Publications by authors named "Denis Le Bihan"

126 Publications

Diffusion functional MRI reveals global brain network functional abnormalities driven by targeted local activity in a neuropsychiatric disease mouse model.

Neuroimage 2020 12 1;223:117318. Epub 2020 Sep 1.

Departemnt of Neuropsychiatry, Keio University School of Medicine, 35 Shinanomachi, Shinjuku, Tokyo, Japan.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as an alternative functional imaging method to detect brain activity without confounding hemodynamic effects. Here, taking advantage of this DfMRI feature, we investigated abnormalities of dynamic brain function in a neuropsychiatric disease mouse model (glial glutamate transporter-knockdown mice with obsessive-compulsive disorder [OCD]-related behavior). Our DfMRI approaches consisted of three analyses: resting state brain activity, functional connectivity, and propagation of neural information. We detected hyperactivation and biased connectivity across the cortico-striatal-thalamic circuitry, which is consistent with known blood oxygen-level dependent (BOLD)-fMRI patterns in OCD patients. In addition, we performed ignition-driven mean integration (IDMI) analysis, which combined activity and connectivity analyses, to evaluate neural propagation initiated from brain activation. This analysis revealed an unbalanced distribution of neural propagation initiated from intrinsic local activation to the global network, while these were not detected by the conventional method with BOLD-fMRI. This abnormal function detected by DfMRI was associated with OCD-related behavior. Together, our comprehensive DfMRI approaches can successfully provide information on dynamic brain function in normal and diseased brains.
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http://dx.doi.org/10.1016/j.neuroimage.2020.117318DOI Listing
December 2020

Simultaneous proton density, T , T , and flip-angle mapping of the brain at 7 T using multiparametric 3D SSFP imaging and parallel-transmission universal pulses.

Magn Reson Med 2020 12 3;84(6):3286-3299. Epub 2020 Jul 3.

Université Paris-Saclay, CEA, CNRS, BAOBAB, NeuroSpin, Gif-sur-Yvette, France.

Purpose: Performing simultaneous quantitative MRI at ultrahigh field is challenging, as B and heterogeneities as well as specific absorption rate increase. Too large deviations of flip angle from the target can induce biases and impair SNR in the quantification process. In this work, we use calibration-free parallel transmission, a dedicated pulse-sequence parameter optimization and signal fitting to recover 3D proton density, flip angle, T , and T maps over the whole brain, in a clinically suitable time.

Methods: Eleven optimized contrasts were acquired with an unbalanced SSFP sequence by varying flip-angle amplitude and RF phase-cycling increment, at a 1.0 × 1.0 × 3.0 mm resolution. Acquisition time was 16 minutes 36 seconds for the whole brain. Parallel transmission and universal pulses were used to mitigate heterogeneity, to improve the results' reliability over 6 healthy volunteers (3 females/3 males, age 22.6 ± 2.7 years old). Quantification of the physical parameters was performed by fitting the acquired contrasts to the simulated ones using the Bloch-Torrey equations with a realistic diffusion coefficient.

Results: Whole-brain 3D maps of effective flip angle, proton density, and relaxation times were estimated. Parallel transmission improved the robustness of the results at 7 T. Results were in accordance with literature and with measurements from standard methods.

Conclusion: These preliminary results show robust proton density, flip angle, T , and T map retrieval. Other parameters, such as ADC, could be assessed. With further optimization in the acquisition, scan time could be reduced and spatial resolution increased to bring this multiparametric quantification method to clinical research routine at 7 T.
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http://dx.doi.org/10.1002/mrm.28391DOI Listing
December 2020

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

PLoS One 2020 21;15(5):e0228759. Epub 2020 May 21.

NeuroSpin/Joliot, CEA-Saclay Center, Gif-sur-Yvette, France.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0228759PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241787PMC
September 2020

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

PLoS One 2020 15;15(5):e0229702. Epub 2020 May 15.

NeuroSpin/Joliot, CEA-Saclay Center, Gif-sur-Yvette, France.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0229702PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228049PMC
July 2020

Diffusion-weighted MRI-based Virtual Elastography for the Assessment of Liver Fibrosis.

Radiology 2020 04 11;295(1):127-135. Epub 2020 Feb 11.

From the Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo, Yamanashi 409-3898, Japan (M.L.K., S.I., U.M.); Department of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, Greifswald, Germany (M.L.K.); Neurospin, Bât 145, CEA-Saclay Center, Gif-sur-Yvette, France (D.L.B.); and Department of Radiology, Kyoto University Graduate School of Medicine, Kyoto, Japan (D.L.B.).

Background Diffusion-weighted (DW) MRI-based elastography has recently been proposed for noninvasive liver fibrosis staging but requires evaluation in a larger number of patients. Purpose To compare DW MRI and MR elastography for the assessment of liver fibrosis. Materials and Methods In this retrospective study, patients underwent MR elastography and DW MRI between November 2017 and April 2018. Shear modulus measured by MR elastography (μ) was obtained in each patient from regions of interest placed on liver stiffness maps by two independent readers. Shifted apparent diffusion coefficient (ADC) was calculated from DW MRI ( = 200 and 1500 sec/mm) and converted to DW MRI-based virtual shear modulus (μ). MRI-based liver fibrosis stages were estimated from μ and μ values (F0-F4) and serum fibrosis markers were assessed. Statistical analyses included Bland-Altman plots, Bayesian prediction, and receiver operating characteristic analyses. Results Seventy-four patients (mean age, 68 years ± 9 [standard deviation]; 45 men) were evaluated. Interreader coefficient of reproducibility was 0.86 kPa for DW MRI and 1.2 kPa for MR elastography. Strong correlation between shifted ADC and μ was observed ( = 0.81; < .001), showing high agreement between μ and μ values (mean difference, -0.02 kPa ± 0.88; < .001). DW MRI-based fibrosis staging agreed with MR elastography-based staging in 55% of patients (41 of 74) and within one stage difference in 35% of patients (26 of 74). Binarization into insignificant (F0-F1) and significant fibrosis (F2-F4) showed agreement in 85% of patients (63 of 74; κ = 0.85). Compared with serum markers (area under the receiver operating characteristic curve [AUC], 0.50-0.69), μ showed better performance in discriminating fibrosis stages F0-F2 from F3-F4 (AUC, 0.79; 95% confidence interval: 0.69, 0.90), whereas serum markers showed slightly better results for F0-F1 versus F2-F4 differentiation (fibrosis stages were estimated by using MR elastography). Combining DW MRI with serum markers provided a trend toward highest discriminative performance (AUC, μ + aspartate aminotransferase-to-platelet radio index: F0-F1 vs F2-F4, 0.81 [95% confidence interval: 0.69, 0.93], = .17; F0-F2 vs F3-F4, 0.83 [95% confidence interval: 0.74, 0.92], = .07; and AUC μ + Fibrosis 4 score: F0-F1 vs F2-F4, 0.78 [95% confidence interval: 0.64, 0.92], < .30; F0-F2 vs F3-F4, 0.81 [95% confidence interval: 0.71, 0.91], = .08). Conclusion MR elastography and diffusion-weighted (DW) MRI-based estimation of liver fibrosis stage showed high agreement. DW MRI shows potential as an alternative to MR elastography for noninvasive fibrosis staging without the need for mechanical vibration setup. © RSNA, 2020
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http://dx.doi.org/10.1148/radiol.2020191498DOI Listing
April 2020

