The possible influence of third-order shim coils on gradient-magnet interactions: an inter-field and inter-site study.

OBJECTIVE: To assess the possible influence of third-order shim coils on the behavior of the gradient field and in gradient-magnet interactions at 7 T and above. MATERIALS AND METHODS: Gradient impulse response function measurements were performed at 5 sites spanning field strengths from 7 to 11.7 T, all of them sharing the same exact whole-body gradient coil design. Mechanical fixation and boundary conditions of the gradient coil were altered in several ways at one site to study the impact of mechanical coupling with the magnet on the field perturbations. Vibrations, power deposition in the He bath, and field dynamics were characterized at 11.7 T with the third-order shim coils connected and disconnected inside the Faraday cage. RESULTS: For the same whole-body gradient coil design, all measurements differed greatly based on the third-order shim coil configuration (connected or not). Vibrations and gradient transfer function peaks could be affected by a factor of 2 or more, depending on the resonances. Disconnecting the third-order shim coils at 11.7 T also suppressed almost completely power deposition peaks at some frequencies. DISCUSSION: Third-order shim coil configurations can have major impact in gradient-magnet interactions with consequences on potential hardware damage, magnet heating, and image quality going beyond EPI acquisitions.

From Black Holes Entropy to Consciousness: The Dimensions of the Brain Connectome.

It has been shown that the theory of relativity can be applied physically to the functioning brain, so that the brain connectome should be considered as a four-dimensional spacetime entity curved by brain activity, just as gravity curves the four-dimensional spacetime of the physical world. Following the most recent developments in modern theoretical physics (black hole entropy, holographic principle, AdS/CFT duality), we conjecture that consciousness can naturally emerge from this four-dimensional brain connectome when a fifth dimension is considered, in the same way that gravity emerges from a 'flat' four-dimensional quantum world, without gravitation, present at the boundaries of a five-dimensional spacetime. This vision makes it possible to envisage quantitative signatures of consciousness based on the entropy of the connectome and the curvature of spacetime estimated from data obtained by fMRI in the resting state (nodal activity and functional connectivity) and constrained by the anatomical connectivity derived from diffusion tensor imaging.

Diffusion kurtosis imaging as a biomarker of breast cancer.

Diffusion kurtosis imaging (DKI) is a diffusion-weighted imaging method that describes non-Gaussian signal behavior using a relatively simple mathematical model. A parameter, kurtosis K, describes the deviation of the diffusion signal decay from a Gaussian pattern. The deviation reflects the complexity of the tissue microstructure affecting water diffusion. Several studies have investigated the diagnostic performance of DKI in distinguishing malignant from benign breast lesions. DKI has been reported to correlate with subtypes and with several molecular and other factors related to the treatment and prognosis of breast cancer. Some technical considerations remain to be resolved for the clinical application of DKI in the breast. Advances in knowledge: DKI, which increases the sensitivity to complex tissue microstructure compared to standard DWI, has been applied in the breast, allowing to increase clinical performance in distinguishing malignant from benign lesions and in predicting prognosis or treatment response in breast cancer.

XLF/Cernunnos loss impairs mouse brain development by altering symmetric proliferative divisions of neural progenitors.

XLF/Cernunnos is a component of the ligation complex used in classical non-homologous end-joining (cNHEJ), a major DNA double-strand break (DSB) repair pathway. We report neurodevelopmental delays and significant behavioral alterations associated with microcephaly in Xlf-/- mice. This phenotype, reminiscent of clinical and neuropathologic features in humans deficient in cNHEJ, is associated with a low level of apoptosis of neural cells and premature neurogenesis, which consists of an early shift of neural progenitors from proliferative to neurogenic divisions during brain development. We show that premature neurogenesis is related to an increase in chromatid breaks affecting mitotic spindle orientation, highlighting a direct link between asymmetric chromosome segregation and asymmetric neurogenic divisions. This study reveals thus that XLF is required for maintaining symmetric proliferative divisions of neural progenitors during brain development and shows that premature neurogenesis may play a major role in neurodevelopmental pathologies caused by NHEJ deficiency and/or genotoxic stress.

The road to breast cancer screening with diffusion MRI.

