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Purpose: To evaluate potential modeling paradigms and the impact of relaxation time effects on human blood-brain barrier (BBB) water exchange measurements using FEXI (BBB-FEXI), and to quantify the accuracy, precision, and repeatability of BBB-FEXI exchange rate estimates at 3 (Formula presented.). Methods: Three modeling paradigms were evaluated: (i) the apparent exchange rate (AXR) model; (ii) a two-compartment model ((Formula presented.)) explicitly representing intra- and extravascular signal components, and (iii) a two-compartment model additionally accounting for finite compartmental (Formula presented.) and (Formula presented.) relaxation times ((Formula presented.)). Each model had three free parameters. Simulations quantified biases introduced by the assumption of infinite relaxation times in the AXR and (Formula presented.) models, as well as the accuracy and precision of all three models. The scan–rescan repeatability of all paradigms was quantified for the first time in vivo in 10 healthy volunteers (age range 23–52 years; five female). Results: The assumption of infinite relaxation times yielded exchange rate errors in simulations up to 42%/14% in the AXR/ (Formula presented.) models, respectively. Accuracy was highest in the compartmental models; precision was best in the AXR model. Scan–rescan repeatability in vivo was good for all models, with negligible bias and repeatability coefficients in grey matter of (Formula presented.) (Formula presented.), (Formula presented.) (Formula presented.), and (Formula presented.) (Formula presented.). Conclusion: Compartmental modelling of BBB-FEXI signals can provide accurate and repeatable measurements of BBB water exchange; however, relaxation time and partial volume effects may cause model-dependent biases.

A technique for quantifying regional blood-brain barrier (BBB) water exchange rates using contrast-enhanced arterial spin labelling (CE-ASL) is presented and evaluated in simulations and in vivo. The two-compartment ASL model describes the water exchange rate from blood to tissue,kb, but to estimatekbin practice it is necessary to separate the intra- and extravascular signals. This is challenging in standard ASL data owing to the small difference inT1values. Here, a gadolinium-based contrast agent is used to increase thisT1difference and enable the signal components to be disentangled. The optimal post-contrast bloodT1at 3T was determined in a sensitivity analysis, and the accuracy and precision of the method quantified using Monte Carlo simulations. Proof-of-concept data were acquired in six healthy volunteers (five female, age range 24 – 46 years). The sensitivity analysis identified the optimalat 3T as 0.8 s. Simulations showedkbcould be estimated in individual cortical regions with a relative errorϵ< 1% and coefficient of variation CoV = 30 %; however, a high dependence on bloodT1was also observed. In volunteer data, mean parameter values in grey matter were: arterial transit timetA= 1.15±0.49 s, cerebral blood flowf= 58.0±14.3 ml blood / min / 100 ml tissue, water exchange ratekb= 2.32 ± 2.49 s−1. CE-ASL can provide regional BBB water exchange rate estimates; however, the clinical utility of the technique is dependent on the achievable accuracy of measuredT1values.

Purpose A fundamental goal in the drive to understand and find better treatments for dementia is the identification of the factors that render the aging brain vulnerable to neurodegenerative disease. Recent evidence indicates the integrity of the blood–brain barrier (BBB) to be an important component of functional failure underlying age‐related cognitive decline. Practical and sensitive measurement is necessary, therefore, to support diagnostic and therapeutic strategies targeted at maintaining BBB integrity in aging patients. Here, we investigated changes in BBB permeability to endogenous blood water in the aging brain. Methods A multiple‐echo‐time arterial spin‐labeling MRI technique, implemented on a 9.4T Bruker imaging system, was applied to 7‐ and 27‐month‐old mice to measure changes in water permeability across the BBB with aging. Results We observed that BBB water permeability was 32% faster in aged mice. This occurred along with a 2.1‐fold increase in mRNA expression of aquaporin‐4 water channels and a 7.1‐fold decrease in mRNA expression of α‐syntrophin protein, which anchors aquaporin‐4 to the BBB. Conclusion Age‐related changes to water permeability across the BBB can be captured using noninvasive noncontrast MRI techniques., Click here for author‐reader discussions

The blood–cerebrospinal fluid barrier (BCSFB) is a highly dynamic transport interface that serves brain homeostasis. To date, however, understanding of its role in brain development and pathology has been hindered by the absence of a non-invasive technique for functional assessment. Here we describe a method for non-invasive measurement of BSCFB function by using tracer-free MRI to quantify rates of water delivery from arterial blood to ventricular cerebrospinal fluid. Using this method, we record a 36% decrease in BCSFB function in aged mice, compared to a 13% decrease in parenchymal blood flow, itself a leading candidate biomarker of early neurodegenerative processes. We then apply the method to explore the relationship between BCSFB function and ventricular morphology. Finally, we provide proof of application to the human brain. Our findings position the BCSFB as a promising new diagnostic and therapeutic target, the function of which can now be safely quantified using non-invasive MRI., The blood–cerebrospinal fluid barrier (BCSFB) is an important interface for brain homeostasis. Here the authors describe a non-invasive MRI technique for the quantitative assessment of BCSFB function.

There is currently a lack of non-invasive tools to assess water transport in healthy and pathological brain tissue. Aquaporin-4 (AQP4) water channels are central to many water transport mechanisms, and emerging evidence also suggests that AQP4 plays a key role in amyloid-β (Aβ) clearance, possibly via the glymphatic system. Here, we present the first non-invasive technique sensitive to AQP4 channels polarised at the blood-brain interface (BBI). We apply a multiple echo time (multi-TE) arterial spin labelling (ASL) MRI technique to the mouse brain to assess BBI water permeability via calculation of the exchange time (Texw), the time for magnetically labelled intravascular water to exchange across the BBI. We observed a 31% increase in exchange time in AQP4-deficient (Aqp4−/−) mice (452 ± 90 ms) compared to their wild-type counterparts (343 ± 91 ms) (p = 0.01), demonstrating the sensitivity of the technique to the lack of AQP4 water channels. More established, quantitative MRI parameters: arterial transit time (δa), cerebral blood flow (CBF) and apparent diffusion coefficient (ADC) detected no significant changes with the removal of AQP4. This clinically relevant tool may be crucial to better understand the role of AQP4 in water transport across the BBI, as well as clearance of proteins in neurodegenerative conditions such as Alzheimer's disease., Graphical abstract Image 1

International audience; Phase images of biological specimens were obtained by the method of Quadriwave Lateral Shearing Interferometry (QWLSI). The QWLSI technique produces, at high resolution, phase images of the cells having been exposed to a plasma treatment and enables the quantitative analysis of the changes in the surface area of the cells over time. Morphological changes in the HTori normal thyroid cells were demonstrated using this method. There was a comparison of the cell behaviour between control cells, cells treated by plasma of a nanosecond dielectric barrier discharge, including cells pre-treated by catalase, and cells treated with an equivalent amount of H2O2. The major changes in the cell membrane morphology were observed at only 5 min after the plasma treatment. The primary role of reactive oxygen species (ROS) in this degradation is suggested. Deformation and condensation of the cell nucleus were observed 2-3 h after the treatment and are supposedly related to apoptosis induction. The coupling of the phase QWLSI with immunofluorescence imaging would give a deeper insight into the mechanisms of plasma induced cell death.