Six DWI questions you always wanted to know but were afraid to ask: clinical relevance for breast diffusion MRI.

Eur Radiol 2020 May 21;30(5):2561-2570. Epub 2020 Jan 21.

NeuroSpin/Joliot, CEA-Saclay Center, Paris-Saclay University, Gif-sur-Yvette, France.

Diffusion MRI (often called diffusion-weighted imaging or DWI) has enjoyed a tremendous growth since its introduction in the mid-1980s, especially to investigate neurological disorders and in oncology. At a time when standardization and quality control appear as critical as ever to support widespread utilization, our aim was to address common fundamental questions that arise regarding results obtained with DWI. We focus on six questions taking breast DWI as an example, as breast DWI is increasingly used in clinical practice, but most of our conclusions would apply to DWI in general. We show especially that noise can act in a pernicious way specific to DWI. Ignoring such noise effects could lead to incorrect data interpretations or conclusions, of which authors and readers may be genuinely unaware. While addressing these six questions, we give practical examples of how noise effects can be understood, corrected when possible, or taken to our advantage. Key Points • Ignoring noise effects in DWI could lead to incorrect data interpretations or conclusions, of which authors and readers may be genuinely unaware. • In vivo apparent diffusion coefficient (ADC) decreases with b value, which must therefore be reported along with ADC. • Synthesized DWI boosts contrast at the expense of accurate diffusion/microstructure characterization.
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http://dx.doi.org/10.1007/s00330-019-06648-0DOI Listing
May 2020

Empirical and Theoretical Characterization of the Diffusion Process of Different Gadolinium-Based Nanoparticles within the Brain Tissue after Ultrasound-Induced Permeabilization of the Blood-Brain Barrier.

Contrast Media Mol Imaging 2019 1;2019:6341545. Epub 2019 Dec 1.

NeuroSpin, Institut des Sciences de La Vie Frédéric Joliot, Direction de La Recherche Fondamentale, Commissariat à L'Energie Atomique et Aux Energies Alternatives, Université Paris Saclay, Gif-sur-Yvette, France.

Low-intensity focused ultrasound (FUS), combined with microbubbles, is able to locally, and noninvasively, open the blood-brain barrier (BBB), allowing nanoparticles to enter the brain. We present here a study on the diffusion process of gadolinium-based MRI contrast agents within the brain extracellular space after ultrasound-induced BBB permeabilization. Three compounds were tested (MultiHance, Gadovist, and Dotarem). We characterized their diffusion through experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from studies and of apparent diffusion coefficients from experiments, we have assessed tortuosity in the right striatum of 9 Sprague Dawley rats through a model correctly describing both vascular permeability as a function of time and diffusion processes occurring in the brain tissue. This model takes into account acoustic pressure, particle size, blood pharmacokinetics, and diffusion rates. Our model is able to fully predict the result of a FUS-induced BBB opening experiment at long space and time scales. Recovered values of tortuosity are in agreement with the literature and demonstrate that our improved model allows us to assess that the chosen permeabilization protocol preserves the integrity of the brain tissue.
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http://dx.doi.org/10.1155/2019/6341545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6914891PMC
July 2020

Diffusion-weighted imaging of the breast-a consensus and mission statement from the EUSOBI International Breast Diffusion-Weighted Imaging working group.

Eur Radiol 2020 Mar 30;30(3):1436-1450. Epub 2019 Nov 30.

NeuroSpin, Frédéric Joliot Institute, Gif Sur Yvette, France.

The European Society of Breast Radiology (EUSOBI) established an International Breast DWI working group. The working group consists of clinical breast MRI experts, MRI physicists, and representatives from large vendors of MRI equipment, invited based upon proven expertise in breast MRI and/or in particular breast DWI, representing 25 sites from 16 countries. The aims of the working group are (a) to promote the use of breast DWI into clinical practice by issuing consensus statements and initiate collaborative research where appropriate; (b) to define necessary standards and provide practical guidance for clinical application of breast DWI; (c) to develop a standardized and translatable multisite multivendor quality assurance protocol, especially for multisite research studies; (d) to find consensus on optimal methods for image processing/analysis, visualization, and interpretation; and (e) to work collaboratively with system vendors to improve breast DWI sequences. First consensus recommendations, presented in this paper, include acquisition parameters for standard breast DWI sequences including specifications of b values, fat saturation, spatial resolution, and repetition and echo times. To describe lesions in an objective way, levels of diffusion restriction/hindrance in the breast have been defined based on the published literature on breast DWI. The use of a small ROI placed on the darkest part of the lesion on the ADC map, avoiding necrotic, noisy or non-enhancing lesion voxels is currently recommended. The working group emphasizes the need for standardization and quality assurance before ADC thresholds are applied. The working group encourages further research in advanced diffusion techniques and tailored DWI strategies for specific indications. Key Points • The working group considers breast DWI an essential part of a multiparametric breast MRI protocol and encourages its use. • Basic requirements for routine clinical application of breast DWI are provided, including recommendations on b values, fat saturation, spatial resolution, and other sequence parameters. • Diffusion levels in breast lesions are defined based on meta-analysis data and methods to obtain a reliable ADC value are detailed.
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http://dx.doi.org/10.1007/s00330-019-06510-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7033067PMC
March 2020

Adding a Model-free Diffusion MRI Marker to BI-RADS Assessment Improves Specificity for Diagnosing Breast Lesions.

Radiology 2019 07 21;292(1):84-93. Epub 2019 May 21.