Breast cancer is the leading cause of cancer in women with a huge medical, social and economic impact. Mammography (MMG) has been the gold standard method until now because it is relatively inexpensive and widely available. However, MMG suffers from certain limitations, such as exposure to X-rays and difficulty of interpretation in dense breasts. Among other imaging methods, MRI has clearly the highest sensitivity and specificity, and breast MRI is the gold standard for the investigation and management of suspicious lesions revealed by MMG. Despite this performance, MRI, which does not rely on X-rays, is not used for screening except for a well-defined category of women at risk, because of its high cost and limited availability. In addition, the standard approach to breast MRI relies on Dynamic Contrast Enhanced (DCE) MRI with the injection of Gadolinium based contrast agents (GBCA), which have their own contraindications and can lead to deposit of gadolinium in tissues, including the brain, when examinations are repeated. On the other hand, diffusion MRI of breast, which provides information on tissue microstructure and tumor perfusion without the use of contrast agents, has been shown to offer higher specificity than DCE MRI with similar sensitivity, superior to MMG. Diffusion MRI thus appears to be a promising alternative approach to breast cancer screening, with the primary goal of eliminating with a very high probability the existence of a life-threatening lesion. To achieve this goal, it is first necessary to standardize the protocols for acquisition and analysis of diffusion MRI data, which have been found to vary largely in the literature. Second, the accessibility and cost-effectiveness of MRI examinations must be significantly improved, which may become possible with the development of dedicated low-field MRI units for breast cancer screening. In this article, we will first review the principles and current status of diffusion MRI, comparing its clinical performance with MMG and DCE MRI. We will then look at how breast diffusion MRI could be implemented and standardized to optimize accuracy of results. Finally, we will discuss how a dedicated, low-cost prototype of breast MRI system could be implemented and introduced to the healthcare market.

A survey by the European Society of Breast Imaging on the implementation of breast diffusion-weighted imaging in clinical practice.

OBJECTIVES: To perform a survey among all European Society of Breast Imaging (EUSOBI) radiologist members to gather representative data regarding the clinical use of breast DWI. METHODS: An online questionnaire was developed by two board-certified radiologists, reviewed by the EUSOBI board and committees, and finally distributed among EUSOBI active and associated (not based in Europe) radiologist members. The questionnaire included 20 questions pertaining to technical preferences (acquisition time, magnet strength, breast coils, number of b values), clinical indications, imaging evaluation, and reporting. Data were analyzed using descriptive statistics, the Chi-square test of independence, and Fisher's exact test. RESULTS: Of 1411 EUSOBI radiologist members, 275/1411 (19.5%) responded. Most (222/275, 81%) reported using DWI as part of their routine protocol. Common indications for DWI include lesion characterization (using an ADC threshold of 1.2-1.3 × 10-3 mm2/s) and prediction of response to chemotherapy. Members most commonly acquire two separate b values (114/217, 53%), with b value = 800 s/mm2 being the preferred value for appraisal among those acquiring more than two b values (71/171, 42%). Most did not use synthetic b values (169/217, 78%). While most mention hindered diffusion in the MRI report (161/213, 76%), only 142/217 (57%) report ADC values. CONCLUSION: The utilization of DWI in clinical practice among EUSOBI radiologists who responded to the survey is generally in line with international recommendations, with the main application being the differentiation of benign and malignant enhancing lesions, treatment response assessment, and prediction of response to chemotherapy. Report integration of qualitative and quantitative DWI data is not uniform. KEY POINTS: • Clinical performance of breast DWI is in good agreement with the current recommendations of the EUSOBI International Breast DWI working group. • Breast DWI applications in clinical practice include the differentiation of benign and malignant enhancing, treatment response assessment, and prediction of response to chemotherapy. • Report integration of DWI results is not uniform.

Investigation of breast cancer microstructure and microvasculature from time-dependent DWI and CEST in correlation with histological biomarkers.

We investigated the associations of time-dependent DWI, non-Gaussian DWI, and CEST parameters with histological biomarkers in a breast cancer xenograft model. 22 xenograft mice (7 MCF-7 and 15 MDA-MB-231) were scanned at 4 diffusion times [Td = 2.5/5 ms with 11 b-values (0-600 s/mm2) and Td = 9/27.6 ms with 17 b-values (0-3000 s/mm2), respectively]. The apparent diffusion coefficient (ADC) was estimated using 2 b-values in different combinations (ADC0-600 using b = 0 and 600 s/mm2 and shifted ADC [sADC200-1500] using b = 200 and 1500 s/mm2) at each of those diffusion times. Then the change (Δ) in ADC/sADC between diffusion times was evaluated. Non-Gaussian diffusion and intravoxel incoherent motion (IVIM) parameters (ADC0, the virtual ADC at b = 0; K, Kurtosis from non-Gaussian diffusion; f, the IVIM perfusion fraction) were estimated. CEST images were acquired and the amide proton transfer signal intensity (APT SI) were measured. The ΔsADC9-27.6 (between [Formula: see text] and [Formula: see text] and ΔADC2.5_sADC27.6 (between [Formula: see text] and [Formula: see text]) was significantly larger for MCF-7 groups, and ΔADC2.5_sADC27.6 was positively correlated with Ki67max and APT SI. ADC0 decreased significantly in MDA-MB-231 group and K increased significantly with Td in MCF-7 group. APT SI and cellular area had a moderately strong positive correlation in MDA-MB-231 and MCF-7 tumors combined, and there was a positive correlation in MDA-MB-231 tumors. There was a significant negative correlation between APT SI and the Ki-67-positive ratio in MDA-MB-231 tumors and when combined with MCF-7 tumors. The associations of ΔADC2.5_sADC27.6 and API SI with Ki-67 parameters indicate that the Td-dependent DW and CEST parameters are useful to predict the histological markers of breast cancers.

