuits, but this approach degrades the signal-to-noise ratio (SNR) and image quality compared to a single-resonant coil and this is a limiting factor. In this work, we have designed the required hardware for multinuclear MR imaging experiments employing six single-resonant coil sets and a purpose-built animal bed; these have been implemented into a home-integrated 9.4 T preclinical MRI scanner. System capabilities are demonstrated by distinguishing concentration differences and sensitivity of X-nuclei imaging and spectroscopy without SNR penalty for any nuclei, no subject interruption and no degradation of the static shim conditions.

Interest in white matter hyperintensities (WMH), a radiological biomarker of small vessel disease, is continuously increasing. This is, in most part, due to our better understanding of their association with various clinical disorders, such as stroke and Alzheimer’s disease, and the overlapping pathology of WMH with these afflictions. Although post-mortem histological studies have reported various underlying pathophysiological substrates, in vivo research has not been specific enough to fully corroborate these findings. Furthermore, post-mortem studies are not able to capture which pathological processes are the driving force of the WMH severity. The current study attempts to fill this gap by non-invasively investigating the influence of WMH on brain tissue using quantitative MRI (qMRI) measurements of the water content (H2O), the longitudinal (T1) and effective transverse relaxation times (T2∗), as well as the semi-quantitative magnetization transfer ratio (MTR), and bound proton fraction (ƒbound). In total, seventy subjects (age range 50–80 years) were selected from a population-based aging cohort study, 1000BRAINS. Normal appearing grey (NAGM) and white matter (NAWM), as well as deep (DWMH) and periventricular (PWMH) white matter hyperintensities, were segmented and characterized in terms of their quantitative properties. The subjects were then further divided into four grades according to the Fazekas rating scale of severity. Groupwise analyses of the qMRI values in each tissue class were performed. All five qMRI parameters showed significant differences between WMH and NAWM (p

Positron emission tomography (PET) using O-(2-[Ten patients with untreated cerebral gliomas and one patient with a recurrent glioblastoma (GBM) were investigated by dynamic [NaT (p = 0.05), tumor-to-brain ratios (TBR) of NaT (p = 0.02), NaNR (p = 0.003), and the ratio of NaT/NaR (p 0.001) were significantly higher in IDH-mutated than in IDH-wild-type gliomas (n = 5 patients each) while NaR was significantly lower in IDH-mutated gliomas (p = 0.01). [Sodium MRI appears to be more strongly related to the IDH mutational status than are [

A new parameter estimation algorithm, MERLIN, is presented for accurate and robust multi-exponential relaxometry using magnetic resonance imaging, a tool that can provide valuable insight into the tissue microstructure of the brain. Multi-exponential relaxometry is used to analyze the myelin water fraction and can help to detect related diseases. However, the underlying problem is ill-conditioned, and as such, is extremely sensitive to noise and measurement imperfections, which can lead to less precise and more biased parameter estimates. MERLIN is a fully automated, multi-voxel approach that incorporates state-of-the-art l

ObjectivesTo apply the MB (multiband) excitation and blipped-CAIPI (blipped-controlled aliasing in parallel imaging) techniques in a spin and gradient-echo (SAGE) EPI sequence to improve the slice coverage for vessel architecture imaging (VAI).Materials and methodsBoth MB excitation and blipped-CAIPI with in-plane parallel imaging were incorporated into a gradient-echo (GE)/spin-echo (SE) EPI sequence for simultaneous tracking of the dynamic MR signal changes in both GE and SE contrasts after the injection of contrast agent. MB and singleband (SB) excitation were compared using a 20-channel head coil at 3 Tesla, and high-resolution MB VAI could be performed in 32 glioma patients.ResultsWhole-brain covered high resolution VAI can be achieved after applying multiband excitation with a factor of 2 and in-plane parallel imaging with a factor of 3. The quality of the images resulting from MB acceleration was comparable to those from the SB method: images were reconstructed without any loss of spatial resolution or severe distortions. In addition, MB and SB signal-to-noise ratios (SNR) were similar. A relative low g-factor induced from the MB acceleration method was achieved after using a blipped-CAIPI technique (1.35 for GE and 1.33 for SE imaging). Performing quantitative VAI, we found that, among all VAI parametric maps, microvessel type indicator (MTI), distance map (I) and vascular-induced bolus peak-time shift (VIPS) were highly correlated. Likewise, VAI parametric maps of slope, slope length and short axis were highly correlated.ConclusionsMultiband accelerated SAGE successfully doubles the number of readout slices in the same measurement time when compared to conventional readout sequences. The corresponding VAI parametric maps provide insights into the complexity and heterogeneity of vascular changes in glioma.