From the Department of Radiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi Hirokoji, Kamigyoku, Kyoto 602-8566, Japan (M.G., M.Y., K.S., K.Y.); and NeuroSpin, Gif-sur-Yvette, France (D.L.B.).

Background The apparent diffusion coefficient (ADC) is a commonly used quantitative diffusion-weighted (DW) imaging marker in breast lesion assessment; however, reported ADC values to distinguish malignant and benign lesions show wide variability. Purpose To investigate the diagnostic performance of a tissue signature index (S-index) as a model-free diffusion marker to differentiate malignant and benign breast lesions. Materials and Methods This was a single-institution retrospective study of patients who underwent breast MRI from April 2017 to September 2018. Dynamic contrast-enhanced (DCE) MRI and DW imaging were performed with a 3-T MRI system. For DW imaging, three values (0, 200, and 1500 sec/mm) were used for Breast Imaging Reporting and Data Systems (BI-RADS) scoring and to calculate the S-index and a shifted ADC. The diagnostic performances of S-index, shifted ADC, and BI-RADS scoring were evaluated by using receiver operating coefficient analysis. Results The study involved 99 women (mean age, 54 years ± 14 [standard deviation]) with 69 malignant and 38 benign lesions. The S-index was higher for malignant lesions (mean, 75.9 ± 17.4) than for benign lesions (mean, 31.6 ± 21.0; < .001). Overall diagnostic performance was identical for S-index and shifted ADC (area under the receiver operating characteristic curve [AUC], 0.95; 95% confidence interval [CI]: 0.91, 0.99) and slightly higher than for BI-RADS (AUC, 0.91; 95% CI: 0.87, 0.96; = .22). The AUC of S-index combined with BI-RADS reached 0.98 (95% CI: 0.96, 1.00), higher than for BI-RADS alone ( < .001), yielding high sensitivity (65 of 69 [94%]; 95% CI: 85%, 98%) and specificity (36 of 38 [95%]; 95% CI: 81%, 99%). Significant differences were identified with the S-index for progesterone receptor and human epidermal growth factor receptor type 2 status ( = .003 and < .001, respectively). Conclusion The signature index has the potential to enable classification of breast lesion types with high accuracy, especially in combination with dynamic contrast-enhanced MRI and correlates with histologic prognostic factors in invasive breast cancer. © RSNA, 2019
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http://dx.doi.org/10.1148/radiol.2019181780DOI Listing
July 2019

Time-of-flight angiography at 7T using TONE double spokes with parallel transmission.

Magn Reson Imaging 2019 09 17;61:104-115. Epub 2019 May 17.

CEA/DRF/Joliot/NeuroSpin, Université Paris-Saclay, 91191 Gif-sur-Yvette, France. Electronic address:

Purpose: To demonstrate that fast-k spokes can be used in parallel transmission to homogenize flip angle ramp profiles (known as TONE) in slab selections, and thereby improve Time-Of-Flight angiography of the whole human brain at 7T.

Methods: B and B maps were measured on seven human brains with a z-segmented coil connected to an 8-channel pTx system. Tailored two-spoke pulses were designed under strict hardware and SAR constraints for uniform slab profile before transforming their subpulse waveforms for linearly-increasing flip-angle ramps. Increasing angulations along the feet-head direction were prescribed in 2-slab and 3-slab TOF acquisitions. Excitation patterns were simulated and compared with RF-shimmed (single spoke) ramp pulses. Excitation performances were assessed in ~10-min TOF acquisitions by visually inspecting Maximal Intensity Projections angiograms.

Results: The flip-angle ramp fidelity achieved by double spokes inside slabs of interest was improved by 30-40% compared to RF-shimmed ramps. This allowed better homogenizing signal along arteries, and depicting small vessels in distal areas of the brain, in comparison with RF-shimmed ramp pulses or double-spoke uniform excitation.

Conclusion: Ramp double spokes used in conjunction with parallel transmission yield better blood saturation compensation and more finely resolved TOF angiograms than mere double spokes or ramp single spokes at 7T.
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http://dx.doi.org/10.1016/j.mri.2019.05.018DOI Listing
September 2019

The functional database of the ARCHI project: Potential and perspectives.

Neuroimage 2019 08 4;197:527-543. Epub 2019 May 4.

NeuroSpin, CEA, 91191, Gif-sur-Yvette, France. Electronic address:

More than two decades of functional magnetic resonance imaging (fMRI) of the human brain have succeeded to identify, with a growing level of precision, the neural basis of multiple cognitive skills within various domains (perception, sensorimotor processes, language, emotion and social cognition …). Progress has been made in the comprehension of the functional organization of localized brain areas. However, the long time required for fMRI acquisition limits the number of experimental conditions performed in a single individual. As a consequence, distinct brain localizations have mostly been studied in separate groups of participants, and their functional relationships at the individual level remain poorly understood. To address this issue, we report here preliminary results on a database of fMRI data acquired on 78 individuals who each performed a total of 29 experimental conditions, grouped in 4 cross-domains functional localizers. This protocol has been designed to efficiently isolate, in a single session, the brain activity associated with language, numerical representation, social perception and reasoning, premotor and visuomotor representations. Analyses are reported at the group and at the individual level, to establish the ability of our protocol to selectively capture distinct regions of interest in a very short time. Test-retest reliability was assessed in a subset of participants. The activity evoked by the different contrasts of the protocol is located in distinct brain networks that, individually, largely replicate previous findings and, taken together, cover a large proportion of the cortical surface. We provide detailed analyses of a subset of regions of relevance: the left frontal, left temporal and middle frontal cortices. These preliminary analyses highlight how combining such a large set of functional contrasts may contribute to establish a finer-grained brain atlas of cognitive functions, especially in regions of high functional overlap. Detailed structural images (structural connectivity, micro-structures, axonal diameter) acquired in the same individuals in the context of the ARCHI database provide a promising situation to explore functional/structural interdependence. Additionally, this protocol might also be used as a way to establish individual neurofunctional signatures in large cohorts.
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http://dx.doi.org/10.1016/j.neuroimage.2019.04.056DOI Listing
August 2019

Brain sugar consumption during neuronal activation detected by CEST functional MRI at ultra-high magnetic fields.

Sci Rep 2019 03 14;9(1):4423. Epub 2019 Mar 14.

NeuroSpin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Univerisité Paris-Saclay, Gif-sur-Yvette, France.

Blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) indirectly measures brain activity based on neurovascular coupling, a reporter that limits both the spatial and temporal resolution of the technique as well as the cellular and metabolic specificity. Emerging methods using functional spectroscopy (fMRS) and diffusion-weighted fMRI suggest that metabolic and structural modifications are also taking place in the activated cells. This paper explores an alternative metabolic imaging approach based on Chemical Exchange Saturation Transfer (CEST) to assess potential metabolic changes induced by neuronal stimulation in rat brains at 17.2 T. An optimized CEST-fMRI data acquisition and processing protocol was developed and used to experimentally assess the feasibility of glucoCEST-based fMRI. Images acquired under glucose-sensitizing conditions showed a substantial negative contrast that highlighted the same brain regions as those activated with BOLD-fMRI. We ascribe this novel fMRI contrast to CEST's ability to monitor changes in the local concentration of glucose, a metabolite closely coupled to neuronal activity. Our findings are in good agreement with literature employing other modalities. The use of CEST-based techniques for fMRI is not limited to glucose detection; other metabolic pathways involved in neuronal activation could be potentially probed. Moreover, being non invasive, it is conceivable that the same approach can be used for human studies.
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http://dx.doi.org/10.1038/s41598-019-40986-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6418181PMC
March 2019

Mesoscopic and microscopic imaging of sensory responses in the same animal.

Nat Commun 2019 03 7;10(1):1110. Epub 2019 Mar 7.

INSERM U1128, Laboratory of Neurophysiology and New Microscopy, Université Paris Descartes, Paris, 75006, France.

Imaging based on blood flow dynamics is widely used to study sensory processing. Here we investigated the extent to which local neuronal and capillary responses (two-photon microscopy) are correlated to mesoscopic responses detected with fast ultrasound (fUS) and BOLD-fMRI. Using a specialized chronic olfactory bulb preparation, we report that sequential imaging of the same mouse allows quantitative comparison of odour responses, imaged at both microscopic and mesoscopic scales. Under these conditions, functional hyperaemia occurred at the threshold of neuronal activation and fUS-CBV signals could be detected at the level of single voxels with activation maps varying according to blood velocity. Both neuronal and vascular responses increase non-linearly as a function of odour concentration, whereas both microscopic and mesoscopic vascular responses are linearly correlated to local neuronal calcium. These data establish strengths and limits of mesoscopic imaging techniques to report neural activity.
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http://dx.doi.org/10.1038/s41467-019-09082-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6405955PMC
March 2019

Spatial contribution of hippocampal BOLD activation in high-resolution fMRI.

Sci Rep 2019 02 28;9(1):3152. Epub 2019 Feb 28.

Commissariat à l'énergie atomique et aux energies alternatives, DRF, Joliot, NeuroSpin, Paris-Saclay University, Gif-sur-Yvette, France.

While the vascular origin of the BOLD-fMRI signal is established, the exact neurovascular coupling events contributing to this signal are still incompletely understood. Furthermore, the hippocampal spatial properties of the BOLD activation are not elucidated, although electrophysiology approaches have already revealed the precise spatial patterns of neural activity. High magnetic field fMRI offers improved contrast and allows for a better correlation with the underlying neuronal activity because of the increased contribution to the BOLD signal of small blood vessels. Here, we take advantage of these two benefits to investigate the spatial characteristics of the hippocampal activation in a rat model before and after changing the hippocampal plasticity by long-term potentiation (LTP). We found that the hippocampal BOLD signals evoked by electrical stimulation at the perforant pathway increased more at the radiatum layer of the hippocampal CA1 region than at the pyramidal cell layer. The return to the baseline of the hippocampal BOLD activation was prolonged after LTP induction compared with that before most likely due vascular or neurovascular coupling changes. Based on these results, we conclude that high resolution BOLD-fMRI allows the segregation of hippocampal subfields probably based on their underlying vascular or neurovascular coupling features.
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http://dx.doi.org/10.1038/s41598-019-39614-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395694PMC
February 2019

TSPO-PET and diffusion-weighted MRI for imaging a mouse model of infiltrative human glioma.

Neuro Oncol 2019 06;21(6):755-764

UMR 1023, IMIV, Service Hospitalier Frédéric Joliot, CEA, Inserm, Université Paris Sud, CNRS, Université Paris-Saclay, Orsay, France.

Background: Glioblastoma (GBM) is the most devastating brain tumor. Despite the use of multimodal treatments, most patients relapse, often due to the highly invasive nature of gliomas. However, the detection of glioma infiltration remains challenging. The aim of this study was to assess advanced PET and MRI techniques for visualizing biological activity and infiltration of the tumor.

Methods: Using multimodality imaging, we investigated [18F]DPA-714, a radiotracer targeting the 18 kDa translocator protein (TSPO), [18F]FET PET, non-Gaussian diffusion MRI (apparent diffusion coefficient, kurtosis), and the S-index, a composite diffusion metric, to detect tumor infiltration in a human invasive glioma model. In vivo imaging findings were confirmed by autoradiography and immunofluorescence.

Results: Increased tumor-to-contralateral [18F]DPA-714 uptake ratios (1.49 ± 0.11) were found starting 7 weeks after glioma cell implantation. TSPO-PET allowed visualization of glioma infiltration into the contralateral hemisphere 2 weeks earlier compared with the clinically relevant biomarker for biological glioma activity [18F]FET. Diffusion-weighted imaging (DWI), in particular kurtosis, was more sensitive than standard T2-weighted MRI to detect differences between the glioma-bearing and the contralateral hemisphere at 5 weeks. Immunofluorescence data reflect in vivo findings. Interestingly, labeling for tumoral and stromal TSPO indicates a predominant expression of TSPO by tumor cells.

Conclusion: These results suggest that advanced PET and MRI methods, such as [18F]DPA-714 and DWI, may be superior to standard imaging methods to visualize glioma growth and infiltration at an early stage.
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http://dx.doi.org/10.1093/neuonc/noz029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556856PMC
June 2019

Tissue sodium concentration and sodium T mapping of the human brain at 3 T using a Variable Flip Angle method.

Magn Reson Imaging 2019 05 26;58:116-124. Epub 2019 Jan 26.

Department of Neurology, RWTH Aachen University, Aachen, Germany. Electronic address:

Purpose: The state-of-the-art method to quantify sodium concentrations in vivo consists in a fully relaxed 3D spin-density (SD) weighted acquisition. Nevertheless, most sodium MRI clinical studies use short-TR SD acquisitions to reduce acquisition durations. We present a clinically viable implementation of the Variable Flip Angle (VFA) method for robust and clinically viable quantification of total sodium concentration (TSC) and longitudinal relaxation rates in vivo in human brain at 3 T.