The diffusion MRI signature index is highly correlated with immunohistochemical status and molecular subtype of invasive breast carcinoma.

OBJECTIVES: To evaluate the relationship of the signature index (S-index), an advanced diffusion MRI marker, and the immunohistochemical (IHC) status, proliferation rate, and molecular subtype of invasive breast cancers. METHODS: A retrospective study of patients with invasive carcinoma was conducted between 2017 and 2021. All patients underwent dynamic contrast-enhanced MRI and DWI using a 3-T system. For DWI, three b values (0, 200, and 1500 s/mm2) were used to derive the S-index. Three-dimensional ROIs were manually placed over the whole tumor on DWI. Mean and 85th percentile S-index values were compared to the IHC status, proliferation rate, and molecular subtypes of lesions. RESULTS: The study included 153 patients (mean age, 60 ± 13 years) with 160 invasive carcinomas. S-index values were significantly higher in estrogen receptor-positive (mean, p = .005; 85th percentile, p < .001) and progesterone receptor-positive (mean, p = .003; 85th percentile, p < .001) tumors, and significantly lower in human epidermal growth factor receptor 2 (HER2) - positive tumors (mean, p = .023; 85th percentile, p < .001). Mean and 85th percentile S-index values were significantly different among breast cancer subtypes (mean, p = .015; 85th percentile, p = .002), and the AUC of these values for the prediction of IHC status were 0.64 and 0.66 for HER2, and 0.70 and 0.74 for hormone receptors, respectively. CONCLUSIONS: The DWI S-index showed significantly higher values in invasive carcinomas with immunohistochemical status associated with good prognosis, suggesting its usefulness as a noninvasive imaging biomarker to estimate IHC status and orient treatment. KEY POINTS: • The signature index, an advanced diffusion MRI marker, showed good discrimination of immunohistochemical status in invasive breast carcinomas. • The signature index has the potential to differentiate noninvasively invasive breast carcinoma subtypes and appears as an imaging biomarker of prognostic factors and molecular phenotypes.

Neural substrates of accurate perception of time duration: A functional magnetic resonance imaging study.

Time duration, an essential feature of the physical world, is perceived and cognitively interpreted subjectively. While this perception is deeply connected with arousal and interoceptive signals, the underlying neural mechanisms remain elusive. As the insula is critical for integrating information from the external world with the organism's inner state, we hypothesized that it might have a central role in the perception of time duration and contribute to its estimation accuracy. We conducted a functional magnetic resonance imaging study with 27 healthy participants performing temporal duration and pitch bisection tasks that used the same stimuli. By comparison with two referents with short and long duration in the time range of 1 s (close to the heart rate period), or low and high pitch, participants had to decide whether target stimuli were closer in duration or pitch to the referent stimuli. The temporal bisection point between short and long duration perception was obtained through a psychometric response curve analysis for each participant. The deviation between the bisection point and the average of reference stimuli durations was used as a marker of duration accuracy. Duration discrimination-specific activation, contrasted to pitch discrimination, was found in the dorsomedial prefrontal cortex, bilateral cerebellum, and right anterior insular cortex (AIC), extending to the inferior frontal gyrus (IFG), inferior parietal lobule, and frontal pole. The activity in the right AIC and IFG was positively correlated with the accuracy of duration discrimination. The right AIC is known to be related to the reproduction of duration, whereas the right IFG is involved in categorical decisions. Thus, the comparison between the referent durations reproduced in the AIC and the target duration may occur in the right IFG. We conclude that the right AIC and IFG contribute to the accurate perception of temporal duration.

