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    A novel mechanism of contrast in MRI: pseudo super-diffusion of water molecules unveils microstructural details in biological tissues

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    The goal of this work is to investigate the properties of the contrast provided by Anomalous Diffusion (AD) γ-imaging technique and to test its potential in detecting tissue microstructure. The collateral purpose is to implement this technique by optimizing data acquisition and data processing, with the long term perspective of adoption in massive in vitro, in vivo and clinical studies. The AD γ-imaging technique is a particular kind of Diffusion Weighted- Magnetic Resonance Imaging (DW-MRI). It represents a refinement of conventionally used DW-MRI methods, sharing with them the advantage of being non invasive, since it uses water as an endogenous contrast agent. Besides, it is more suitable to the study of complex tissues, because it is based on a theoretical model that overcomes the simplistic Gaussian assumption. While the Gaussian assumption predicates the linearity between the average molecular displacement of water and the diffusing time, as in case of diffusion in isotropic, homogeneous and infinite environments, a number of experiments performed in vitro and in vivo on both animals and humans showed an anomalous behavior of water molecules, with a non linear relation between the distance travelled and the elapsed time. In particular, the γ-parameter quantifies water pseudo super-diffusion, a peculiarity due to the fact that water diffusion occurs in multi-compartments and it is probed by means of MRI. In fact, a restricted diffusion is rather predicted for water diffusing in biological tissues. Recently, the trick that allows to make the traditional DW-MRI acquisition sequence suitable for pseudo super-diffusion quantification has been unveiled, and in short it consists in performing DW experiments varying the diffusion gradient strengths, at a constant diffusive time. The γ-parameter is extracted by fitting DW-data to a stretched-exponential function. Finally, probing water diffusion in different directions allows to reconstruct a γ-tensor, with scalar invariants that quantify the entity of AD and its anisotropy in a given volume element. In vitro results on inert materials revealed that γ correlates with internal gradients arising from magnetic susceptibility differences (Δ) between neighboring compartments, and that it reflects the multi-compartmentalization of the space explored by diffusing molecules. Furthermore, values of γ compatible with a description of super-diffusive motion were found. This anomaly can be explained considering that the presence of Δ induce an additional attenuation to the signal, simulating a pseudo super-diffusion. Finally, In vivo results on human brain showed that γ is more effective in discriminating among different brain regions compared to conventional DWMRI parameters. These studies suggest that the contrast provided by AD γ-imaging is influenced by an interplay of two factors, Δ -effects on one hand, multicompartmentalization on the other hand, through which γ could reflect tissue microstructure. With the aim to shed some light on this issue I performed AD γ-imaging in excised mouse spinal cord (MSC) at 9.4 T and healthy human brain at 3.0 T. The adoption of MSC was motivated by its current use in studies of demyelination due to an induced pathology that mimics Multiple Sclerosis alterations, and by its simplified geometry. I acquired DW-data with parameters optimized for the particular system chosen: the MSC was scanned along 3 orthogonal directions, thus an apparent γ was derived; for the in vivo studies I used more directions and I extracted a γ-tensor. I found that γ and its anisotropy reflected the microstructure of spinal cord tracts (such as the axon diameters and the axonal density). I investigated both in MSC and human brain the relation between γ and the rate of relaxation (R2*), a parameter well-known to reflect Δ, and found significant linear correlations. Because of this γ was able to differentiate white matter regions on the basis of their spatial orientation, and gray matter regions on the basis of their intrinsic iron content in human brain imaged at 3.0 T. These results suggest that AD γ-imaging could be an alternative or complementary technique to DW-MRI in the field of neuroscience. Indeed it could be useful for the assessment of the bulk susceptibility inhomogeneity, which reflects iron deposition, the hallmark of several neurodegenerative diseases. The part of this thesis work concerning the in vivo experiment in human brain gave rise to a paper published on NeuroImage, a relevant scientific journal in the field of MRI applied to brain investigation

    Anomalous diffusion stretched exponential gamma-imaging model provides new information on spinal cord microstructure - e-poster #2907

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    Anomalous diffusion (AD) stretched-exponential g-imaging model, was applied to investigate a fixed mouse spinal cord by using gradient strength varying PGSTE sequence at 9.4T. To highlight the new additional information provided by AD approach, we compared AD images with results obtained by using conventional DTI, relaxometry and histological data. Mean g (Mg), g-anisotropy (Ag), gpar and gortho are able to detect microstructural information of white matter (WM) in spinal cord more specific and complementary to those provided by DTI. Specifically, the correlation between Ag and myelin fraction is in agreement with the anisotropic rearrangement of myelin along WM fibers

    Anomalous diffusion gamma-imaging to assess spinal cord white matter microstructure #2907

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    Anomalous diffusion (AD) stretched-exponential gamma-imaging model, was applied to investigate a fixed mouse spinal cord by using gradient strength varying PGSTE sequence at 9.4T. To highlight the new additional information provided by AD approach, we compared AD images with results obtained by using conventional DTI, relaxometry and histological data. Mean gamma , gamma-anisotropy , gammapar and gammaortho are able to detect microstructural information of white matter (WM) in spinal cord more specific and complementary to those provided by DTI. Specifically, the correlation between gamma-anisotropy and myelin fraction is in agreement with the anisotropic rearrangement of myelin along White Matter fibers