Methods: Two non-Cartesian steady-state spoiled ultrashort echo time (UTE) scans, performed at optimized flip angles, repetition time and pulse length determined under specific absorption rate constraints, are used to simultaneously compute T and total sodium concentration (TSC) maps using the VFA method. Images are reconstructed using the non-uniform Fast Fourier Transform algorithm and TSC maps are corrected for possible inhomogeneity of coil transmission and reception profiles. Fractioned acquisitions are used to correct for potential patient motion. TSC quantifications obtained using the VFA method are validated at first in comparison with a fully-relaxed SD acquisition in a calibration phantom. The robustness of similar VFA acquisitions are compared to the short-TR SD approach in vivo on seven healthy volunteers.

Results: The VFA method resulted in consistent TSC and T estimates across our cohort of healthy subjects, with mean TSC of 38.1 ± 5.0 mmol/L and T of 39.2 ± 4.4 ms. These results are in agreement with previously reported values in literature TSC estimations and with the predictions of a 2-compartment model. However, the short-TR SD acquisition systematically underestimated the sodium concentration with a mean TSC of 31 ± 4.5 mmol/L.

Conclusion: The VFA method can be applied successfully to image sodium at 3 T in about 20 min and provides robust and intrinsically T-corrected TSC maps.
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http://dx.doi.org/10.1016/j.mri.2019.01.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6927040PMC
May 2019

Robust nonadiabatic T preparation using universal parallel-transmit k -point pulses for 3D FLAIR imaging at 7 T.

Magn Reson Med 2019 05 16;81(5):3202-3208. Epub 2019 Jan 16.

NeuroSpin, Commissariat à l'Energie Atomique, Université Paris-Saclay, Gif sur Yvette, France.

Purpose: The fluid attenuated inversion recovery sequence is a pillar technique to detect brain lesions in MRI. At ultrahigh field, the lengthening of T often advocates a T -weighting preparation module to regain signal and contrast between tissues, which can be affected by transmit RF field inhomogeneity. In this note, we report an extension of a previous fluid attenuated inversion recovery study that now incorporates the T preparation with parallel transmission calibration-free universal pulses to mitigate the problem.

Methods: The preparation consisted of a 90°-τ-180 -τ-90° module to implement an effective inversion in the CSF and a saturation in the brain tissues. Care was taken for the pulses to have the desired phase relationship in every voxel by appropriate pulse design. The RF pulse design made use of the k -point parametrization and was based on a database of 20 B and ΔB maps previously acquired on different subjects at 7 T. Simulations and experiments on 5 volunteers, not contained in the database, were performed for validation.

Results: Simulations reported very good inversion efficiency for the preparation module with 8% variation, with respectively 4 and 6 times less power and specific absorption rate than for the adiabatic version. Experiments revealed fluid attenuated inversion recovery images free of B artifacts.

Conclusion: This work contributes further to the panel of 3D sequences validated and now available with universal pulses at 7 T. The drop in power and specific absorption rate demand compared with adiabatic pulses in the T preparation leads to more freedom for the design of the readout train.
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http://dx.doi.org/10.1002/mrm.27645DOI Listing
May 2019

Simultaneous multi-parametric mapping of total sodium concentration, T, T and ADC at 7 T using a multi-contrast unbalanced SSFP.

Magn Reson Imaging 2018 11 25;53:156-163. Epub 2018 Jul 25.

NeuroSpin, CEA, DRF/JOLIOT, Université Paris-Saclay, Gif-sur-Yvette, France. Electronic address:

Purpose: Quantifying multiple NMR properties of sodium could be of benefit to assess changes in cellular viability in biological tissues. A proof of concept of Quantitative Imaging using Configuration States (QuICS) based on a SSFP sequence with multiple contrasts was implemented to extract simultaneously 3D maps of applied flip angle (FA), total sodium concentration, T, T, and Apparent Diffusion Coefficient (ADC).

Methods: A 3D Cartesian Gradient Recalled Echo (GRE) sequence was used to acquire 11 non-balanced SSFP contrasts at a 6 × 6 × 6 mm isotropic resolution with carefully-chosen gradient spoiling area, RF amplitude and phase cycling, with TR/TE = 20/3.2 ms and 25 averages, leading to a total acquisition time of 1 h 18 min. A least-squares fit between the measured and the analytical complex signals was performed to extract quantitative maps from a mono-exponential model. Multiple sodium phantoms with different compositions were studied to validate the ability of the method to measure sodium NMR properties in various conditions.

Results: Flip angle maps were retrieved. Relaxation times, ADC and sodium concentrations were estimated with controlled precision below 15%, and were in accordance with measurements from established methods and literature.

Conclusion: The results illustrate the ability to retrieve sodium NMR properties maps, which is a first step toward the estimation of FA, T, T, concentration and ADC of Na for clinical research. With further optimization of the acquired QuICS contrasts, scan time could be reduced to be suitable with in vivo applications.
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http://dx.doi.org/10.1016/j.mri.2018.07.012DOI Listing
November 2018

Longitudinal Study of Irradiation-Induced Brain Microstructural Alterations With S-Index, a Diffusion MRI Biomarker, and MR Spectroscopy.

Int J Radiat Oncol Biol Phys 2018 11 2;102(4):1244-1254. Epub 2018 Feb 2.

NeuroSpin, Frédéric Joliot Institute, Division of Fondamental Research, French Alternative Energy and Atomic Energy Commission, Université Paris-Saclay, Gif-sur-Yvette, France. Electronic address:

Purpose: Radiation therapy is widely used for the treatment of brain tumors, but it may lead to severe cognitive impairments. Previous studies have shown that ionizing irradiation induces demyelination, blood-brain barrier alterations, and impaired neurogenesis in animal models. Hence, noninvasive and sensitive biomarkers of irradiation injury are needed to investigate these effects in patients and improve radiation therapy protocols.

Methods And Materials: The heads of 3-month-old male C57BL/6RJ mice (15 control mice and 15 irradiated mice) were exposed to radiation doses of 3 fractions of 5 Gy from a Co source with a medical irradiator. A longitudinal study was performed to investigate cranial irradiation-induced (3 fractions of 5 Gy) microstructural tissue alterations using water diffusion magnetic resonance imaging and magnetic resonance spectroscopy in different areas of the mouse brain (cortex, thalamus, striatum, olfactory bulbs [OBs], hippocampus, and subventricular zone [SVZ]). In addition to the quantification of standard non-Gaussian diffusion parameters, apparent diffusion coefficient (ADC) and kurtosis (K), we evaluated a new composite diffusion metric, designated the S-index (ie, "signature index").