Diffusion-Based Virtual MR Elastography of the Liver: Can It Be Extended beyond Liver Fibrosis?

Background: Strong correlation has been reported between tissue water diffusivity and tissue elasticity in the liver. The purpose of this study is to explore the capability of diffusion-based virtual MR elastography (VMRE) in the characterization of liver tumors by extending beyond liver fibrosis assessments. Methods: Fifty-four patients (56 liver tumors: hepatocellular carcinoma (HCC), 31; metastases, 25) who underwent MRE, diffusion-weighted imaging (DWI) (b: 0, 800 s/mm2), and VMRE (b: 200, 1500 s/mm2) were enrolled. The MRE shear modulus (µMRE), apparent diffusion coefficient (ADC), and shifted ADC (sADC) were obtained. Virtual stiffness (µdiff) was estimated from the relationship between µMRE and sADC. A linear discriminant analysis combining VMRE and MRE to classify HCC and metastases was performed in a training cohort (thirty-two patients) to estimate a classifier (C), and evaluate its accuracy in a testing cohort (twenty-two patients). Pearson's correlations between µMRE, sADC, and ADC were evaluated. In addition to the discriminant analysis, a receiver operating characteristic (ROC) curve was used to assess the discrimination capability between HCC and metastases. Results: The correlations between µMRE and sADC were significant for liver, HCC, and metastases (r = 0.91, 0.68, 0.71; all p < 0.05). Those between µMRE and ADC were weaker and significant only for metastases (r = 0.17, 0.20, 0.55). µdiff values were not significantly different between HCC and metastases (p = 0.56). Areas under the curves (AUC) to differentiate HCC from metastases were as follows: VMRE, 0.46; MRE alone, 0.89; MRE + VMRE, 0.96. The classifier C also provided better performance than MRE alone, in terms of sensitivity (100 vs. 93.5%, respectively) and specificity (92 vs. 76%, respectively, p = 0.046). Conclusions: The correlation between sADC and µMRE was strong both in the liver and in tumors. However, VMRE alone could not classify HCC and metastases. The combination of MRE and VMRE, however, allowed discriminant performance between HCC and metastases.

Noncontrast Pediatric Brain Perfusion: Arterial Spin Labeling and Intravoxel Incoherent Motion.

Noncontrast magnetic resonance imaging techniques for measuring brain perfusion include arterial spin labeling (ASL) and intravoxel incoherent motion (IVIM). These techniques provide noninvasive and repeatable assessment of cerebral blood flow or cerebral blood volume without the need for intravenous contrast. This article discusses the technical aspects of ASL and IVIM with a focus on normal physiologic variations, technical parameters, and artifacts. Multiple pediatric clinical applications are presented, including tumors, stroke, vasculopathy, vascular malformations, epilepsy, migraine, trauma, and inflammation.

Simultaneous proton density, T1 , T2 , and flip-angle mapping of the brain at 7 T using multiparametric 3D SSFP imaging and parallel-transmission universal pulses.

PURPOSE: Performing simultaneous quantitative MRI at ultrahigh field is challenging, as B0 and B1+ 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, T1 , and T2 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 mm3 resolution. Acquisition time was 16 minutes 36 seconds for the whole brain. Parallel transmission and universal pulses were used to mitigate B1+ 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, T1 , and T2 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.

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

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

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

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

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

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 (µMRE) 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 (b = 200 and 1500 sec/mm2) and converted to DW MRI-based virtual shear modulus (µDiff). MRI-based liver fibrosis stages were estimated from µMRE and µDiff 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 µMRE was observed (r2 = 0.81; P < .001), showing high agreement between µMRE and µDiff values (mean difference, -0.02 kPa ± 0.88; P < .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), µDiff 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, µDiff + aspartate aminotransferase-to-platelet radio index: F0-F1 vs F2-F4, 0.81 [95% confidence interval: 0.69, 0.93], P = .17; F0-F2 vs F3-F4, 0.83 [95% confidence interval: 0.74, 0.92], P = .07; and AUC µDiff + Fibrosis 4 score: F0-F1 vs F2-F4, 0.78 [95% confidence interval: 0.64, 0.92], P < .30; F0-F2 vs F3-F4, 0.81 [95% confidence interval: 0.71, 0.91], P = .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 Online supplemental material is available for this article.

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

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.

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

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.

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.

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 in vivo experimental tests supported by theoretical models. Specifically, by estimation of the free diffusion coefficients from in vitro studies and of apparent diffusion coefficients from in vivo 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.

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

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.