    New Insights From MRI and Cell Biology Into the Acute Vascular-Metabolic Implications of Electronic Cigarette Vaping

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    : The popularity of electronic cigarettes (e-cigs) has grown at a startling rate since their introduction to the United States market in 2007, with sales expected to outpace tobacco products within a decade. Spurring this trend has been the notion that e-cigs are a safer alternative to tobacco-based cigarettes. However, the long-term health impacts of e-cigs are not yet known. Quantitative magnetic resonance imaging (MRI) approaches, developed in the authors' laboratory, provide conclusive evidence of acute deleterious effects of e-cig aerosol inhalation in the absence of nicotine in tobacco-naïve subjects. Among the pathophysiologic effects observed are transient impairment of endothelial function, vascular reactivity, and oxygen metabolism. The culprits of this response are currently not fully understood but are likely due to an immune reaction caused by the aerosol containing thermal breakdown products of the e-liquid, including radicals and organic aldehydes, with particle concentrations similar to those emitted by conventional cigarettes. The acute effects observed following a single vaping episode persist for 1-3 h before subsiding to baseline and are paralleled by build-up of biological markers. Sparse data exist on long-term effects of vaping, and it is likely that repeated regular exposure to e-cig aerosol during vaping will lead to chronic conditions since there would be no return to baseline conditions as in the case of an isolated vaping episode. This brief review aims to highlight the potential of pairing MRI, with its extraordinary sensitivity to structure, physiology and metabolism at the holistic level, with biologic investigations targeting serum and cellular markers of inflammation and oxidative stress. Such a multi-modal framework should allow interpretation of the impact of e-cigarette vaping on vascular health at the organ level in the context of the underlying biological alterations. Applications of this approach to the study of other lifestyle-initiated pathologies including hypertension, hypercholesterolemia, and metabolic syndrome are indicated

    Competing striped structures in La2CuO4+y

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    High temperature superconductivity emerges in unique materials, like cuprates, that belong to the class of heterostructures at atomic limit, made of a superlattice of superconducting atomic layers intercalated by spacer layers. The physical properties of a strongly correlated electronic system, emerge from the competition between different phases with a resulting inhomogeneity from nanoscale to micron scale. Here, we focus on the spatial arrangements of two types of structural defects in the cuprate La2CuO4+y : (i) the local lattice distortions in the CuO2 active layers and (ii) the lattice distortions around the charged chemical dopants in the spacer layers. We use a new advanced microscopy method: scanning nano X-ray diffraction (nXRD). We show here that local lattice distortions form incommensurate nanoscale ripples spatially anticorrelated with puddles of self-organized chemical dopants in the spacer layers

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Acute Effects of Electronic Cigarette Aerosol Inhalation on Vascular Function Detected at Quantitative MRI

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    Background Previous studies showed that nicotinized electronic cigarettes (hereafter, e-cigarettes) elicit systemic oxidative stress and inflammation. However, the effect of the aerosol alone on endothelial function is not fully understood. Purpose To quantify surrogate markers of endothelial function in nonsmokers after inhalation of aerosol from nicotine-free e-cigarettes. Materials and Methods In this prospective study (from May to September 2018), nonsmokers underwent 3.0-T MRI before and after inhaling nicotine-free e-cigarette aerosol. Peripheral vascular reactivity to cuff-induced ischemia was quantified by temporally resolving blood flow velocity and oxygenation (SvO2) in superficial femoral artery and vein, respectively, along with artery luminal flow-mediated dilation. Precuff occlusion, resistivity index, baseline blood flow velocity, and SvO2 were evaluated. During reactive hyperemia, blood flow velocity yielded peak velocity, time to peak, and acceleration rate (hyperemic index); SvO2 yielded washout time of oxygen-depleted blood, rate of resaturation, and maximum SvO2 increase (overshoot). Cerebrovascular reactivity was assessed in the superior sagittal sinus, evaluating the breath-hold index. Central arterial stiffness was measured via aortic pulse wave velocity. Differences before versus after e-cigarette vaping were tested with Hotelling T2 test. Results Thirty-one healthy never-smokers (mean age, 24.3 years ± 4.3; 14 women) were evaluated. After e-cigarette vaping, resistivity index was higher (0.03 of 1.30 [2.3%]; P < .05), luminal flow-mediated dilation severely blunted (-3.2% of 9.4% [-34%]; P < .001), along with reduced peak velocity (-9.9 of 56.6 cm/sec [-17.5%]; P < .001), hyperemic index (-3.9 of 15.1 cm/sec2 [-25.8%]; P < .001), and delayed time to peak (2.1 of 7.1 sec [29.6%]; P = .005); baseline SvO2 was lower (-13 of 65 %HbO2 [-20%]; P < .001) and overshoot higher (10 of 19 %HbO2 [52.6%]; P < .001); and aortic pulse wave velocity marginally increased (0.19 of 6.05 m/sec [3%]; P = .05). Remaining parameters did not change after aerosol inhalation. Conclusion Inhaling nicotine-free electronic cigarette aerosol transiently impacted endothelial function in healthy nonsmokers. Further studies are needed to address the potentially adverse long-term effects on vascular health. © RSNA, 2019 Online supplemental material is available for this article
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