Results: We observed a significant decrease in the S-index in the SVZ from 1 month to 8 months after brain irradiation (P < .05). An interesting finding was that, along with a decrease in taurine levels (up to -15% at 2 months, P < .01), a delayed S-index drop was observed in the OBs from 4 months after irradiation and maintained until the end of our experiment (P < .0001). These observations suggest that S-index variations revealed the irradiation-induced decline of neurogenesis that was further confirmed by a decrease in neural stem cells in the SVZ and in newborn neurons in the OBs of irradiated animals.

Conclusions: This study demonstrates that diffusion magnetic resonance imaging, especially through the S-index approach, is a relevant imaging modality to monitor brain irradiation injury and probe microstructural changes underlying irradiation-induced cognitive deficits.
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http://dx.doi.org/10.1016/j.ijrobp.2018.01.070DOI Listing
November 2018

What can we see with IVIM MRI?

Authors:
Denis Le Bihan

Neuroimage 2019 02 22;187:56-67. Epub 2017 Dec 22.

NeuroSpin, Frédéric Joliot Institute, Bât 145, CEA-Saclay Center, Gif-sur-Yvette, 91191 France. Electronic address:

Intravoxel Incoherent Motion (IVIM) refers to translational movements which within a given voxel and during the measurement time present a distribution of speeds in orientation and/or amplitude. The IVIM concept has been used to estimate perfusion in tissues as blood flow in randomly oriented capillaries mimics a pseudo-diffusion process. IVIM-based perfusion MRI, which does not require contrast agents, has gained momentum recently, especially in the field oncology. In this introductory review the basic concepts, models, technical requirements and limitations inherent to IVIM-based perfusion MRI are outlined, as well as new, non-perfusion applications of IVIM MRI, such as virtual MR Elastography.
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http://dx.doi.org/10.1016/j.neuroimage.2017.12.062DOI Listing
February 2019

Design of universal parallel-transmit refocusing k -point pulses and application to 3D T -weighted imaging at 7T.

Magn Reson Med 2018 07 29;80(1):53-65. Epub 2017 Nov 29.

CEA, DRF, Joliot, NeuroSpin, Unirs, CEA Saclay, Gif sur Yvette, France.

Purpose: T -weighted sequences are particularly sensitive to the radiofrequency (RF) field inhomogeneity problem at ultra-high-field because of the errors accumulated by the imperfections of the train of refocusing pulses. As parallel transmission (pTx) has proved particularly useful to counteract RF heterogeneities, universal pulses were recently demonstrated to save precious time and computational efforts by skipping B calibration and online RF pulse tailoring. Here, we report a universal RF pulse design for non-selective refocusing pulses to mitigate the RF inhomogeneity problem at 7T in turbo spin-echo sequences with variable flip angles.

Method: Average Hamiltonian theory was used to synthetize a single non-selective refocusing pulse with pTx while optimizing its scaling properties in the presence of static field offsets. The design was performed under explicit power and specific absorption rate constraints on a database of 10 subjects using a 8Tx-32Rx commercial coil at 7T. To validate the proposed design, the RF pulses were tested in simulation and applied in vivo on 5 additional test subjects.

Results: The root-mean-square rotation angle error (RA-NRMSE) evaluation and experimental data demonstrated great improvement with the proposed universal pulses (RA-NRMSE ∼8%) compared to the standard circularly polarized mode of excitation (RA-NRMSE ∼26%).

Conclusion: This work further completes the spectrum of 3D universal pulses to mitigate RF field inhomogeneity throughout all 3D MRI sequences without any pTx calibration. The approach returns a single pulse that can be scaled to match the desired flip angle train, thereby increasing the modularity of the proposed plug and play approach. Magn Reson Med 80:53-65, 2018. © 2017 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.27001DOI Listing
July 2018

Homogeneous non-selective and slice-selective parallel-transmit excitations at 7 Tesla with universal pulses: A validation study on two commercial RF coils.

PLoS One 2017 21;12(8):e0183562. Epub 2017 Aug 21.

CEA/DRF/Joliot/NeuroSpin/Unirs, Gif sur Yvette, France.

Parallel transmission (pTx) technology, despite its great potential to mitigate the transmit field inhomogeneity problem in magnetic resonance imaging at ultra-high field (UHF), suffers from a cumbersome calibration procedure, thereby making the approach problematic for routine use. The purpose of this work is to demonstrate on two different 7T systems respectively equipped with 8-transmit-channel RF coils from two different suppliers (Rapid-Biomed and Nova Medical), the benefit of so-called universal pulses (UP), optimized to produce uniform excitations in the brain in a population of adults and making unnecessary the calibration procedures mentioned above. Non-selective and slice-selective UPs were designed to return homogeneous excitation profiles throughout the brain simultaneously on a group of ten subjects, which then were subsequently tested on ten additional volunteers in magnetization prepared rapid gradient echo (MPRAGE) and multi-slice gradient echo (2D GRE) protocols. The results were additionally compared experimentally with the standard non-pTx circularly-polarized (CP) mode, and in simulation with subject-specific tailored excitations. For both pulse types and both coils, the UP mode returned a better signal and contrast homogeneity than the CP mode. Retrospective analysis of the flip angle (FA) suggests that the FA deviation from the nominal FA on average over a healthy adult population does not exceed 11% with the calibration-free parallel-transmit pulses whereas it goes beyond 25% with the CP mode. As a result the universal pulses designed in this work confirm their relevance in 3D and 2D protocols with commercially available equipment. Plug-and-play pTx implementations henceforth become accessible to exploit with more flexibility the potential of UHF for brain imaging.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0183562PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5565195PMC
October 2017

Modulation of water diffusion by activation-induced neural cell swelling in Aplysia Californica.

Sci Rep 2017 07 21;7(1):6178. Epub 2017 Jul 21.

NeuroSpin, Bât 145, Joliot Institute, CEA-Paris-Saclay Center, Point Courrier 156, 91191, Gif-sur-Yvette, France.

Diffusion functional magnetic resonance imaging (DfMRI) has been proposed as a method for functional neuroimaging studies, as an alternative to blood oxygenation level dependent (BOLD)-fMRI. DfMRI is thought to more directly reflect neural activation, but its exact mechanism remains unclear. It has been hypothesized that the water apparent diffusion coefficient (ADC) decrease observed upon neural activation results from swelling of neurons or neuron parts. To elucidate the origin of the DfMRI response at cellular level we performed diffusion MR microscopy at 17.2 T in Aplysia californica buccal ganglia and compared the water ADCs at cellular and ganglia levels before and after neuronal activation induced by perfusion with a solution containing dopamine. Neural cell swelling, evidenced from optical microscopy imaging, resulted in an intracellular ADC increase and an ADC decrease at ganglia level. Furthermore, the intracellular ADC increase was found to have a significant positive correlation with the increase in cell size. Our results strongly support the hypothesis that the ADC decrease observed with DfMRI upon neuronal activation at tissue level reflects activation-induced neural cell swelling.
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http://dx.doi.org/10.1038/s41598-017-05586-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5522485PMC
July 2017

Diffusion and Intravoxel Incoherent Motion MR Imaging-based Virtual Elastography: A Hypothesis-generating Study in the Liver.

Radiology 2017 11 12;285(2):609-619. Epub 2017 Jun 12.

From Neurospin, Bât 145, CEA-Saclay Center, Gif-sur-Yvette 91191, France (D.L.B.); Department of Radiology, Kyoto University Graduate School of Medicine, Kyoto, Japan (D.L.B.); and Department of Radiology, University of Yamanashi, Yamanashi, Japan (S.I., U.M.).

Purpose To investigate the potential of diffusion magnetic resonance (MR) imaging to provide quantitative estimates of tissue stiffness without using mechanical vibrations in patients with chronic liver diseases and to generate a new elasticity-driven intravoxel incoherent motion (IVIM) contrast. Materials and Methods This retrospective study, conducted from January to April 2016, was approved by an institutional review board that waived the requirement for informed consent. Fifteen subjects were included (13 men and two women; mean age ± standard deviation, 73 years ± 8). MR elastography and diffusion MR imaging were performed at 3 T. A search for an empirical relationship between MR elastographic shear modulus, µ, and a shifted apparent diffusion coefficient (sADC) was performed. The sADC was then inverted to estimate patient liver shear modulus directly from diffusion MR imaging signals. Results A significant correlation (r = 0.90, P = 1 · 10) was observed between µ and sADC calculated by using diffusion MR imaging signals acquired with b values of 200 (S) and 1500 (S ) sec/mm (sACD). On the basis of the relationship between the µ and sADC, a diffusion-based shear modulus, µ, could be estimated with the following equation: µ = (-9.8 ± 0.8) ln(S/S) + (14.0 ± 0.9). IVIM virtual elastograms also could be generated to reveal new contrast features in lesions, depending on pseudovibration frequency and amplitude. Conclusion Diffusion MR imaging, through a calibration of sADC with standard MR elastography, can be converted quantitatively into shear modulus without using mechanical vibrations to provide information on the degree of liver fibrosis; these virtual elastograms require only two b values to be acquired and processed. Propagating shear wave can also be emulated, leading to a new elasticity-driven IVIM contrast with ranges of virtual vibration frequencies and amplitudes not limited by MR elastography or MR imaging hardware capacities. RSNA, 2017 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2017170025DOI Listing
November 2017

Water diffusion closely reveals neural activity status in rat brain loci affected by anesthesia.

PLoS Biol 2017 04 13;15(4):e2001494. Epub 2017 Apr 13.

NeuroSpin, Joliot Institute, Commissariat à l'énergie atomique et aux énergies alternatives, Gif-sur-Yvette, France.

Diffusion functional MRI (DfMRI) reveals neuronal activation even when neurovascular coupling is abolished, contrary to blood oxygenation level-dependent (BOLD) functional MRI (fMRI). Here, we show that the water apparent diffusion coefficient (ADC) derived from DfMRI increased in specific rat brain regions under anesthetic conditions, reflecting the decreased neuronal activity observed with local field potentials (LFPs), especially in regions involved in wakefulness. In contrast, BOLD signals showed nonspecific changes, reflecting systemic effects of the anesthesia on overall brain hemodynamics status. Electrical stimulation of the central medial thalamus nucleus (CM) exhibiting this anesthesia-induced ADC increase led the animals to transiently wake up. Infusion in the CM of furosemide, a specific neuronal swelling blocker, led the ADC to increase further locally, although LFP activity remained unchanged, and increased the current threshold awakening the animals under CM electrical stimulation. Oppositely, induction of cell swelling in the CM through infusion of a hypotonic solution (-80 milliosmole [mOsm] artificial cerebrospinal fluid [aCSF]) led to a local ADC decrease and a lower current threshold to wake up the animals. Strikingly, the local ADC changes produced by blocking or enhancing cell swelling in the CM were also mirrored remotely in areas functionally connected to the CM, such as the cingulate and somatosensory cortex. Together, those results strongly suggest that neuronal swelling is a significant mechanism underlying DfMRI.
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http://dx.doi.org/10.1371/journal.pbio.2001494DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390968PMC
April 2017

After over 200 years, 7 T magnetic resonance imaging reveals the foliate structure of the human corpus callosum in vivo.

Br J Radiol 2017 May 3;90(1073):20160906. Epub 2017 Apr 3.

3 Siemens Healthcare GmbH, Diagnostic Imaging, Magnetic Resonance, Erlangen, Germany.

Objective: A fine structure of the corpus callosum (CC), consisting of radial lines, is seen in historical anatomical atlases as far back as that of Vicq d'Azyr (1786). This study examines a similar pattern observed in vivo using high-resolution MR images at 7 T.

Methods: 8 healthy subjects were examined with 7.0-T MRI. Anatomical images were collected with a gradient echo scan with 0.5-mm isotropic resolution, which were rated for visibility of the radial pattern. In addition, the second eigenvector of the diffusion tensor images was examined.

Results: The fine radial lines are detected not only in the sagittal view but also in the axial view of the in vivo MR images. From this, it is likely that these structures are two-dimensional ribbons. Interestingly, and confirming the structural nature of these stripes, the second eigenvector of the diffusion tensor imaging data shows an extremely similar pattern of oriented foliate structure. A similar modular structure involving transient septa has been observed previously in histological sections of human fetal CC.

Conclusion: The separate sets of data-the atlas of Klingler, anatomical images and second eigenvector images-all indicate a ribbon-like arrangement of the fibres in the CC. As such, they closely match the structures shown in the drawn atlases of as old as 1786. Advances in knowledge: This ribbon arrangement of fibres in the CC, previously unseen in CT or lower field MRI, can now be observed in vivo. This appears to match over two centuries of ex vivo observations.
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http://dx.doi.org/10.1259/bjr.20160906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5605111PMC
May 2017

New method to characterize and correct with sub-µs precision gradient delays in bipolar multispoke RF pulses.

Magn Reson Med 2017 Dec 23;78(6):2194-2202. Epub 2017 Jan 23.

CEA, DRF, I2BM, NeuroSpin, Unirs, Gif-sur-Yvette, Cedex, France.

Purpose: Small gradient delays with respect to radiofrequency (RF) events can have disastrous effects on the performance of bipolar spokes RF pulses used in parallel transmission (pTx). In this work, we propose a new method to characterize and correct this delay with sub-µs precision.

Methods: By determining experimentally the phase Δφ producing a 0 ° flip angle excitation in a α0°-α180°+Δφ bipolar two-spoke pulse configuration at multiple slice locations, we demonstrate the possibility of deducing the underlying gradient delay with precision. The technique also suggests prospectively compensating for the same delay by altering the phase of the second pulse. The approach was tested with a multislice gradient echo sequence on a phantom and on one healthy volunteer at 7 Tesla.

Results: Application of the method returned an accuracy of approximately 50 ns on the gradient delay measurement, a performance shown in fact to be desirable for high-performance pTx 2D applications. Phase corrections of up to 180 ° on the second spoke RF pulse in the bipolar configuration allowed us to obtain similar performance as for unipolar designs, yet with significantly shorter excitations.

Conclusions: A simple and accurate gradient-delay calibration method was proposed that offers the possibility of using bipolar multispoke pulses in multislice protocols. Magn Reson Med 78:2194-2202, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26614DOI Listing
December 2017

Water apparent diffusion coefficient correlates with gamma oscillation of local field potentials in the rat brain nucleus accumbens following alcohol injection.

J Cereb Blood Flow Metab 2017 Sep 6;37(9):3193-3202. Epub 2017 Jan 6.

NeuroSpin, Commissariat à l'Energie Atomique et aux Energies Alternatives, CEA Saclay, Gif-sur-Yvette, France.

Ethanol is a vasoactive agent as well as psychoactive drug. The neurovascular response, coupled with neuronal activity, can be disturbed by alcohol intake. Hence, blood oxygenation level-dependent (BOLD) fMRI, which relies on neurovascular coupling, might not be reliable to reflect alcohol-induced neuronal responses. Recently, diffusion fMRI has been shown to be more sensitive to neural activity than BOLD fMRI even when neurovascular coupling is disrupted. Especially, the apparent diffusion coefficient (ADC) is sensitive to changes occurring in the cellular tissue structure upon activation. In the present study, we compared BOLD fMRI signals, ADC, and local field potentials (LFPs) in the nucleus accumbens (NAc) following injection of an ethanol solution (0.4 g/kg body weight) in rats under medetomidine anesthesia. An increase in the gamma oscillation power of LFP and an ADC decrease were observed 5 min after the injection of EtOH. The BOLD signals showed a negative slow drift, similar to mean arterial pressure with a peak approximately 10 min after the injection. These results confirm that DfMRI can be a better marker of the neuronal activity than BOLD fMRI, especially when the brain hemodynamic status is changed by vasoactive drugs such as ethanol.
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http://dx.doi.org/10.1177/0271678X16685104DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5584694PMC
September 2017

A two-pool model to describe the IVIM cerebral perfusion.

J Cereb Blood Flow Metab 2017 Aug 1;37(8):2987-3000. Epub 2016 Jan 1.

1 NeuroSpin, CEA Saclay-Center, Gif-sur-Yvette, France.

IntraVoxel Incoherent Motion (IVIM) is a magnetic resonance imaging (MRI) technique capable of measuring perfusion-related parameters. In this manuscript, we show that the mono-exponential model commonly used to process IVIM data might be challenged, especially at short diffusion times. Eleven rat datasets were acquired at 7T using a diffusion-weighted pulsed gradient spin echo sequence with b-values ranging from 7 to 2500 s/mm at three diffusion times. The IVIM signals, obtained by removing the diffusion component from the raw MR signal, were fitted to the standard mono-exponential model, a bi-exponential model and the Kennan model. The Akaike information criterion used to find the best model to fit the data demonstrates that, at short diffusion times, the bi-exponential IVIM model is most appropriate. The results obtained by comparing the experimental data to a dictionary of numerical simulations of the IVIM signal in microvascular networks support the hypothesis that such a bi-exponential behavior can be explained by considering the contribution of two vascular pools: capillaries and somewhat larger vessels.
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http://dx.doi.org/10.1177/0271678X16681310DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5536805PMC
August 2017

In vivo demonstration of whole-brain multislice multispoke parallel transmit radiofrequency pulse design in the small and large flip angle regimes at 7 Tesla.

Magn Reson Med 2017 09 23;78(3):1009-1019. Epub 2016 Oct 23.

CEA, DRF, I2BM, NeuroSpin, Unirs, France.

Purpose: A multispoke specific absorption rate (SAR) -aware pulse design approach for homogeneous multiple-slice small and large flip angle (FA) excitations with parallel transmission is proposed. The approach aims at optimizing in a slice-specific manner the spokes locations and radiofrequency pulses.

Methods: The problem is posed as a set of slice-specific magnitude-least-squares problems, linked together by hardware and SAR constraints, and solved jointly using an active-set algorithm. Average Hamiltonian theory is exploited in the large FA case to greatly reduce the computational burden. The approach is validated numerically by means of simulations and experimentally on two volunteers at 7 Tesla through application of a high-resolution T2*-weighted brain imaging protocol.

Results: The optimization of up to 1300 variables under 745 explicit constraints could be performed in less than 1 and 4 min for the small and large FA cases, respectively. The joint design proves valuable for SAR demanding protocols. Compared with the conventional circularly polarized mode, the designed pulses increased the signal by more than 40% in 70% of the voxels.

Conclusion: The B1+ inhomogeneity problem was mitigated efficiently in a multislice near whole-brain coverage protocol in the small and large FA regimes using a rapid slice-specific pulse design algorithm where the pulses were optimized jointly. Magn Reson Med 78:1009-1019, 2017. © 2016 International Society for Magnetic Resonance in Medicine.
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http://dx.doi.org/10.1002/mrm.26491DOI Listing
September 2017